INVITED LECTURES

27 March | WEDNESDAY
THINKING MORE: HEPATITIS B AND C population, the number of CHB patients with metabolic comorbidities
and metabolic dysfunction associated steatotic liver disease (MASLD)
ELIMINATION DIALOGUE IN ASIA PACIFIC is increasing rapidly. Presence of metabolic comorbidities and MASLD
09:00-16:00 | Auditoriuml is associated with an increased risk of adverse liver related outcomes
in patients with CHB. Early diagnosis and treatment of metabolic
comorbidities is therefore of major importance. Whether presence of
26TM0103 metabolic comorbidities and MASLD should influence the threshold to
Progress of Hepatitis C Eliminationn initiate antiviral therapy remains a matter of controversy.
Jian Li1, Weijuan Yan1 Given the availability of well-tolerated oral antiviral therapies, many
1
National Center for AIDS/STD Control and Prevention, Chinese of our patients have initiated treatment over the last decade. Most of
Center for Disease Control and Prevention, Beijing, China these patients have been treated with nucleo(s)tide analogues for a
prolonged period but have not achieved HBsAg clearance. Some of
Since the World Health Organization (WHO) proposed the vision of
these patients may be eligible for therapy withdrawal, as this could
eliminating the public health threat of viral hepatitis by 2030 in 2016,
increase the probability of HBsAg loss. However, this potential benefit
China has actively advanced efforts to eliminate the hazard of hepatitis
of finite therapy is counterbalanced by a significant risk of potentially
C. “China’s viral hepatitis prevention and control plan (2017-2020)”
severe withdrawal flares which can precipitate liver failure. Selection
and “Action plan for eliminating public health hazards of hepatitis C
of patients for finite nucleo(s)tide analogue therapy therefore requires
(2021-2030)” have been developed to guide the elimination efforts.
individualized decision-making based on the patient’s risk profile and
Some technical guidelines including “Diagnostic criteria for hepatitis
viral antigen levels. In patients who have discontinued antiviral therapy,
C” and “Guidelines for the prevention and treatment of hepatitis C”
careful off-treatment follow-up is essential to identify patients who
were also updated and released.
require urgent retreatment. The decision to re-initiate treatment should
In China, HCV prevention and control efforts have been integrated with
be based on HBV DNA and HBsAg levels, and could be further refined
HIV - prevention programs, adopting a “multi - disease prevention and
using novel biomarkers such as HBcrAg and HBV RNA.
control” strategy. HCV control and prevention has made significant
Finally, given the high risk of HCC in patients with CHB, identification of
progress in recent years. Firstly, new HCV infections have been
patients at significant risk is essential for optimizing HCC surveillance
effectively controlled by implementing blood safety, strengthening
programs. Historically, selection of patients for HCC surveillance was
nosocomial infection control, and conducting comprehensive
based on either presence of cirrhosis, or a combination of patient
interventions among key populations. Secondly, HCV testing was
ethnicity, age, and family history. Given the aging CHB population,
expanded and detection rates were improved by implementing the
the number of patients eligible for HCC surveillance based on these
strategies of “testing all in need” in medical institutions and among
criteria is increasingly rapidly, and since HCC risk may vary widely
key populations, “testing all of those with the willingness to be tested”
across patient subpopulations, more effective risk stratification tools
for the general public, and “nucleic acid testing for anyone tested
are required. The use of HCC prediction models can help individualize
positive for anti-HCV.” Thirdly, treatment coverage was improved
the decision to initiate HCC surveillance, and can be used to tailor
by establishing a designated hospital healthcare service model for
HCC surveillance in patients on prolonged antiviral therapy.
“treating all eligible” people living with chronic HCV infection. Fourthly,
patients’ financial burden was reduced and affordability of care was
improved by implement healthcare insurance policies. Three direct- 26TM0402
acting antivirals (DAAs) were listed into National Reimbursement Drug Adult Vaccination for Hepatitis B
List (NRDL) through national negotiant at end of 2019, with average
Fuqiang Cui
85% reduction in price. By the end of 2024, eight DAAs had been
Beijing
included in NRDL, comprising five domestic innovative drugs and
three imported ones. Fifthly, a unified web-based national information China is a country with a high prevalence of HBV infection. In 1992,
system for hepatitis C prevention and treatment was developed to the hepatitis B vaccination was implemented, and in 2001, hepatitis
collect information along the continuum of HCV care from diagnosis to B vaccines were provided free of charge to infants. By 2005, hepatitis
treatment initiation, completion, and cure. By the end of 2024, percent B vaccination became free of charge across the country. Since
of newly reported anti-HCV positive cases tested for HCV RNA neared the introduction of hepatitis B vaccination for children, vaccination
80%. The treatment rate for newly reported HCV cases eligible for coverage among children has reached a high level. After 40 years
treatment reached 60%. Existing HCV cases declined from around 3 of effort, hepatitis B vaccination in children has significantly reduced
million in 2021 to approximately 2.2 million. their chances of HBV infection. The prevalence of HBsAg among
Despite progress, challenges remain. A large population of chronic children under 5 years old has declined from 9.67% in 1992 to
HCV patients exists, leading to the potential of a huge burden of 0.3% in 2020, while the overall prevalence of HBsAg in the general
hepatitis C-related liver cirrhosis and HCC. There are large gaps population has decreased from 9.75% to 5.86%. Due to the still large
between targets and current progress, such as for testing and number of infected individuals in China, acute hepatitis B continues to
treatment coverage. Looking ahead, China must strengthen its multi- occur in adults. To achieve the global goals by 2030, it is necessary
faceted approach to HCV elimination. This includes increasing financial to further reduce the incidence of new HBV infections. This requires
investment, improving healthcare infrastructure, and expanding access not only maintaining a high childhood vaccination coverage but also
to testing and treatment. With sustained commitment and coordinated vaccinating adults who are susceptible to HBV, thereby reducing the
efforts, China aims to eliminate Hepatitis C as a public health threat opportunities for high-risk groups to become infected with HBV. Only
and reduce the burden of HCV-related disease. in this way can we accelerate the achievement of the goal of reducing
the incidence of new cases by 90% by 2030.

26TM0301
Overseas Experience - Personalized Healthcare for Patients with APASL-EASL JOINT WORKSHOP
Timely Clinical Decision Making for Advanced
Chronic Hepatitis B
Milan J. Sonneveld
Amsterdam Chronic Liver Disease
Chronic hepatitis B virus infection (CHB) is associated with a high risk 08:30-17:00 | Function Hall C
of developing hepatocellular carcinoma (HCC) and other adverse
liver related outcomes. As CHB affects 2-3% of the global population,
effective management of these patients requires an individualized 26AE0105
approach in order to balance benefits, risks and costs. In the aging CHB
Preventing First Decompensation in Alcohol-Related Liver hepcidin- ferroportin axis and are designed to increase hepcidin
Disease: A Paradigm Shift in Early Detection and Intervention expression and reduce intestinal iron absorption.
Aleksander Krag
Odense 26AE0204
Alcohol-related liver disease (ALD) remains the leading cause of Inherited hyperbilirubinemia-problems and perspectives
chronic liver disease globally, accounting for 50–75% of cases. Haitian Yu, Sujun Zheng1
Despite its high prevalence, ALD is often diagnosed at advanced 1
Beijing You’an Hospital, Capital Medical University, Beijing, China
stages, when treatment options are limited. However, recent advances
in biomarker discovery have revolutionized early detection, offering not Hereditary hyperbilirubinemia refers to a group of bilirubin metabolism
only diagnostic tools but also prognostic insights to identify individuals disorders caused by genetic factors. Based on the type of bilirubin
at risk of disease progression. elevation, it can be classified into Gilbert syndrome(GS), Crigler-Najjar
A key conceptual shift has emerged with the updated nomenclature syndrome, Dubin-Johnson syndrome, and Rotor syndrome. Among
of steatotic liver disease (SLD), positioning ALD within a broader these, GS is the most common disorder, with an incidence of 3-12%
continuum that integrates cardiometabolic risk factors. More than in the general poulation. It is characterized by mild unconjugated
95% of patients with ALD exhibit cardiometabolic comorbidities, and hyperbilirubinemia and has a benign prognosis. This presentation are
studies show that approximately 75% present with three or more focused on the area required further research in GS. First, UGT1A1
cardiometabolic risk factors. This highlights the urgent need for a gene mutation is considered to be a major factor contributed to GS.
combined, multidisciplinary approach that addresses both alcohol However other potential genetic variations (such as SLCO1B1, HMOX-
consumption and metabolic dysfunction. 1, and BLVRA) may also affect unconjugated bilirubin levels and need
At this crucial disease stage, intervention strategies can significantly further study. Second, GS may benefit from the mild hyperbilirubinemia
alter disease trajectory. Alcohol reduction strategies, alongside and are virtually protected from the development of a wide variety of
targeted therapies for metabolic dysfunction, present promising “diseases of civilization”. However, this conclusion remains controversial
opportunities for preventing first decompensation. Additionally, across different cohort studies. Third, UGT1A1 enzyme is a phase II
emerging evidence from preclinical and observational studies enzyme in drug metabolism, and the interaction between UGT1A1
suggests that GLP-1 receptor agonists and FGF21 analogues not gene mutations and commonly drug used in GS deserves attention.
only improve metabolic health but also reduce alcohol intake. With Both chronic hepatitis B (CHB) and GS are common diseases, and
two Phase II clinical trials currently underway, the landscape of ALD the efficacy and safety of antiviral therapy in CHB patients with GS are
treatment is rapidly evolving. worth studying.
This talk will explore the latest breakthroughs in ALD prevention,
focusing on the role of biomarkers, novel therapeutic targets, and 26AE0401
integrated intervention strategies. By leveraging these advances, we Inherited hyperbilirubinemia-problems and perspectives
have the potential to redefine the management of ALD, shifting the
Debbie Shawcross
focus from late-stage treatment to proactive, preventive care.
London
Hepatic encephalopathy (HE) is a syndrome that is associated with
26AE0201
both acute and chronic liver injury manifesting as a wide spectrum
Hereditary Haemochromatosis – Iron and the Liver of neuropsychological abnormalities ranging from subtle impairments
Darrell H.G. Crawford1 in executive higher functions observed in cirrhosis through to coma
1
Gallipoli Medical Research and The University of Queensland in acute liver failure (ALF). In ALF, the central role of ammonia in the
Brisbane. Australia development of brain oedema has remained undisputed for 130 years.
Haemochromatosis is an inherited disorder of iron metabolism more The association of systemic inflammation with brain dysfunction dates
prevalent in European populations. Despite some underlying genetic back over 2500 years to Hippocrates of Kos (460-370 BCE) who
heterogeneity, in nearly all cases there is an inappropriately high described patients with abscesses and fever as having ‘phrenitis’ or
cellular release of iron from professional iron exporting cells such inflammation of the mind. Later, in 200 CE Claudius Galen offered the
as enterocytes and macrophages. The increase in intestinal iron first description of delirium, suggesting inflammation affected the mind
absorption results in the deposition of excess iron in parenchymal cells ‘sympathetically’ and much later in the 19th century Sir William Osler
of the liver and other organs with complications including cirrhosis, described septicaemia where “organisms enter the blood from some
diabetes mellitus, arthritis, cardiomyopathy, and hypogonadotropic local septic focus” being associated with impaired brain function in the
hypogonadism. The condition is most often due to a mutation in the form of “early delirium or marked mental prostration and apathy.”
HFE gene with homozygosity for the C282Y mutation accounting for In ALF, the association of inflammation with HE has long been
80–90% of hemochromatosis in persons of northern European descent. demonstrated through correlation with the Systemic Inflammatory
Mutations in other genes involved in iron metabolism can result in iron Response Syndrome (SIRS). Rolando et al. were able to show that ALF
overload and there are multiple reports of non-HFE iron overload in patients with a higher SIRS score on admission to the intensive care
Asian subjects. Hepcidin is a key regulator of iron metabolism, and unit were more likely to develop worsening encephalopathy, raised
hepcidin deficiency is the basic pathophysiological defect in most intracranial pressure and death. This was regardless of a diagnosis of
cases of hemochromatosis. This liver-derived peptide represses infection. It latterly became apparent that infection and inflammation
basolateral iron export from intestinal enterocytes and iron release from were profound determinants for the development of severe HE
macrophages and other cells by binding to ferroportin. associated with the development of cerebral oedema and intracranial
The expression of the disease is variable and modified by alcohol hypertension.
consumption, blood loss associated with menstruation and pregnancy, In cirrhosis, the role of ammonia is less clear and clinical and
and blood donation. The disease is now often diagnosed during its early mechanistic studies point towards a synergistic effect primarily
stages when iron overload and organ damage are minimal. Recent modulated by the presence of inflammation. Numerous clinical
population studies indicate that ~40% of homozygous men develop studies have demonstrated that ammonia has a pathogenic role to
iron overload–related complications and about 6% develop hepatic play in the development of cirrhosis related HE, with those patients
cirrhosis. For women, iron overload–related complications occur in with more severe grades of HE exhibiting higher serum ammonia
~ 10%. The therapy of hemochromatosis involves phlebotomy. Oral levels. However, serum ammonia can be elevated in patients with
iron chelating agents are also available. These agents are effective in no clinical evidence of overt HE. Mechanistic studies to explain how
thalassemia and secondary iron overload but are expensive, carry the chronic hyperammonaemia and peripheral inflammation induce
risk of significant side effects and remove less iron than phlebotomy. neuroinflammation and how this subsequently leads to impaired
Emerging therapies for iron overload diseases are focussed on the cognitive and motor function are abundant.
A perturbed gut microbiome and the presence of an impaired gut comparisons among studies and clinical decision-making and
epithelial barrier that facilitates translocation of bacteria and bacterial establishing novel therapies. Many scholars and scientific societies
degradation products into the systemic circulation inducing systemic including WGO,CMA,ACG ,AASLD and APASL have been working
inflammation and innate and adaptive immune dysfunction has now to establish a consensus definition of ACLF. Recently, CMA-CSH
become the focus of therapies that treat HE in cirrhosis and may proposed ACLF can be reclassified as types I and II based on clinical
explain why the prebiotic lactulose and rifaximin are efficacious. Over study in China in 2023 and Chinese guideline in 2018. ACLF -Type I
the last three decades a significant body of evidence has accumulated highlights acute hepatic deterioration resulting in hepatic failure. ACLF-
to support the theory of synergism of inflammation and ammonia in Type II highlights acute hepatic dysfunction at onset, accompanied by
the pathogenesis of HE. More recently, advances in our understanding at least one extrahepatic organ failure. APASL AARC also proposed
of gut-derived systemic inflammation and the gut-brain-liver axis has ACLF can be reclassified as types A and B in Kyoto Consensus.
driven advances in new treatment modalities. Currently, these are Chinese Society of Infectious Diseases & Chinese Society of
mainly focussed on targeting gut dysbiosis with faecal microbiota Hepatology, Chinese Medical Association(CMA) jointly formulated
transplantation and probiotics. However, there remains an untapped CMA Guidelines for diagnosis and treatment of liver failure in 2006,
area that directly targets peripheral and neuroinflammation and new followed by updates in 2012 , 2018 and 2024.Guideline for diagnosis
therapeutic options are desperately needed to treat the debilitating and treatment of acute-on-chronic liver failure has been established
and sometimes fatal complication of HE. by Chinese Society of Hepatology (CSH).In Chinese guidelines,ACLF
is defined as clinical syndrome characterized by acute deterioration
of liver function due to acute insult on underlying chronic liver disease
26AE0402
(with or without cirrhosis) accompanied by hepatic and/or extrahepatic
Portal Hypertension and Variceal Bleeding organ failure with high short-term mortality.
Necati Örmeci1 ACLF is diagnosed functionally in clinical practice.A trans-jugular liver
1
İstanbul Health and Technology University biopsy can be performed in order to provide more reliable pathological
Portal hypertension is a major complication of cirrhosis that leads to information in some cases.Pathogenesis of ACLF involves systemic
the formation of gastroesophageal varices, posing a significant risk inflammatory response and immune metabolic imbalance, leading to
of life-threatening hemorrhage. Primary and secondary prophylaxis organ dysfunction and organ failure. Patients at higher risk of ACLF
strategies are crucial for managing patients at risk or with a history development should be considered as pre-ACLF stage in Chinese
of variceal bleeding. This abstract summarizes current approaches to guidelines.Based on the COSSH criteria , ACLF is divided into three
primary and secondary prophylaxis, including pharmacological and grading severity. Prognostic scores (e.g., MELD or MELD-Na, or AARC
endoscopic interventions. ACLF, COSSH,CLIF-C, NACSELD scores) are recommended.Dynamic
Primary prophylaxis aims to prevent the first episode of variceal evaluation of ACLF-specific prognostic scores is useful for further
bleeding in patients with high-risk varices. Non-selective beta- assessment of prognosis among patients with ACLF.
blockers (NSBBs), such as propranolol and carvedilol, are the first- Comprehensive management should be implemented throughout
line agents that reduce portal pressure by decreasing cardiac output clinical course of ACLF.Chinese guidelines emphasize‘Three-Early
and splanchnic vasoconstriction. Endoscopic variceal ligation (EVL) and One-System’strategy. Artificial liver support system in China
is recommended for patients who are intolerant to NSBBs or those has undergone continuous evolution,transitioning from single
with contraindications. Comparative studies indicate that EVL and modality of plasma exchange,replacement, adsorption, and filtration
NSBBs have similar efficacy in preventing first-time bleeding, but EVL to an optimized combination of different modalities based on the
is associated with fewer systemic adverse effects. disease condition.Non-bioartificial liver support system has been
Secondary prophylaxis is intended to prevent recurrent bleeding recommended for ACLF patients with COSSH grades 1-2(early
in patients who have survived an initial variceal hemorrhage. The -intermediate stages).For ACLF patients with COSSH grade 3
combination of NSBBs and EVL is the preferred approach, as it (advanced stage ) should be a cautious decision,and actively seek
significantly reduces rebleeding rates compared to either therapy opportunities for liver transplantation.Current bioartificial and hybrid
alone. In patients with advanced liver disease (Child-Pugh B/C), early artificial liver support system is not recommended outside clinical
transjugular intrahepatic portosystemic shunt (TIPS) placement within trials. Liver transplantation is the curative approach for eligible ACLF
72 hours of acute bleeding has demonstrated improved survival and patients.Early LT is recommended for patient with ACLF grade 2-3
reduced rebleeding rates compared to standard treatment. However, after CMT and ALSS.Patients with > 3 OFs or CLIF-C ACLF score >64
the risk of hepatic encephalopathy must be considered when using should be evaluated daily and listed for LT when improves to ≤3 OFs
TIPS. or CLIF-C ACLF score ≤ 64.
Recent studies have explored the use of pre-emptive TIPS in high-
risk patients, showing improved rebleeding-free survival, particularly in 26AE0404
those with Child-Pugh B or C scores. Pharmacological advancements,
Portal Vein Thrombosis
including the use of vasoactive agents like terlipressin, have also been
investigated for acute variceal bleeding management but require Juan Carlos GARCIA-PAGAN1
further validation for prophylactic use. Additionally, novel endoscopic
1
Barcelona
techniques, such as thrombin injection and cyanoacrylate glue, have Portal vein thrombosis (PVT) is a common complication in cirrhotic
shown promising results in controlling gastric variceal bleeding, patients, occurring in up to 15.8% of cases and in over 17% of liver
although their role in prophylaxis remains to be clearly defined. transplant candidates. Despite its prevalence, its exact causes and
clinical consequences remain debated. While the impact of PVT on the
natural history of cirrhosis is unclear, it significantly affects morbidity
26AE0403
and mortality after liver transplantation (LT), particularly when a non-
Timely Clinical Decision-Making for Acute-on-chronic Liver Failure physiological anastomosis is required.
Tao Han1 PVT is often asymptomatic and incidentally detected during routine
1
Tianjin Union Medical Center,The First Affiliated Hospital of Nankai imaging. Doppler ultrasound is the preferred diagnostic tool,
University,China though contrast-enhanced CT or MRI is necessary characterization.
Acute-on-chronic liver failure (ACLF) is clinical syndrome characterized Classification systems for PVT are primarily based on thrombosis
by rapid deterioration in patients with chronic liver disease or cirrhosis extent, its effect on blood flow, and its influence on portal hypertension.
that is associated with high short-term mortality. Management of PVT depends on the severity, age of the thrombus
Early warning/ identification,timely clinical decision-making for ACLF (recent vs. chronic), and whether the patient is a liver transplant
significantly reduce mortality. candidate.
Heterogeneity among the various definitions of ACLF hampers In transplant candidates, the goal is to prevent clot progression
and preserve sufficient portal vein patency to enable physiological
anastomosis during LT. Anticoagulation is the first-line treatment, with Introduction
vitamin K antagonists (VKAs), low-molecular-weight heparin (LMWH), Data is ubiquitous in today’s digital age, with vast amounts generated
and direct oral anticoagulants (DOACs) being the most used agents. from internet usage, social media, mobile devices, and digital services.
In recent PVT, anticoagulation may lead to recanalization, with success This data is invaluable for analyzing trends, patterns, and making
rates ranging from 39% to 75%, especially when initiated within six connections between events, particularly in clinical research using
months of onset. electronic health records (EHRs).
In chronic PVT, the goal of anticoagulation shifts from recanalization Strengths of Clinical Research with EHRs
to preventing further thrombosis progression, ensuring enough patent EHRs allow for the establishment of diverse study cohorts and enable
portal vein remains for physiological portal-to-portal vein anastomosis studies with large sample sizes, enhancing statistical power. They are
during LT. If chronic PVT extends to the spleno-mesenteric particularly useful for studying rare events or conditions that take time
confluence and already precludes physiological anastomosis, to manifest.
portal vein recanalization combined with transjugular intrahepatic Case Study: Bone Safety with HBV Antiviral Treatment
portosystemic shunt (PVR-TIPS) is considered to restore flow. PVR- A retrospective cohort study using data from an electronic healthcare
TIPS is also recommended for patients with progressive PVT despite database in Hong Kong examined the bone safety of long-term HBV
anticoagulation. antiviral treatment. The study included elderly subjects with chronic
For non-transplant candidates, the only absolute indication for hepatitis B. Primary outcome was fracture defined by ICD-9 codes.
treatment is thrombosis extending into the superior mesenteric Handling Missing Data
vein causing intestinal ischemia, though this is rare. In other cases, Missing data is a common issue in EHRs due to inconsistent testing
treatment decisions remain controversial. Arguments for and against across patients. Methods to address missing data include single
anticoagulation depend on thrombosis extent, spontaneous evolution imputation (mean/mode imputation, regression imputation, last value
(progression vs. regression), and its potential impact on cirrhosis carried forward) and multiple imputation, which accounts for the
progression. However, multiple studies suggest that anticoagulation, uncertainty of missing values.
even without achieving recanalization, reduces portal hypertension- Propensity Score
related complications and improves survival. Propensity score (PS) methods were used to balance baseline
Despite limited high-quality evidence, our current approach in non- characteristics between treatment groups, mimicking randomized
LT candidates is to initiate anticoagulation in cases where thrombosis controlled trials. Inverse probability of treatment weighting (IPTW)
affects multiple segments of the portal venous system, shows imaging and propensity score matching (PSM) are common methods. Some
evidence of progression, or is associated with severe complications of common treatment effects that can be estimated include the average
portal hypertension. treatment effect (ATE), average treatment effect for the treated (ATT),
and average treatment effect for the overlap population (ATO).
26AE0501 Survival Analysis
Kaplan-Meier (KM) and Aalen-Johansen (Gray’s) methods can be
Gastroesophageal Variceal Bleeding in Portal Hypertension: The used to estimate cumulative incidence. The KM method overestimates
Endoscopic and Radiological Interventional Treatments cumulative incidence when competing risks exist. The Fine-Gray
Xu Wen1,2, Gao Yan3, Ding Huiguo1 subdistribution hazards model can be employed to estimate
1
Department of Gastroenterology and Hepatology, Beijing subdistribution hazard ratios, adjusting for competing risks.
You’an Hospital Affiliated to Capital Medical University China Challenges of Clinical Research with EHRs
100069,2Department of Gastroenterology, Taihe Hospital, Shiyan City, EHRs provide real-world data representing a broader patient spectrum
Hubei Medical University, 3Department of Anatomy, School of Basic than randomized controlled trials (RCTs), making findings more
Medicine, Capital Medical University, China. applicable to routine clinical practice. However, challenges include
Portal hypertension is a major resulted from the cirrhosis, leading defining clinical outcomes, exposures, covariates, and potential
not only to esophageal gastric variceak bleeding but also to the confounders, as well as dealing with undercoding or misclassification.
development of spontaneous portosystemic shunts (SPSS). SPSS is the Conclusion
main obstacles the choice of endoscopic or radiological interventional Analyzing EHRs requires statistical and data science expertise, and
treatment by clinicians. Current guidelines recommendations for collaboration with statisticians or data scientists is recommended.
the management of gastric varices vary between China and other
international committee recommendations, and they do not explicitly 26AA0201
mention the treatment modalities for gastric varices with SPSS.
Recent advancements in understanding the vascular anatomy using Liver Related Journals: Impact Factor and Journal Selection
CT imaging and artificial intelligence of gastric varices, will provide Sang Hoon Ahn1,2.3
precise strategies for the treatment of gastric varices by endoscopic 1
Department of Internal Medicine, 2Institute of Gastroenterology,
and radiological interventional treatment. Endoscopic treatment Yonsei University College of Medicine, Seoul, Republic of Korea;
includes direct injection of tissue glue through endoscopy, banding,
3
Yonsei Liver Center, Severance Hospital, Seoul, Republic of Koreaa
and injection of tissue glue or and coil through ultrasound endoscopy. For young doctors embarking on a career in hepatology, publishing
Radiological intervention includes TIPS and or BRTO. Currently, there research is a critical milestone. However, navigating the complex
is still a lack of high-quality evidences from head-to-head randomized landscape of academic journals can be challenging, particularly
clinical study between endoscopy and radiological intervention. when deciding where to submit and how to evaluate the impact of
a publication. This presentation is designed to provide early-career
hepatologists in the Asia-Pacific region with essential knowledge
APASL-AASLD JOINT WORKSHOP about key journal metrics, such as the impact factor and H-index, while
Be-A-Professional: Research and Publication offering practical guidance on selecting the right journal for their work.
We will explore the concept of the impact factor, detailing its calculation
09:00-16:45 | Function Hall A and significance in assessing journal influence. Attendees will also
learn about the H-index as a measure of an individual’s research
productivity and citation impact, and how these metrics complement
26AA0104 each other in academic evaluations. The session will spotlight leading
Data Management and Statistical Analyses journals in hepatology, including Journal of Hepatology, Hepatology,
Terry Cheuk-Fung Yip1 Liver Cancer, and Clinical and Molecular Hepatology (CMH). Each
1
Medical Data Analytics Centre, Department of Medicine and journal’s scope, audience, and impact factor will be reviewed to help
Therapeutics, The Chinese University of Hong Kong, Hong Kong participants align their research topics with the most suitable outlets.
SAR, China Journal of Hepatology and Hepatology remain the highest-impact
journals, covering a wide spectrum of liver-related research. Liver on the future investigation of cccDNA biology, as well as strategies
Cancer serves as a key platform for research on liver malignancies, and progress in therapeutic elimination and/or transcriptional silence
while CMH has seen a remarkable increase in its impact factor in of cccDNA for the functional cure of chronic hepatitis B will also be
recent years, reflecting its growing influence as a high-quality journal discussed.
for clinical and translational liver research.
In addition to journal selection, we will address practical strategies
27BS0103
for preparing manuscripts, understanding peer review processes,
and enhancing the visibility and impact of published work. Tips on Interconnection of cellular autophagy and endosomal vesicle
avoiding predatory journals and balancing the pursuit of high-impact trafficking and its role in hepatitis B virus replication and release
publications with realistic goals will also be discussed. By the end of Mengji Lu
this session, attendees will gain a deeper understanding of how to Institute for Virology, University Hospital Essen, University of
select the most suitable journal, confidently navigate the publishing Duisburg-Essen, Essen, Germany
process, build a strong academic profile, and contribute meaningfully Hepatitis B virus (HBV) produces and releases various particle types,
to the field of hepatology. This presentation aims to empower young including complete virions, subviral particles with envelope proteins,
hepatologists in the Asia-Pacific region to make informed decisions in and naked capsids. Recent studies demonstrate that HBV exploits
their research journey and excel in their careers. distinct intracellular membrane trafficking pathways, including the
endosomal sorting complexes required for transport (ESCRT) pathway
26AA0503 and autophagy, to assemble and release viral and subviral particles.
The findings about the distinct roles of autophagy and endosomal
How to respond to Q&A and discussion?
membrane trafficking and the interaction of both pathways in HBV
Carmen C.L. Wong replication, assembly, and release are summarized and discussed.
Hong Kong To date, limited evidence supports that HBV and exosomes have a
Responding to questions and engaging in discussions during a common pathway for their biogenesis and secretion. The final steps
research presentation are vital for effectively communicating your of HBV production and release have not yet been well studied. We
work and connecting with your audience. Although often overlooked, targeted host factors neutral sphingomyelinase (nSMase) and
the Q&A session is one of the most critical aspects for demonstrating RAB27A/B that are involved in exosome release. The results from these
the quality of a presentation. This presentation highlights essential experiments demonstrate the involvement of the autophagosome-
strategies for preparing and managing Q&A sessions to maximize the late endosome/MVB-exosome axis in regulating HBV production and
overall impact of your research presentation. We will delve into the release, highlighting amphisomes as a potential platform for HBV
importance of preparation, understanding the audience’s background, release.
and techniques for addressing challenging questions.
27BS0201
BASIC SCIENCE COURSE Classic biomarkers in current clinical practice
Henry LY Chan
Biomarkers: Diagnosis and Drug Discovery Hong Kong
08:00-17:00 | Function Hall A HBsAg, HBeAg, and HBV DNA have been used widely in the
assessment of chronic hepatitis B. The key clinical applications are
to assess for commencement of antiviral therapy, monitor for efficacy
27BS0101 of antiviral treatment, and decide for stopping of antiviral therapy. In
Mechanism of covalently closed circular DNA (cccDNA) formation all regional guidelines, patients who have elevated HBV DNA and
Ju-Tao Guo ALT levels should receive antiviral therapy due to a higher risk of HBV
Baruch S. Blumberg Institute, Doylestown, Pennsylvania, USA related complications. There is increasing evidence that treatment
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) threshold should be relaxed towards patients in indeterminate
associates with nucleosomes to form a minichromosome in the nucleus phase, i.e. patients with borderline viraemia and ALT elevation. One
of infected hepatocyte to support the transcription of viral RNA and controversy is immune tolerant phase (or HBeAg-positive chronic
subsequent reverse transcriptional replication of viral genome and infection), in which patients have positive HBeAg, very high (> 7 log
production of progeny virions and subviral particles. Elimination and/ IU/ml) HBV DNA, normal ALT, and insignificant liver histologic damage.
or transcriptional silence of cccDNA are thus essential for the cure Although there are theoretical benefits to treat immune tolerant patients,
of chronic HBV infection. CCC DNA is synthesized in the nucleus of current antiviral therapies are insufficient to bring down HBV DNA to
hepatocyte from the relaxed circular DNA (rcDNA) or double-stranded undetectable levels. Once patients are put on nucleos(t)ide analogues
linear DNA (dslDNA) in the nucleocapsid of infecting HBV virion, the de (NA), the goal is to control HBV DNA down to undetectable levels.
novo synthesis pathway, or progeny mature nucleocapsid produced Incomplete viral suppression is associated with higher residual risk of
in the cytoplasm of infected hepatocyte, the intracellular amplification HCC. There are recommendations to use HBeAg and HBV DNA to
pathway. While the circularization of dslDNA by intramolecular monitor for timing of stopping NA, but relapse is frequent even HBeAg
nonhomologous recombination at its ends results in the formation of has turned negative and HBV DNA has been undetectable after 1 year.
cccDNA molecule with deletions and/or insertions around the site of HBsAg seroclearance is associated with excellent prognosis. HBsAg
joining and serving as intermediates in further DNA replication through seroclearance, both spontaneous and induced by NA, is very durable
a few generations of nonhomologous recombination in a process and can be use as a reliable biomarker to stop NA. HBsAg < 100
called illegitimate replication, dslDNA is also the primary precursor IU/ml is associated with a reasonable chance of subsequent HBsAg
of the integrated HBV DNA in host cellular chromosomes, which seroclearance after stopping NA, and can be used as a guide to stop
can be the major source of mRNA supporting HBsAg production in NA in selected patients.
chronic HBV carriers and thus an barrier for the functional cure of
chronic hepatitis B. However, the conversion of rcDNA by cellular 27BS0202
DNA repair machinery results in the formation of authentic cccDNA Novel and Emerging Biomarkers of chronic HBV infection-
that supports the transcription of all the viral RNA. This lecture will Implications for diagnosis and treatment
provide a comprehensive overview on the molecular pathways and
Peter Revill
biochemical mechanisms of cccDNA synthesis from dslDNA and
Victorian Infectious Diseases Reference Laboratory, Peter Doherty
rcDNA and highlight the common and distinct molecular features of de
Institute for Infection and Immunity, Melbourne, Australia
novo cccDNA synthesis and intracellular amplification. Perspectives
Chronic hepatitis B infection caused by infection with hepatitis B virus When combined with iTACT-HBsAg (cutoff: 0.0005 IU/mL), it provides
(HBV) affects almost 300 million people worldwide, including more valuable insights into NA withdrawal and enables early detection of HBV
than 110 million people in the Asia-Pacific region. Chronic Hepatitis B reactivation in HBV-resolved patients. Furthermore, declining HBcrAg
causes liver disease, including liver cancer, resulting in up to 1 million levels have been associated with a lower risk of HCC progression and
deaths per year. Despite the availability of an effective preventative recurrence, reinforcing its clinical relevance.
vaccine, chronic hepatitis B rates are increasing in many areas of the Additionally, a novel anti-HBV compound (SAG-comp; IC50 = 1.4 nM)
globe. The World Health Organisation (WHO) aims to eliminate viral has been identified through high-throughput screening. This orally
hepatitis as a public health problem by 2030, but to achieve this, all available agent effectively destabilizes HBV-RNA and suppresses
persons living with chronic HBV will need to be diagnosed and provided HBsAg, demonstrating potential for functional cure when used in
access to medical care. At present nearly 220 million people living combination with NA therapy.
with hepatitis B are undiagnosed. This is partly due to the absence of In conclusion, HBcAg and pHBcAg, along with the highly sensitive
appropriate point of care tests for low and middle income countries iTACT-HBcrAg and iTACT-HBsAg, serve as valuable biomarkers for
where HBV is highly prevalent. Another barrier to HBV elimination is HBV monitoring. Their integration into treatment strategies targeting
that although HBV is treatable with antivirals which effectively suppress HBV replication, antigen suppression, and functional cure will enhance
HBV replication and reduce the risk of liver cancer, these treatments precision medicine approaches in CHB management, ultimately
do not eliminate HBV infection, due to the presence of a reservoir improving patient outcomes.
of covalently closed circular HBV DNA (cccDNA) in the nucleus of
HBV infected cells that is not targeted by current treatments. Urgent
27BS0302
efforts are underway world-wide to develop finite curative therapies for
chronic HBV infection by targeting different aspects of the HBV life- Biomarkers of portal hypertension and chronic liver disease:
cycle and/or stimulating/restoring anti-HBV host immunity. advances and clinical implications
A major barrier to developing effective HBV cures is the absence of Jordi Gracia-Sancho
appropriate biomarkers to monitor the impact of the novel therapies Department of Gastroenterology and Hepatology, Kumamoto
in development, on HBV replication, antigen expression and host University
immune responses. For example, as liver biopsy material becomes Chronic liver disease (CLD) is a major global health burden, leading
increasingly difficult to obtain, the need for surrogate biomarkers to fibrosis, cirrhosis, and portal hypertension (PH), which significantly
in patient serum which accurately reflect HBV cccDNA levels and contribute to morbidity and mortality. The early identification of patients
expression is paramount. Importantly, markers such as secreted core- at risk for disease progression and complications remains a critical
related antigen and HBV RNA show promise as markers of cccDNA challenge in hepatology. Invasive procedures such as liver biopsy and
expression in some settings, but biomarkers that accurately reflect hepatic venous pressure gradient (HVPG) measurement are the gold
cccDNA activity at all stages of chronic HBV natural history are still standard for assessing fibrosis and PH, respectively. However, these
lacking. methods are limited by their invasiveness, cost, and availability. The
This presentation will explore current knowledge regarding novel need for non-invasive, reliable biomarkers that reflect the dynamic
and emerging biomarkers and their role in predicting or measuring nature of CLD and PH is therefore paramount.
treatment outcome across phases of chronic HBV natural history and Recent advances in molecular profiling and bioinformatics have
their implications for diagnosis and treatment. enabled the identification of novel biomarkers that can serve as
diagnostic, prognostic, and predictive tools for CLD and PH. These
27BS0203 biomarkers can be classified into serological, imaging-based, and
transcriptomic/proteomic categories. Among serological markers,
Hepatitis B Core-Related Antigen (HBcrAg): A Key Biomarker for
indirect fibrosis scores such as the AST-to-Platelet Ratio Index (APRI),
HBV Monitoring and Therapeutic Decision-Making
Fibrosis-4 (FIB-4) index, and Enhanced Liver Fibrosis (ELF) test have
Yasuhito Tanaka shown utility in assessing liver fibrosis, yet they lack specificity for PH.
Department of Gastroenterology and Hepatology, Kumamoto Direct markers such as von Willebrand factor (vWF), angiopoietin-2,
University E-Cadherin and Spink1, and soluble fms-like tyrosine kinase-1 (sFLT-
Hepatitis B core-related antigen (HBcrAg) is an essential biomarker 1) have been proposed as more specific indicators of endothelial
for evaluating intrahepatic covalently closed circular DNA (cccDNA) dysfunction and PH severity.
activity in chronic hepatitis B (CHB). This study assessed the clinical Transcriptomic and proteomic studies have further expanded our
utility of highly sensitive HBcrAg and HBsAg assays in CHB patients, understanding of PH pathophysiology. Single-cell RNA sequencing
highlighting their role in monitoring HBV replication and informing and gene deconvolution techniques have revealed specific gene
therapeutic strategies. signatures associated with sinusoidal capillarization, hepatic stellate
The HBcrAg measurement system was developed with two primary cell activation, and macrophage polarization—key processes driving
objectives: (1) a fully automated, highly sensitive HBcrAg assay (iTACT- CLD progression. Our recent findings have identified three sinusoidal
HBcrAg) and (2) a point-of-care testing (POCT) system for resource- scores (endothelial, mesenchymal, and macrophage) that correlate
limited settings. iTACT-HBcrAg serves as a reliable alternative to HBV with PH severity, fibrosis progression, and clinical decompensation.
DNA quantification for monitoring HBV reactivation and predicting These signatures, validated in large patient cohorts, provide a
hepatocellular carcinoma (HCC) risk. It has already been integrated promising avenue for precision medicine in CLD.
into routine clinical practice in Japan. Despite these advancements, the translation of biomarkers into
To enhance HBV monitoring, we evaluated the performance and routine clinical practice requires validation in prospective studies and
clinical significance of three assays: iTACT-HBcrAg, HBcAg, and standardization across different patient populations. The integration
phosphorylated HBcAg (pHBcAg). These assays exhibited high of biomarker panels with artificial intelligence-driven predictive
sensitivity and specificity, with cutoff values of 2.50 and 2.10 LogU/ models could further enhance risk stratification and guide therapeutic
mL for HBcAg and pHBcAg, respectively. Strong correlations interventions. Additionally, the role of biomarkers in monitoring
among HBcrAg components were observed, particularly in HBeAg- treatment response—particularly in the context of novel anti-fibrotic
positive cases. Importantly, HBcAg and pHBcAg levels significantly and vasoactive therapies—warrants further investigation.
declined during NA therapy, independent of HBV DNA suppression. In conclusion, the identification of non-invasive biomarkers for
Density gradient analysis identified pHBcAg as the predominant PH and CLD represents a transformative step in Hepatology. The
HBcrAg component, primarily associated with empty viral particles, convergence of molecular, imaging, and computational approaches
underscoring its potential as an independent biomarker for HBV offers the potential to replace invasive procedures, personalize patient
activity and treatment response. management, and improve outcomes. Future research should focus
The fully automated iTACT-HBcrAg assay offers approximately 10-fold on refining biomarker-driven strategies to optimize early diagnosis,
greater sensitivity (2.1 LogU/mL) than conventional HBcrAg assays. prognostication, and treatment selection in patients with CLD.
 27BS0303 tissue. Potential for diagnostic confirmation but not yet validated for
Biomarkers of Drug Induced Liver Injury surveillance.
2. MicroRNAs (miRNAs):Profiles (e.g., miR-21, miR-122, miR-223)
Robert J. Fontana
show promise in distinguishing HCC from cirrhosis. Panels like miR-
Department of Medicine, University of Michigan Medicine 122/miR-21/miR-223 are under study.
According to the US FDA, a biomarker is defined as “A characteristic 3. Exosomes and Circulating Tumor DNA (ctDNA):Tumor-derived
that is measured as an indicator of normal biological processes exosomes and ctDNA mutations (e.g., TERT promoter) may offer early
or biological responses to an exposure or intervention”. Human detection and monitoring potential.
biomarkers may measure molecular, histologic, radiographic 4. Proteomic/Genomic Signatures:High-throughput techniques
or physiological charcteristics. In the context of DILI and drug identifying protein/gene clusters (e.g., SCCA, heat shock proteins) are
development, a given biomarker may fall into one or more categories in exploratory phases.
depending on its proposed context of use such as a diagnostic, In summery: while AFP remains central to HCC surveillance, its
efficacy, safety, predictive, and prognostic biomarker. Examples of a limitations drive the exploration of multimarker strategies and novel
diagnostic biomarker that confirms the presence of a disease is the biomarkers. Emerging tools like miRNA panels and exosome analysis
HCV- RNA test to identify a patient with active hepatitis C infection. hold promise but require validation in diverse populations. Current
The lymphocyte stimulation test and in vitro exposure of human liver practice emphasizes combining ultrasound with selective biomarker
organoids to drugs are being explored as DILI specific biomarkers. use, underscoring the need for continued innovation to improve early
Examples of efficacy/ pharmacodynamic biomarkers that demonstrate detection rates.
a biological response has occurred in an individual also include HCV
RNA negativity 12 weeks after use of an oral antiviral agent in a patient
27BS0502
with chronic HCV infection.
A monitoring or liver safety biomarker is typically measured at baseline Biomarkers for early detection and diagnosis of hepatocellular
and serially during therapy to asses the status of a disease or for carcinoma: insights from proteomics
evidence of drug exposure. Examples of commonly used liver safety Xuehong Zhang
biomarkers are serum AST, ALT, and ALP levels that can be used to Yale University
detect the presence of liver injury and total bilirubin and INR levels to Background: Hepatocellular carcinoma (HCC) is the third cancer-
determine the severity of liver injury. Of note, routine liver biochemistries leading cause of cancer death worldwide and represents a major
are not currentlly qualified as liver safety biomarkers by regulatory global health burden. The emerging epidemiological data indicate a
agencies. Development of new liver safety biomarkers requires a set shift in etiological risk factors for HCC from virus- to non-viral causes,
of biobanked baseline and serial samples that have been handled especially in Western countries. Despite improvements in treatment,
and processed in a standardized manner and can be compared to the prognosis for HCC remains dismal, highlighting the needs for early
standard liver safety tests and also validated in independent datasets. detection and diagnosis. However, such biomarkers remain be fully
Current studies are exploring total cytokeratin-18, caspase cleaved elucidated.
CK-18, miR122, glutamate dehydrogenase (GLDH), HMGB1, and Research Efforts: Our team has been evaluating risk factors contributing
sorbitol dehydrogenase as potential diagnostic liver safety biomarkers to liver disease and HCC risk, including environmental exposures
that reflect various mechanisms of hepatocyte injury from drugs. (e.g., diet, obesity, per- and polyfluoroalkyl substances, and bacterial
There are a number of predictive or susceptibility biomarkers under infection, co-infections), genetic predispositions, and molecular
development for DILI susceptibility. For example, HLA-B * 57:01 profiling through proteomics and metabolomics. These multi-omics
allele testing shows promise as a susceptibility factor for flucloxacillin approaches provide valuable insights into disease pathogenesis and
induced liver injury and HLA- B 35:01 as a suscepibility factor for offer potential values for biomarker discovery.
polygonum multiforme, Green tea extract, and tumeric hepatotoxicity. Key Findings: Our recent studies published in the Journal of the National
These tests may also have diagnostic value as well. There are Cancer Institute (PMID: 38688524) and the International Journal of
numerous prognostic biomarkers used in patients with acute and Cancer (PMID: 38861327) highlight the latest findings in proteomics
chronic liver disease to identify the likelihood of a future clinical event and HCC. These findings reveal novel protein biomarkers associated
or outcomes such as death or the need for liver transplantation. with HCC risk, which could inform potential tools for risk stratification
Prognostic biomarker indices include the MELD score, Hy’s Law, and early detection and diagnosis. We used pre-diagnostic plasma of a
and ALFSG prognostic index. Studies are also underway to explore case-control study nested within well characterized US cohort studies
the utility of serum macrophage colony stimulating factor receptor 1 to evaluate associations between proteomics biomarkers and HCC
(MCSFR1) and osteopontin in DILI patients. The current and future use risk via different proteomic platforms including Olink and SomaScan.
of DILI biomarkers will be reviewed in this presentation. We identified circulating proteins including chitinase-3-like protein
1, growth differentiation factor 15, interleukin-1 receptor antagonist
27BS0501 protein, E-selectin, as well as inflammatory proteins that could predict
Biomarkers for Liver Cancer Surveillance the future risk of HCC. The integration of proteomic signatures with
clinical data further enhances predictive accuracy. The findings were
Xiaoguang Dou
replicated in independent cohort study in the UK.
Shengjing Hospital of China Medical University 27BS0504
Liver cancer, particularly hepatocellular carcinoma (HCC), requires Prognostic Indicator and Recurrence Risk Prediction after HCC
effective surveillance for early detection, especially in high-risk Resection
populations such as those with cirrhosis. Biomarkers play a crucial Pei-Jer Chen
role alongside imaging, though challenges in sensitivity and specificity Hepatitis Research center, National Taiwan University & Hospital,
persist. Below is a structured summary of key biomarkers and Taipei
emerging trends:
Surgical resection is one of the standard treatment for early stage
Established Biomarkers
HCC. Curative resection results in a 50% five-year overall survival.
1. Alpha-Fetoprotein (AFP);
However, the survival is much lower than early stage colorectal cancer
2. AFP-L3 (Lens culinaris Agglutinin-Reactive AFP)
or renal cell carcinoma. The major reason comes from a much higher
3. Des-gamma-carboxy Prothrombin (DCP/PIVKA-II)
HCC recurrence rate, at 25% in the first year and to 50% at five years.
Multimarker Panels and Scores
Therefore, the prognostic indicator and clinical risk factors become
- GALAD Score: Combines clinical data (gender, age) with biomarkers
important not only for the natural outcome, but also for the application
(AFP, AFP-L3, DCP).
of adjuvant therapy.
Emerging Biomarkers
Conventional prognostic indicators for post-resection HCC include the
1. Glypican-3 (GPC-3): Overexpressed in HCC; detected in serum or
characters of HCC itself and the accompanying liver disease stages. a unique spatial architecture with Treg/CAF clusters specifically
The stages of baseline HCC, especially the tumor sizes, tumor number located at the tumor margins in SLD-HCC. Crucially, we identified Treg-
and microscopic vascular invasions constitute main factors. Regarding CAF interactions as a key mediator associated with lack of response
the background liver disease stages, the stage of liver fibrosis counts, to immunotherapy in SLD-HCC. Our findings highlight the intricate
especially cirrhosis. Other factors, such as HBV or HCV viral loads immune dynamics of SLD-HCC, indicating potential therapeutic
become less important after universal antiviral therapies after resection. targets to counteract immune evasion and restore anti-tumor immunity
These baseline prognostic factors are useful in considering intensity of in SLD-HCC.
follow-up schedule and adjuvant therapy for patients.
Moreover, it is imperative to study the real-time biomarkers in following
27BS0604
HCC recurrence, especially the minimal residual disease (MRD).
Conventional biomarkers for HCC, such as AFP, PIVKA-II, are protein Identification of Predictive Biomarker for Response to Immune
biomarkers, are useful for recurrence HCC larger than 1 cm in size, Checkpoint Inhibitors in Liver Cancer
but not sensitive enough for detecting MRD. One interesting and Jian Zhou
promising development is the circulating cell-free tumor DNAs. Either Shanghai
the ctDNAs with signature mutations, or with relevant methylations, are Immune checkpoint inhibitors (ICIs) are playing an increasingly
under active investigations. However, the sensitivity of these ctDNA is important role in the treatment of advanced liver cancer, including
around 0.1% of total cf DNA, about 1 cm HCC in size. An emerging hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
group of cfDNA with better sensitivity is the ctDNA with unique gene- However, the efficacy of ICIs varies widely among patients. Mechanisms
rearrangements, such as the junctions of HBV DNA integration to of response and resistance to ICIs remain less well understood, and
HCC or host chromosomal re-arrangement, as the sensitivity of such it is crucial to find biomarkers that can predict the efficacy of ICIs in
mutated DNAs might reach 0.01% of total ctDNAs. If the translational liver cancer. As more and more multicenter, prospective, randomized,
researches can succeed in the future, these ctDNAs will become controlled trials of ICIs have yielded positive results, biomarkers that
useful in managing post-curative HCC patients, especially their need can be used to predict the efficacy of ICIs have also been summarized
for adjuvant therapies. from these studies. In addition, researchers around the world have
made their own contributions to the search for biomarkers to predict
27BS0601 the efficacy of ICIs. In this lecture, we will introduce the biomarkers that
have been found to predict the efficacy of ICIs for liver cancer from the
Biomarker Discovery and Validation in Omics-Based Research
aspects of pathology, imaging, genomics, proteomics, etc. We will also
Aleksander Krag present the results of our research center in this area.
Odense
The rapid advancement of omics technologies has revolutionized
biomarker discovery, paving the way for a deeper understanding of APASL-WHO ELIMINATION FORUM
disease biology and precision medicine. In particular, breakthroughs
in mass spectrometry have enabled comprehensive profiling
Evidence-Based Policy-Making in Public
of proteomics and metabolomics across multiple biological Health
compartments, including tissue, circulation, stool, and urine. Beyond
these, the integration of multi-omics layers—from genomics and 08:15-17:00 | Auditorium
transcriptomics to gene regulation and metabolic pathways—offers a
comprehensive biological landscape, with more than 20 distinct omics 27EF0105
modalities now contributing to disease characterization.
Elimination Mother-to-child Transmission of HBV: Shield Program
The increasing demand for non-invasive biomarkers in disease
in China
diagnosis, prognosis, and treatment response monitoring has
driven the need for robust omics-based approaches. While these Jinlin Hou
technologies hold immense promise, their clinical translation remains a Department of Infectious Diseases, Nanfang Hospital, Southern
significant challenge due to barriers in validation, standardization, and Medical University; State Key Laboratory of Multi-organ Injury
regulatory approval. This talk will explore the latest advancements in Prevention and Treatment; Key Laboratory of Infectious Diseases
omics-driven biomarker discovery, highlighting strategies to overcome Research in South China, Ministry of Education; Guangdong
Provincial Key Laboratory of Viral Hepatitis Research; Guangdong
translational roadblocks and accelerate clinical implementation. By
Provincial Clinical Research Center for Viral Hepatitis; Guangdong
bridging the gap between technological innovation and clinical utility,
Institute of Hepatology
omics-based biomarkers have the potential to reshape personalized
medicine and improve patient outcomes. The WHO Global Health Sector Strategy on Viral Hepatitis calls for
eliminating hepatitis B as a public health threat by 2030. Reducing
hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a
27BS0602 fundamental step toward the elimination goal. The SHIELD program
Spatial Transcriptomics for Biomarker Discovery in HCC aims to accelerate the elimination of HBV MTCT using an intense
Valerie Chew intervention package via a mobile health application called the “SHIELD
Singapore app”. The program comprised three stages and was conducted in
diverse health settings across China, encompassing 30,109 (Stage
Despite recent success in cancer immunotherapies, the complex
II) pregnant women from 178 hospitals and 8,642 (Stage II) pregnant
dynamics within tumor-immune microenvironment (TIME) remain elusive.
women from 160 community-level health facilities. At the beginning
Particularly, steatotic liver disease-related hepatocellular carcinoma
of the SHIELD program, a standardized management algorithm for
(SLD-HCC) poses significant challenges in liver cancer management.
preventing HBV MTCT in China was lacking, especially regarding
Our current study investigates the tumor microenvironment (TME) of
various antiviral practices; thus, experts in the fields of infectious
SLD-HCC using single-cell transcriptomic, proteomic and spatial
diseases, hepatology, immunology, obstetrics, and public health were
transcriptomic analyses. We identified altered immune-related
recruited by the SHIELD program to adapt the algorithm for preventing
and lipid metabolism pathways, particularly in regulatory T cells
MTCT to clinical practice in China. This was the first technical
(Tregs) and cancer-associated fibroblasts (CAFs) within the SLD-HCC
guidance on the management preventing HBV MTCT in China. The
microenvironment, suggesting distinct cellular adaptations to a high-
program found that the overall MTCT rate was 0.88% in stage I, 0.23%
fat TME and general immunosuppression. Cytometry by time-of-flight
in stage II and 0.23% in stage III. These findings demonstrate that the
revealed a cold and immunosuppressive TME depleted with CD8+ T
comprehensive interventions among HBV-infected pregnant women
cells and enriched with Tregs, while spatial transcriptomics uncovered
by using mobile health application were feasible and effective in
dramatically reducing MTCT. However, several critical issues remain approaches will help maintain high treatment efficacy and move closer
unresolved, including the long-term safety of tenofovir alafenamide to achieving WHO’s 2030 hepatitis elimination goals.
fumarate (TAF) during pregnancy and the safety of antiviral therapy in
early pregnancy. Addressing these challenges in the future is essential
27EF0303
to advancing HBV MTCT prevention and accelerating progress toward
the 2030 goals. Elimination of viral hepatitis in Azerbaijan-outstanding issues
Gulnara Aghayeva
Liver Disease Center, Reference Medical group, Baku, Azerbaijan
27EF0301
Background
Dynamic Changes in Epidemiology and Disease Burden in the
The health system in Azerbaijan has undergone significant reforms
Hepatitis C Elimination Era: Insights from Kazakhstan
in recent decades, including changes in governance, funding, and
Alexander V. Nersesov, Elmira K. Kuantay, Arailym M. Maikenova responsibilities within the Ministry of Health and other public health
Kazakh National Medical University named after S.D. Asfendiyarov, institutions.
Institute of Gastroenterology, Hepatology and Metabolism “Interna Despite these reforms, the response to viral hepatitis remains
Clinic”, Almaty, Kazakhstan fragmented, with surveillance, prevention, and treatment responsibilities
Chronic hepatitis C (CHC) remains a significant public health concern distributed across various public entities.
despite global advances in antiviral therapy. The World Health Methods
Organization (WHO) has set ambitious targets to eliminate viral hepatitis From 2014 to 2020, the first commission for the control of viral hepatitis
as a public health threat by 2030, aiming to reduce new infections by functioned in Azerbaijan
90% and mortality by 65%. Kazakhstan has taken steps to expand During this time, 11,300 patients were examined, of which 11,000
access to direct-acting antivirals (DAAs), which has contributed to a received free examination and antiviral treatment. In case of chronic
decline in CHC incidence and improved treatment outcomes. hepatitis C, 7,000 patients received treatment for 12 months, and
The estimated CHC prevalence in Kazakhstan is 3.2%, with notable patients at the stage of liver cirrhosis - 15 months.
regional disparities. As of 2023, 28,415 patients with CHC are officially In case of chronic viral hepatitis B, 4,000 patients received free
registered. The majority (55%) are infected with HCV genotype examination and treatment for 6 months
1b, followed by genotype 3 (35%) and genotype 2 (10%). Disease Results
severity varies, with 22% of patients having F0 fibrosis stage, 20% – Since 2020, the commission was reorganized. for the period 2020-
F1, 19% – F2, 14% – F3, 14% – F4/compensated cirrhosis, and 1% 2022, 3,700 patients received free examination and antiviral treatment,
– decompensated cirrhosis, while fibrosis staging remains undefined of which 60% (2,220 patients) of hepatitis C patients received Sof +
in 10% of cases. Dak for 3 months
Since 2018, Kazakhstan has reimbursed direct-acting antiviral (DAA) and 40% (1,480 patients) of chronic hepatitis B patients received long-
therapy (sofosbuvir + daclatasvir ± ribavirin) under the National term free treatment with entecavir and tenofovir .
“Roadmap on Prophylaxis, Diagnostics, Treatment, and Prevention Since 2020, the commission was reorganized. for the period 2020-
of Consequences of Viral Hepatitis.” This initiative has improved 2022, 3,700 patients received free examination and antiviral treatment,
treatment accessibility. As of now, 15,389 patients have undergone of which 60% (2,220 patients) of hepatitis C patients received Sof +
or are undergoing antiviral therapy. The efficacy of DAAs is reflected Dak for 3 months
in SVR12 rates, with 8,094 out of 8,164 treated patients (99.1%) and 40% (1,480 patients) of chronic hepatitis B patients received long-
achieving sustained virological response, while 0.9% were classified term free treatment with entecavir and tenofovir .
as non-responders. Since 2020, the commission was reorganized. for the period 2020-
Between 2018 and 2023, the CHC incidence rate declined from 18.4 2022, 3,700 patients received free examination and antiviral treatment,
to 9.7 per 100,000 population, demonstrating the impact of improved of which 60% (2,220 patients) of hepatitis C patients received Sof +
screening programs and expanded access to DAAs. However, Dak for 3 months
CHC remains a leading cause of liver cirrhosis and hepatocellular and 40% (1,480 patients) of chronic hepatitis B patients received long-
carcinoma (HCC), contributing to 54.2% of virus-related HCC cases. term free treatment with entecavir and tenofovir .
Late-stage diagnoses remain a challenge, as 42.7% of CHC patients Since 2020, the commission was reorganized. for the period 2020-
are diagnosed at the stage of decompensated cirrhosis, highlighting 2022, 3,700 patients received free examination and antiviral treatment,
the need for earlier detection and intervention. of which 60% (2,220 patients) of hepatitis C patients received Sof +
A multicenter retrospective matched case-control study across 13 Dak for 3 months
regions of Kazakhstan analyzed 812 CHC patients to assess predictors and 40% (1,480 patients) of chronic hepatitis B patients received long-
of antiviral treatment failure. Logistic regression identified significant term free treatment with entecavir and tenofovir .
risk factors associated with treatment non-response: Since 2020, the commission was reorganized. for the period 2020-
• Arterial hypertension (OR: 2.31, 95% CI: 1.20–4.45, p=0.012) 2022, 3,700 patients received free examination and antiviral treatment,
• Hepatocellular carcinoma (OR: 4.79, 95% CI: 1.61–14.32, p=0.005) of which 60% (2,220 patients) of hepatitis C patients received Sof +
• Alcohol consumption (32.6% of non-responders vs. 18.3% of Dak for 3 months
responders, p<0.001) and 40% (1,480 patients) of chronic hepatitis B patients received long-
• Smoking (27.1% vs. 14.8%, p=0.002) term free treatment with entecavir and tenofovir .
Additionally, advanced fibrosis (F3-F4) was present in 68.5% of non- Conclusion
responders, indicating that disease progression plays a crucial role Treatment for viral hepatitis in Azerbaijan is hindered by barriers in
in treatment outcomes. Despite these challenges, adherence to access, including high costs of medication and limited availability
therapy remains a key factor, with SVR12 rates exceeding 90% among of state-funded treatment. The lack of reliable and accurate data on
compliant patients, confirming the overall efficacy of DAAs. viral hepatitis poses a challenge for developing and implementing a
The introduction of direct-acting antivirals (DAAs) in Kazakhstan has national strategy.
significantly improved treatment outcomes for chronic hepatitis C, with
high SVR12 rates and a notable decline in incidence over the past five
27EF0408
years. The availability of antiviral therapy under the National Roadmap
has expanded access to care, contributing to the reduction of CHC- Elimination of Hepatitis in Russia: Just Go Forward, Not a Step
associated complications, including liver cirrhosis and hepatocellular Back
carcinoma. Olga Tarasova
Sustained efforts in early detection, optimized treatment strategies, and RUDN University, Moscow, Russia
long-term patient management remain essential for further progress. In November 2022, the government approved an action plan to
Continued epidemiological monitoring and integration of innovative
eliminate chronic viral hepatitis C in Russia by 2030. On September 1 with Egypt’s Ministry of Health, providing not only drug supplies but
of 2024, the federal registry of patients with chronic viral hepatitis was also exchange of public health expertise.
officially launched in Russia. The aim of the initiative is to develop a Preliminary results show the program’s effectiveness. As of January
system for providing medical care to patients with viral hepatitis and to 14, 2025, over 1.5 million people have been tested, with detection
improve payment mechanisms for such treatment within the framework rates of 3.0% for hepatitis B and 3.3% for hepatitis C.
of compulsory medical insurance. This means that now all those who Plans for 2025-2030 include continuing to screen 2.5-3 million adults
become ill, coming to the attention of the healthcare system, will be and treat 75-80 thousand patients annually. This comprehensive
able to apply for specific medical care from the state. An innovation in program aims to significantly reduce the prevalence of viral hepatitis
2024 was the inclusion of hepatitis C antibody testing in the population’s in Uzbekistan and improve population health in line with WHO global
medical examination program. Screening is conducted for citizens goals.
over the age of 25 once every 10 years. Screening for viral hepatitis
C by 2030, according to the target of the new project, will cover 67.6
27EF0503
million people.[1]
Since 2025, preferential drug provision has been carried out within the Viral Hepatitis Elimination in Mongolia: Progress and Challenges
framework of the national project “Long and Active Life”. It is planned Oidov Baatarkhuu1,2
to provide additional treatment to more than 60,000 people annually, 1
Department of Infectious diseases, Mongolian National University
which will reduce the number of patients to 15-20% annually. All drugs of Medical Sciences, 2Mongolian Association for the Study of Liver
that are necessary for the treatment of chronic viral hepatitis are Disease, Ulaanbaatar, Mongolia
registered and available in the Russian Federation. Epidemiology: A 2004 study showed 84% of children aged 7-12
A number of manufacturers have expressed their willingness to reduce had HAV antibodies. Since the introduction of the HAV vaccine, HAV
prices by 20-30%. Since 2024, pangenomic therapy regimens have incidence has decreased significantly. Seroprevalence of Hepatitis E
been produced in the Russian Federation (HEV) infection in the pediatric population are 1% (Tsatsralt-Od et al.,
In terms of hepatitis B vaccine prevention programs, Russia is a 2007). The prevalence of HBV is 0.47% among children under 5 years
world leader. But even before the introduction of vaccine prevention old (WHO 2020), 2.7% among adolescents aged 15-19 (Dambadarjaa
programs, quite a lot of people were infected, and the pool of patients et al., 2022), and 11.1% among adults (Dashtseren et al., 2017).
with chronic hepatitis B is also quite large. Hepatitis B vaccination Additionally, 60%-65% of HBV-positive individuals are co-infected with
has been included in the national calendar of preventive vaccinations hepatitis D (HDV). The prevalence of HCV in Mongolia is 9.3% (MOH,
since 1996. In 1999, the Ministry of Health of the Russian Federation 2021).
began vaccinating newborns against hepatitis B. After 2006, the National program and strategy of eliminating viral hepatitis: The
hepatitis B vaccination program is carried out entirely at the expense of Government of Mongolia implemented several key strategies and
public funds and the management of the program lies entirely with the policies, including the Targeted Prevention and Control Program
Ministry of Health and Social Development. Over the past 10 years, the to Eradicate Viral Hepatitis in Mongolia (1988–2000), mandatory
incidence of acute hepatitis В in Russia has decreased fourfold. The inclusion of HBV in the national immunization schedules, and the
incidence of acute hepatitis C has decreased one and a half times. [3] Healthy Liver programs (2016–2020 and 2022–2025) to reduce its
Along with a decrease in the incidence of acute forms of hepatitis burden on the population. The mission of the “Healthy Liver” program
B and C, high levels of new cases of chronic forms of viral hepatitis was to eliminate HCV by 2024 and significantly reduce liver cirrhosis
continue to be registered in the country. [3] and HCC caused by liver hepatitis. The Program received funding
of US$ 96 million from the Government. Funding covered amongst
27EF0502 others, the costs and expenses associated with laboratory tests,
inclusive of screening, diagnostic and viral load, and dispensing of
National Program to reduce the incidence and complications of
antiviral medicines for HBV and HCV. Stage 1 of the program started
viral hepatitis C and B in Uzbekistan
with screening the general population from 40 to 65 years for HBV and
Erkin I. Musabaev HCV infection. In the subsequent year, HBV and HCV screening was
Institute of Virology Tashkent, Uzbekistan conducted for individuals aged between 15 and 39 years. The initial
Uzbekistan is implementing a national initiative to combat hepatitis B stage covered 353,445 or 47.1% of people in the target age group of
and C, aligned with the World Health Organization’s 2030 goals. This those aged 40–65 years. In 2018, the second stage involved 61.2%
comprehensive program, implemented under Presidential Decree No. of individuals aged 15–39 years old (425,611 people). By September
243 for the period from 2023 to 2025, is a multifaceted strategy to 30 2021, 1,099,862 citizens with health insurance were screened by
combat viral hepatitis nationwide. The initiative covers various aspects the “Healthy Liver” national program. Based on the Action Plan of the
of prevention, detection and treatment, demonstrating Uzbekistan’s Government of Mongolia for 2020–24, the Health Minister of Mongolia
commitment to improving public health and eradicating disease. endorsed extending the “Healthy Liver” national program (2022–25)
As part of the program, large-scale population screening is being to involve more than 50% of citizens with hepatitis D in treatment and
conducted for early detection of hepatitis B and C. By mid-2024, bring up the level of early cancer detection to the international average.
over 1.5 million people had been screened, with plans to increase Immunization and Health Programs: Mongolia has made substantial
coverage to 2 million in 2025. Screening results are entered into a progress in viral hepatitis control through various vaccination and
unified electronic database, allowing for effective situation monitoring health programs. The HAV vaccine, introduced in 2012, covers children
and future planning. aged 6 months to 16 years, with 93.9% coverage by 2021. Mongolia
Special attention is given to treating identified cases of hepatitis C. pioneered HBV vaccination in 1991, ensuring 99% of newborns
Patients receive free treatment with modern direct-acting antiviral received the birth dose by 2023.
drugs - Sofosbuvir and Daclatasvir, supplied from Egypt as part of Treatment Access and Healthcare Financing: Mongolia provides
international cooperation. In 2024, treatment drugs were provided to WHO recommended antiviral treatments for HBV and HCV, with partial
45,000 patients, with plans to increase the number of treated HCV reimbursement through health insurance. However, high out-of-pocket
patients to 60,000 in 2025. costs remain a barrier to treatment access, particularly for HCV.
The program also includes disease prevention measures, including Additionally, HDV treatment is available in Mongolia since 2024.
hepatitis B vaccination for high-risk groups, such as healthcare Challenges: Despite these achievements, challenges such as the
workers. The goal is to increase vaccination rates to 90% by 2030. limited treatment options for certain genotypes of HCV, inaccessibility
To improve disease diagnosis and monitoring, new technologies are HDV treatment and high cost of treatment. Strengthening viral hepatitis
being introduced, including quantitative HBsAg determination and laboratory capacity especially rural area.
testing for tumor markers for early liver cancer detection. Conclusion: Mongolia is on track to meet the WHO’s 2030 hepatitis
International cooperation plays a crucial role in the program’s elimination targets, having reduced the incidence of viral hepatitis and
implementation. A memorandum of understanding has been signed improved access to treatments through vaccination, screening, and
strong government-NGO partnerships. However, continued efforts are the translocation of lipopolysaccharides, which stimulate inflammatory
needed to address treatment affordability, enhance early diagnosis, cascades. Additionally, oxidative stress induced by excess fatty acids
and strengthen healthcare infrastructure. Expanding testing capacity and impaired lipid metabolism contributes to neuroinflammation and
and improving public awareness of viral hepatitis and its complications cognitive decline in obesity-associated neurodegenerative diseases.
will be crucial in sustaining the country’s progress toward elimination. Mediterranean diets rich in monounsaturated fatty acids have been
shown to attenuate chronic inflammation and improve metabolic
health. Understanding the complex interactions between overnutrition,
POSTGRADUATE COURSE metabolic dysfunction, and inflammation provides critical insights into
the pathophysiology of obesity. Targeting inflammatory pathways and
Obesity, Metabolism and the Liver modulating dietary intake represent promising therapeutic strategies
08:00-17:00 | Function Hall B+C for mitigating the adverse health effects of obesity and improving
metabolic outcomes.

27PG0201
27PG0501
Pathogenesis of Metabolic Dysfunction and the Organs
Diabetes and Endocrine/MASH
Jingmin Zhao
Norbert Stefan
Beijing
Tübingen
Metabolic syndrome (MetS) is a global health challenge driving the
widespread occurrence of MASLD with a prevalence exceeding Metabolic dysfunction-associated steatotic liver disease (MASLD) has
31%. Metabolic comorbidities such as type 2 diabetes, impaired become an epidemic, much like other non-communicable diseases
insulin response, hypertriglyceridemia, hypertension and dyslipidemia (NCDs), such as cancer, obesity, diabetes, and cardiovascular
are commonly observed in MASLD/MASH patients. Meanwhile, disease. The pathophysiology of MASLD, particularly involving insulin
MASLD/MASH is highly associated with other extrahepatic metabolic resistance and subclinical inflammation, is closely linked to that of
comorbidities (50%–80%). MASLD/MASH is characterized by those NCDs. Genetics alone cannot explain the large increase in the
hepatic steatosis, inflammation, and fibrosis, with various intra- and prevalence of MASLD during the past 2 decades and the increase
extrahepatic manifestations. Notably, the multiple-mutual hits between that is projected for the next decades. Impairment of glucose and
liver and other organs forms a liver-extrahepatic organs axis through lipid metabolic pathways, which has been promoted by the worldwide
intra-hepatic inflammation “spill over”, involving a panel of inflammatory increase in the prevalence of obesity and insulin resistance, is most
cytokines, especially hepatokines and adipokines. The intrahepatic likely behind the increase in people with MASLD. People with MASLD
inflammation “spill over” plays a central role in systemic pathologies can progress to cirrhosis and hepatocellular carcinoma and are at
of cardiovascular disease, chronic kidney disease, sarcopenia, fatty increased risk of developing type 2 diabetes, cardiovascular disease,
pancreas, and polycystic ovary syndrome, etc. MASLD/MASH is also chronic kidney disease, and extrahepatic cancers. Most people with
independently linked to an increased risk of neoplasms including MASLD die from cardiac-related causes. This outcome is attributed
hepatocellular carcinoma, cholangiocarcinoma, colorectal and to the shared pathogenesis of MASLD and cardiometabolic diseases,
pancreatic cancers and so on. Despite growing insights into these involving unhealthy dietary habits, dysfunctional adipose tissue, insulin
multiple hits, the underlying mechanism in intra- and extrahepatic resistance, and subclinical inflammation. In addition, the steatotic and
organs remain poorly understood. Future research should focus on inflamed liver affects the vasculature and heart via increased glucose
elucidating these pathways to develop multi-disciplinary management production and release of procoagulant factors, dyslipidaemia, and
strategies addressing the multi-organ involvement in MASLD/MASH dysregulated release of hepatokines and microRNAs. However, there
pathogenesis. is substantial heterogeneity in the contributors to the pathophysiology
of MASLD, which might influence its rate of progression, its relationship
with cardiometabolic diseases, and the response to therapy. Although
27PG0202 there is currently insufficient evidence for the implementation of
Obesity and Overnutrition: Interplay of Metabolism and precision medicine for risk prediction, prevention, and treatment of
Inflammation MASLD, knowledge about this heterogeneity might help achieving this
Necati Örmeci goal in the future.
İstanbul Health and Technology University
Obesity, characterized by excessive fat accumulation due to 27PG0504
overnutrition, is a major global health concern linked to metabolic Viral Hepatitis/MASH
disorders such as type 2 diabetes, cardiovascular diseases, Jie Li
and neurodegenerative conditions. A growing body of evidence Nanjing
suggests that the interplay between metabolism and inflammation
plays a pivotal role in the pathogenesis of obesity-related diseases. Hepatitis B virus (HBV) infection remains a significant global public
Obesity induces a state of chronic low-grade inflammation, termed health challenge, affecting approximately 254 million people worldwide,
“metaflammation,” which is orchestrated by metabolic cells in including 75 million in China. Simultaneously, the prevalence of
response to excess nutrients and energy. This inflammatory state is metabolic dysfunction-associated fatty liver disease (MAFLD) is
characterized by elevated circulating pro-inflammatory cytokines such increasing due to the rising incidence of obesity and type 2 diabetes
as IL-6, TNF-α, and CRP, which contribute to insulin resistance and mellitus. Our previous meta-analysis demonstrated that the prevalence
metabolic dysfunction.Adipose tissue, especially visceral fat, acts as of MAFLD in Asia has surged from an estimated percentage of 25.28%
an endocrine organ, releasing adipokines and cytokines that modulate in 1999-2005 to nearly 30% in 2019. Consequently, the coexistence
immune responses and metabolic processes. Chronic nutrient excess of chronic hepatitis B (CHB) and hepatic steatosis (HS) has become
leads to adipocyte hypertrophy and hypoxia, triggering endoplasmic increasingly common. Our study found that the prevalence of HS
reticulum stress and mitochondrial dysfunction. These cellular in CHB patients was 36.5% in Asia, a figure comparable to global
stressors activate inflammatory signaling pathways, including the NF- estimates. However, the mechanistic interplay between CHB and
κB and JNK pathways, promoting the recruitment of macrophages MAFLD remains largely unclear. Our prior research indicated that a
and other immune cells into adipose tissue. This shift from an high-fat environment can suppress HBV replication, and proteomic
anti-inflammatory (M2) to a pro-inflammatory (M1) macrophage analysis suggested that enhanced HBV clearance is associated
phenotype further propagates systemic inflammation and metabolic with inflammatory responses and the activation of various metabolic
disturbances. Gut microbiota dysbiosis, associated with a high-fat, pathways. The precise mechanisms underlying the interaction between
high-calorie diet, exacerbates intestinal permeability and promotes CHB and HS warrant further investigation.
Both CHB and MAFLD/HS are significant contributors to fibrosis, ELB related equipment and protocols are needed.
cirrhosis, and hepatocellular carcinoma. However, the natural history
of CHB patients with concurrent HS remains uncertain. Several
27IG0102
factors contribute to these inconsistencies. First, the status of antiviral
therapy plays a crucial role. Among treatment-naïve CHB patients, the Ultrasound Imaging for Diagnosis of Liver Fibrosis
presence of HS has been identified as a risk factor for hepatic fibrosis Manoj K. Sharma
progression. In contrast, in CHB patients receiving antiviral therapy, Department of Hepatology and Liver transplantation, Institute of Liver
HS has been associated with a reduced risk of cirrhosis and HCC. and Biliary Sciences, New Delhi, India
Additionally, variations in MAFLD severity and differences in diagnostic Accurately diagnosing liver fibrosis is .the most important factor for
methods for HS may further influence liver-related outcomes. determining the stage of the disease, assessing the patient’s prognosis,
Given the significant overlap between CHB and HS, precise assessment and predicting treatment responses. Assessing liver fibrosis has
of liver inflammation and fibrosis is essential for guiding timely treatment traditionally been done with liver biopsy but clinical practice has been
decisions. While liver biopsy remains the gold standard, its invasive changing because liver biopsy has several disadvantages.
nature limits its routine use for diagnosis and disease monitoring. Non- Elastography and conventional morphologic cross-sectional are
invasive tests (NITs), such as the fibrosis-4 index (FIB-4), aspartate imaging-based procedures to measure liver fibrosis. While ultrasound-
aminotransferase-to-platelet ratio index (APRI), and non-alcoholic based elastography is primarily used to assess hepatic fibrosis, it can
fatty liver disease fibrosis score (NFS), are widely utilized in clinical also be used to predict complications in patients with cirrhosis.
practice. However, our study found that the predictive accuracy Liver stiffness (elasticity and viscosity) depends on many factors.
of these NITs for detecting significant liver fibrosis in CHB patients Fibrosis is an important factor contributing to liver stiffness and is often
with HS decreases when applied individually. Notably, combining the factor focused on in studies. However, other factors also influence
NFS and APRI improved classification performance. Interestingly, as liver stiffness.
the number of cardiometabolic risk factors (CMRFs) increased, the There are two primary ultrasound-based elastography techniques
diagnostic accuracy of these NITs for identifying significant fibrosis used in clinical practice for evaluating liver stiffness: shear wave
declined further. In contrast, the novel NIT, Agile 3+, demonstrated elastography (SWE) and strain elastography . Both use mechanical
excellent performance in diagnosing advanced fibrosis among CHB excitation of the hepatic parenchyma with monitoring of the resulting
patients with HS. However, given the limited availability of Agile 3+ in tissue response. Fibrotic tissue differs from healthy tissue in the way it
clinical practice, we have developed machine-learning-based models responds to excitation (shear waves propagate faster in fibrotic tissue,
to enhance the precision of liver inflammation and fibrosis diagnosis in and fibrotic tissue when compressed shows less strain displacement
this specific population. than healthy tissue).
This lecture will focus on CHB patients with concurrent MAFLD/HS, SWE and strain elastography differ in the way the external mechanical
discussing the latest findings on epidemiology, pathogenesis, natural excitation is applied and what quantity is measured.
history, diagnostic methodologies, and comprehensive management There are several methods for performing SWE: Vibration controlled
strategies for this population. transient elastography(VCTE) and Acoustic radiation force impulse
shear wave elastography(ARFI-SWE). AFRI-SWE includes point
SWE(pSWE), 2D-SWE., and shear wave dispersion (SWD). 2D-SWE
LIVER IMAGING COURSE can be integrated with conventional morphologic liver imaging in the
Non-invasive Diagnosis and Precision same sitting.
Liver elastography must be interpreted considering the etiology of liver
Intervention disease and the clinical and laboratory data.
Combining serologic panels with imaging elastography may improve
08:30-16:30 | 402 (A+B) the ability to correctly assess the degree of a patient’s fibrosis: examples
include FAST, AGILE-3 and AGILE 4 for metabolic associated fatty liver
27IG0101 disease assessment.
Endoscopic Ultrasound-Guided Liver Biopsy
Ke-Qin Hu 27IG0104
UCI School of Medicine and Medical Center, CA, USA Vibration controlled transient elastography and Magnetic
Although non-invasive tests (NITs) and elastography are gradually resonance elastography of liver stiffness
gaining interest and applicability, liver biopsy (LB) remains a key Seung Up Kim
diagnostic approach for hepatologists. Traditionally, LB is performed Department of Internal Medicine, Institute of Gastroenterology, Yonsei
percutaneously (PLB) and trans-jugularly (TJLB). EUS-LB (ELB) was University College
first reported in 2007. The introduction of 19 G fine needle biopsy of Medicine, Seoul, Republic of Korea, Yonsei Liver Center,
(FNB) needles in 2012 promoted further development and clinical Severance Hospital, Seoul, Republic of Korea
application of EUS-LB. Together with other related technical advances, Introduction
many studies have demonstrated ELB represents a novel and highly Liver stiffness measurement (LSM) is a critical component in the
valuable addition to our current practice in liver biopsy. Application of 19 non-invasive assessment of liver diseases, providing valuable
G FNB needles provides better specimen quality, a higher diagnostic insights into hepatic fibrosis, steatosis, and portal hypertension. Two
accuracy and less needle passes. ELB procedure successful rates key imaging modalities for LSM are Vibration-Controlled Transient
have been reported to be 100%. An adequate LB specimen is defined Elastography (VCTE) and Magnetic Resonance Elastography (MRE).
a liver core tissue of 20 mm in length containing at least 10 portal These techniques have revolutionized the management of chronic
tracts. ELB has been confirmed superior or at least not inferior to PLB liver diseases by reducing the need for invasive liver biopsies and
in total tissue lengthy, number of portal tracts, and overall sample enabling longitudinal monitoring of disease progression. This lecture
adequacy. ELB has also been used to diagnose and stage various offers an in-depth exploration of VCTE and MRE, comparing their
hepatic malignancies. ELB holds some unique advantages. First, it methodologies, diagnostic performance, clinical applications, and
avoids percutaneous approach, carries less risk for pain and more emerging advancements.
acceptable by patients. ELB could biopsy both liver lobes at the same Principles and Methodologies of VCTE and MRE
time. ELB could be done with other endoscopic procedures, such as - VCTE (Vibration-Controlled Transient Elastography):
EGD, EUS-portal pressure gradient (PPG) measurement. Studies also VCTE, widely known through FibroScan, utilizes low-frequency (50
indicated that ELB is cost-effective. Surely, ELB is a great addition to our Hz) shear waves and ultrasound-based pulse-echo measurements
current practice in liver biopsy. In order to further promote ELB clinical to assess liver stiffness. The device calculates the shear wave
applications, further multicenter clinical trials and standardization of
velocity, which correlates directly with liver stiffness, expressed - 3D MRE: Innovations in 3D MRE are providing more detailed and
in kilopascals (kPa). Additionally, VCTE incorporates Controlled accurate liver stiffness maps, offering deeper insights into diffuse liver
Attenuation Parameter (CAP) to quantify liver steatosis, providing a diseases.
dual assessment of fibrosis and fat content. VCTE is notable for its Challenges and Unmet Needs
rapid examination time (usually less than 10 minutes) and point-of-care - Cost and Accessibility: Despite their clinical value, MRE remains
utility. underutilized due to high costs and limited availability, particularly in
- MRE (Magnetic Resonance Elastography): low-resource settings.
MRE is an advanced MRI-based imaging technique that measures - Interpretation of Confounding Factors: Both VCTE and MRE results
liver stiffness by analyzing the propagation of mechanical shear waves can be affected by inflammation, congestion, and hepatic fat content,
through hepatic tissue. The technique uses an external acoustic driver requiring careful interpretation.
to generate shear waves, which are captured and mapped into 3D - Patient Compliance: The relatively longer acquisition time for MRE can
images of tissue stiffness. MRE provides a quantitative stiffness map reduce patient compliance compared to the quick VCTE examination.
(elastogram) of the liver, offering high spatial resolution and the ability Conclusion
to analyze larger liver volumes than VCTE. VCTE and MRE are indispensable tools in modern hepatology,
Comparative Diagnostic Performance each with unique strengths that complement one another in clinical
- Accuracy and Sensitivity: practice. VCTE offers a rapid, cost-effective solution for liver fibrosis
MRE is recognized for its superior diagnostic accuracy, especially and steatosis assessment, making it ideal for broad screening and
for detecting early-stage fibrosis (F1–F2) and differentiating between longitudinal monitoring. MRE, with its superior diagnostic accuracy and
advanced fibrosis and cirrhosis. VCTE, while highly effective for comprehensive liver assessment capabilities, is invaluable for detailed
detecting significant fibrosis and cirrhosis, has reduced sensitivity in evaluation and complex cases. Understanding the appropriate use,
cases of mild fibrosis. benefits, and limitations of these modalities is essential for optimizing
- Reproducibility and Reliability: patient outcomes and advancing the management of chronic liver
MRE demonstrates greater reproducibility and is less operator- diseases.
dependent than VCTE. However, VCTE remains widely adopted due to This lecture aims to empower healthcare providers, hepatologists,
its cost-effectiveness, ease of use, and rapid assessment. radiologists, and researchers with practical knowledge of VCTE and
- Limitations: MRE, enabling them to make informed decisions and integrate these
VCTE may produce unreliable results in patients with obesity, ascites, techniques into clinical practice effectively.
or significant hepatic inflammation. MRE, though more comprehensive,
is less accessible due to higher costs, longer acquisition times, and
27IG0402
the need for specialized MRI equipment.
Clinical Applications in Liver Disease Stereotactic ablative radiotherapy (SABR/SBRT) for hepatocellular
- Chronic Hepatitis and Cirrhosis: Both VCTE and MRE are valuable carcinoma
for staging fibrosis and monitoring treatment response in patients with Jason Chia-Hsien Cheng
hepatitis B and C. Graduate Institute of Oncology, National Taiwan University College of
- Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Medicine
Steatohepatitis (NASH): VCTE, with CAP, offers a dual assessment of Division of Radiation Oncology, Department of Oncology, National
fibrosis and steatosis, making it a practical tool for screening. MRE, Taiwan University Hospital, Taipei
with its multiparametric capabilities, provides additional insight into Radiotherapy (RT) has been integrated into one of the treatment
disease progression. modalities for hepatocellular carcinoma (HCC). Higher-intensity
- Alcohol-Related Liver Disease: MRE may be more useful in detecting radiation by higher dose-per-fraction and fewer-fraction
subtle fibrosis changes in patients with alcohol-related liver injury. hypofractionated RT or ultra-short stereotactic body radiation therapy
- Portal Hypertension: MRE can help assess the severity of portal (SBRT) demonstrates improved control of irradiated liver tumor
hypertension, providing valuable insights for risk stratification in but reduced injury of non-cancerous liver. Two types of radiation,
cirrhotic patients. electromagnetic photon (X-ray) therapy or particle (proton and carbon)
Guidelines and Recommendations therapy, are used in treating HCC. Photon therapy is widely accessible
Leading organizations, including the American Association for the with mature technology and full-option image guidance. Proton therapy
Study of Liver Diseases (AASLD) and the European Association for with the dosimetric sparing advantage has the growing users in HCC,
the Study of the Liver (EASL) as well as The Korean Association for the but the accessibility of carbon therapy is limited. Technically SBRT to
Study of the Liver (KASL), recognize VCTE and MRE as essential tools HCC requires respiratory control for the moving organ and the image
for non-invasive liver disease assessment. Current guidelines suggest guidance in the high-throughput dose delivery. Despite the acceptable
using VCTE as a first-line tool for fibrosis staging and reserving MRE local control in the irradiated hepatic tumor, a certain proportion of
for cases requiring more detailed evaluation or when VCTE results are patients develop intrahepatic and/or extrahepatic metastasis. For
inconclusive. small-/medium-sized HCC, the comparison studies between SBRT
Case Studies and Real-World Applications and radiofrequency ablation (RFA) started from the US single-institute
The lecture will present case studies illustrating how VCTE and and Asian collaborative retrospective studies with the non-inferior
MRE are used in clinical practice. Examples will include patients control, but the concerned worse survival by SBRT from the US NCDB
with NAFLD, hepatitis, and cirrhosis, highlighting the role of these study indicated the selection biases of patients with different disease
techniques in treatment planning and disease monitoring. Additionally, burden. Korean randomized trial on patients of early HCC treated
the integration of elastography results with laboratory findings and with proton therapy compared with RFA showed the comparable
other imaging modalities for comprehensive liver assessment will be survival and local control. Chinese randomized trial on single small
discussed. recurrent HCC demonstrated better local progression-free survival by
Advancements and Future Directions SBRT than RFA but similar out-field control and overall survival. For
- Multiparametric Imaging: Emerging MRI protocols combine advanced HCC, Korean randomized trial on HCC patients with major
elastography with fat and iron quantification, enabling a holistic liver vascular invasion treated with combined TACE and SBRT showed the
assessment. superior survival to sorafenib. RTOG 1112 randomized trial on HCC
- Artificial Intelligence (AI): AI-driven image analysis is improving the patients unsuitable for or refractory to standard locoregional therapies
interpretation of elastography results, reducing operator dependency, and eligible for systemic therapy compared SBRT with sorafenib, and
and enhancing diagnostic accuracy. reported the borderline significant survival advantage overall survival
- Portable VCTE Devices: Advances in technology are making VCTE by SBRT than sorafenib alone. As combined immune checkpoint
more accessible in outpatient and primary care settings, broadening inhibitor and anti-angiogenesis agent become the standard of care in
its use in early liver disease detection. advanced/metastatic HCC, the evolving integration of SBRT into such
a combination is still immature in defining the potential role. One China α-fetoprotein levels. Additionally, our multicenter, large-sample study
randomized study on HCC patients with portal vein tumor thrombosis highlighted that after ablation, female HCC patients exhibited better
comparing combined camrelizumab and apatinib with or without cancer-specific survival outcomes compared to males but in an age-
SBRT showed the superior responses, progression-free survival, and dependent way. A prospective multicenter study published in The
overall survival with the added SBRT. More cooperative multi-center Lancet by Chinese authors demonstrated that adjuvant treatment
trials are needed to translate the benefit of improved local control and improved recurrence-free survival (RFS) in HCC patients at high risk
out-field systemic effect to survival, and help form the consensus by of recurrence following ablation. Another multicenter study involving
establishing more supportive evidence. a large cohort of intrahepatic cholangiocarcinoma patients found that
MWA could provide survival outcomes comparable to liver resection
for primary or recurrent tumors within Milan criteria, provided an
27IG0403
adequate margin was achieved. This suggests that MWA is a viable
The Current Status and Advance of Yuttrium 90 SIRT for HCC alternative for intrahepatic cholangiocarcinoma patients who are
Xiaobin Feng unsuitable for liver resection or general anesthesia. In the context of
Beijing colorectal liver oligo-metastases, upfront ablation was associated with
This report systematically reviews the historical development significantly higher 1-, 3-, and 5-year progression-free survival (PFS)
of Yttrium-90 (Y90) microspheres, outlines their global clinical rates compared to delayed ablation. Finally, artificial intelligence (AI)
applications and research advancements, and documents the phased is increasingly integrated into the ablation process, playing a critical
introduction of Y90 therapy in mainland China—beginning with its first role in pre-ablation planning, intra-ablation navigation, and post-
implementation in Hainan Boao and expanding to over 60 centers ablation prognosis prediction, thereby enhancing the precision and
nationwide, collectively treating 2,000+ cases of hepatic tumors. effectiveness of treatment.
Focusing on Beijing Tsinghua Changgung Hospital (BTCH), the study
summarizes clinical data from 328 patients treated between September 27IG0501
28, 2022, and early 2025. The cohort includes 192 hepatocellular
Utilizing Automated Extraction of Imaging Features within
carcinoma (HCC), 79 metastatic colorectal cancer (mCRC), and 57
Computed Tomography
other tumor types, with detailed analyses of tumor characteristics
and overall survival outcomes. Based on these findings, promising Grace L. Su
patient subgroups and optimized therapeutic strategies are proposed, Ann Arbor
emphasizing precision dosimetry and multidisciplinary collaboration. Computed tomography (CT) scans are routinely performed in clinical
Key Highlights care to address specific diagnostic questions and are systematically
Historical Milestones: Traces Y90 microspheres from early vascular stored within electronic medical records. These scans capture a
biology studies to modern ablation-focused protocols like radiation patient’s phenotype at a single point in time, providing valuable
segmentectomy. quantitative data. Key imaging features, such as body composition and
Standardization: Aligns with China’s 2024 expert consensus and organ characteristics, have been shown to hold significant prognostic
updated 2025 international guidelines for HCC. value in predicting clinical outcomes in liver disease. However,
Clinical Validation: Reinforces efficacy in complex cases (e.g., leveraging this digital data for routine use has been challenging due
perivascular tumors) and combination therapies with immunotherapy. to the need for manual delineation and the complexity of feature
extraction. Advances in artificial intelligence have now made automated
segmentation and imaging feature extraction increasingly feasible. Our
27IG0404
research has demonstrated strong concordance between manual and
Image-Guide Ablation for Liver Cancer automated segmentation methods. More importantly, automatically
Ping Liang extracted imaging features can predict critical clinical outcomes,
Chinese PLA General Hospital including mortality and hepatic decompensation, in patients with liver
Liver cancer ranks as the sixth most common cancer globally, with disease. Moreover, integrating these imaging features with traditional
over 900,000 new cases diagnosed annually. Notably, the Asia- health data further enhances risk prediction for individuals with chronic
Pacific region accounts for nearly 70% of these cases worldwide. In liver disease, offering a powerful tool for clinical decision-making.
this region, ablation is increasingly utilized, representing 35-45% of
local treatments for liver cancer. The compound annual growth rate 27IG0502
of the liver cancer ablation market is projected to be 14% from 2024
Digital Pathology/Artificial Intelligence and qFibrosis
to 2030. Since its first application in 1992 for liver tumor treatment,
ablation has become the most widely used technique for treating liver Aileen Wee
tumors globally and is now considered the first-line radical treatment Department of Pathology, Yong Loo Lin School of Medicine, National
for liver cancers ≤3 cm in size. Among various ablation modalities, University of Singapore
radiofrequency ablation (RFA) remains the most widely used, Department of Pathology, National University Hospital, Singapore
while microwave ablation (MWA) is the fastest-growing technique. Digital Pathology (DP) driven by Artificial intelligence (AI) provides
Importantly, liver cancer ablation is recommended by 19 international cutting-edge computational analytics to maximize the potential of DP
guidelines and consensus statements. images. DP generates quantitative metrics, thereby, eliminating the
The volume of publications on image-guided liver cancer ablation subjectivity of manual staging/scoring. DP driven by AI is the future of
has been steadily increasing, with Chinese research contributing diagnosis and assessments.
32.9% of the publications in Asia. In one of our studies comparing qFibrosis is one of a few platforms for DP/AI analysis of histological
MWA versus laparoscopic resection as first-line therapy for solitary tissue. It is a fully-quantitative stain-free method for the automated
3-5 cm hepatocellular carcinoma (HCC), we found that both MWA assessment of fibrosis incorporating spatial architectural features of
and laparoscopic resection offered comparable overall survival (OS) pathological relevance at tissue levels. Second harmonic generation/
and disease-free survival (DFS). Consequently, MWA may emerge as Two photon excitation fluorescence (SHG/TPEF) is a non-linear
the preferred treatment option for patients with solitary 3-5 cm HCC technique that takes advantage of the physical properties of collagen
who are unsuitable for laparoscopic resection. Furthermore, a 10-year filaments and tissue. SHG imaging can analyze the 3-dimensional
survival analysis of RFA for primary versus recurrent HCC in patients architecture of fibrillar collagen, whereas TPEF provides visualization
with solitary tumors ≤5 cm revealed no significant differences in 1-, of the cellular tissue for separate analysis such as the recognition of
3-, 5-, or 10-year overall survival between the two groups, indicating steatotic vacuoles or inflammatory foci. qFIBS was developed for the
similar long-term outcomes. Prognostic risk factors for recurrent assessment of Fibrosis, Inflammation, Ballooning of hepatocytes, and
HCC patients included tumor size, portal hypertension, and serum Steatosis.
How is SHG/AI translated into Hepatology for application in clinical Laboratory tests and serum markers need to be interpreted critically
practice and therapeutic/clinical trials? SHG/AI has the potential to because some of their individual components may be affected by a
revolutionize histological analysis of liver biopsies. It has translational variety of comorbidities.
capabilities for drug candidate screening and validation. It can This integration of AI enables cost-effective and scalable non-invasive
enable research into the biological mechanisms underpinning the screening methods across the disease spectrum, from early fibrosis
development of metabolic dysfunction-associated steatohepatitis to decompensated cirrhosis. However, integrating non-invasive
(MASH), including progressive and regressive features in advanced screening methods into clinical practice remains challenging, and
fibrosis/cirrhosis, and the histological differences between adult and more data are needed to establish consensus on standard practice
pediatric MASH. Furthermore, DP/AI can support the development and implementation.
of new MASH preclinical models and non-invasive tests (NITs) for
diagnosis and monitoring of patients.
What are the benefits of SHG/AI in Digital Pathology of the liver? SHG/ OPENING AND PRESIDENTIAL LECTURES
AI enables characterization and quantification of morphology, lobular 09:45-11:45 | Plenary Hall A
architecture with zonation, and spatial distribution of histopathological
structures (portal tracts, central veins), cell types and features.
SHG/TPEF characterizes and quantifies collagen fibrils in different STATE-OF-THE-ART LECTURES
compartments of the hepatic lobule; thus, allowing for staging of
fibrosis. qFibrosis provides qF continuous values with cut-off and qF 15:45-18:45 | Plenary Hall A
stages for assessment of fibrosis, which is a continuum, potentially
replacing the use of conventional ordinal stages/grades, such as NASH 28SL0102
CRN scoring system. SHG/AI as an aiding tool has been validated to Evolving Strategies in LDLT for Hepatocellular Carcinoma
enhance pathologist confidence and inter-rater reliability for fibrosis
Chao-Long Chen
assessment in liver biopsies of MASH patients. These data support the
use of SHG/AI to increase the efficiency of clinical trials and reliability Kaohsiung Chang Gung Memorial Hospital
of fibrosis readouts of response from trials. With the recent advances in surgical techniques, locoregional and
Machine-learned automated assessment of SHG/TPE slides can medical therapies in the management of HCC, prognosis of patients
identify changes in collagen fibrillar properties and quantify septal with HCC has tremendously improved. Liver transplantation has
thickness (progressive versus regressive septum) and cellularity within undoubtedly become the definitive standard treatment in providing
the various types of septa. With the aid of machine-learning algorithms, the longest overall and recurrence-free survival when performed within
subtle patterns and changes in the longitudinal tracking of liver one of many validated criteria. In Asia, where LDLT has been more
histology in response to treatment can be detected and quantified; widely accepted and has flourished, we have continuously explored
thus, greatly affecting the outcomes of current drug trials. and produced innovative surgical techniques that have effectively
The practical aim of DP/AI and qFibrosis is to produce a clinical model expanded not only the donor pool but likewise extended recipient
for determining disease severity; predicting disease course - cirrhosis indications for LDLT.
decompensation, portal hypertension (nodules, HPVG, varices), In recent 5 years, rather than excluding locally advanced HCC or with
hepatocellular carcinoma and mortality; and identifying therapeutic unfavorable histopathology, we have started to selectively utilize proton
benefits of pharmacotherapies in development. The preclinical aim is beam or Yttrium-90 radioembolization as an alternative locoregional
to enable research into the biological mechanisms and pathogenesis therapy to bridge or downstage locally advanced or aggressive HCC
of liver fibrosis as well as its relationship to the other histological to improve recurrence-free survival.
parameters of MASH for the purpose of studying drug actions. Our experience has demonstrated that down-staged HCC patients
have similar survival outcomes to that of patients who initially fit the
criteria. Attempts to achieve complete pathological response by loco-
27IG0503
regional therapy before transplant may further improve recurrence-free
Detection of Cirrhosis and Portal Hypertension by AI survival.
Xiaolong Qi Powerful modern locoregional therapies like proton beam and Y-90
Nanjing combined with target and/or immunotherapy may effectively bridge
Liver fibrosis, portal hypertension, and especially clinically significant or downstage locally advanced or aggressive HCC in preparation
portal hypertension (CSPH) are progressive stages of chronic for timely LDLT, with promising survival outcomes in patients with
liver disease. Early detection of fibrosis—a reversible precursor to otherwise dismal prognoses.
cirrhosis—is vital for preventing irreversible organ damage. Clinically
significant portal hypertension (CSPH) is associated with symptomatic
gastro-oesophageal varices (GOV), the development of hyperdynamic
CURRENT SESSION 01
circulation, and with patients with compensated advanced Translation of Science into Hepatitis B Cure -
chronic liver disease who are at risk of clinical decompensation.
Hepatic venous pressure gradient (HVPG) measurement and Virological Perspective
esophagogastroduodenoscopy are the gold standard methods for
13:15-14:45 | Function Hall A
assessing CSPH (HVPG ≥10 mm Hg) and GOV, respectively. However,
they are limited by their invasiveness in clinical practice. In recent
years, there have been many new technologies focusing on the 28CS0102
development of non-invasive approaches to the diagnosis and serial Blocking HDV/HBV Entry Through NTCP for Curative Therapy:
monitoring of portal hypertension. Opportunities and Challenges
AI-powered solutions now bridge this gap by analyzing non-invasive Wenhui Li
data (imaging, elastography, biomarkers). Imaging techniques used
National Institute of Biological Sciences, Beijing
for portal hypertension include ultrasound, computed tomography Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua
(CT), and magnetic resonance (MR). Elastography techniques University
measure liver and spleen stiffness by quantifying the velocity of an
induced shear wave, including transient elastography, point-shear The sodium taurocholate cotransporting polypeptide (NTCP) is an
wave elastography, and two-dimensional shear wave elastography, indispensable receptor for hepatitis B virus (HBV) and its satellite
as well as MR elastography. Liver stiffness measurement has been hepatitis D virus (HDV), playing an essential role in mediating their entry
proved to be sufficiently accurate to identify CSPH and safe to screen into hepatocytes. Disruption of the receptor engagement provides an
high-risk varices combined with platelet count in clinical practice. exceptional opportunity to eliminate de novo viral infections and re-
infections of the hepatocytes, which significantly contribute to viral surgical resection using the recent advance of systemic therapy for
persistence in the liver of infected patients with no or limited anti-viral advanced HCC.
immune control and, is a missing part for curative therapy. Several
investigational new drugs, which employ different mechanisms of
blocking viral entry of HBV and/or HDV, are currently under clinical CURRENT SESSION 04
studies. Libevitug is a human monoclonal antibody targeting the HBV/
HDV Large envelop protein and directly blocks viral engagement
Hepatology in the Age of Artificial Intelligence
to NTCP. Clinical trials of Libevitug have shown good safety profile (AI)
across various patient groups infected by HBV and /or HDV, and
monotherapy of HH-003 exhibits promising antiviral activity in chronic 13:15-14:45 | 402 (A+B)
hepatitis B patients and particularly in patients coinfected by HDV. The
therapeutic efficacy of Libevitug and other entry inhibitors is yet to be 28CS0402
more thoroughly assessed in combination - based treatments for the
Application of AI in MASH
purpose of achieving curative therapies.
Feng Liu
Beijing
28CS0104
Research on the application of AI in MASH is increasingly. Model
Gene Editing Technologies and HBV DNA construction based on big data electronic medical record is suitable
Thomas Tu for epidemiological investigation and screening of risk factors. Image
Sydney recognition based on liver imaging and pathology is closer to clinical
Hepatitis B virus (HBV) persists in the liver due to the stability of practice. In particular, several AI pathology tools are developed for the
covalently closed circular DNA (cccDNA) and integrated DNA study of MASH liver biopsies, including those to assist pathologists by
forms. HBV cccDNA and integrated DNA are not targeted by current improving reproducibility in grading and staging, improved assessment
therapies, however recent innovations in gene editing technologies of MASH progression, and regression of fibrosis. These AI techniques
have emerged as promising tools for disrupting HBV DNA. Gene could improve diagnostic and prognostic information clinically and
editors can induce effects ranging from inducing indels, changing aid in improving the identification of endpoints in drug development
bases, transcriptional inactivation, or complete degradation of target of MASH. In addition, genomics, metabolomics, associated AI are
genomes. However, there are several challenges in efficacy and also emerging in MAFLD research. AI is promising in the diagnosis of
safety to overcome before these therapies should be used for chronic MASH, which is expected to improve the level of MASH diagnosis and
hepatitis B. treatment.

28CS0403
CURRENT SESSION 02
Machine learning for the prediction of HCC
Genetic and Rare Liver Diseases Terry Cheuk-Fung Yip
Medical Data Analytics Centre, Department of Medicine and
13:15-14:45 | Function Hall B Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related
CURRENT SESSION 03 mortality worldwide, necessitating accurate and early prediction to
improve patient outcomes. Traditional risk prediction models for HCC,
Multidisciplinary Approach and usually based on statistical regression methods, have been proposed
Transplantation in HCC for decades. These models, such as the REACH-B, PAGE-B, and
aMAP scores, rely on demographic, clinical, and laboratory values
13:15-14:45 | Function Hall C to estimate HCC risk. Machine learning (ML) offers a promising
alternative, leveraging its ability to handle complex, non-linear
relationships and large datasets to improve predictive performance.
28CS0303 ML models, such as random forests, gradient boosting, and neural
Surgical Treatments for Advanced Liver Malignant Tumors networks, have demonstrated superior accuracy in HCC prediction
Kiyoshi Hasegawa, Akihiko Ichida, Yoshikuni Kawaguchi, Satoru compared to traditional methods. Despite these advantages, the
Abe, Yuichiro Nishioka, Kyoji Ito, Yuichiro Mihara, Takehiro Chiyoda, “black box” nature of many ML algorithms raises concerns about their
Takeshi Takamoto, and Nobuhisa Akamatsu interpretability and clinical utility. Interpretable artificial intelligence
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, techniques, such as SHAP (SHapley Additive exPlanations) and
The University of Tokyo, Tokyo, Japan LIME (Local Interpretable Model-agnostic Explanations), are critical
Surgical resection has been established as a curative treatment option for bridging this gap, enabling clinicians to understand and trust ML-
for hepatocellular carcinoma (HCC). However, the recurrence rate is driven predictions. External validation of ML models is also essential to
high (70% within 3 years even after curative resection), which remains ensure their robustness and applicability across different populations
an unsolved problem. Recently, the advance of systemic therapy and settings. Furthermore, the integration of ML with electronic
using immune-checkpoint inhibitors and/or molecular target agents health records holds the potential to revolutionize precision medicine,
is remarkable, which is now inducing another paradigm shift in the enabling tailored risk stratification and early interventions for patient
therapeutic approach for HCC. subgroups. In conclusion, while ML represents a transformative
According to the BCLC guidelines, only systemic therapy is tool for HCC prediction, its successful implementation requires
recommended for advanced HCC with macroscopic vascular invasion addressing challenges related to interpretability, validation, and ethical
(MVI), however, the MST was not satisfactory (shorter than 2 years). considerations.
Japanese liver surgeons have challenged to treat HCC with MVI by
surgery, and reported much better survival than systemic therapy. To 28CS0404
obtain even better outcomes, preoperative systemic therapy is now Application of AI in ACLF Prediction
being introduced for advanced HCC. Recently, we have conducted
Nipun Verma
several prospective phase II trials to evaluate efficacy of combination
Chandigarh
strategy of systemic therapy followed by surgical resection for
advanced HCC. In my presentation, I will show the current role of Acute-on-chronic liver failure (ACLF) remains one of the most
challenging conditions in hepatology, with rapid deterioration and concurrent hepatitis C, and 1 had chronic hepatitis B. Of 150 patients
high short-term mortality. In our presentation, we explore how artificial with AIH exclusively, the female-to-male sex ratio was 2.26, the mean
intelligence (AI) is revolutionizing the way we understand, diagnose, age was 51.09 years, and the baseline cirrhosis rate was 11.3%.
and treat ACLF in the Asia Pacific region. All except 1 patient had AIH type 1. The cumulative incidences of
Recent advances in AI and machine learning offer new ways to cirrhosis, hepatocellular carcinoma, cancer, extrahepatic cancer, and
analyze complex clinical and molecular data. By integrating diverse mortality/liver transplantation were 64.2%, 13.3%, 32.5%, 21.1%, and
datasets—such as clinical records, imaging, and proteomics—AI 23.4%, respectively. Overall, high posttherapy relapse rates warrant
can identify hidden patterns that traditional methods may miss. For special attention, particularly for patients with high baseline alkaline
instance, analysis of longitudinal data in ACLF patients has revealed phosphatase levels. Baseline age, cirrhosis and serum antinuclear
novel trends: some clinical variables that appear similar at baseline antibody titer are crucial for the outcome of AIH patients.
may diverge as the disease progresses, while others show early
differences that level out over time. These insights are critical for
28AC0004
pinpointing prognosis that could guide early interventions. We believe
that AI have the potential to inform personalized treatment strategies Autoimmune hepatitis presenting as acute liver failure and acute-
and ultimately improve patient outcomes. on-chronic liver failure
In addition to technical innovation, the current paradigm faces Soek-Siam Tan
challenges in implementing AI in clinical practice. In this lecture, we will Selangor
discuss the importance of high-quality data, ethical considerations, and Acute and severe presentation of autoimmune hepatitis (AIH) is not
the need for collaborative efforts between clinicians, data scientists, uncommon accounting for 22-43% of AIH and it has been reported
and bioinformaticians. The integration of AI is not about replacing to be increasing in trends. This type of AIH results in a diverse clinical
traditional clinical expertise, but rather enhancing it—providing a spectrum determined by the pre-existing chronic AIH and the severity,
powerful tool to better understand complex biological processes and there are two possible entities: acute exacerbation form of undiagnosed
tailor treatments to individual patient needs. or misdiagnosed chronic AIH cases or genuine acute AIH without
In conclusion, the application of AI in ACLF is opening new avenues for chronic histological changes. Thus acute AIH or acute exacerbation
early diagnosis and personalized care. By transforming raw data into of AIH may present to the clinicians as acute liver failure (ALF) and
actionable insights, AI holds promise not only for improving prognosis acute-on-chronic liver failure (ACLF) as defined by the APASL ACLF
but also for deepening our understanding of the disease itself. We criteria. There is no standardized definition for these acute onset AIH.
invite the liver research community to join us in embracing these In contrast to chronic AIH, acute AIH or acute exacerbation of AIH have
innovations, as we work together toward a future of more precise and been found to have normal immunoglobulin, negative for autoimmune
effective care for ACLF patients. markers and in AIH presenting with ALF (AIH-ALF) there is atypical liver
histology predominantly affecting the centrilobular zone. Moreover the
28AC0003 widely used scoring systems for AIH have not been validated for acute
AIH or acute exacerbation of AIH and because of the above mentioned
AIH in HBV-epidemic area
clinical features these patients may not fulfill the criteria especially
Ming-Ling Chang with the simplified scoring system making it not useful. Consequently
Department of Medicine, College of Medicine, Chang Gung misdiagnosis or delay in diagnosis and treatment is common with
University, Taoyuan bad outcomes. The response to corticosteroids is highly variable at
Autoimmune hepatitis (AIH) is a necroinflammatory liver disease that about 36-100% with the sicker cohorts having poorer response. Timely
occurs in patients of all ages. AIH is a prototypical autoimmune disease liver transplantation is needed for patients with acute AIH or acute
with a female predominance. The etiology of AIH remains mostly exacerbation of AIH who did not respond to corticosteroids. The on-
unresolved but likely results from various environmental exposures in treatment response to corticosteroid can be guided by assessing the
the background of a permissive genetic architecture and failure of the SURFASA or MELD scores but not by the serum transaminases. In
native immune system, resulting in chronic inflammation of hepatocytes patients with AIH-ALF, the response to corticosteroids is suboptimal
and subsequent liver fibrosis. The typical histological features of AIH and for those with high MELD scores corticosteroid therapy was found
include signs of chronic hepatitis with predominant plasma cell-rich to increase mortality. Liver transplantation may be the only effective
interface activity in the periportal area and liver lobules, rosetting treatment for some patients with AIH-ALF and AIH-ACLF. Intensive
of hepatocytes, and emperipolesis. The disease is characterized care management, sequential monitoring of prognostic scores and
by elevated serum aminotransferases, the presence of circulating organ supports may be needed to stabilize the physiological and
autoantibodies and immunoglobulin G hyperglobulinemia. In addition metabolic conditions of ALF and ACLF patients and to optimally bridge
to these typical findings, diagnosis of AIH requires exclusion of similar to liver transplant. The outcome of liver transplant is comparable to
diseases. In most patients, an AIH diagnosis justifies life-long treatment other causes of ALF. However in the post transplant period there is
to prevent development of end-stage liver disease or cirrhosis. Most increased risk in both acute and late graft rejections and recurrence
AIH patients respond well to standard immunosuppressive therapy of AIH.
with steroids and/or azathioprine. However, an insufficient response to
standard therapy occurs in 20% of patients. AIH displays considerable
28AC0007
heterogeneity, as it might occur with acute onset or with fulminant
hepatic failure. The pooled annual incidence rates of AIH for the Epidemiology of Primary Biliary Cholangitis in the Asia-Pacific
Asian, European, and American populations are similar at 1.31/105, Region
1.37/105, and 1.00/105, respectively. However, the prevalence rate is Sook-Hyang Jeong
lowest in Asia, as the pooled prevalence rates for Asian, European, Seoul
and American populations are 12.99/105, 19.44/105, and 22.80/105, Primary Biliary Cholangitis (PBC) is a rare cholestatic autoimmune
respectively. That the majority of AIH patients in South Asia are disease characterized by the progressive destruction of intrahepatic
diagnosed at an advanced stage and have high mortality rates might small bile ducts. This condition can lead to liver cirrhosis and
account for the disproportional low AIH prevalence in Asia. Moreover, hepatocellular carcinoma (HCC), contributing to significant liver-related
the prevalence of concurrent extrahepatic autoimmune diseases is morbidity and mortality, along with various extrahepatic manifestations.
reported to be as high as 40% in UK AIH patients, and AIH has been The pathophysiology of PBC has been linked to genetic susceptibility
associated with an increased risk of death from cardiovascular disease and environmental factors such as infections and exposure to toxic
in Sweden. To elucidate the phenotype and outcome of AIH in Taiwan, substances.
where is hyperendemic for chronic hepatitis B, we have surveyed The global prevalence of PBC ranges from 1.92 to 40.2 per 100,000
169 patients with AIH. Of these 169 patients, 16 were diagnosed individuals, with an annual incidence between 0.23 and 5.31 per
with overlap syndrome (AIH and primary biliary cholangitis), 2 had
100,000, exhibiting considerable geographic variation. A 2021 meta- autoantibodies have proven useful in PSC cases without UC.
analysis reported that the incidence and prevalence of PBC in the Asia- Regarding IgG4-related SC, a separate committee under the
Pacific region were 0.84 and 9.81 per 100,000 persons, respectively— MHLW has also been established to develop diagnostic criteria and
both significantly lower than those observed in North America and guidelines. IgG4-related disease (IgG4-RD) involves multiple organs,
Europe. Specifically, the prevalence per 100,000 was reported as and comprehensive diagnostic criteria were published in 2021(4).
follows: 12.32 in South Korea (2019), 8.09 in Taiwan (2023), 5.6 in Most cases of IgG4-SC are associated with autoimmune pancreatitis,
Hong Kong (2017), 49.2 in China (2010), 33.8 in Japan (2016), 5.1 in though a small number of isolated cases exist. The diagnostic criteria
Australia (2004), and 9.9 in New Zealand (2012). The incidence and for isolated IgG4-SC, published by Nakazawa et al. in 2021 (5), have
prevalence of PBC tend to increase with age, peaking between 60 and been particularly useful in distinguishing IgG4-SC from PSC.
79 years across all three regions. In this lecture, we will introduce the latest diagnostic criteria and
Over recent years, the prevalence of PBC has risen, largely due guidelines for SC and provide insights into ongoing research and
to increased awareness, early detection, and advancements in activities in this field (6).
treatment, including the introduction of second-line therapeutics. While
PBC incidence and prevalence remain higher in females than in males
across all regions, the female-to-male ratio has generally declined over CURRENT SESSION 05
time. Notably, this ratio has historically been higher in the Asia-Pacific
region compared to Europe and North America, but a decreasing
Translation of Science into Hepatitis B Cure -
trend has been observed. Studies suggest that male PBC patients Immunological Perspective
present at a more advanced disease stage, as evidenced by older age
at diagnosis, higher bilirubin levels, more pronounced liver fibrosis, 15:00-16:30 | Function Hall A
and shorter exposure to ursodeoxycholic acid (UDCA) therapy.
Furthermore, male PBC patients consistently exhibit a significantly 28CS0502
higher risk of developing HCC and experiencing mortality, even after
Intrahepatic T cell response and hepatitis B virus clearance
adjusting for age, comorbidities, UDCA response, and disease stage.
In population-based studies conducted in South Korea, the five-year Dongliang Yang
transplant-free survival rate between 2009 and 2019 was 87.8%, with Department of Infectious Disease, Institute of Infection and Immunity
male sex and low adherence to UDCA therapy identified as significant Union Hospital of Tongji Medical College, Huazhong University of
risk factors for overall mortality. The cumulative incidence of HCC in Science and Technology, Wuhan, P.R. China
PBC patients varied across regions: 1.3% at five years in South Korea, Chronic hepatitis B virus (HBV) infection remains a major global public
2.8% at ten years in Hong Kong, and 9.11% at fourteen years post- health challenge. While current antiviral therapies can effectively
diagnosis in Taiwan. A recent Korean population study reported an suppress viral replication, achieving complete viral clearance and
HCC incidence rate of 3.7 per 1,000 person-years, with independent disease cure remains elusive. HBV infection is restricted to the
risk factors including advanced age, male sex, smoking, and diabetes. liver, where it drives exhaustion of virus-specific T and B cells and
These findings align with Japan’s reported incidence rate of 3.4–3.6 pathogenesis through dysregulation of intrahepatic immunity. Previous
per 1,000 person-years. studies on immune regulation during HBV infection have demonstrated
The epidemiology of PBC continues to evolve, demonstrating that clearance of HBV relies primarily on the coordinated activation
substantial regional and temporal variability. Further studies focusing of different immune system components, and virus-specific T-cell
on PBC epidemiology in the Asia-Pacific region are essential to responses play a pivotal role in eliminating HBV-infected hepatocytes.
improving disease management and patient outcomes. However, the activation and regulation mechanism underline the
28AC0010 intrahepatic T cell immune response and how the host coordinates
Current status of PSC and IgG4-SC their activation and responses between peripheral immune organs and
Hiroyuki Isayama the liver remains largely unknown. Based on the development of new
technology such as elective liver tissue sampling and next generation
Department of Gastroenterology, Graduate School of Medicine,
single-cell RNA sequencing (scRNA-seq), more data has been
Juntendo University, Tokyo, Japan
accumulated not only to better understand the critical immunological
Sclerosing cholangitis (SC) is a challenging disease to diagnose
mechanisms of HBV clearance and pathogenesis but also to provide a
and is characterized by distinctive cholangiographic findings. There
foundation for developing novel immunotherapies to achieve functional
are various causes of SC, with primary sclerosing cholangitis (PSC)
cure in chronic HBV infection.
and IgG4-related sclerosing cholangitis (IgG4-SC) being the most
representative forms. The pathogenesis of PSC remains unknown, and
no radical treatment is available, making its management particularly CURRENT SESSION 06
difficult.
In Japan, the Subcommittee on Sclerosing Cholangitis and Intrahepatic Drug Induced Liver Injury (DILI)
Bile Duct Stones (Chief: Hiroyuki Isayama) within the Intractable
Hepatobiliary Disease Research Group (Chairperson: Atsushi Tanaka) 15:00-16:30 | Function Hall B
of the Japanese Ministry of Health, Labour and Welfare (MHLW) has
focused on PSC. The subcommittee plays a key role in developing 28CS0602
diagnostic criteria and guidelines (1, 2), organizing patient registry,
Immune Checkpoint Inhibitor-Induced Liver Injury (ICILI):
and conducting national surveys. Recently, the diagnostic criteria for
Challenges and Considerations
PSC were revised, and a new version is currently under review in a
medical journal following public commentary through the Japanese Nelia Hernandez
Society of Gastroenterology (JSGE). Montevideo
Key updates in the revised criteria include the incorporation of pediatric The advent of immune checkpoint inhibitors (ICIs) has transformed
PSC, small-duct PSC, and PSC recurrence after liver transplantation. the therapeutic landscape of malignancies, including hepatobiliary
These updates will be presented in this lecture. Additionally, efforts to cancers, establishing them as a cornerstone of treatment. However,
revise the guidelines based on the updated criteria have begun. At immune checkpoint inhibitor-induced liver injury (ICILI) has emerged
present, we are formulating background information, clinical questions, as a significant complication, requiring heightened awareness among
and future research directions. oncologists and hepatologists. The expanding indications and
Another significant recent development in Japan is the discovery of increased availability of ICIs have contributed to a rising incidence
novel autoantibodies, specifically anti-integrin αvβ6 autoantibodies, of ICILI, necessitating early recognition and prompt intervention to
in both PSC and ulcerative colitis (UC) (3). Interestingly, these mitigate potential morbidity and mortality.
ICILI presents multiple diagnostic and therapeutic challenges. Patients the risk of HCC in HCV-infected individuals.
receiving ICIs are often clinically vulnerable, frequently exposed to The advent of direct-acting antiviral (DAA) therapy has revolutionized
polypharmacy, and commonly treated with ICI combinations, which HCV treatment, achieving sustained virologic response (SVR) rates
may elevate the risk of drug-induced liver injury (DILI). Distinguishing exceeding 95%. However, while viral eradication reduces the overall
ICILI from hepatic tumor progression can be challenging. Given the risk of HCC, it does not eliminate it completely, particularly in patients
high antitumor efficacy of ICIs and limited alternative therapeutic with advanced fibrosis or cirrhosis. Post-SVR patients with pre-
options, rechallenge decisions are frequently required. The role of existing or post-SVR risks require continuous surveillance due to the
immunosuppressive therapy remains controversial and necessitates potential for residual oncogenic risk. Emerging evidence suggests that
individualized risk-benefit assessment. Corticosteroids are the first persistent hepatic inflammation and fibrosis, gut microbiota dysbiosis,
treatment option, but optimal timing, dosing, and duration remain unchanged epigenetic scars and metabolic reprogramming may
uncertain. Additionally, the utility of liver biopsy in diagnosis and contribute to HCC development even after HCV clearance.
guiding management remains an area of ongoing debate, further Several risk factors associated with post-SVR HCC have been
emphasizing the need for case-by-case evaluation. identified, including advanced fibrosis, diabetes, alcohol consumption,
Published data highlight the variable incidence of ICILI depending higher bilirubin levels, persistent high FIB-4 scores, elevated baseline
on the specific ICI regimen. While the overall ICILI rate is 1.72%, alpha-fetoprotein (AFP) levels, and specific host genetic variations
the highest incidence of immune-mediated all-grade and grade 3–5 (MICA, PNPLA3, MBOAT7, TM6SF2, and GCKR). Several non-
hepatotoxicity was observed for PD-1 inhibitors+CTLA-4 inhibitors invasive markers have been associated with risk of HCC after HCV
(19%-37%) compared to monotherapies. However, data on ICILI in cure. Consistent HCC surveillance in high-risk populations should
patients with cirrhosis remain limited. Even if the incidence is similar, utilize surrogate markers and risk stratification. Re-setting threshold of
the clinical course in this population may be more severe due to annual HCC incidence for cost-effectiveness of HCC surveillance is
reduced hepatic reserve and altered immune responses, potentially mandatory. Promising chemo-preventive effects have been observed
leading to acute-on-chronic liver failure, decompensation, and with aspirin, metformin, and statins, reducing HCC risk in large cohort
increased mortality. Moreover, diagnosing ICILI in cirrhotic patients is studies among HCV-cured patients. Strategies targeting modifiable
particularly challenging, as liver enzyme fluctuations can result from risks could further mitigate the risk of HCC after achieving HCV SVR.
multiple factors beyond DILI. Despite recent advancements, challenges remain in the global
The most common presentation of ICILI is a hepatocellular injury eradication of HCV and the effective management of HCV-associated
pattern, typically manifesting within approximately six to twelve HCC. Barriers to access for antiviral therapy, disparities in healthcare
weeks of treatment initiation, with a severity spectrum ranging from infrastructure, and late-stage HCC diagnosis in resource-limited
asymptomatic elevation of transaminases to severe cases, though settings continue to hinder progress. Future research should focus
fulminant hepatic failure remains rare, occurring in less than 0.5% of on identifying novel biomarkers for early detection, elucidating
cases. In contrast to autoimmune hepatitis-like, autoantibodies are the mechanisms underlying post-SVR hepatocarcinogenesis, and
usually absent. Also mixed, and cholestatic injury pattern may appear. optimizing therapeutic interventions to improve long-term survival.
While biliary tree enlargement is infrequent, it has been observed, In conclusion, HCV-related liver cancer remains a significant clinical
predominantly in association with nivolumab and pembrolizumab. challenge, necessitating a multidisciplinary approach that integrates
Further research is crucial to establish optimal diagnostic and antiviral therapy, regular surveillance, and targeted treatments.
management strategies, risk stratification, and develop evidence- Continued efforts in public health, early screening, and novel
based approaches to rechallenge and immunosuppressive therapy in therapeutic strategies will be essential in reducing the burden of HCV-
affected patients. related HCC and improving patient outcomes globally.

CURRENT SESSION 07 CURRENT SESSION 08

Etiology and Disease Burden of Liver Cancer Gut Microbiota and the Liver Health
15:00-16:30 | Function Hall C 15:00-16:30 | 402 (A+B)

28CS0702 28CS0803
HCV-Related Liver Cancer Microbiome Markers: Prediction and Prevention
Ming-Lung Yu Dong Joon Kim
Kaohsiung Medical University and Hospital, Kaohsiung Department of Internal Medicine
Hepatitis C virus (HCV) infection is a major global health concern, Hallym University College of Medicine, South KOREA
contributing significantly to the development of hepatocellular Human microbiomes are essential throughout the lifespan and are
carcinoma (HCC), the most prevalent form of liver cancer in Western increasingly recognized and studied for their roles in metabolic,
countries and Japan, and the second leading cause of liver cancers immunological and neurological processes. Although the complexity
worldwide. Chronic HCV infection leads to persistent hepatic of these microbial communities is not yet fully understood, their clinical
inflammation, fibrosis, and ultimately cirrhosis, which significantly and industrial exploitations are rapidly advancing and expanding.
increases the risk of HCC. Unlike hepatitis B virus (HBV), which The growing interest in the gut microbiome encompasses its potential
can directly integrate into the host genome, HCV is an RNA virus in the diagnosis, prognostication, and risk assessment for liver
that promotes hepatocarcinogenesis through indirect mechanisms, diseases; the prediction of patient responses to specific therapies; the
including chronic liver injury, oxidative stress, and metabolic alterations. development of therapies aimed at modulating the gut microbiome;
The molecular pathogenesis of HCV-associated HCC involves and the monitoring of therapeutic efficacy.
multiple pathways, including the dysregulation of host oncogenes Despite this enthusiasm, evidence supporting its clinical usefulness
and tumor suppressor genes, activation of inflammatory cytokines, remains scarce and the application of gut microbiome research in
and epigenetic modifications. HCV core protein and non-structural clinical practice is still minimal. This is largely due to several factors,
proteins play pivotal roles in hepatocyte proliferation, apoptosis including the complexity of microbiota, the challenge of disentangling
inhibition, and immune evasion. Furthermore, metabolic dysfunction, correlation from causation, the reliance on pre-clinical models with
such as insulin resistance, steatosis, and dyslipidemia, exacerbates limited generalizability to humans, the absence of validated tests for
liver damage and contributes to carcinogenesis. Several genetic and therapeutic follow-up, and the lack of established regulations and
environmental factors, including co-infection with HBV, excessive frameworks for clinical translation.
alcohol consumption, obesity, and diabetes mellitus, further elevate Meanwhile, an increasing number of commercial providers offer
direct-to-consumer microbiome diagnostic tests without standardized Nepetin in compound Phyllanthus urinaria L. inhibits the growth
regulations or proven clinical value. This may result in a considerable and metastasis of hepatitis B-associated hepatocellular carcinoma
waste of individual and healthcare resources, along with potential via HBx/HIF-1α/VEGFA pathway
drawbacks in patient management. Mianmian Liao1,2*, Haiyan Du1,2*, Yuhang Zhou3, Zhijuan Wang4,
To address these issues, an international multidiciplinary expert panel Rui An4, Tuantuan Cheng4, Huanhuan Zhang4, Danping Huang4,
has convened to standardize and define best practices for microbiome Guangdong Tong1,2,3
testing in clinical implementation. Their recommendations cover 1
.The Affiliated Dongguan Songshan Lake Central Hospital,
general principles, minimum requirements, indications, pre-testing Guangdong Medical University, Dongguan 523326, China
protocols, methods of analyses, result reporting, and potential clinical 2
.Department of Hepatology, Shenzhen Traditional Chinese Medicine
value. Hospital, The Fourth Clinical Medical College of Guangzhou
In this presentation, current knowledge gaps and future directions are University of Chinese Medicine, Shenzhen, 518033, China
also evaluated to minimize the use of inappropriate tests and pave 3
.Department of Hepatology, Shenzhen Traditional Chinese Medicine
the way for the evidence-based development of human microbiome Hospital Affiliated to Nanjing University of Chinese Medicine,
diagnostics in clinical medicine. Shenzhen, 518033, China
4
. The First Clinical Medical School of Guangdong Pharmaceutical
University, Guangzhou, 511400, China
TRADITIONAL MEDICINE COURSE Objectives: In traditional Chinese medicine, compound Phyllanthus
16:00-17:15 | Auditorium urinaria L. (CP) has demonstrated clinical efficacy in treating hepatitis
B virus (HBV)-induced hepatocellular carcinoma (HCC). However, its
therapeutic mechanisms and the bioactive ingredients (BIs) remain
28TC0001 poorly understood. Therefore, this study aimed to identify these active
Traditional Chinese Medicine improves liver fibrosis by regulating ingredients and elucidate the mechanisms underlying their action in
epigenetics HBV-HCC.
Xiaojiaoyang Li Methods: Xenograft tumor and pulmonary metastasis mouse
Beijing University of Chinese Medicine, School of Life Sciences models were established to evaluate the effects of CP on the growth
Cholestatic liver fibrosis is a common pathological feature of various and metastasis of HBV-induced HCC. Ultra-high-performance
biliary tract diseases. The underlying pathological mechanisms are liquid chromatography (UHPLC)-tandem mass spectrometry and
not fully elucidated, posing significant obstacles to the discovery of metabolomics analyses were conducted to construct a fingerprint
new drug targets. Epigenetics refers to the study of changes in gene profile of CP and identify its BIs. A series of molecular biology
expression or cellular phenotype that occur without alterations to the experiments, along with an orthotopic hepatoma mouse model, was
underlying DNA sequence. As a reversible regulatory mechanism, employed to elucidate the anti-cancer and anti-metastatic properties
epigenetic modification is implicated in many biological processes, of BIs as well as the underlying molecular mechanisms involved.
including cholestatic liver fibrosis. Hyodeoxycholic acid (HDCA) is Results: In vivo experiments demonstrated that CP effectively
the key component of the traditional Chinese medicine (TCM) pig suppressed the proliferation and metastasis of HBV-HCC cells. The
bile powder, known for its heat-clearing and detoxifying properties. fingerprint profile of CP was successfully established using UHPLC,
Recently, our team reported that HDCA levels were decreased in leading to the identification of 1033 BIs in CP, 180 BIs in female
both cholestatic patients and mice, while HDCA supplementation Sprague–Dawley (SD) rats, and 72 BIs in male SD rats. Concurrent
significantly ameliorated cholestatic liver fibrosis. By inducing E-twenty- in vitro experiments confirmed that nepetin was the most bioactive
six-specific sequence variant 4 (ETV4) expression in cholangiocytes, ingredient in CP that inhibited the growth and metastasis of HBV-HCC
HDCA induced MMP9 secretion, facilitating extracellular matrix cells. Furthermore, mechanistic studies revealed that the hepatitis
(ECM) degradation. Findings in cholestatic fibrosis patients and B virus X protein mediated the tumor hypoxic microenvironment,
Etv4-/- mice further revealed a promising role of ETV4 in improving sustaining hypoxia-inducible factor-1α (HIF-1α) expression and
liver fibrosis and in the therapeutic effects of HDCA. Mechanistically, subsequently activating vascular endothelial growth factor A (VEGFA),
HDCA promoted m6A modification of ETV4 mRNA, promotes IGF2BP1 which promoted HBV-HCC growth and metastasis. Notably, in vitro
recognition and PABPC1 recruitment to inhibit the deadenylation of and in vivo functional studies demonstrated that nepetin inhibited
ETV4 mRNA, leading to increased mRNA stability, storage in P-bodies, cell proliferation and metastasis of HBV-HCC via the HIF-1α/VEGFA
and prolonged translation. The mutation of m6A site on ETV4 mRNA signaling pathway.
or knocking down critical genes involved in m6A modification Conclusions: This study not only elucidated the material basis for the
significantly abolished the regulative effects of HDCA. In addition to efficacy of CP against HBV-HCC, but also identified nepetin as its
HDCA, Chuanxiong Rhizoma (CX), also known as famous traditional primary active ingredient. Functional studies further confirmed that the
Chinese medicine (TCM), is clinically used for treating cardiovascular HIF-1α/VEGFA signaling pathway serves as a key target mediating the
and hepatobiliary diseases. We recently also found that the aqueous development and metastasis of HBV-HCC, thereby presenting nepetin
and phthalide extracts of CX (CXPHL) significantly reduced ductular as a potential therapeutic strategy for this condition.
reaction (DR) and improved liver fibrosis in the BDL mice and in vitro.
CXPHL suppressed the transcription and transfer of plasminogen 28TC0003
activator inhibitor-1 (PAI-1) and fibronectin (FN) from the ‘DR-like’ Traditional Chinese Medicine Treatment for Metabolic-Associated
cholangiocytes to activate hepatic stellate cells. Mechanistically, the Fatty Liver Disease at Shuguang Hospital
inhibition of PAI-1 and FN by CXPHL was attributed to the untight
Xuehao Sun
combination of the acetyltransferase KAT2A and SMAD3, followed by
Shanghai
the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated
transcription in cholangiocytes. Our findings offer valuable insights for This presentation outlines the clinical and mechanistic research
future therapeutic strategies that focus on regulating m6A-dependent conducted by the Department of Hepatology at Shuguang Hospital
or H3K9ac-mediated epigenetic modifications of anti-fibrotic targets on the treatment of Metabolic Associated Fatty Liver Disease (MAFLD)
and developing new interventions utilizing TCM. using Traditional Chinese Medicine (TCM) methodologies.
Our nationwide survey encompassing 2,261 MAFLD patients from
23 hospitals across China revealed that the most prevalent TCM
28TC0002 syndrome patterns, in descending order, were spleen deficiency with
phlegm-dampness, stomach heat with spleen deficiency, phlegm-
stasis intermingling, spleen and kidney deficiency, liver depression with
spleen deficiency, liver and kidney yin deficiency, and dampness-heat
accumulation. Notably, the spleen deficiency with phlegm-dampness widely practiced. While traditional treatments show promising results,
pattern was the most common across all age groups. challenges remain regarding scientific validation, standardization,
In alignment with the primary pathogenesis of MAFLD, we developed herbal toxicity, and integration with modern medicine.
the Shenge Granule, a formulation designed to invigorate the spleen, Conclusion
resolve dampness, clear heat, and dissolve stasis. Comprising Traditional medicine continues to be an essential component of liver
Atractylodes macrocephala, Salvia miltiorrhiza, Pueraria lobata, disease management worldwide. However, further scientific studies,
Sedum sarmentosum, Curcuma zedoaria, and Ligustrum lucidum, this clinical trials, and regulatory measures are necessary to ensure the
formulation has been granted a national invention patent (Patent No.: safety, efficacy, and compatibility of these treatments with modern
ZL200910057416.6) and is widely utilized as an in-house preparation medical practices. The future of liver disease treatment may benefit
at Shuguang Hospital. A 12-week randomized, double-blind, placebo- from a holistic approach that combines traditional knowledge with
controlled study involving 154 MAFLD patients demonstrated that the modern biomedical research.
Shenge Granule group exhibited a significant reduction in MRI-PDFF
values post-treatment compared to the control group [37.18% (IQR,
17.84 to 50.93) vs. 4.07% (IQR, -13.94 to 18.15), P<0.05]. Animal CURRENT SESSION 09
studies further revealed that Shenge Granule alleviates high-fat diet
(HFD)-induced hepatic steatosis both in vivo and in vitro. Through
Novel Concept and Future Therapy for
quantitative proteomic analysis and validation via both in vivo and Hepatitis B
in vitro experiments, ACOX1 was identified as a potential target of
Shenge Granule, which activates the PPARα signaling pathway by 09:15-10:45 | Function Hall A
inhibiting ACOX1.
Another empirical formula from Shuguang Hospital for treating 29CS0901
MAFLD, the Compound Xiaozhi Formula, designed to clear heat,
Achieving Functional Cure and Elimination of HBV
drain dampness, dispel phlegm, and dissolve stasis, consists of
Anna S. Lok
Nelumbo nucifera, Gynostemma pentaphyllum, Trichosanthes
University of Michigan, Ann Arbor, MI, USA
kirilowii, Benincasa hispida peel, Salvia miltiorrhiza, and Polygonum
perfoliatum. This formula has also been granted a national invention Current treatment of chronic hepatitis B – nucleos(t)ide analogues (NA)
patent (ZL202211392355.0). A 12-week randomized, double-blind, and pegylated interferon are effective in suppressing HBV replication
placebo-controlled study involving 100 MAFLD patients demonstrated but rarely results in HBsAg loss. A major drawback with NA therapy
that, compared to placebo, Xiaozhi Formula treatment significantly is that it has minimal effect on eliminating covalently closed circular
reduced relative hepatic fat content by MRI-PDFF (-32.75% vs. (ccc) DNA and viral relapse is universal when NA is stopped. Thus,
-14.58%; least squares mean difference, -18.16% [95% CI, -26.79% most patients need to remain on long-term and in many cases lifelong
to -9.53%]; P < 0.001) and absolute hepatic fat content by MRI-PDFF treatment to derive continued clinical benefit.
(-6.17% vs. -2.67%; least squares mean difference -3.51% [95% CI, The remarkable success of hepatitis C direct-acting antivirals has
-5.10 to -1.91]; P < 0.001). Animal studies confirmed that Xiaozhi spurred research into a cure for hepatitis B. Sterilizing HBV cure is
Formula ameliorates MAFLD by regulating lipid metabolism through unlikely to be feasible in the foreseeable future; thus, the current goal
the activation of AMPK and PPAR signaling pathways. is functional cure defined as undetectable HBsAg and HBV DNA
Additionally, the presentation highlights the efficacy of acupuncture below quantification at least 24 weeks after completion of a course of
and catgut embedding therapy in the treatment of MAFLD. treatment. Many classes of novel antivirals including capsid assembly
modulators, small interfering RNAs (siRNA), antisense oligonucleotides
(ASO), and entry inhibitors are being evaluated in clinical trials generally
28TC0004 in combination with NAs; however, few have resulted in functional cure.
Traditional medical treatments of liver diseases around the world In parallel, multiple immunomodulatory approaches are evaluated
Amarsanaa Jazag including toll-like receptor agonists, therapeutic vaccines, and immune
Mongolian Association for the Study of Liver Diseases (MASLD) checkpoint inhibitors with limited success. Several combinations of
new antivirals with immune modulatory therapies including pegylated
Background
interferon have resulted in higher rates of HBsAg loss mainly in patients
Traditional medicine has played a significant role in the treatment of
with low baseline HBsAg levels. A major challenge in eliminating HBV
liver diseases worldwide. Various cultures have developed herbal,
is the need to not only eliminate or permanently silence ccc DNA but
dietary, and therapeutic approaches that aim to support liver function,
also integrated HBV DNA. Although siRNA and ASO can target both
detoxify the body, and alleviate liver-related conditions. Despite the
ccc and integrated HBV DNA and sustained reduction in circulating
increasing integration of traditional and modern medical practices,
HBsAg level has been postulated to restore HBV-specific immune
a comprehensive understanding of their efficacy, mechanisms, and
response, limited data of patients who received siRNA therapy showed
challenges remains limited. In fact, many of modern day medical
that reduced HBsAg levels were maintained in only half the patients
treatments were derived from Traditional Medicine.
with no further decline in HBsAg levels or HBsAg loss during long-term
Methods
follow-up.
This study explores traditional liver treatments across different cultural
Development of alternative therapeutic targets is critical in the quest for
healing systems, including Traditional Chinese Medicine (TCM),
HBV cure, but other facets such as setting realistic goals, using novel
Ayurveda, Tibetan medicine, European herbal medicine, Mongolian
clinical trial designs such as platform trials to improve efficiency, and
medicine, African traditional medicine, Native American medicine, South
soliciting patient input into their values and preferences are equally
American indigenous medicine, and Unani medicine. A comparative
important. Finally, these new therapies must be simple, safe, and
analysis was conducted by reviewing documented herbal remedies,
affordable to have an impact on the global burden of HBV infection.
therapeutic techniques, and their underlying principles. Furthermore,
In parallel, efforts to maximize birth dose HBV vaccination, increase
scientific research on key medicinal plants was examined to evaluate
diagnosis of those infected, and improve access to existing therapies
their hepatoprotective properties.
should continue.
Findings
The study identified commonly used medicinal plants such as milk
thistle (Silybum marianum), turmeric (Curcuma longa), Phyllanthus 29CS0903
niruri, Schisandra (Schisandra chinensis), licorice root (Glycyrrhiza Novel Concept and Future Therapy for Hepatitis B - Combination
glabra), and dandelion (Taraxacum officinale), which have Therapies of Direct-Acting Antivirals and Immunomodulatory
demonstrated hepatoprotective, anti-inflammatory, and detoxifying Agents
properties. Various therapeutic methods, including acupuncture, Markus Cornberg, MD1,2,3,4,5
moxibustion, bloodletting, cupping therapy, and fasting were also
1
Department of Gastroenterology, Hepatology, Infectious Diseases 29CS0904
and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse
Sequential Therapy: Strategies for Functional Cure of Chronic
1, 30625 Hannover, Germany
Hepatitis B
2
Centre for Individualised Infection Medicine (CiiM), a joint venture
Hong Ren
between Helmholtz-Centre for Infection Research and Hannover
Chongqing
Medical School, Feodor-Lynen-Strasse 11, 30625 Hannover, Germany
3
German Center for Infection Research (DZIF), partner site Hannover- Background: Functional cure, defined as sustained hepatitis B
Braunschweig, Germany surface antigen (HBsAg) loss and undetectable hepatitis B virus
4
TWINCORE, Centre of Experimental and Clinical Infection Research, (HBV) DNA after 24 weeks off therapy, is now the goal of treatment
a joint venture between Helmholtz-Centre for Infection Research and for chronic hepatitis B (CHB) but is rarely achieved through nucleos(t)
Hannover Medical School, Feodor-Lynen-Strasse 7, 30625 Hannover, ide analogue (NA) or pegylated interferon (Peg-IFN) monotherapy.
Germany Sequential therapy with NA and Peg-IFN can increase HBsAg loss
5
Cluster of Excellence RESIST (EXC2155), Hannover Medical School, rates to a limited extent. With novel agents emerging, studies on
Carl-Neuberg-Strasse 1, 30625 Hannover, Germany sequential therapy regimens with different agents are needed to to
Chronic infection with the hepatitis B virus (HBV) remains a major further enhance HBsAg loss rates.
global health challenge, affecting over 250 million people and causing Methods: HBV-carrier mice on entecavir therapy were used to assess
significant morbidity and mortality. Nucleos(t)ide analogues (NAs) the safety, efficacy, and peripheral and intrahepatic immune responses
effectively suppress viral replication but rarely result in a functional cure of either concurrent or sequential administration of anti-PD-1 antibody
– defined as a sustained loss of hepatitis B surface antigen (HBsAg) (αPD-1) and Peg-IFNα. Based on results from mice, the sequential
with undetectable HBV DNA off therapy. Achieving a functional cure therapy regimen (sequential Peg-IFNα after αPD-1 or after anti-PD-L1
is now an important treatment goal, which probably cannot yet be antibody [αPD-L1]) was chosen for further investigation in virally-
achieved with the new therapies when used as monotherapy. Novel suppressed patients with CHB on nucleos(t)ide analogue (NA) by
therapeutic strategies therefore target both the viral life cycle and the comparing with NA monotherapy, Peg-IFNα add-on therapy, or αPD-1
host immune dysfunction underlying HBV persistence 1,2. (or αPD-L1) add-on therapy.
This lecture will explore the rationale and current evidence supporting Results: No significant adverse events (AEs) were observed by clinical
emerging combination therapies that integrate direct-acting antivirals, observation, blood tests, and histopathology in mice on entecavir
antigen-reducing agents, and immunomodulators. Agents such as under sequential therapy of αPD-1 and Peg-IFNα, while hair loss was
small interfering RNAs (siRNAs) and antisense oligonucleotides noted in one mouse under the combination therapy. The sequential
(ASOs) can substantially reduce viral protein production, particularly therapy demonstrated greater reductions in HBsAg levels and higher
HBsAg, with some achieving >2 log IU/mL reduction. However, in many frequencies of HBsAg-specific IL-21+, IFN-γ+, and TNF-α+ CD8+T
cases this effect is not sustained. One promising ASO, Bepiroviruses cells compared to other treatments in mice (P<0.05). In NA-treated
(Bepi), has been shown to induce HBsAg loss in approximately 10% of CHB patients, sequential therapy of αPD-1 and Peg-IFNα showed
patients. Notably, Bepi has dual activity in that it also activates toll-like similar overall incidences of AEs with Peg-IFNα add-on therapy. All
receptor 8 (TLR8), potentially enhancing immune stimulation 3. In view AEs were self-limiting or resolved following drug discontinuation and/or
of this dual mechanism, combining direct-acting antivirals – especially symptomatic treatment. At 36-week follow-up, sequential therapy with
those that are able to reduce HBsAg – with immunomodulatory αPD-1 and Peg-IFNα induced greater HBsAg reductions compared
agents is a compelling strategy. Recent data 4 showed that the siRNA to adding αPD-1 or Peg-IFNα alone (P<0.05). Furthermore, this
Xalniseran could achieve HBsAg loss in only 3-7% when used with sequential therapy significantly enhanced HBV-specific T and B cell
NA alone, but showed greater efficacy when combined with a TLR7 responses. Similar observations were noted in the αPD-L1 cohorts.
agonist (12%) or pegylated interferon alfa (PEG-IFN) (23%), which is Conclusions: In NA-treated HBV-carrier mice and CHB patients,
regaining interest as an immunomodulatory backbone 1,2. sequential therapy of αPD-1 (or αPD-1) and Peg-IFNα was
In addition to stimulating the innate immune system with PEG-IFN or demonstrated to be safe, and to induce stronger HBsAg reductions
TLR agonists, approaches to influence the adaptive immune system, than either agent alone. This novel sequential therapy might be a
such as therapeutic vaccines, monoclonal antibodies and T-cell- potential strategy to achieve CHB functional cure.
based therapies, are also being investigated 1,2. Their efficacy can
be increased when they are given after sufficient antigen reduction,
thereby allowing reactivation or re-priming of HBV-specific T cells. CURRENT SESSION 10
Restoration of HBV-specific immune responses is crucial for durable
cure. Immune checkpoint inhibitors (ICI) have shown modest
Mechanism and Therapeutic Targets: Incretin
efficacy, particularly in patients with low baseline HBsAg. Emerging and Endocrine Based Therapies
data suggest that triple or quadruple combination treatments –
including NAs, siRNAs or ASO, and different immunotherapies such 09:15-10:45 | Function Hall B
as therapeutic vaccines plus ICI – may improve response rates 1,2.
However, safety concerns such as ALT increases must be carefully 29CS1001
considered. Additionally, the epigenetic imprinting of exhausted T cells Old and New Classes of Lipid Metabolism and Glucose Control
may limit the immune response with ICI, suggesting a potential role for Agents: PAN-PPAR-Agonist
epigenetically modifying agents in future therapies 5. Won Kim
Significant challenges remain, including identifying optimal drug Division of Gastroenterology and Hepatology, Department of Internal
combinations, understanding how different immune pathways may Medicine, Seoul National University College of Medicine, Seoul
synergize or interfere with one another, determining whether therapies Metropolitan Government Boramae Medical Center, Seoul, Republic
should be administered sequentially or concurrently, managing of Korea
immune-related toxicities, and selecting patients most likely to benefit
Metabolic dysfunction-Associated Steatohepatitis (MASH) represents
from treatment. Patient stratification based on baseline HBsAg levels
a significant global health burden, affecting a substantial portion of
and biomarker-driven treatment selection are increasingly recognized
the general population, yet remains largely undiagnosed. MASH is
as essential to optimizing treatment outcomes.
strongly associated with end-stage liver disease and cardiovascular
Despite these challenges, the future of HBV therapy lies in
disease, with patients twice as likely to die from cardiovascular
personalized treatment approaches that take into account both viral
disease compared to the general population. Despite its prevalence
and host immune factors. Ongoing clinical trials will further refine
and severity, there remains a critical unmet need for effective
these strategies and bring us closer to the goal of a functional cure for
pharmacological interventions.
chronic HBV infection.
The therapeutic landscape for MASH is evolving rapidly, with several
agents in phase III clinical trials targeting various mechanisms,
including GLP-1 receptor agonists, FGF21 agonists, and pan-PPAR traditional approaches tend to overlook. These innovative strategies
agonists. Among these emerging therapies, pan-PPAR agonists— not only enhance predictive accuracy but also support dynamic
particularly lanifibranor—have shown promising results through their monitoring and real-time clinical intervention.
unique mechanism of action. Furthermore, the incorporation of explainable artificial intelligence
Peroxisome proliferator-activated receptors (PPARs) are nuclear (XAI) methods, such as SHAP and LIME, ensures that these “black-
receptors with key regulatory functions in metabolism, inflammation, box” models provide interpretable outputs, building greater clinical
and fibrogenesis. The three PPAR subtypes have distinct but trust and facilitating their adoption in diverse healthcare settings. Case
complementary functions: PPARα predominates in liver and regulates studies have demonstrated the utility of these integrated models,
fatty acid oxidation; PPARγ is abundant in adipose tissue controlling particularly in forecasting HCC recurrence post-treatment and refining
adipogenesis and insulin sensitivity; while PPARδ/β influences fatty risk assessments in HBV-infected patients. The use of federated
acid metabolism in muscle and regulates inflammation. Lanifibranor, as learning also promotes secure, cross-center data collaboration,
a pan-PPAR agonist, simultaneously activates all three PPAR subtypes, thereby enhancing model reliability and fostering global partnerships.
potentially offering a comprehensive approach to MASH treatment by In summary, novel models for HCC prediction—centered on
addressing multiple disease pathways. multidimensional data integration and advanced analytical methods—
The Phase 2b NATIVE trial demonstrated lanifibranor’s efficacy, with offer a significant leap forward in precision oncology, especially for
45% of patients achieving resolution of MASH without worsening fibrosis high-risk HBV-associated patients. These approaches are poised
at the 1200mg dose, compared to 19% with placebo. Additionally, to transform current paradigms in HCC management by enabling
42% of patients showed fibrosis improvement of at least one stage. personalized, dynamic, and interpretable risk assessments.
Beyond histological benefits, lanifibranor improved multiple metabolic
parameters including significant reductions in triglycerides, increased
29CS1102
HDL-C, reduced fasting insulin and HOMA-IR, and improvements in
liver enzymes and non-invasive fibrosis markers. Predicting Chronic Hepatitis C-Related HCC
Preclinical and clinical studies have revealed additional benefits of Chia-Yen Dai
lanifibranor, including improved portal hypertension and hepatic Kaohsiung Medical University Hospital, Kaohsiung Medical University,
fibrosis in experimental advanced chronic liver disease, reduced portal Kaohsiung
pressure through effects on splanchnic vasculature, and significant Hepatocellular carcinoma (HCC) remains a major cause of cancer-
improvements in insulin resistance and hepatic steatosis in patients related mortality, with chronic hepatitis C (CHC) as a leading risk factor.
with type 2 diabetes and MASLD. A placebo-controlled randomized While direct-acting antivirals (DAAs) have revolutionized hepatitis C
clinical trial showed lanifibranor reduced liver fat by 44% in patients virus (HCV) treatment, the risk of HCC persists, particularly in patients
with T2D and MASLD treated for 24 weeks. with advanced fibrosis or cirrhosis. The non-invasive markers such
Future directions for pan-PPAR therapy include potential combination as elastography-based liver stiffness measurements have been used
strategies with GLP-1 receptor agonists or SGLT2 inhibitors for to reduce the need for invasive liver biopsies. Identifying high-risk
synergistic effects, precision medicine approaches using biomarkers individuals through accurate predictive models is crucial for effective
for patient selection, and development of selective PPAR modulators surveillance and early intervention. Various clinical, metabolic, genetic,
(SPPARMs) that may retain benefits while minimizing adverse effects. and inflammatory factors contribute to post-SVR HCC risk. Advanced
Pan-PPAR agonists represent a paradigm shift in MASH management fibrosis, diabetes, obesity, and persistent hepatic inflammation are key
by simultaneously addressing multiple aspects of disease determinants. Other risk factors include older age, male sex, alcohol
pathophysiology. With compelling phase 2b data and ongoing phase consumption, smoking, and co-infections such as hepatitis B virus
3 trials, lanifibranor may become a cornerstone therapy for MASH, (HBV) or HIV. Chronic liver inflammation and immune dysregulation
though long-term studies are still needed to monitor potential adverse play a crucial role in hepatocarcinogenesis even after viral eradication.
effects such as weight gain, edema, heart failure, and fracture risk. Genetic and epigenetic markers are being explored for their potential
to refine risk assessment. Several predictive models have been
developed to stratify HCC risks such as the GALAD model, which
CURRENT SESSION 11 incorporates gender, age, AFP-L3, AFP, and DCP, enhances predictive
power, particularly in individuals with cirrhosis, and the aMAP score,
Prediction and Risk Stratification of HCC which uses albumin, bilirubin, age, platelet count, and prothrombin time,
has demonstrated effectiveness in HCC prediction. Recent advances
09:15-10:45 | Function Hall C
in artificial intelligence (AI)-driven algorithms have tried to further
improve predictive accuracy. The implications of these predictive tools
29CS1101 extend beyond risk assessment. By identifying high-risk individuals,
Novel Models for Better HCC Prediction clinicians can tailor surveillance strategies, ensuring timely imaging
Yuanyuan Kong and biomarker testing to detect early-stage HCC. This personalized
Beijing approach improves early detection, allowing for curative interventions
Hepatocellular carcinoma (HCC) remains one of the leading causes of such as surgical resection, liver transplantation, or loco-regional
cancer-related mortality worldwide, with a significant burden observed therapies. Refining predictive models through AI, biomarker validation,
in regions with high incidences of hepatitis B virus (HBV) infection. and large-scale cohort studies will enhance accuracy and applicability
Traditional risk assessment tools, such as the Milan criteria and ALBI in clinical practice. Addressing modifiable risks such as metabolic
score, have contributed to clinical decision-making yet mostly rely control, lifestyle interventions, and antiviral prophylaxis in high-risk
on static, single-point data. These conventional methods often fall populations is essential in mitigating HCC development. Collaborative
short in capturing the dynamic progression of disease, particularly in efforts between hepatologists, data scientists, and genetic researchers
HBV-related cases where viral activity and treatment responses can will be pivotal in advancing predictive methodologies. While achieving
significantly fluctuate over time. SVR is a significant milestone, ongoing research and improved
Recent advances suggest that successful risk prediction for HCC predictive modeling will optimize long-term surveillance and ultimately
requires the integration of multidimensional data—clinical records, reduce HCC incidence.
imaging studies, pathological findings, molecular markers, and
genomic profiles—to establish a more robust and personalized risk 29CS1103
stratification framework. Novel models leveraging deep learning Liver Cancer Risk Estimation in Chronic Hepatitis B: Metabolic
architectures (e.g., CNNs and Transformers) and machine learning Dysfunction and Alcohol Intake
techniques (such as gradient boosting machines) have shown promise Sang Hoon Ahn
in extracting complex, non-linear relationships among variables that 1
Department of Internal Medicine, 2Institute of Gastroenterology,
Yonsei University College of Medicine, Seoul, Republic of Korea; CURRENT SESSION 13
3Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
Hepatocellular carcinoma (HCC) remains a major clinical challenge New Discovery in HBV: Detection, Monitoring
for patients with chronic hepatitis B (CHB), particularly in East Asian and Prediction
populations, where the burden of disease is disproportionately high.
Although long-term antiviral therapy with potent oral nucleos(t)ide 09:15-10:45 | Function Hall B
analogs has achieved significant milestones—effectively suppressing
HBV DNA replication, reducing hepatic necroinflammation and
29CS1302
fibrosis, and markedly lowering HCC risk—the complete elimination
of HCC remains elusive. This persistent risk underscores the pivotal Visualization of HBV RNA, DNA, ccc DNA and its Significance
role of non-viral factors in hepatocarcinogenesis. Among these, Zhenghong Yuan
metabolic dysfunction and alcohol consumption have emerged as key Key Lab of Medical Molecular Virology, School of Basic Medical
determinants in HCC risk assessment. Sciences, Shanghai Institute of Infectious Diseases and Biosecurity,
Shanghai Medical College of Fudan University, Shanghai
Metabolic dysfunction is increasingly recognized as a modifiable yet
critical risk factor for HCC development. Recent evidence highlights Hepatitis B virus (HBV) is a hepatotropic, double-stranded DNA virus
a synergistic interaction between metabolic dysfunction and CHB, with complex life cycle. During viral replication, HBV RNA, DNA, and
which substantially amplifies HCC risk. Insulin resistance, a hallmark covalently closed circular DNA (cccDNA) play distinct and critical
of metabolic dysfunction, has been implicated in driving hepatic roles. They are also of great clinical significance as markers of active
inflammation and fibrosis—both of which are fundamental to the viral replication and targets of antiviral therapies. The key biological
hepatocarcinogenic process. characteristics and significance of HBV RNA, DNA, and ccc DNA
Alcohol consumption is another well-established risk factor for HCC, have been studied by traditional detection means based on biological
accounting for nearly 50% of mortality in patients with cirrhosis. The purification and bulk measurements such as Southern, Northern blot
pathogenic mechanisms linking alcohol consumption to HCC involve and PCR etc, which could not provide their spatiotemporal information
liver damage mediated by acetaldehyde, oxidative stress-induced at the subcellular, single-cell and tissue level. The absence of such
DNA damage, and chronic inflammation. Excessive and prolonged crucial information undermines the effort to develop effective treatments
alcohol intake leads to a spectrum of liver pathologies, from simple and achieve a functional or complete cure for HBV infection.
steatosis to alcoholic hepatitis, fibrosis, cirrhosis, and eventually HCC. Based on bDNA-based fluorescence in situ hybridization combined
In the context of CHB, alcohol consumption further exacerbates the risk with immunofluorescence and CRISPR-Tag real-time fluorescence
of HCC, necessitating its careful consideration in clinical risk models. in live cells, we have developed a microscopic imaging method that
This lecture will cover the roles of metabolic dysfunction and alcohol can visualize viral nucleic acids and proteins at the cellular and tissue
intake in modulating HCC risk in CHB patients. It will also explore levels, respectively. The kinetic characteristics of slow replication of
emerging avenues for the development of targeted prevention HBV progeny viral nucleic acid were confirmed in hepatitis B virus-
strategies to mitigate this persistent and multifactorial threat. infected cells, and the intranuclear spatial relationship between the
minichromosome and key epigenetic markers (H3K27ac, PolII) of
the virus was obtained, and the sequential process of translation
29CS1104
and packaging of HBV virus pregenomic RNA (pgRNA) at the
Prediction of HCC Recurrence after Curative Surgery single-molecule level was discovered. It was revealed that cellular
Wai-Kay Seto microtubule structure plays a key role in nucleocapsid transport
The University of Hong Kong and virus maturation and secretion through multivesicular bodies.
HCC has a high rate of recurrence after curative therapies, reaching Intracellular dynamic analysis of cccDNA showed that cccDNA did
>70% after 5 years. Various clinical risk scores have been developed for not adhere to chromosomes and did not amplify during cell division,
post-resection prognostication, but with varying results. Microvascular and about 80% of cccDNA was lost during a round of mitosis, and
invasion is the prime histological feature associated with an aggressive the remaining cccDNA was randomly assigned to daughter cells.
tumor behavior, but only has a modest performance in predicting Using the liver biopsy specimens of patients with chronic hepatitis B,
recurrence or liver-related mortality. Microvascular invasion is also in situ hybridization was combined with immunohistochemical staining
only determined post-operatively by histological sampling. Radiomics, of the main antigens of hepatitis B virus at the tissue level, and a
enabling detailed extraction and quantitation of scans, can be used as comprehensive image of viral nucleic acid and protein was obtained,
an imaging biomarker, yet is limited by suboptimal reliability and limited and it was found that the antigen and nucleic acid of hepatitis B virus
reproducibility. showed an amazing “mosaic” distribution at the single-cell level. In the
Can artificial intelligence play a role in post-resection prognostication? study of liver puncture specimens from patients with chronic hepatitis
Deep learning automatically recognizes complex patterns and B who have undergone antiviral therapy for more than one year, the
quantifies subtle radiological features that may not be noticeable positive rate of ccc DNA for hepatitis B virus was not significantly
by the human eye. Deep learning models have been developed for reduced.
cancer diagnosis, but to incorporate clinical factors, a multimodal Using the visualization technology created, our group confirmed
model would be needed to integrate clinical characteristics with visual some key replication links of HBV at the cellular level, discovered new
information from radiological images. A recently developed multimodal dynamic biological characteristics of cccDNA, directly observed the
deep learning model achieved excellent accuracy in predicting early molecular mechanism of viral components replication at the subcellular
and late post-resection recurrence, and outperformed both multiple level, revealed the distribution characteristics of proteins and nucleic
clinical risk factors and microvascular invasion in both internal acids in HBV replication at the tissue single cell level, and revealed the
validation and external testing. This is just one example on how deep distribution of viral cccDNA in patients’ hepatocytes and the clearance
learning can fundamentally change the clinical practice of chronic liver after antiviral therapy, filling in the spatiotemporal information of some
disease. key links in the life history of HBV. It has deepened the understanding
of HBV infection and provided a new perspective for the development
and development of new antiviral strategies. The new visualization
CURRENT SESSION 12 technology can be used to monitor viral proteins and nucleic acids,
especially the clearance of cccDNA, after antiviral therapy in patients
Alcohol Intake and the Body with chronic hepatitis B, which can help clinicians formulate better
treatment plans and help guide the development of new drugs.
09:15-10:45 | 402 (A+B)

29CS1303
Biomarkers-Guided Treatment Decisions in Chronic Hepatitis B ascites, esophageal variceal bleeding, or hepatic encephalopathy.5-6
Loey L.Y. Mak Despite remarkable progress in our understanding of the basic
Hong Kong research of reversing liver cirrhosis, currently there are no effective
Chronic hepatitis B infection is a major public health challenge. With antifibrotic therapies for liver cirrhosis by large-scale clinical trials.
the advancement in technology, the products of viral replication Although liver cirrhosis is typically considered to be irreversible at
activities can now be measured in the blood instead of directly looking later stages, reversal has been documented in many individuals with
at the intrahepatic changes. HBV biomarkers can be classified as compensated cirrhosis after treating the underlying cause.3,7-12
genomic materials (HBV DNA and RNA) or translational products Our research previously demonstrated that an anti-fibrotic Chinese
(HBsAg, HBeAg, HBcrAg, HBcAg). Viral biomarker assessment is medicine therapies (Biejia-Ruangan compound, BRC) combined
indispensable in clinical management of patients with CHB. In the with entecavir (ETV), significantly increased the rate of reversal
current era with highly effective NUC therapy as the mainstay of in compensated cirrhosis for patients with CHB.7,8 This finding
treatment, HBV DNA will be expectedly undetectable and novel viral challenges the conventional belief that liver cirrhosis regression can
biomarkers can provide further insights into disease phase, treatment only be achieved with long-term antiviral therapy, suggesting that
efficacy, defining treatment endpoints, risk prediction for hepatocellular an anti-fibrotic agent can further improve cirrhosis regression when
carcinoma (HCC) and risk stratification for partial cure, defined as off- used alongside etiology-targeted treatment. However, it is crucial
therapy virological control, or functional cure, defined as hepatitis B to acknowledge that the extend of regression in compensated
surface antigen (HBsAg) seroclearance plus undetectable serum HBV cirrhosis varies among patients. While some patients may experience
DNA for ≥6 months, which is the primary outcome of phase III trials in pronounced regression, others may see minimal improvement or even
chronic hepatitis B. Appropriate viral biomarkers can potentially inform progression. Cirrhosis involves a complex interplay between multiple
the efficacy of novel compounds. Early viral biomarker response can non-parenchymal cell (NPC) lineages including immune, endothelial
help with prioritization of subjects into clinical trials. Because of the and mesenchymal cells spatially located within areas of scarring,
lack of a universal and easily measurable set of biomarkers, clinical termed the fibrotic niche. Currently, we do not fully understand the
practice guidelines remain controversial, aiming for a balance between variables that most significantly influence the degree of regression in
simplifying treatment decisions by reducing biomarker requirements compensated cirrhosis.
and using all available biomarkers to avoid overtreatment of patients Recent advances in spatial and single-nucleus transcriptomic
with low risk for disease progression. As of now, novel biomarkers technologies have provided unprecedented insights into the
are largely used in studies as research-basis but not ready yet to be heterogeneity and molecular dynamics of various cell types and
used directly in patient management. Optimization of assay sensitivity, states within the fibrotic or cirrhotic liver.13-17 These advancements
standardization of assays and validation studies are needed before have deepened our understanding of scar-associated subpopulations
these biomarkers can be broadly implemented in clinical use. in cirrhotic human liver. However, these studies are usually limited
to specific stages of liver fibrosis, are cross-sectional and non-
prospective, or are primarily at the animal level. This hinders our
CURRENT SESSION 14 comprehension of the entire post-treatment process. Herein, our study
aims to decipher the atlas of liver cirrhosis reversal following treatment,
New Pharmacological Agents Discovery for focusing on the long-term clinical outcomes of Chinese patients
MASH and Liver Fibrosis with CHB, derived from a well-monitored, double-blind, randomized
placebo-controlled trial (CHBALT-F).7,8,18 We integrated spatially
09:15-10:45 | Function Hall B resolved transcriptomics with single-nucleus sequencing data to
characterize the cellular microenvironment alteration of liver cirrhosis
reversal. This approach delineated the dynamic crosstalk between
29CS1401
cholangiocytes, myofibroblasts, and profibrotic macrophages,
Impact of PNPLA3 rs738409 polymorphism on MAFLD providing insights into the mechanisms by which Osteopontin (SPP1)
Jing Zhang expressed in activated cholangiocytes induces ductular reaction (DR),
Beijing contributing to ongoing fibrogenesis, thereby blocking liver fibrosis
A common genetic variant (rs738409) encoding isoleucine to reversal following treatment.
methionine at position 148 in the PNPLA3 protein is a determinant of
hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related
29CS1404
mortality. Lean MAFLD patients are a special group with a higher
frequency of PNPLA3 mutations and a higher risk of liver cirrhosis than Research progress of drug targets for liver fibrosis
non-lean MAFLD. However, they are difficult to benefit from weight Chenghai Liu
loss or GLP-1RA based drug therapy. Currently, several companies Department of medicine at Institute of Liver Disease, Shuguang
are developing drugs targeting PNPLA3 which might bring hope for Hospital Shanghai University of Traditional Chinese Medicine
those patients. The report will introduce the mechanism of PNPLA3, its Liver fibrosis, characterized by excessive accumulation of extracellular
impact on the occurrence and development of MAFLD, as well as the matrix (ECM) in liver, is a common pathological process in chronic
current status of drug development and preliminary clinical trial results. liver diseases by various etiologies, through which the chronical liver
diseases could progress into cirrhosis, hepatocellular carcinoma,
and liver-related death. Therefore, the identification of drug targets
29CS1403
and development efficient drugs against liver fibrosis was crucial
Spatial and single-nucleus transcriptomic architecture decipher for the treatment of chronic liver diseases. Since the understanding
cellular and molecular features underlying liver cirrhosis reversal of the molecular and cellular mechanisms of liver fibrosis was
after treatment increased recent years, numerous targets have emerged and driven
Yongping Yang the development of anti-liver fibrotic drugs. These drug targets
Beijing played at least one role in complicated mechanisms of fibrogenesis
Liver cirrhosis is a significant contributor to morbidity and mortality including hepatic inflammation, metabolic regulation, apoptosis and
among patients with chronic liver disease, accounting for over 1.32 inflammation, proliferation and activation of HSCs, hepatic sinusoidal
million deaths and with a rising incidence.1,2 The most common endothelial cell dedifferentiation and synthesis and degradation of the
causes of liver cirrhosis include chronic hepatitis B (CHB) and C, extracellular matrix, etc. Most clinical trials for the above mentioned
alcohol-related liver disease, and non-alcoholic steatohepatitis.3-4 In targets were conducted in patients with MASH. According to the
its initial stages, cirrhosis is considered compensated, most patients features and functions of targets, the drug targets may be summarized
remain asymptomatic. However, ongoing fibrogenesis can often lead as follows:
to decompensation, generally marked by the initial occurrence of Table 1. Examples of drug targets for liver fibrosis
CURRENT SESSION 15 overall survival (OS) compared to those with symptomatic presentation,
primarily due to a higher likelihood of receiving curative treatments
Early Diagnosis and Surveillance for Liver such as resection, liver transplantation, or ablation.
Recent advances in imaging and biomarker research have enhanced
Cancer the early detection of HCC. Contrast-enhanced ultrasound (CEUS),
09:15-10:45 | Function Hall B dynamic magnetic resonance imaging (MRI), and multiphasic
computed tomography (CT) have improved sensitivity and specificity
in detecting early-stage tumors. In particular, MRI with hepatobiliary
29CS1502 contrast agents has shown superior performance in identifying small
A-HOC and APASL Guidelines Perspective HCC lesions. Additionally, novel blood-based biomarkers, including
Ryosuke Tateishi1 the GALAD score (a combination of gender, age, AFP, AFP-L3, and
1
Department of Gastroenterology, Graduate School of Medicine, The des-gamma-carboxy prothrombin), are emerging as promising non-
University of Tokyo invasive tools for early HCC detection.
Hepatocellular carcinoma (HCC) is the most common primary liver However, there are considerable differences in the implementation
malignancy and a leading cause of cancer-related mortality worldwide. of surveillance programs across Asian countries, primarily due to
Due to its often asymptomatic progression, most cases are diagnosed variations in the availability of diagnostic modalities and healthcare
at an advanced stage, limiting treatment options and reducing survival systems for managing high-risk populations. To address these
rates. Surveillance programs and early diagnostic modalities have disparities, we have established the APASL Hepatology/Oncology
demonstrated the potential to improve patient outcomes by enabling Consortium (A-HOC) to investigate the current state of clinical practice
timely intervention. HCC surveillance is primarily recommended for for HCC in the Asia-Pacific region, including its etiology, diagnosis,
high-risk populations, including patients with cirrhosis and chronic treatment, and prognosis. As of the end of February 2025, we have
viral hepatitis. Biannual ultrasound (US) with or without serum alpha- collected data on more than 6,000 cases of hepatocellular carcinoma
fetoprotein (AFP) measurement has been the standard screening from seven regions.
approach. Several cohort studies have demonstrated that patients In terms of etiology, hepatitis B virus (HBV) remains the predominant
diagnosed through surveillance programs have significantly improved cause of HCC in most countries, except for Japan, where hepatitis C
overall survival (OS) compared to those with symptomatic presentation, virus (HCV) is the leading cause. However, over the past decade, Japan
primarily due to a higher likelihood of receiving curative treatments has seen a rapid decline in HCV-related cases and a corresponding
such as resection, liver transplantation, or ablation. increase in non-viral causes of HCC. Regarding the stage at initial
Recent advances in imaging and biomarker research have enhanced diagnosis, more than 50% of cases in Japan and South Korea were
the early detection of HCC. Contrast-enhanced ultrasound (CEUS), classified as Barcelona Clinic Liver Cancer (BCLC) Stage 0/A, whereas
dynamic magnetic resonance imaging (MRI), and multiphasic the proportion of advanced-stage cancers was significantly higher in
computed tomography (CT) have improved sensitivity and specificity China, Indonesia, and Turkey. These findings provide valuable insights
in detecting early-stage tumors. In particular, MRI with hepatobiliary for Asian countries to develop and refine their surveillance strategies,
contrast agents has shown superior performance in identifying small ultimately aiming to improve early detection and patient outcomes.
HCC lesions. Additionally, novel blood-based biomarkers, including
the GALAD score (a combination of gender, age, AFP, AFP-L3, and 29CS1503
des-gamma-carboxy prothrombin), are emerging as promising non-
Cell-Free DNA Testing for Early HCC Surveillance: Opportunities
invasive tools for early HCC detection.
and Challenges
However, there are considerable differences in the implementation
Rong Fan
of surveillance programs across Asian countries, primarily due to
Guangzhou
variations in the availability of diagnostic modalities and healthcare
systems for managing high-risk populations. To address these epatocellular carcinoma (HCC) is the sixth most common cancer
disparities, we have established the APASL Hepatology/Oncology and the third leading cause of cancer-related deaths globally. Early
Consortium (A-HOC) to investigate the current state of clinical practice detection is crucial, as early-stage HCC has survival rates exceeding
for HCC in the Asia-Pacific region, including its etiology, diagnosis, 55%, yet fewer than 30% of cases are diagnosed early. Current
treatment, and prognosis. As of the end of February 2025, we have guidelines recommend semi-annual ultrasound and AFP testing for
collected data on more than 6,000 cases of hepatocellular carcinoma cirrhotic patients, but its sensitivity is only 63%, leaving 37% of early-
from seven regions. stage cases undetected. Novel biomarkers (e.g., DCP, AFP-L3) and
In terms of etiology, hepatitis B virus (HBV) remains the predominant digital algorithms are being explored to improve the sensitivity and
cause of HCC in most countries, except for Japan, where hepatitis C specificity of surveillance. However, a critical gap persisted in the
virus (HCV) is the leading cause. However, over the past decade, Japan effectiveness and generalizability of existing surveillance strategies.
has seen a rapid decline in HCV-related cases and a corresponding Recently, Liquid biopsy techniques have recently gained attention for
increase in non-viral causes of HCC. Regarding the stage at initial improving HCC diagnostic efficacy. cfDNA (cell-free DNA) represents
diagnosis, more than 50% of cases in Japan and South Korea were DNA molecules released from cells into bodily fluids (e.g., blood,
classified as Barcelona Clinic Liver Cancer (BCLC) Stage 0/A, whereas urine) through apoptosis, necrosis and shedding. The first applications
the proportion of advanced-stage cancers was significantly higher in of liquid biopsies are based on the detection of genetic markers in
China, Indonesia, and Turkey. These findings provide valuable insights cfDNA. In a multicenter study from China, Wu T, et al developed an
for Asian countries to develop and refine their surveillance strategies, integrated diagnostic model (called Combined method) by combining
ultimately aiming to improve early detection and patient outcomes. three mutation sites (TERT, TP53, and CTNNB1) and three serum
Hepatocellular carcinoma (HCC) is the most common primary liver biomarkers (AFP, AFP-L3, and DCP). Combined method outperformed
malignancy and a leading cause of cancer-related mortality worldwide. AFP, with sensitivities of 81.25% for all stages and 66.67% for early
Due to its often asymptomatic progression, most cases are diagnosed HCC, respectively. Additionally, nongenetic features have further
at an advanced stage, limiting treatment options and reducing survival broadened diagnostic applications of cfDNA. The top twenty HCC-
rates. Surveillance programs and early diagnostic modalities have specific methylation biomarkers were integrated into the HepaAiQ
demonstrated the potential to improve patient outcomes by enabling model, with superior sensitivity for early-stage HCC to AFP (82.0% vs.
timely intervention. HCC surveillance is primarily recommended for 52.0%) and DCP (85.5% vs. 66.1%). The use of genome-wide cfDNA
high-risk populations, including patients with cirrhosis and chronic fragment features to detect HCC held high sensitivity and specificity,
viral hepatitis. Biannual ultrasound (US) with or without serum alpha- as demonstrated by the DELFI Model from high-risk populations
fetoprotein (AFP) measurement has been the standard screening in the U.S. and Hong Kong. Taken together, emerging evidence
approach. Several cohort studies have demonstrated that patients demonstrated that different molecular signatures present on cfDNA,
diagnosed through surveillance programs have significantly improved are related to cancer pathobiology and have been shown as a feasible
biomarker in HCC detection. where the disease remains untreated or the response to treatment
cfDNA features also offer significant advantages in guiding HCC is incomplete, it advances to cirrhosis and ultimately liver failure.
surveillance. Compared to the performances of the recommended Substantial evidence supports the classification of PBC as an
surveillance strategy, Monte-Carlo simulations suggest that cfDNA- autoimmune disease. Anti-mitochondrial antibodies (AMAs), which
based early detection tests could significantly benefit population-wide target mitochondrial proteins such as the E2 component of the pyruvate
HCC surveillance, increasing detection rates 2.5-fold and reducing dehydrogenase complex located in the inner mitochondrial membrane,
false negative rates. Moreover, Fan R et al. demonstrated that are detected in more than 90% of patients with PBC. Histopathological
incorporating longitudinal cfDNA features into the aMAP and aMAP- analyses reveal marked infiltration of inflammatory cells around the
2 HCC risk models significantly improved their efficacy in cirrhotic affected bile ducts. Furthermore, PBC frequently coexists with other
patients, leading to the development of the aMAP-2 Plus model. autoimmune diseases, including Sjögren’s syndrome and rheumatoid
Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 arthritis. Genome-wide association studies have identified susceptibility
Plus) stratified patients with cirrhosis into two groups, with an annual genes linked to PBC, including HLA alleles, as well as non-HLA genes
HCC incidence of 0.8% and 12.5%, respectively. associated with antigen presentation, IL-12 production, T-cell activation
Nevertheless, there are two major challenges. First, technical and IFN-γ production, and B-cell activation and immunoglobulin
challenges must be addressed to ensure the accuracy and stability production. Collectively, these findings establish PBC as a prototypical
of results. Second, validation across diverse ethnicities and etiologies autoimmune disease in which an abnormal immune response against
is essential, alongside evaluating its performance in dynamic changes biliary epithelial cells (BECs) in the intrahepatic bile ducts constitutes
and comparing it to current HCC diagnostic algorithms. The mutual the “initial stage” of pathogenesis.
goal is explore diverse cfDNA molecular features (e.g., fragmentation It is important to note, however, that current therapeutic strategies
patterns, topological characteristics) and identify optimal HCC- do not directly target the autoimmune response against BECs but
specific cfDNA markers, using accessible liquid biopsy techniques. instead focus on mitigating chronic cholestasis—the “second stage”
Ultimately, with advanced AI-driven data interpretation, multi-analyte of the disease—resulting from bile duct damage. To date, clinical
panels incorporating cfDNA features and other practical biomarkers or trials investigating agents targeting IL-12, CTLA-4, and chemokines
algorithms could significantly expand their clinical application in HCC aberrantly expressed in intrahepatic bile ducts have failed to achieve
detection and surveillance. their primary endpoints. Consequently, the mainstay treatments for
PBC remain ursodeoxycholic acid (UDCA), farnesoid X receptor
(FXR) agonists, and peroxisome proliferator-activated receptor (PPAR)
29CS1504
agonists, all of which primarily function to alleviate cholestasis.
Early Detection and Care of Liver Cancer Currently, the long-term prognosis of patients with PBC is favorable with
Grace L.H. Wong UDCA and PPAR agonists. However, delayed diagnosis and treatment
Medical Data Analytics Centre (MDAC), The Chinese University of can result in disease progression to the “third stage”, characterized
Hong Kong by hepatic fibrosis or cirrhosis. It is well established that the efficacy
Liver cancer, specifically hepatocellular carcinoma (HCC), presents
of these therapeutic agents diminishes once cirrhosis has developed.
significant challenges in terms of early detection and effective
Accordingly, the treatment of PBC faces three major challenges. First,
management. This lecture outlines the importance of early detection
early diagnosis and intervention are crucial to prevent the onset of
strategies and integrated care approaches to improve patient
liver fibrosis. Second, there is an urgent need for the development of
outcomes. Early diagnosis of liver cancer is paramount, as it is often
asymptomatic in its initial stages, leading to late-stage presentations antifibrotic agents that remain effective even in advanced stages of
when treatment options are limited. Utilising advanced imaging liver fibrosis. Finally, the development of therapeutic strategies that
techniques, such as ultrasound, computed tomography (CT), and directly modulate the autoimmune response—the underlying driver of
magnetic resonance imaging (MRI), together serum biomarkers like disease pathogenesis—offers the potential to achieve a definitive cure
alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II for PBC.
(PIVKA-II), can enhance the accuracy of early detection. Additionally, 29CS1604
the implementation of regular screening protocols for high-risk PBC: Putting the Patient First
populations, including individuals with chronic liver disease and Carrie Frenette
cirrhosis, is essential. Foster City
Integrated care models that combine multidisciplinary teams, including PBC is a progressive disease which can result in end-stage liver
hepatologists, oncologists, radiologists, and primary care providers, disease (cirrhosis, liver failure, and liver transplant) with a 10-year
can facilitate timely interventions and personalised treatment plans. survival rate of 77%. Up to 50% of untreated patients develop cirrhosis
Furthermore, patient education and engagement play crucial roles after 4 years, underscoring the importance of early diagnosis and
in promoting awareness of risk factors and the importance of regular treatment. However, due to limited choice and efficacy of treatment,
screenings. By prioritising early detection and holistic care strategies, there is large unmet needs for PBC patients including disease
we aim to reduce mortality rates associated with liver cancer and progression, extrahepatic manifestations, biochemical response as
improve the overall quality of life for affected individuals. Future well as symptom response.
research should focus on refining screening methodologies and Pruritus is one of the most common symptoms seen at all stages of PBC
exploring novel therapeutic options for early-stage liver cancer. affecting >80% patients. There are some characteristics of pruritus in
CURRENT SESSION 16 PBC like diurnal rhythm, most affects limbs, intense scratching can
cause secondary skin lesions. The mechanism of pruritus in patients
Transforming Management Landscape of with PBC is not fully known; cytokine release (e.g., IL-31) caused by
Primary Biliary Cholangitis bile acids has been assessed to play a role. Pruritus significantly
impacts patients’ quality of life (QoL) on many aspects like sleep,
13:30-15:00 | 402 (A+B) social life, emotion and so on. However, as many as 70% have never
been assessed for pruritus at clinical visits. The discordance between
29CS1601 patient-reported and medical record-documented pruritus suggests it
is overlooked or under-recorded by HCPs. Patients’ subjective feeling
Pathophysiology of PBC
is always ignored compared with test result.
Atsushi Tanaka
HCPs need to ask every patient with PBC if they have itch at every
Teikyo University School of Medicine, Tokyo, Japan visit, consider the characteristics of the itch to determine if it is related
Primary biliary cholangitis (PBC) is characterized by damage to the to PBC or another cause. If patients have itch, HCPs need to evaluate
small- or medium-sized intrahepatic bile ducts, leading to chronic and understand its severity, impact on QoL and whether it requires
intrahepatic cholestasis and progressive hepatic fibrosis. In cases daily medication to control, then document itch to enable assessment
over time. There are several pruritus assessment scales including can occur concomitantly with HBV in the acute infection setting (acute
Numerical Rating Score (NRS), Visual Analog Scale (VAS), PBC-40 HBV/HDV coinfection) or in hepatitis B surface antigen (HBsAg)
and 5-D (5-Dimensional) Itch which offer evaluations with varying carriers (HDV superinfection on HBsAg carriers). For the former, risk of
degrees of complexity & assessment frequency. acute liver failure exists, but usually clearance of both viruses occurs
AASLD and EASL Guidelines recommend treating pruritus based on in approximately 95% of the subjects. For the latter, chronic HBV/HDV
addressing PBC and severity of symptoms, but current PBC treatment infection will be followed in more than 90% of the subjects, and lead to
options fail to manage pruritus and there is a lack of evidence on the more severe liver diseases than HBV infection alone.
efficacy of available pruritus treatments. Diagnosis of HDV infection is made based on serologic testing, and
should be considered in all subjects positive for HBsAg. The presence
of IgM antibody to hepatitis B core antibody (IgM anti-HBc) confirms
CURRENT SESSION 17 the diagnosis of acute coinfection, and differentiates it from HDV
superinfection. During acute HBV/|HDV coinfection, HDV RNA appears
The Hope of Hepatitis Delta Cure transiently. In contrast, in HBsAg carriers with HDV superinfection,
serum total/IgM anti-HDV and HDV RNA will be persistently present.
15:15-16:45 | Function Hall A Assessment of treatment effects against chronic hepatitis D relies on
quantitative serum HDV RNA levels.
29CS1701 However, there are unresolved issues regarding diagnosis and
Epidemiology of Hepatitis D screening of HDV infection. Currently, awareness of HDV infection is
Jie Li inadequate and screening rate is low in both high-income and low-
income countries. Reflex testing for anti-HDV in subjects positive for
Department of Microbiology & Infectious Disease Center, School of
HBsAg may increase the HDV screening rate. Variable sensitivity and
Basic Medical Sciences, Peking University Health Science Center, 38
specificity of serologic testing for HDV infection should be improved.
Xueyuan Road, Haidian District, Beijing
Currently, there is no FDA approved quantitative test for serum HDV
Hepatitis D virus (HDV) is a defective virus that needs the help of RNA..
hepatitis B virus (HBV) to establish infection in the body. Compared
with HBV infection alone, HBV-infected patients with HDV super-
infection have more severe and rapid disease progression and are at CURRENT SESSION 18
significantly increased risk of developing cirrhosis and liver cancer.
HBV vaccines prevent HDV infection by preventing HBV infection. Clinical Trials for Steatosis and Fibrosis: In-
However, there is no vaccine that protects HBV-infected individuals between Success and Failure
from HDV super-infection.
Knowledge of the global epidemiology of HDV is currently limited 15:15-16:45 | Function Hall B
due to different methods of screening for HDV and bias in screening
populations. It has been estimated that 12 to 72 million people
29CS1803
worldwide are currently infected with HDV. There are regional variations
in the prevalence of HDV. In North America and Northern Europe, the Non-Invasive Diagnosis and Artificial Intelligence: Catalyst for
prevalence of HDV in the general population is less than 1%, whereas Success?
in some countries, such as sub-Saharan Africa, Central Asia and Vincent W.S. Wong
Eastern Europe, the prevalence is more than 2%. Countries with a Hong Kong
high prevalence of HDV include Benin, Gabon, Mauritania, Nauru and The evolving landscape of metabolic dysfunction-associated fatty
Mongolia. After adjustment for geographic distribution, disease stage liver disease (MAFLD) necessitates innovative approaches to clinical
and special populations, the anti-HDV prevalence in the HBsA-positive trial design, particularly in the context of non-invasive diagnostics and
population is significantly lower than previously reported because artificial intelligence (AI). This talk will explore the integration of non-
previous meta-analyses focused primarily on studies conducted invasive tests in identifying suitable patients and assessing treatment
in groups/regions with a higher likelihood of HBV infection, such as responses within MAFLD clinical trials.
tertiary care centers, specific risk groups or geographic regions. China In MAFLD studies, non-invasive tests play a crucial role in selecting
is a low prevalence area for HDV, while the absolute number of HDV patients who meet specific inclusion and exclusion criteria, particularly
infections in China is estimated to be the highest in the world due to the in Phase 2 trials targeting “at-risk metabolic dysfunction-associated
large number of HBV infections in the country. steatohepatitis” (MASH). This population is characterized by the
People at high risk of HDV infection include those with advanced liver presence of MASH alongside stage 2 to 3 fibrosis. Additionally, certain
disease, as well as injecting drug users, sex workers, men who have Phase 3 studies may include patients with compensated MASH-related
sex with men, patients on hemodialysis, and people with HCV and/or cirrhosis, broadening the scope of potential participants.
HIV infection, etc. Previous research has highlighted the diagnostic efficacy of various
Eight genotypes of HDV have been identified, with genotype 1 having non-invasive tests in evaluating liver fibrosis and identifying patients
a broad global distribution, while genotypes 2 and 4 are predominantly at risk for MASH. These tests have demonstrated the ability to predict
found in Asia, including China and Japan. Genotype 3 is predominantly major adverse liver outcomes with a reliability comparable to that
found in the Amazon Basin region of Latin America, and genotypes of traditional liver histology. However, a notable gap exists in the
5 through 8 are predominantly found in Africa. Studies have shown application of non-invasive tests for assessing treatment response.
that patients infected with HDV genotype 1 have more severe clinical While liver histology remains the gold standard for treatment evaluation
outcomes than those infected with genotype 2. Genotypes 2 and 4 in Phase 2b and Phase 3 trials, its invasive nature poses challenges
can cause relatively mild disease, while genotype 3 is associated with for patient acceptance and presents issues of intraobserver and
fulminant hepatitis. interobserver variability, which can undermine its reliability as an
assessment tool.
29CS1702 To address these limitations, emerging AI platforms have shown
Diagnosis of Hepatitis D Virus Infection promise in enhancing histological assessments, providing consistent
and objective evaluations. By converting AI-generated parameters
Chun-Jen Liu
into continuous scores, researchers can potentially identify smaller
Hepatitis Research Center, Department of Internal Medicine differences in treatment effects that might be overlooked by
National Taiwan University Hospital, Taipei
conventional histological methods. However, the clinical significance
Hepatitis D virus (HDV) infection is not rare but often neglected in of these smaller differences detected by AI remains an area requiring
subjects infected with hepatitis B virus (HBV) infection. HDV infection further exploration.
CURRENT SESSION 19 ETS2 and VSIG4, represents significant advancements in predicting
outcomes and guiding therapeutic decisions. Furthermore, the
More and Longer Survival Opportunity for integration of these biomarkers into clinical practice may enhance
early risk stratification and guide personalized therapeutic strategies
Early-Intermediate Stage Liver Cancer for ACLF. Future research should focus on validating these models in
15:15-16:45 | Function Hall C diverse patient populations and exploring novel biomarkers to further
refine risk stratification and treatment strategies for ACLF.

CURRENT SESSION 20 29CS2003

ACLF Consensus and Controversy REVERSAL OF ACLF
Zaigham Abbas
15:15-16:45 | 402 (A+B) Department of Hepatogastroenterology, Dr. Ziauddin University
Hospital Clifton Karachi, Pakistan
29CS2002 Reversal of acute-on-chronic liver failure (ACLF) refers to improving the
Prognostic Model for Predicting Survival Outcomes in Acute-on- condition to a point where the patient no longer meets the criteria for
Chronic Liver Failure (ACLF) ACLF. According to APASL definition, reversal of ACLF is defined as a
Jun Li decrease in bilirubin levels below 5 mg/dL, reversal of coagulopathy
State Key Laboratory for Diagnosis and Treatment of Infectious to an INR below 1.5, and no encephalopathy, with or without the
Diseases, National Clinical Research Center for Infectious Diseases, resolution of ascites. The focus is on liver function recovery over 3-6
National Medical Center for Infectious Diseases, The First Affiliated months. The median time to reversal of ACLF is approximately 30
Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., days. Early reversal is considered if achieved within 90 days. Scoring
Hangzhou systems help predict outcomes. APASL AARC Score includes bilirubin,
INR, creatinine, hepatic encephalopathy grade, and lactate levels.
Acute-on-chronic liver failure (ACLF) is a complex and life-threatening
EASL-CLIF definition focuses on multi-organ recovery and short-term
clinical syndrome characterized by the acute hepatic failure on
survival (28 days) and CLIF-C ACLF score Includes age, white cell
chronic liver disease, leading to multi-organ failure and high short-term
count, and CLIF organ failure score. CANONIC Study based on this
mortality. Given its rapid progression, early diagnosis and predicting
scoring showed that the most frequent clinical course for ACLF-1 was
survival outcomes are critical for effective clinical management.
resolution (54.5%), with lower reversal rates for ACLF-2 (34.6%) and
However, the definition of ACLF remains controversial, particularly
ACLF-3 (16%). The median time for resolution was 14 days. About 70%
regarding its etiology and the inclusion of non-cirrhosis patients.
of survivors achieved reversal by day 90, which could be maintained
This heterogeneity has led to the development of various diagnostic
for up to a year. Predictors of mortality or survival from ACLF from
criteria and prognostic models by different international societies, each
different studies include age, underlying etiology, hepatic reserves,
tailored to different patient populations and etiologies.
stage of hepatic encephalopathy, elevated serum bilirubin, low blood
Three widely used prognostic scores have been developed to stratify
pH, presence of acute kidney injury, prothrombin activity, albumin
patients based on mortality risk. The CLIF-C ACLF score, developed
level, neutrophil percentage, platelet levels, multiple organ failures,
by the European Association for the Study of the Liver-Chronic Liver
and specific biomarkers. The baseline ACLF grade and any shift
Failure (EASL-CLIF) Consortium, is widely used for predicting mortality
in the grade within the first week can also identify patients likely to
in alcohol-related ACLF patients. It incorporates variables such as
reverse. Early Intervention in the first 7 days post-acute insult is
organ failure, age, and white blood cell count to estimate individual
critical in improving outcomes. This includes antiviral therapy for HBV,
mortality risk. Similarly, the COSSH-ACLF score, developed by the
corticosteroids for alcoholic hepatitis, and early management of sepsis,
Chinese Group on the Study of Severe Hepatitis B (COSSH), has
coagulopathy, and portal hypertension. Liver Transplantation remains
demonstrated superior predictive accuracy for short-term mortality in
the definitive treatment for irreversible ACLF, with timely consideration
HBV-related ACLF patients compared to other scores, including the
important. Reversal of ACLF is a critical therapeutic endpoint and can
CLIF-C ACLF, CLIF-C OF, MELD, MELD-Na, and Child-Pugh scores.
be considered for delisting patients from the transplant waitlist.
The AARC ACLF score, proposed by the Asian Pacific Association
for the Study of the Liver (APASL), has also shown better prognostic
performance than the MELD and CLIF-SOFA scores, particularly in EDITORS FORUM
patients with acute liver failure and coagulopathy.
Despite their utility, the complexity of these scoring systems, particularly 13:30-16:45 | Auditorium
those requiring intricate organ failure calculations, has limited their
routine clinical applicability. To address this, the COSSH-ACLF II score 29ED0103
was developed, incorporating six predictor variables to to simplify risk
Getting Published in Clinical Gastroenterology and Hepatology
stratification while maintaining high accuracy in predicting short-term
mortality in HBV-ACLF patients. This score not only identifies patients Charle J. Kahi
at high risk of death on the transplant waitlist but also predicts the Indianapolis
survival benefit of LT, particularly for patients with COSSH-ACLF II Clinical Gastroenterology and Hepatology (CGH) is the official clinical
scores between 7 and 10, who derive a significantly higher net survival practice journal of the American Gastroenterological Association
benefit from transplantation. (AGA). CGH is one of 5 journals in the AGA portfolio. Its impact factor
In addition to prognostic scores, biomarkers such as ETS2 and in 2023 was 11.6, ranking 9th among 143 GI-Hepatology journals. The
VSIG4 have emerged as valuable tools for early diagnosis and risk current acceptance rate for research papers is about 9%, and the
stratification. ETS2 exerts a protective effect by mitigating excessive mean turnaround time for peer-reviewed manuscripts is 31 days.
inflammation, a key driver of ACLF progression, while VSIG4 is closely CGH focuses on publishing high quality clinical research papers
correlated with the pathophysiological basis of ACLF and is associated that cover the entire spectrum of GI-Hepatology subspecialties. The
with immune dysfunction and systemic inflammatory response, serving Journal prioritizes clinical trials, meta-analyses, and highly impactful
as a marker for patients at high risk of mortality. These biomarkers not observational studies. In Hepatology, all subspecialties are well-
only enhance prognostic accuracy but also offer potential therapeutic represented, including steatotic liver disease, viral hepatitis, portal
targets. hypertension and its complications, non-invasive tests, alcohol-
In conclusion, the development of accurate prognostic models and related disorders, and hepatocellular carcinoma, among others. The
biomarkers is crucial for improving the management of ACLF. The breadth of topics covered is exemplified by the “Updates in Clinical
COSSH-ACLF II score, along with emerging biomarkers such as Hepatology” special issue that was published in July 2023 to coincide
with the journal’s 20th anniversary. of just 8 to 12 weeks in most cases. Patients without significant
The types of papers that are likely to succeed are those that impact fibrosis can be discharged from care. There are notable differences
clinical care, clinical research, and policy, that are innovative, in screening recommendations for HCC post-SVR based on the region
generalizable, and that have citation potential. Conversely, papers with of the world, demographics, and resources. Most societies suggest
minimal novelty, that are not hypothesis-driven (such as large database surveillance post-SVR for those with hepatitis C-related cirrhosis,
exploration efforts), that are more relevant to medical specialties other primarily using ultrasound and AFP, though risk-based approaches
than GI-Hepatology, and those that are too basic science-focused are are also employed. In many parts of Asia, individuals with hepatitis
unlikely to be accepted. C are deemed high risk, and screening for HCC is advised. High-risk
All submissions are reviewed first by the Editor-in-Chief with the help patients may also have more frequent ultrasounds (every 3 months) or
of specialized Associate Editors as needed. Thus, a well-written but utilize additional biomarkers.
succinct cover letter is very helpful to explain the merit of the research Despite our successes with hepatitis C antiviral therapy, rates
presented, and the knowledge gap being addressed. About 25% to of screening for hepatocellular carcinoma post SVR can be
30% of papers pass this initial review round, which is intended to be disappointing. This is due to many factors, including the inability to
rapid so as to not waste the investigators’ time and allow them to submit recognize advanced fibrosis, patient resources to attend screening
promptly to another journal. For papers that are sent out for external ultrasound tests, and lack of resources, including reimbursement for
peer review, the possible outcomes are reject, reject with hope and more expensive biomarkers. Optimizing screening and surveillance
accept with revision. Papers that may be potentially published after rates leads to improved survival rates when hepatocellular carcinoma
revisions are discussed and decided upon by the full Board of Editors. is diagnosed at an earlier stage. Strategies to improve surveillance
All decisions are accompanied by comments from the Board to explain effectiveness and reduce HCC mortality include patient education and
the rationale. practitioner training to recognize those at risk for HCC. System-level
CGH has a truly global footprint; about 75% of submissions are interventions may also be beneficial with dedicated clinical pathways
received from outside the USA, and China is the leader in terms of and clinical reminder systems improving screening rates. Future
number of papers submitted annually. The expertise and dedication research on predictive biomarkers and refinement of risk prediction
of the editorial board members and reviewers ensure a rigorous and models can identify those at different levels of risk post-SVR. Ideally,
fair peer-review process and high standards. CGH owes its success blood-based biomarkers could be used to screen for hepatocellular
to the investigators that entrust it with their research. We hope that you carcinoma, and there are predictive biomarkers, such as the GALAD
will continue to consider CGH as a destination for your highest quality score and others, that are being investigated as screening tools for
work! early diagnosis of hepatocellular carcinoma.
29ED0204
Strategies for publishing success
30CS2102
Rob Brierley
Simplified HCV Treatment for Eligible Patients with Pan-Genotypic
The Lancet Gastroenterology and Hepatology, UK
Regimens
This presentation will give an overview of publishing options within Wan-Long Chuang
The Lancet Group, what happens after you submit a manuscript,
Department of Internal Medicine, Kaohsiung Medical University
and insights into what editors at high-impact journals look for when Hospital, Kaohsiung Medical University, Kaohsiung
considering papers for possible publication.
Hepatitis C virus (HCV) infection is a major health problem throughout
the world. Chronic hepatitis C (CHC) may lead to liver cirrhosis and
CURRENT SESSION 21 hepatocellular carcinoma (HCC). The goal of antiviral treatment for CHC
is to suppress progression to liver failure and development of HCC by
Hepatitis C Beyond Cure reduction of liver inflammation and fibrosis. World Health Organization
implements the global health sector strategies on the elimination of
09:00-10:30 | Function Hall A viral hepatitis before 2030. To achieve the targets of viral hepatitis C,
a simplified treatment of chronic hepatitis C with pangenotypic direct
30CS2101 acting antivirals (DAAs) regimens could be used in patients without
Screening for hepatocellular cancer post-SVR, challenges and liver cirrhosis or with compensated (Child-Pugh A) cirrhosis. Therefore,
opportunities universal screening is necessary to find out the HCV-infected patients.
And pretreatment assessment should be conducted to exclude the
Paul Y. Kwo
ineligible patients, including patients with current or prior episode of
Stanford decompensated cirrhosis, hepatocellular carcinoma, hepatitis B or
Hepatitis C remains one of the most common blood-borne infections HIV coinfection, prior hepatitis C treatment failure with DAAs, history of
worldwide and, along with hepatitis B, is a major cause of hepatocellular organ transplantation, advanced liver fibrosis, and current pregnancy.
carcinoma. The introduction of direct-acting antiviral agents (DAA’s) Patients with old age (> 70 years old), chronic kidney disease or
has revolutionized the treatment of hepatitis C with short durations of elevated bilirubin could receive simplified treatment with DAAs after
therapy of 8 to 12 weeks, leading to sustained response rates (SVR) of consulting with a specialist. Pangenotypic DAAs, i.e. glecaprevir/
greater than 95% across virtually all populations, including those with pibrentasvir for 8 weeks or sofosbuvir/velpatasvir for 12 weeks, should
cirrhosis. Even in the presence of decompensated cirrhosis, sustained be used to simplify the treatment. Quantitative HCV RNA and hepatic
response rates of 85% or greater can be achieved. In addition to the function should be assessed at 12 weeks after completion of therapy to
high sustained response rates, multiple clinical benefits are derived, assure sustained virologic response. Assessment for other causes of
which are most apparent in those with cirrhosis and decompensated liver disease is recommended for patients with elevated transaminase
cirrhosis with regression of hepatic fibrosis, reduced MELD scores, levels after achieving sustained virologic response. Patients with
and some degree of recompensation. The most important benefit advanced liver fibrosis who achieve sustained virologic response
is a reduction in the risk of developing hepatocellular carcinoma, should undergo surveillance for HCC every 6 months by means of
though this risk is not eliminated. Indeed, it is widely agreed upon that imaging and serum tumor markers.
those with cirrhosis who undergo successful DAA therapy should be
screened regularly for hepatocellular carcinoma (HCC).
30CS2103
Screening for HCC in individuals who achieve SVR presents unique
challenges. Unlike hepatitis B, which requires long-term longitudinal A decade following direct acting antiviral therapy: Long term
care and where HBV DNA can be entirely suppressed—though clinical outcomes in Chronic hepatitis C patients following SVR
with low functional cure rates—hepatitis C’s sustained response is Gamal Shiha
effectively a cure of the infection after a short, finite treatment duration
Internal Medicine Department, Faculty of Medicine, Mansoura 3
Department of Medicine, Division of Gastroenterology and
University, Egypt. Hepatology, University of Illinois at Chicago, 840 S. Wood St., suite
Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, 1020N, MC 787, Chicago, IL 60612, USA
Egypt.
4
Research & Development Service, Jesse Brown Veterans Affairs
Medical Center, Chicago, IL, USA. .
Background
The impact of direct-acting antivirals (DAAs) on long-term clinical Background & Aims: high-mobility group box-1 (HMGB1) significantly
outcomes in chronic hepatitis C virus (HCV) patients remains debated. increases and undergoes post-translational modifications (PTMs) in
This study aims to document the incidence of all-cause mortality, response to liver injury. Since oxidant stress plays a major role in liver
hepatocellular carcinoma (HCC), and decompensated cirrhosis fibrosis and induces PTMs in proteins, we hypothesized that redox-
in DAAs treated patients enrolled in the “Educate, Test, and Treat” sensitive HMGB1 isoforms contribute to liver fibrosis progression and
outreach program. resolution. Methods & Results: using electrospray ionization-liquid
Methods chromatography-mass spectrometry (ESI-LC-MS), we identified
This prospective observational study included chronic hepatitis C that disulfide ([O]) and sulfonated ([SO3]) HMGB1 rise during
patients enrolled between June 2015 and June 2018 at the Egyptian CCl4-induced liver fibrosis progression, however while [O] HMGB1
Liver Research Institute and Hospital (ELRIAH). Patients were declines, [SO3] HMGB1 drops but remains, during fibrosis resolution.
recruited from 12 out of 73 villages included in the outreach program Conditional knockout mice of Hmgb1 revealed that production of [O]
in the Nile delta. Patients with decompensated liver disease, HBV/HIV and [SO3] HMGB1 occurs mostly in hepatocytes. Co-injection of [O]
co-infection, HCC, or severe co-morbidities were excluded. Antiviral HMGB1 worsens CCl4-induced liver fibrosis more than co-injection
treatment followed national and international guidelines, and patients of [H] HMGB1. Conversely, ablation of [O] Hmgb1 in hepatocytes
were followed up till the end of 2024 with clinical, biochemical, and reduces liver fibrosis. Moreover, ablation of the receptor for advanced-
abdominal ultrasound and liver fibrosis assessment including Fibro glycosylation end-products (Rage), reveals that the pro-fibrogenic
Scan. The primary outcomes were all-cause mortality, HCC incidence, effect of [O] HMGB1 occurs through RAGE signaling in hepatic stellate
and decompensated cirrhosis. Secondary outcomes included cells (HSCs). Notably, injection of [SO3] HMGB1 accelerates fibrosis
changes in fibrosis stage and liver function tests. Statistical analysis resolution due to RAGE-dependent stimulation of HSC apoptosis.
employed Kaplan-Meier curves and Cox proportional hazards models, Notably, gene signatures activated by redox-sensitive HMGB1 isoforms
adjusted for baseline predictors. in mice classify fibrotic patients according to fibrosis and inflammation
Results scores. Conclusion: dynamic changes in hepatocyte-derived [O]
A total of 3,328 patients were eligible, with follow-up data available and [SO3] HMGB1, signal through RAGE-dependent mechanisms on
for 3,017. 53% were male. The mean follow-up duration was 84.5 ± HSCs, to drive their pro-fibrogenic phenotype and fate, contributing to
28.9 months. 1,125 (37.3%) had advanced fibrosis (F3-F4), The study the progression and resolution of liver fibrosis.
recorded 593 deaths (2.58/100 person-years), 271 cases of HCC
(1.24/100 person-years), and 281 cases of decompensated cirrhosis
(1.30/100 person-years). Advanced fibrosis was associated with CURRENT SESSION 23
increased all-cause mortality (HR 1.72, 95% CI 1.46–2.03, p<0.001) Revolution in the Management of Advanced
and decompensated cirrhosis (HR 2.23, 95% CI 1.74–2.85, p<0.001),
but not with HCC after adjustment (HR 1.17, 95% CI 0.92–1.49, Liver Cancer
p=0.192). Fibrosis reversal occurred in 11.9% of patients while 17.8%
showed a one-stage improvement, 50.5% remained stationary, while
09:00-10:30 | Function Hall C
19.8% progressed
Conclusion 30CS2301
To the best of our knowledge, this is the first decade long-term Systemic Therapy for Advanced HCC
follow-up prospective study in a large cohort which provides robust Stephen L. Chan
evidence that direct-acting antivirals (DAAs) significantly improve liver
functions, reduced all-cause mortality and liver disease progression Hong Kong
in chronic hepatitis C patients. In addition to a substantial decline in Hepatocellular carcinoma (HCC) is among the most prevalent forms
HCC incidence and decompensated cirrhosis reinforcing the benefits of liver cancer, ranking as the third leading cause of cancer-related
of early antiviral therapy in preventing long-term complications. deaths globally. The management of advanced HCC presents a
significant clinical challenge due to its late diagnosis and underlying
liver disease that complicates therapeutic interventions. Systemic
CURRENT SESSION 22 therapy has emerged as a cornerstone in the treatment of advanced
HCC, particularly for patients who are not candidates for surgical
Pathopysiology of Liver Cirrhosis in 2025: resection or local ablative therapies.
Better Patient Care and Potential Therapeutic The advent of molecularly targeted therapies and immunotherapies has
transformed the therapeutic landscape for advanced HCC. Recently,
Targets four immunotherapy-based combination, namely the atezolizumab-
bevacizumab, tremelimumab-durvalumab, camrelizumab-rivoceranib
09:00-10:30 | Function Hall B
and ipilimumab-nivolumab have shown to improve overall survival of
patients as compared to monotherapy TKI. The lecture will review the
30CS2201 results of key clinical trials and discuss the future development.
REDOX-SENSITIVE HIGH-MOBILITY GROUP BOX-1 ISOFORMS
CONTRIBUTE TO LIVER FIBROSIS PROGRESSION AND 30CS2302
RESOLUTION IN MICE
Advances in Combination Therapy for Advanced Hepatocellular
Xiaodong Ge 1, Romain Desert 1, Fernando Magdaleno 1, Hui Han
Carcinoma
1
, Zhuolun Song 1, Sukanta Das 1, Dipti Athavale 1, Wei Chen 1, Ines
Tian Yang
Barahona 1, Daniel Lantvit 1, Hui Chen 2, Sunil Hwang 2, Natalia Nieto
, ,
1 3 4 Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery
Hospital,
1
Department of Pathology, University of Illinois at Chicago, 840 S. Second Military Medical University (Naval Medical University),
Wood St, suite 130 CSN, MC 847, Chicago, IL 60612, USA Shanghai, China
2
Mass Spectrometry Core, University of Illinois at Chicago, 835 S.
Advanced hepatocellular carcinoma (HCC) continues to pose
Wolcott Ave., suite E12, Chicago, IL 60612, USA
formidable therapeutic challenges, with systemic therapies undergoing
rapid evolution. The integration of immune checkpoint inhibitors (ICIs), Clinical trials and future prospects
tyrosine kinase inhibitors (TKIs), and locoregional therapies has At present, many clinical trials on heavy particle irradiation therapy are
redefined treatment paradigms, achieving unprecedented survival underway, and its effectiveness and safety are being further verified.
outcomes. Major guidelines now recognize immune-based regimens In a review by Matsumoto et al. (2020), it was concluded that there
as first-line standards, with atezolizumab-bevacizumab (IMbrave150: is a high possibility that this treatment method will be established as
mOS 19.2 vs. 13.4 months) and durvalumab-tremelimumab one of the standard treatments for HCC in the future. In particular, it
(HIMALAYA: mOS 16.4 vs. 13.8 months) demonstrating survival is expected that further improvements in treatment efficacy will be
superiority over sorafenib. The CheckMate-9DW trial further showed achieved by combining it with other treatment methods. In particular,
nivolumab-ipilimumab reduced mortality risk by 21% versus TKIs (HR combined therapy with immune complex therapy is expected to
0.79), though with increased grade 3–4 immune toxicity (35% vs. enhance the immune response against tumor cells, and in combination
15%). Asia-specific strategies combining systemic and locoregional with the increased exposure of tumor antigens that occurs after heavy-
therapies show particular promise given the high HBV prevalence. The ion irradiation, it is also expected to suppress ectopic lesions in the
LEAP-012 trial reported prolonged PFS in BCLC-B patients receiving liver (the Abscopal effect).
TACE with lenvatinib-pembrolizumab versus TACE alone (12.1 vs. Conclusion
8.2 months), corroborated by China’s CHANCE001 cohort (TACE Heavy-ion radiotherapy is a very promising option for the treatment of
plus immune-targeted therapy mOS 24 vs. 16 months; HR 0.62). hepatocellular carcinoma, and due to its high treatment outcomes and
However, LEAP-002’s negative results emphasize the importance of safety, it is expected to play a major role as a future treatment option. It
patient selection, where biomarkers like AFP levels and etiology matter. is hoped that further research and clinical trials will lead to the spread
HBV-associated HCC exhibits enhanced ICI responsiveness (meta- and development of this treatment method.
analysis OS HR 0.71 vs. HCV HR 0.89), potentially due to higher PD-L1
expression and TMB. Post-progression strategies remain challenging,
with ASCO 2024 recommending TKI switches (e.g., cabozantinib) CURRENT SESSION 24
or dual immunotherapy rechallenge despite limited evidence.
Emerging resistance mechanisms, including immunosuppressive
Infectious Diesease and the Liver
microenvironment shifts (Treg/M2 macrophage infiltration) and bypass 10:30-12:00 | Function Hall A
signaling, drive exploration of novel agents. Bispecific antibodies (e.g.,
PD-L1/TGF-β-targeting M7824) and neoantigen vaccines show early
efficacy signals, achieving 21% ORR and isolated complete responses 30CS2404
when combined with ICIs. Critical challenges include managing Child- Liver Fluke and Cholangiocarcinoma (CCA)
Pugh B patients (underrepresented in trials) and regional disparities. Kittiyod Poovorawan
Asia’s HBV-dominated HCC epidemiology (>70% cases) necessitates Department of Clinical Tropical Medicine, Faculty of Tropical
tailored approaches addressing viral-immune crosstalk and antiviral Medicine, Mahidol University, Bangkok, Thailand
synergy. While TACE/HAIC-based “China models” demonstrate
At least 13 species of liver flukes have been recovered from humans.
real-world success, their integration into global guidelines requires
They are classified into three families: Opisthorchiidae, Fasciolidae,
prospective validation. In conclusion, combination therapies have
and Dicrocoeliidae. Common diseases from pathogenic liver flukes are
shifted advanced HCC management toward precision medicine,
Opisthorchiasis, Clonochiasis, and Fascioliasis caused by Opisthorchis
achieving mOS beyond 20 months. Prioritizing biomarker-driven
spp., Clonorchis spp., and Fasciola spp.
stratification, rational sequencing, and inclusive trials addressing Asia-
Fascioliasis is caused by Fasciola hepatica and Fasciola gigantica,
Pacific needs will be pivotal to improving progress. Multidisciplinary
which are mainly infected in herbivorous animals globally. Humans
collaboration and region-specific data generation are essential to
sometimes get infected and cause the disease, including the Acute
transform advanced HCC into a chronic controllable disease.
phase (migration of immature fluke) and chronic phase (mature
parasite present in the bile duct) of infection. Eosinophilic liver abscess
30CS2304 is a common presentation of Fascioliasis during the acute phase of
Radiotherapy Strategies for Unresectable HCC infection. There is no evidence of cholangiocarcinoma caused by
Yoshiyuki Ueno Fascioliasis.
Opisthorchis viverrini is primarily found in Southeast Asia, including
Department of Gastroenterology, Yamagata University Faculty of
Medicine, Yamagata, Japan Thailand, Laos, Cambodia, and Vietnam. Thailand has the highest
prevalence, particularly in the northeastern regions; the recent
Hepatocellular carcinoma (HCC) is a major malignancy that occurs in prevalence of Opisthorchis viverrini infection in the Northeastern part
the liver and is one of the leading causes of death worldwide. Treatment of Thailand is still ~15.3% (range; 3.8%-79.8%). The main problems
options include surgery, chemotherapy and radiotherapy, but in recent that keep the burden of Opisthorchis viverrini infection in Thailand are
years, heavy particle beam irradiation therapy has been attracting the eating habits of the raw fish menu and the animal reservoir, which
particular attention. This treatment has superior characteristics hold the complete lifecycle. Clonorchis sinensis is endemic in East
compared to conventional radiotherapy and has the potential to play Asia, including China, South Korea, and Vietnam.
an important role in the treatment of HCC. Both Opisthorchis viverrini and Clonorchis sinensis were classified
Characteristics of heavy particle beam irradiation therapy as Group 1 biological carcinogens by the World Health Organization.
Carbon ion radiotherapy is a form of radiotherapy that uses carbon Clinical related to Opisthorchiasis and Clonochiasis are usually
ions to deliver high-energy particles directly to the tumor. This method asymptomatic in the early infection; in the chronic phase, these flukes
is characterized by its ability to effectively destroy tumor cells while will cause chronic inflammation of the bile ducts, periportal fibrosis,
minimizing damage to normal tissue. According to the literature, cholangitis, biliary cirrhosis, and a high risk of cholangiocarcinoma
carbon ion radiotherapy is particularly effective for large tumors and development. The pathology related to the infection is desquamation of
tumors in locations that are difficult to operate on, and it has been epithelium, chronic inflammation, granulomatous inflammation around
reported to have excellent treatment outcomes (Yamada et al., 2018). eggs, and periductal fibrosis. Mechanisms of carcinogenesis include
Treatment outcomes and safety chronic inflammation, mechanical damage, parasite secretions, and
Heavy ion radiation therapy has been reported to have a high local nitrosamine exposure. Persistent inflammation and cellular damage
control rate and few side effects. For example, in a study by Komatsu et lead to dysplastic changes in the bile duct epithelium. Inflammatory
al. (2019), the 5-year survival rate for HCC patients treated with heavy cells release reactive oxygen species (ROS), reactive nitrogen species
ion radiation therapy was approximately 60%, showing a significant (RNS), and immune modulation, leading to genetic and epigenetic
improvement compared to conventional radiation therapy. It has also changes. The accumulation of genetic and epigenetic alterations
been shown that the treatment can be performed safely and effectively results in the development of cholangiocarcinoma.
in patients with chronic liver disease.
Cholangiocarcinoma associated with liver fluke infections has a poor Altered Mental Status in Cirrhosis : Etiologies other than Hepatic
prognosis and is a leading cause of cancer mortality in endemic Encephalopathy
regions. Most cases present at the late stage of the disease, which Barjesh C. Sharma
is mostly incurable. CCA surveillance in endemic areas is a challenge Department of Gastroenterology, GIPMER, New Delhi (India)
and needs a lot of resources and effort.
Hepatic Encephalopathy (HE) is defined as a spectrum of
The standard diagnosis test of Opisthorchis viverrini infection is stool
neuropsychiatric abnormalities seen in patients with liver dysfunction
testing. Recent immunochromatographic test kits are more convenient,
after exclusion of other known brain diseases. This definition does not
have acceptable accuracy, and will be more accessible. Praziquantel
take into account all the potential causes of altered mental status in
is the standard treatment of Opisthorchis viverrini and Clonorchis
patients with cirrhosis. Altered mentation may be impaired because of
sinensis, which shows high efficacy. The curative rate by Praziquantel
common clinical events besides HE. Altered mental status is defined
is higher in Opisthorchis viverrini than in Clonorchis sinensis. The
as having any of the followings : impaired cognition, diminished
control efforts include Mass drug administration, which is not very
attention, reduced awareness, and/or altered level of consciousness
effective in minimizing the disease burden in endemic areas due to
and not all patients of cirrhosis with altered mental status are HE.
recurrent infection. Health education to reduce the consumption of raw
These changes may be gradual or sudden in onset, fluctuating or
fish and improve sanitation is a vital control measurement.
sustained with an acute or chronic duration. Altered mental status has
been reported to be present in 4% to 10% of patients, and mental
CURRENT SESSION 25 status abnormalities are particularly common in older patients (up to
40%). In a retrospective study on 1218 patients with cirrhosis, 29%
Portal Hypertension and Complications: had altered mental status. The most common cause of altered mental
Consensus and Questions Before 2026 status was HE accounting for half of patients followed by sepsis or
infection as the next most common cause whereas remaining had
10:30-12:00 | Function Hall B metabolic or structural etiologies. The overall mortality among patients
of cirrhosis presenting with altered mental status was significantly
higher than in those with normal mental status. Patients with HE,
30CS2503 metabolic derangements and drug or toxin ingestion had significantly
Comprehensive Management of End-Stage Liver Disease better outcomes than those with structural lesions or sepsis/infections.
Complicated by Infections Structural lesions of brain in cirrhosis with altered mental status are
Qin Ning & Wei Liu uncommon and have focal neurological deficits like aphasia, facial
Tongji Hospital, Tongji Medical College, State Key Laboratory for nerve palsy, hemiplegia, seizures and decortication. There is 24%
Diagnosis and Treatment of Zoonotic Infectious Diseases, Huazhong increase in life long risk of strokes in cirrhosis including ischemic
University of Science and Technology Wuhan China strokes, intracranial hemorrhage and sub-arachnoid hemorrhage with
Bacterial infection is one of the most common complications in End- associated higher mortality as compared to cirrhosis without strokes.
Stage Liver Disease (ESLD), and it is associated with high mortality in CT head is recommended in patients with history of trauma or focal
these patients. The Asia pacific “Expert Consensus on Diagnosis and neurological deficits on clinical examination. Other uncommon causes
Treatment of End-Stage Liver Disease Complicated by Infection” has of altered mental status in cirrhosis include non-convulsive status
been released in March 2024 in Hepatology International and serves epilepticus and dementia. Acute HE with focal neurological signs have
as a clinical guidance for its comprehensive management. been reported in 25% of typical HE patents having transient asymmetry
The management of infections in ESLD is multifaceted, with the most of neurological signs. Focal neurological signs observed in HE may be
critical aspect being the antibiotic treatment. Previous studies have hemiplegia, hemiparesis, hemiagnosia and monoplegia and the CT
shown that adequate antibiotic treatment can improve survival rate scan shows cortical atrophy without structural lesion.
of patients with cirrhosis. The APASL consensus recommends that To summarise one-third of patients with cirrhosis are admitted with
as soon as bacterial infection is suspected or diagnosed, broad altered mental status. The common causes of altered mental status
spectrum antimicrobial agents alone or in combination should be are hepatic encephalopathy, infections and metabolic disorders with
started and thereafter, the therapy should be adjusted according to higher mortality than in patients with normal mental status. Mortality
the results of the antibiotic sensitivity test results. The recommended is higher in cirrhotics with structural lesions of brain or infections or
empirical antimicrobial agents vary depending on the type of infection, combination of causes of altered mental status. At admission in
highlighting the importance of tailored treatment approaches. Liver cirrhotics with altered mental status, causes other than HE should
transplantation is the most effective treatment for ESLD. However,
pre-transplant and post-transplant bacterial or fungal infection are the
common risk factor determining the success of liver transplantation.
CURRENT SESSION 26
The pre-transplant and post-transplant empirical or targeted antibiotic Current Challenge and Future Development of
treatment can be employed accordingly.
Additionally, thrombocytopenia is very common in patients with ESLD Liver Cancer
complicated by infections. Small-sample studies of rhTPO, rhIL-11, and
10:30-12:00 | Function Hall C
leucogen have suggested that these agents may have a certain effect
on improving platelet counts in such patients. Immunomodulatory
treatments, such as albumin, gamma globulin, and thymosin α1, 30CS2604
can be administered via appropriate methods in patients with ESLD Pre-transplant Use of Immune Check Point Inhibitor in Patients
complicated by infection. However, glucocorticoid treatment should with Hepatocellular Carcinoma
be evaluated with caution in patients with severe infections, as it may Ju Dong Yang
carry additional risks. Etiological treatments are equally crucial, such Los Angeles
as antiviral therapy for patients with viral hepatitis related ESLD and
abstaining from alcohol consumption for patients with alcoholic-origin Liver transplantation (LT) is the standard treatment for patients at risk
ESLD. Furthermore, nutritional support, hepatoprotective treatment and of liver-related death, including those with hepatocellular carcinoma
microecological therapy can reduce the infection risks and promote (HCC). It provides a curative option by eliminating both tumors and
recovery in patients with ESLD. Last specialized blood purification underlying liver disease, improving overall and recurrence-free survival.
treatment can effectively remove inflammatory mediators and toxins in However, due to the limited availability of donor organs and the higher
ESLD patients when complicated by infection. recurrence risk in advanced disease, LT is generally reserved for early-
30CS2505 stage HCC. For patients exceeding the Milan criteria, locoregional
treatments (LRTs) can reduce tumor size, enabling LT eligibility, with
successful downstaging rates between 30-70%. However, for those
with a larger tumor burden, success rates drop below 30%, highlighting
the need for more effective downstaging strategies.
Immune checkpoint inhibitors (ICIs) have shown promise as both
adjuvant therapy for surgically treated HCC and first-line treatment for
advanced-stage disease. Their success in advanced HCC has sparked
interest in exploring their role in earlier stages. Several ICI combinations
have been evaluated in clinical trials, including atezolizumab plus
bevacizumab and durvalumab with tremelimumab, both of which
have demonstrated efficacy in advanced HCC. Camrelizumab with
rivoceranib is under FDA review, while atezolizumab-bevacizumab
and durvalumab-tremelimumab are already approved for advanced
cases.
Additionally, retrospective studies suggest that combining ICIs with
LRTs is both safe and effective. Two Phase 3 trials, EMERALD-1 and
LEAP-012, have explored the combination of ICIs, LRTs, and tyrosine
kinase inhibitors (TKIs) for intermediate-stage HCC. EMERALD-1
assessed transarterial chemoembolization (TACE) with durvalumab
with or without bevacizumab, while LEAP-012 evaluated lenvatinib,
pembrolizumab, and TACE. Both trials have demonstrated promising
outcomes, supporting combination therapies for intermediate-stage
HCC and successful downstaging.
TACE, transarterial radioembolization (TARE), and ablation are key
LRTs used for early and intermediate-stage HCC. These treatments
play a critical role in downstaging tumors and reducing waitlist dropout
risk for LT candidates. The increasing evidence supporting ICIs in HCC
treatment has led to growing interest in their use as a pre-transplant
downstaging strategy. ICIs have shown potential in reducing tumor
burden and increasing LT eligibility, offering hope for curative treatment
in advanced HCC.
However, the use of ICIs in the LT setting presents challenges. While
they enhance the immune response against cancer, they also pose
a risk of graft rejection, creating a “double-edged sword” scenario.
Balancing therapeutic benefits with minimizing post-transplant
complications remains a concern. Small-scale studies suggest
rejection rates in ICI-treated patients are comparable to non-ICI-
treated patients, but larger, controlled trials are needed for clearer
insights. Several factors, including patient age, the number of ICI
cycles, washout periods, concurrent therapies, and post-transplant
immunosuppressive regimens, may influence outcomes.
Given these complexities, well-designed prospective studies are
critical to refining strategies for integrating ICIs into HCC treatment and
LT protocols. A deeper understanding of ICI-related risks and benefits
will help optimize patient selection and improve outcomes, potentially
expanding transplant eligibility for those with advanced HCC.
ORAL PRESENTATIONS
27 March | WEDNESDAY
APASL-AASLD JOINT WORKSHOP Evolving Trends in Liver Cirrhosis in Pakistan (2002-2022): Causes
and Future Predictions
Small Group Discussion Om Parkash1, Abhishek Lal1, Mushyada Ali1, Safia Awan1, Zainab
Samad1
1
Aga Khan University
AA0001
Background: Liver Cirrhosis remains a significant global public health
The National Burden of Hospitalized Liver Diseases from 2017 to
challenge associated with significant morbidity and mortality, especially
2022: A Thailand Nationwide Population-Based Cross-Sectional
in Pakistan with evolving trends of etiology, and complications. In LMIC
Time Series Study
Especially in Pakistan where changing trends of liver cirrhosis are
Rungfah Saehan1, Apichat Kaewdech2, Pimsiri Sripongpun2, Naichaya largely due to increased intake of alcohol, obesity, and viral hepatitis.
Chamroonkul2, Suthat Liangpunsakul3,4,5, Ponlagrit Kumwichar6 This cross-sectional study was conducted to review the pattern of
1
Division of Internal Medicine, Faculty of Medicine, Prince of Songkla cirrhosis from years 2008 to 2021.
University, 2Gastroenterology and Hepatology Unit, Division of Method: The data regarding primary index cases with associated
Internal Medicine, Faculty of Medicine, Prince of Songkla University, diagnoses was obtained from Health Information Management Systems
3
Division of Gastroenterology and HepatologDepartment of Medicine, (HIMS) at the Aga Khan University Hospital, Karachi, Pakistan. The
Indiana University School of Medicine, 4Department of Biochemistry
data was collected using the International Classification of Diseases
and Molecular Biology, Indiana University School of Medicine,
(ICD) codes 9th and 10th version.
5
Roudebush Veterans‘ Administration Medical Center, 6Department of
Result: This study included a total of 10,394 patients between the
Epidemiology, Faculty of Medicine, Prince of Songkla University
years 2008 to 2021, distributed across three time periods: 2008-2012
Background: Chronic liver disease (CLD) is a significant global (3371, 32.4%), 2013-2017 (4219, 40.6%), and 2018-2021 (2804, 27%).
public health challenge due to its high morbidity and mortality rates. Significant changing patterns have been observed over the study
In Thailand, the burden of CLD remains underexplored despite its period and these patterns include age onset of cirrhosis ( p-value
considerable impact on healthcare systems. This study investigates <0.001), change in aetiology (p-value <0.001), and gender difference
trends in hospitalizations, etiologies, and in-hospital mortality for HBV (p-value= 0.65). The prevalence of cirrhosis fluctuated around
associated with CLD, including cirrhosis and hepatocellular carcinoma 20%, with no significant changes from 2008 to 2021 (p-value= 0.06).
(HCC), from 2017 to 2022. The primary etiologies of Liver Cirrhosis presented significant changes
Method: A nationwide, population-based, cross-sectional time-series over the years, with HCV being the most common. However, the
study was conducted using inpatient claims data from the National prevalence of HCV decreased from 60.2% in 2008 to 41% in 2021.
Health Security Office (NHSO) in Thailand. Data spanning fiscal Conversely, the prevalence of non-b and non-c liver diseases showed
years 2016 to 2022 were analyzed, focusing on hospitalizations due increased prevalence from 16.8% to 28.8%. The trends of HBV and
to CLD, categorized by etiology using ICD-10 codes. Age- and sex- alcoholic liver disease remained relatively stable over the years. The
standardized incidence and mortality rates were assessed using mortality rates of the patients over the years remained relatively stable.
descriptive and trend analyses, with LOESS smoothing applied to There were notable gender differences where males had higher cases
identify temporal patterns. of HBV infection as compared to females (15.1%, 5.4%). However,
Result: From 2017 to 2022, 77,069 hospitalizations for CLD were high cases of non-b and non-c cases were in higher proportions in
documented, with 76% of patients being male and a median age females in comparison to males (26.6%, 20%).
of 56 years. Alcohol-related liver disease was the leading cause Conclusion: In conclusion, the evolving patterns in the age of onset,
(30%), followed by chronic hepatitis B (10%), hepatitis C (9.6%), and aetiology, and gender disparities in cirrhosis emphasize the dynamic
metabolic dysfunction-associated steatotic liver disease (MASLD, nature of this disease. These findings call for updated public health
9.6%). Approximately 40% of cases had an unidentified etiology. strategies and personalized treatment approaches to address the
Cirrhosis accounted for the majority of hospitalizations, with a stable changing demographics and causative factors of cirrhosis.
incidence of 900–1,000 cases per month. Alcohol-related cirrhosis Dr. Abhishek Lal is a Master’s in Epidemiology and Biostatistics student
was the most prevalent, while hepatitis B- and C-related cirrhosis (1st year) at the Aga Khan University, Karachi, Pakistan.
had the highest mortality rates. The age-standardized mortality rates
for hepatitis B- and C-related cirrhosis declined from 2017 to 2019,
attributed to expanded antiviral treatment and vaccination programs. AA0003
For HCC, incidence rates remained stable, with hepatitis B, hepatitis C, Altered T cell profile may contribute to the cirrhosis-associated
and MASLD contributing 16, 10, and 7 cases per 10 million population immune regulation in paediatric portal hypertension: a pilot study
per month, respectively. By 2019, MASLD-related HCC mortality Tengfei Si1, Huihong Yu2, Qing Shao3, Yun Ma4, Tassos
surpassed alcohol-related causes. Grammatikopoulos5
Conclusion: CLD remains a significant health burden in Thailand, 1
Department of Hepatobiliary and Pancreatic Surgery, The First
with high mortality linked to viral hepatitis, alcohol consumption, Affiliated Hospital, School of Medicine, Zhejiang University, 310003,
and MASLD. Improved prevention strategies, early diagnosis, and Hangzhou, Zhejiang, China, 2Department of Gastroenterology,
equitable access to effective therapies are essential. Strengthened The Second Affiliated Hospital, Chongqing Medical University,
public health interventions and ongoing surveillance are critical to Chongqing, 400016, China., 3King‘s College London, 4Institute of Liver
reducing the growing burden of CLD. Studies, King’s College, London, United Kingdom, 5Paediatric Liver,
Table and Figure:Figure 1.Age-sex standardized incidence rate of newly GI & Nutrition Centre, King‘s College Hospital NHS Trust, London,
hospitalized cases primarily diagnosed with cirrhosis per month in the United Kingdom
population (A), number of all hospitalized cases primarily diagnosed Background: Patients with portal hypertension (PHT) often display an
with cirrhosis (B), and in-hospital mortality rate of hospitalized cases altered immune profile, including the upregulation of pro-inflammatory
primarily diagnosed with cirrhosis (C). cytokines in peripheral blood. However, few studies have investigated
Figure 2.Age-sex standardized incidence rate of newly hospitalized changes in the T cell immune profile in the context of PHT, especially
cases primarily diagnosed with hepatocellular carcinoma per month in pediatric patients. This study is the first to comprehensively explore
in the population (A), number of all hospitalized cases primarily both the quantitative and qualitative changes in T cells in pediatric
diagnosed with hepatocellular carcinoma (B), and in-hospital mortality PHT patients. The novel findings may provide insights into improving
rate of hospitalized cases primarily diagnosed with hepatocellular outcomes for these patients.
carcinoma (C). Method: Forty-four children with PHT (Cirrhosis-related PHT, n=27;
portal vein thrombosis (PVT)-related PHT, n=17) and 15 pediatric
AA0002 controls without liver disease were prospectively recruited. Six paired
blood samples (peripheral and central blood) were collected from PHT
patients (PVT-related PHT, n=4; Cirrhosis-related PHT, n=2). Plasma Conclusion: In hepatocellular carcinoma patients who undergo
and peripheral blood mononuclear cells (PBMCs) were isolated from resection followed by adjuvant PD-1 inhibitor therapy, the presence of
the blood samples. Immune markers, cytokines, and chemokines TLS in tumors may be associated with significantly longer recurrence-
were detected, and T cell phenotyping and functional testing were free and overall survival. This association may reflect synergy between
performed using ELISA or multiparameter flow cytometry. Statistical the structures and PD-1 inhibitor therapy to activate anti-tumor immune
analysis was conducted to assess group differences and correlations responses within tumors.
with liver parameters such as stiffness using GraphPad Prism (version
9).
OP0400
Result: The T cell population was significantly decreased in the
Cirrhosis-related PHT group. Higher expression of CD39 was observed Liver Fibrosis, Based on Fibrosis-4 Index, is Associated with
across T cell subsets in both PHT groups compared to controls, while Coronary Stent Failure and Cardiovascular Outcomes in Patients
the downregulation of CXCR3 expression in double-negative (DN) T After Coronary Stenting.
cells (CD4-CD8- T cells) and upregulation of CCR4 in CD4+ T cells Na Tian1, Tie Xiao1, Haiyang Yuan1, Michael D Shapiro2, Gregory YH
were only observed in PVT-related PHT patients. Cirrhosis-related Lip3,4, Shengjie Wu1, Xi Zhou1, Giovanni Targher5,6, Christopher D
PHT patients exhibited both higher CD39 and CD38 expression in Byrne7, Xiaodong Zhou1, Minghua Zheng8,9,10
CD8+ T cells and DN T cells. Non-CD8 T cells showed enhanced pro- 1
The First Affiliated Hospital of Wenzhou Medical University, 2The
inflammatory capacity, evidenced by increased percentages of IFN-γ- First Center for Prevention of Cardiovascular Disease, Section on
producing cells and decreased percentages of IL-10-producing cells. Cardiovascular Medicine, Wake Forest University School of Medicine,
Compared to peripheral blood, CXCL9 plasma levels were elevated in Affiliated Hospital of Wenzhou Medical University, 3Liverpool Centre
the paired central blood and positively correlated with CXCR3+ T cells. for Cardiovascular Science at University of Liverpool, Liverpool John
Soluble CD25 was significantly decreased in Cirrhosis-related PHT, Moores University and Liverpool Heart & Chest Hospital, Liverpool,
while plasma levels of PD-L1, IFN-γ, and TNF-α increased compared
4
Department of Clinical Medicine, Aalborg University, 5Department of
to the PVT-related PHT and the control group, correlating with liver Medicine, University of Verona,, 6Metabolic Diseases Research Unit,
stiffness. IRCCS Sacro Cuore-Don Calabria Hospital,, 7Southampton National
Conclusion: A higher degree of inflammatory microenvironment is Institute for Health and Care Research Biomedical Research Centre,
University Hospital Southampton, and University of Southampton,
present in Cirrhosis-related PHT patients, resulting in phenotypic and
Southampton General Hospital, 8The First Affiliated Hospital of
functional changes in T cells. The altered T cell profile may contribute
Wenzhou Medical University;, 9Institute of Hepatology, Wenzhou
to the cirrhosis-associated immune regulation in PHT.
Medical University;, 10Key Laboratory of Diagnosis and Treatment for
Table and Figure:Figure 1.Figure 1
the Development of Chronic Liver Disease in Zhejiang Province
Background: Advanced liver fibrosis is associated with adverse
AA0004 cardiovascular outcomes and highly prevalent in patients with
Tertiary lymphoid structures in hepatocellular carcinoma: coronary artery disease (CAD). However, assessment of liver fibrosis
influence on immune cell profiles in tumors and on efficacy of is frequently neglected in clinical practice.
adjuvant PD-1 inhibitor therapy after hepatectomy Method: The study included patients who underwent drug-eluting
JiaYong Su1, JianRong Li1, LiXin Pan1, YiLi Ma1, Wei Tian1, PingPing stent (DES) implantation. These patients were categorized into three
Guo1, Le Li1, DaLong Yang1, ZhuJian Deng1, YuXian Teng1, ZhenZhen groups based on their FIB-4 scores: FIB-4 ≤ 1.3 (low probability
Li1, ChengPiao Luo1, RongRui Huo1, Liang Ma1, JianHong Zhong1 of advanced fibrosis), FIB-4 between 1.3 and 2.67 (intermediate
1
guangxi medical university cancer hospital probability of advanced fibrosis), and FIB-4 > 2.67 (high probability of
advanced fibrosis). The primary outcome was stent failure, defined as
Background: Tertiary lymphoid structures, which function as ectopic
either in-stent restenosis or stent thrombosis. The secondary outcome
lymphoid organs in tumors and other sites of chronic inflammation, may
was major adverse cardiovascular events (MACE), including all-cause
promote adaptive and humoral immune responses to hepatocellular
mortality, myocardial infarction, heart failure or ischemic stroke. Cox
carcinoma and thereby potentiate immune checkpoint inhibitor
proportional hazard models were used to examine the association
therapy. Whether the structures are associated with better prognosis of
between the FIB-4 score and these outcomes.
patients who receive immune checkpoint inhibitors after curative liver
Result: Of 13,987 enrolled CAD patients, 3,173 (22.7%) had a FIB-
resection is unclear.
4 score >2.67. During a median of 3.0 (IQR: 1.0–6.4) years, 1,046
Method: Using data on hepatocellular carcinoma patients from
patients experienced stent failure and 7,302 developed MACE.
The Cancer Genome Atlas as well as retro- and prospective patient
Patients with FIB-4 >2.67 had the highest incidence rate of stent
cohorts at our medical center, we analyzed the prevalence and
failure per 100 persons-years [2.38 (95%CI: 2.08-2.67)] and MACE
maturity of tertiary lymphoid structures in tumors, the associations of
[21.82 (95% CI: 21.02-22.60]. After multivariate adjustment, FIB-
such structures with survival after resection that was followed or not by
4 >2.67 was significantly associated with an increased risk of
adjuvant PD-1 inhibitor therapy, and the associations of the structures
developing stent failure [HR 1.27 (95%CI: 1.06-1.52); P =0.010] and
with the extent and profile of immune cells infiltrating tumors. Our
MACE [HR 1.79 (95% CI: 1.67-1.91); P <0.010]. Subgroups and
analyses of patient samples were complemented through analyses of
sensitivity analyses confirmed these findings.
C57BL/6 mice in which hepatocellular carcinoma was induced through
Conclusion: A FIB-4 score >2.67 is present in approximately 1/4 of
administration of CCl4 and a high-fat diet.
CAD patients after coronary stenting. These patients have an increased
Result: In the TCGA cohort of 304 patients, 183 had TLS, and in our
risk of stent failure and adverse cardiovascular outcomes.
retrospective cohort of 312 patients, 179 showed TLS. Patients with
Table and Figure:Figure 1.Baseline Clinical Characteristics of Patients
TLS had better prognoses in both cohorts. Of 195 patients in our
with CAD Following Percutaneous Coronary Interventions
prospective cohort who underwent resection followed by PD-1 inhibitor
Figure 2.Kaplan-Meier survival curves showing the association
therapy, the tumors in 109 (56%) contained TLS, and those patients
between the FIB-4 category and the risk of developing stent failure (A)
showed significantly better recurrence-free survival (HR 0.69, 95%
and MACE (B).
CI 0.44–0.98) and overall survival (HR 0.57, 95% CI 0.33–0.98) than
those whose tumors lacked such structures. A nomogram taking into
account the presence of such structures predicted recurrence at 1, 2 AA0006
or 3 years with areas under the receiver operating characteristic curve Benefits of terlipressin for the prevention from acute kidney injury
> 0.75. Tumors with TLS contained higher levels of CD3+ CD8+ PD- in patients with liver cirrhosis and ascites
1+ T cells, PD-1+ natural killer T cells, B cells and granzyme B+ cells, Yong He1, Xianxian Zhang1, Ting Wang1, Xiaohui Fang1, Na Sun2,
but lower levels of regulatory T cells and macrophages, than tumors Jian Zhang3, Yibing Li1, Frank Tacke4, Han Chen1, Yunhai Wu2, Lichun
without such structures. Similar findings were observed in the mouse Shao3, Xingshun Qi1
model of hepatocellular carcinoma.
General Hospital of Northern Theater Command, 2The Sixth People’s
1
assessed. Liver tissues were harvested for histological staining, flow
Hospital of Shenyang, 3Air Force Hospital of Northern Theater cytometry, and bulk RNA-seq to evaluate treatment efficacy.
Command, 4Charité - Universitätsmedizin Berlin, Campus Virchow- Result: The stem cell markers and trilineage differentiation potential
Klinikum (CVK) and Campus Charité Mitte (CCM) of hBMSC were preserved after training. The results showed that pro-
Background: Terlipressin is a vasoconstrictive drug used in patients inflammatory genes (IL1β, IL6, IL8) and immunoregulatory genes
with liver cirrhosis and portal hypertension related complications, (PDL-1, IDO) were significantly upregulated in T-hBMSC compared to
especially variceal bleeding. Terlipressin has been recommended as hBMSC. The time trajectory analysis revealed significant differences
the first-line agent for the treatment of hepatorenal syndrome acute in the response of hBMSC to restimulation, with T-hBMSC exhibiting
kidney injury (HRS-AKI). However, its role in the prevention from distinct gene expression profiles, particularly lower expression of pro-
developing renal dysfunction and AKI in cirrhosis and ascites remains inflammatory genes (IL8, CXCL9) compared to hBMSC.
uncertain. Murine liver failure models were established via tail vein injection of
Method: Overall, 905 cirrhotic patients were included from 3 hospitals ConA. The 14-day survival of the T-hBMSC group was significantly
in Shenyang, China. According to the use of terlipressin during higher than NS group, with improved ALT and AST on day1 post-
hospitalization, they were further divided into terlipressin (TERLI) transplantation. Histological analysis showed reduced necrosis area
and standard medical therapy (SMT) groups. A 1:1 propensity score and TUNEL-positive cells in T-hBMSC group. Gene set enrichment
matching (PSM) analysis was performed to balance the characteristics analysis revealed significant enrichment of pro-inflammatory TNF and
of patients between groups. Primary outcomes of interests included IL17 pathways in the hBMSC group compared to T-hBMSC, suggesting
AKI, renal dysfunction, and renal function improvement. milder liver damage in the T-hBMSC-treated mice.
Result: In 784 patients with baseline Scr level <133 μmol/L, TERLI Conclusion: T-hBMSC can alleviate liver injury by regulating the
group had lower incidence of AKI (before PSM: 1.44% vs. 10.26%, inflammatory response of immune cells in mice with liver failure, which
p<0.001; after PSM: 1.67% vs. 16.67%, p=0.004) and renal dysfunction provides a new idea for optimizing stem cell therapy strategy.
(before PSM:0% vs. 8.17%, p<0.001; after PSM: 0% vs. 8.33%, Table and Figure:Figure 1.The mechanism of trained immunity on
p=0.068) than SMT group. In 121 patients with baseline Scr level ≥133 hBMSC
μmol/L, TERLI group had lower incidence of AKI (before PSM: 4.88%
vs. 20.00%, p=0.027; after PSM: 0% vs. 11.76%, p=0.466) and higher AA0009
incidence of renal function improvement (before PSM: 56.10% vs.
Targeting of inflammatory monocytes via CCL2/CCR2 signaling
22.50%, p<0.001; after PSM: 70.59% vs. 23.53%, p=0.476) than SMT
as a therapeutic strategy against autoimmune hepatitis by using
group.
macrophage-derived extracellular vesicles
Conclusion: Terlipressin should be considered an alternative choice
for the prevention from the development of renal dysfunction and AKI Fan Xiaoli1, Fan Yang1
in cirrhotic patients with ascites without renal dysfunction, and may
1
Sichuan University
be beneficial for the improvement of renal function in those with renal Background: Autoimmune hepatitis is a serious chronic liver disease
dysfunction. with immune disorders, histological lesions and liver dysfunction, with
Table and Figure:Figure 1.Graphical Abstract a gradually increasing prevalence. Yet the cellular and molecular
mechanisms of immune dysregulation in AIH are poorly understood.
AA0008 Method: Firstly, human liver of AIH patients were collected for
single-cell sequencing. The recruitment and activation patterns
Trained human bone marrow mesenchymal stem cells improve of mononuclear macrophages in AIH and the mechanism of CCL2/
the therapeutic outcomes in ConA-induced acute liver failure via CCR2 axis activation were investigated. The CCL2/CCR2 axis was
enhancing immunoregulation interfered by different ways to determine its effect on liver inflammation
Bingqi Li1, Xiaofei Zeng2, Jing Jiang1, Jiaojiao Xin1, Dongyan Shi1, Xi injury in AIH mice. Finally, M2-EVs were isolated and extracted as drug
Liang1, Jun Li1 delivery tool of CCR2 antagonists, and its therapeutic effect on AIH
1
State Key Laboratory for Diagnosis and Treatment of Infectious mice as well as its effectiveness and mechanism after loading CCR2
Diseases, National Clinical Research Center for Infectious Diseases, antagonists on AIH mice were determined.
National Medical Center for Infectious Diseases, The First Affiliated Result: Single-cell sequencing revealed an elevated proportion of
Hospital, Zhejiang University School of Medicine, 2Department of mononuclear macrophages in the liver tissue of autoimmune hepatitis
Infectious Diseases, Guizhou Provincial People‘s Hospital, Zunyi (AIH) patients. Flow cytometry analysis demonstrated an increased
Medical University of Medicine percentage of classical monocytes (CD14+CD16-) in the peripheral
Background: The immunoregulation of human bone marrow blood of these patients. AIH mouse models indicated that splenic
mesenchymal stem cells (hBMSC) plays an important role in treating monocytes migrate from the bone marrow and spleen to the liver
liver failure. However, the complex in vivo disease microenvironment, via CCL2-CCR2 axis-mediated recruitment, leading to inflammatory
including inflammatory cytokine storms, poses challenges to the damage. Interventions using CCL2-CCR2 axis antagonists have
survival and homing of hBMSC, thereby affecting their therapeutic been shown to mitigate liver immune damage in AIH mice, whereas
efficacy. Trained immunity has been proven to exist in immune cells and the administration of recombinant CCL2 enhances the recruitment
non-immune cells such as epidermal stem cells. The immune memory of inflammatory monocytes through the bone marrow-liver axis and
enables trained cells to either activate or tolerate upon re-encountering spleen-liver axis, exacerbating liver damage. Utilizing M2 macrophage-
inflammation. This study aims to enhance the immunoregulation of derived extracellular vesicles (M2-EVs) as carriers for CCR2
hBMSC by trained immunity to improve the therapeutic effect on liver antagonists (CCR2 antag-EVs) targets inflammatory mononuclear
failure, and to optimize stem cell therapy strategies. cells in the bone marrow, spleen, and circulation, as well as activated
Method: Trained hBMSC (T-hBMSC) were induced with pro- mononuclear macrophages in the liver, thereby alleviating liver injury
inflammatory cytokines IFN-γ and TNF-α as “trainers” for 24 hours, and in AIH mice.
untrained-hBMSC (control group) were cultured with standard medium. Conclusion: Studies have demonstrated that the CCL2/CCR2 axis
Then same dosage “trainers” were used to restimulate hBMSC after a facilitates the recruitment of inflammatory mononuclear cells from the
48-hour washout period. Cell samples were collected to perform qRT- bone marrow and spleen to the liver during AIH. Meanwhile, CCR2
PCR and transcriptome analysis. Serum derived from patients with antagonist-loaded extracellular vesicles (antag-EV) target activated
acute-on-chronic liver failure was used to simulate the pathological pro-inflammatory mononuclear cells in the circulation and the activated
microenvironment and assess the immune response of T-hBMSC. hepato-splenic mononuclear macrophage system, thereby achieving
Murine liver injury models were established in Balb/c mice via tail multi-targeted and efficient treatment of AIH-induced liver injury.
vein injection of concanavalin A (ConA). Mice were treated with either Table and Figure:Figure 1.Outline of the study
T-hBMSC or hBMSC via intrasplenic injection, with normal saline (NS)
as control. Survival rates, liver function, and inflammatory factors were
 AA0010 liver disease, intrapulmonary vascular dilatations, and abnormal
A Novel and User-Friendly Model for Precise Identification of oxygenation, causes significant morbidity and mortality. Despite liver
Concurrent Bacterial Infections in Older Patients with Acute-on- transplantation being the only cure, no standardized medical therapy
Chronic Liver Diseases (AoCLD): Evidence from a Nationwide, exists. This study hypothesizes that simvastatin, a hydrophobic statin
Multicenter and Prospective Study with anti-inflammatory properties, can improve oxygenation in HPS.
A six-month randomized controlled trial will evaluate the efficacy and
Ju Zou1, Hai Li2, Guohong Deng3, Xianbo Wang4, Xin Zheng5, Jinjun
safety of simvastatin for HPS treatment.
Chen6, Zhongji Meng7, Yubao Zheng8, Yan Huang9, Ruochan Chen9,
Method: This double-blind, randomized, placebo-controlled trial
Feng Liu10, Xiaobo Lu11
was conducted from 2022 to 2024 and included forty-five patients
1
Xiangya Hospital Central South University, 2Department of aged 18-70 years with HPS (diagnosed by chronic liver disease
Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai
with portal hypertension, arterial hypoxemia (PaO2 < 80 mm Hg or
Jiao Tong University,, 3Department of Infectious Diseases, Southwest
an alveolar-arterial oxygen gradient > 15 mm Hg), and evidence of
Hospital, Third Military Medical University (Army Medical University),
intrapulmonary vascular dilatations (IPVDs) demonstrated by contrast-
4
Center of Integrative Medicine, Beijing Ditan Hospital, Capital
enhanced echocardiography or lung perfusion scans), randomized
Medical University, 5Department of Infectious Diseases, Institute of
Infection and Immunology, Union Hospital, Tongji Medical College, in a double blind manner to 2:1 into two arms using the IVR system:
Huazhong University of Science and Technology, 6Hepatology Unit, Simvastatin 40mg and placebo; the study duration was six months.
Department of Infectious Diseases, Nanfang Hospital, Southern The primary outcome was an improvement in the PaO2 gradient. At 6
Medical University, 7Department of Infectious Diseases, Hubei Clinical months, differences in PaO2 improvement were observed: a complete
Research Center for Precise Diagnosis and Treatment of Liver response was an increase of ≥10 mm Hg, a partial response was an
Cancer, Taihe Hospital, Hubei University of Medicine, 8Department increase of ≥5 but <10 mm Hg, and no response was an increase of <5
of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen mm Hg. The code was broken after completed follow-up of last patient.
University, 9Xiangya Hospital, Central South University, 10Department Result: Among the forty-five patients, 89% were male, the most
of Infectious Diseases and Hepatology, The Second Hospital of common etiologies alcohol-associated (47.5%) followed by metabolic
Shandong University, 11Infectious Disease Center, The First Affiliated (44.5%). Both the Simvastatin (n=30) and placebo (n=15) groups were
Hospital of Xinjiang Medical University similar in demographic and clinical parameters at baseline, including
Background: Diagnostic model that can identify older patients with MELD score, oxygenation parameters, and severity of HPS. The primary
acute-on-chronic liver diseases (AoCLD) at higher risk of infections are objective of response (PaO2 ≥5mm of Hg) was seen in 7(15.5%)
lacking. We aim to uncover the epidemiological characteristics and patients; 1(2.2%) and 6(13.3%) patients in placebo and simvastatin
risk factors of infection in older patients with AoCLD and develop a group respectively(p=0.25). No significant differences were observed
specific diagnostic nomogram model for this population. in the severity of HPS, liver fibrosis, HVPG change, inflammatory
Method: Data from 3,970 patients included in the CATCH-LIFE cohort markers (TNF-alpha, S1P levels), pulmonary function tests, or 6-minute
were used. All older individuals were randomly divided into training walk distance between the groups at the end of 6 months. Adverse
and validation cohorts in a 7:3 ratio. In the training cohort, Lasso and events were observed in 5(11%) patients in simvastatin and 2(4%) in
logistic regression analysis was used to identify independent risk placebo arm(p=0.84).
factors, and an easy-to-use model was established. Performance was Conclusion: Simvastatin did not significantly improve oxygenation or
assessed using area under the curve (AUC), calibration plots and other clinical outcomes in patients with hepatopulmonary syndrome
decision curve analysis. Two different cutoff values were determined compared to placebo. Adverse events were similar between the
to stratify infection risk in older AoCLD patients. simvastatin and placebo groups.
Result: The infection rate among older patients with AoCLD was
determined to be 30.28%. Pulmonary infections predominated, AA0012
accounting for 93% of all infections, with gram-negative bacteria being
Cirrhotic and Non-cirrhotic Portal Vein Thrombosis: Is There an
the most frequently isolated pathogens, representing 64% of cases
Association with Coagulation, Platelet-related, Folate Cycle Gene
in this older AoCLD population. The developed diagnostic model
and Janus Kinase 2 Gene Polymorphisms?
to identify bacterial infections included three variables: cirrhosis,
Diana Daduns1, Evelina Trashkun1, Maxim Privalov1, Kseniya
absolute count of neutrophils and C-reactive protein (CRP). The AUC
Gulyaeva1, Maria Nadinskaia1
for the training and validation cohorts were demonstrated a high
accuracy in identifying infections in this patient cohort, (AUC=0.805
1
Sechenov First Moscow State Medical University (Sechenov
and AUC=0.848, respectively). The model significantly outperformed University), Moscow, Russia
either neutrophils count or CRP or procalcitonin level alone in detecting Background: The role of inherited thrombophilia in patient with portal
bacterial infections in older patients with AoCLD. To facilitate clinical vein thrombosis (PVT) with and without liver cirrhosis (LC) is not well
decision-making, we established cutoff values: a low cutoff of 81.96 understood. Aim: To evaluate the association of PVT in adult patients
points to rule out bacterial infection and a high cutoff of 91.75 points to with coagulation, platelet-related and folate cycle gene polymorphisms,
rule in bacterial infection with confidence. as well as polymorphisms of the plasminogen activator inhibitor-1 (PAI-
Conclusion: Our model aids in the early and precise diagnosis of 1) gene, selectin P ligand (SELPLG) gene, and the Janus kinase 2
bacterial infections in older patients with AoCLD, thereby facilitating gene (JAK2).
prompt intervention to prevent adverse outcomes. Method: A cross-sectional study was conducted in 128 patients with
Table and Figure:Figure 1.Graphical abstract newly diagnosed non-tumoral PVT detected by contrast-enhanced
Figure 2.Figure. (A) Forest plots of multivariate logistic regression; (B) abdominal computed tomography. LC was established in 51 patients
A nomogram for predicting bacterial infection in older AoCLD patients. (LC_PVT group). Non-cirrhotic non-malignant PVT was diagnosed in
77 patients (Non_LC_PVT group). Healthy controls were 86 volunteers.
The groups were comparable in age and sex distribution. All were
AA0011
tested for polymorphisms of genes of coagulation factors (F): F2
Simvastatin ineffective in improving hepatopulmonary syndrome (rs1799963), F5 (rs6025), F7 (rs6046), F12 (rs1801020), F13 (rs5985),
in cirrhosis patients (HEPSIM Trial) – results of a double-blind fibrinogen (rs1800790); platelet-related glycoprotein Ib (rs41439349,
randomised controlled trial [NCT05187715]. rs6065) and integrin subunit alpha 2 (rs1126643), beta 3 (rs5918);
Akhil Deshmukh1, Shiv Kumar Sarin1, Harshvardhan Tevethia1, folate cycle: methylenetetrahydrofolate reductase (rs1801133),
Manoj Kumar Sharma1, Chitranshu Vashistha1, Arviind Tomar1, Sukriti methionine synthase (rs1805087), methionine synthase reductase
Baweja1 (rs1801394); PAI-1 gene (rs1799889), selectin P ligand (SELPLG)
1
Institute of liver and biliary sciences gene (rs2228315), and the JAK-2 gene (rs77375493). Real-time
Background: Hepatopulmonary syndrome (HPS), marked by polymerase chain reaction was used to detect polymorphisms.
Groups were compared using the model of common and multiplicative
inheritance. expression. Cytokine array analysis further revealed elevated Rarres2
Result: The distribution of the genotype and allele frequencies levels in mouse serum during the regression phase compared to both
for the studied polymorphisms was in accordance with Hardy- healthy controls and fibrotic states
Weinberg equilibrium in all groups. There were no differences in Conclusion: This study uncovered previously unrecognized molecular
allele and genotype frequencies between the groups for the following and cellular mechanisms of hepatocytes in liver fibrosis regression,
polymorphisms: rs6025, rs6046, rs1801020, rs5985, rs1800790, identifying RARRES2 as a potential biomarker and therapeutic target
rs41439349, rs6065, rs1126643, rs5918, rs1801133, rs1805087, for antifibrotic treatment.
rs1801394, rs1799889, rs2228315. The rs1799963 substitution of the Table and Figure:Figure 1.
F2 gene differed between groups: the frequency of the A allele was Figure 2.
5 times greater in the Non_LC_PVT group (p=0.02), the frequency
of the G/A genotype was 9 times greater in the Non_LC_PVT group
AA0014
(p=0.06) compared to the control group. The rs77375493 of JAK2 also
differed between groups: the frequency of the T allele was 17 times Risk of Variceal Haemorrhage with Calcium Channel Blockers in
greater in the Non_LC_PVT group (p<0.001), the frequency of the G/T Patients with Cirrhosis: A Territory-Wide Retrospective Cohort
genotype was statistically significantly greater in the Non_LC_PVT Study
(p<0.001) compared to the LC_PVT group and controls. The common Junlong Dai1,2, Terry CheukFung Yip1,2,3, YeeKit Tse1,2,4, Vicki WingKi
and multiplicative inheritance models are shown in the table. Hui1,2,4, Grace LaiHung Wong1,2,4, Vincent WaiSun Wong1,2,4, Jimmy
Conclusion: Carrying the A allele rs1799963 of the F2 gene, as well CheTo Lai1,2,4
as the G/A genotype, and the T allele rs77375493 of the JAK2 gene, 1
Medical Data Analytics Centre, The Chinese University of Hong
as well as the G/T genotype is associated with non-cirrhotic non- Kong, Hong Kong SAR, China, 2Department of Medicine and
malignant PVT. Association with polymorphism in coagulation genes Therapeutics, The Chinese University of Hong Kong, Hong Kong
wasn’t established in patients with PVT that developed in the context SAR, China , 3Li Ka Shing Institute of Health Sciences, The Chinese
of LC. University of Hong Kong, Hong Kong SAR, China , 4State Key
Table and Figure:Figure 1.The common and multiplicative models of Laboratory of Digestive Disease, The Chinese University of Hong
prothrombin and Janus kinase 2 genes inheritance. Kong, Hong Kong SAR, China
Background: Calcium channel blockers (CCBs) are widely used to
treat arterial hypertension by its vasodilatory effect. However, it remains
AA0013
unclear whether CCBs impact the risk of variceal haemorrhage (VH) in
Single Cell Fixed RNA Profiling reveals Hepatocytes patients with cirrhosis by altering haemodynamics. This study aimed
(Cyp2e1+Cyp1a2+Tnx1+) drives liver fibrosis regression via to determine whether CCBs influence the risk of VH in patients with
retinoic acid receptor responder 2 cirrhosis, providing guidance on the safe use of the medications in this
Duc Minh Pham1, Thuy ThiThanh Le1, Hai Hoang1, Ha Thi Nguyen1, population.
Norifumi Kawada1 Method: A territory-wide retrospective cohort study was conducted
1
Osaka Metropolitan University on patients with cirrhosis from 2000 to 2023, retrieved from the Clinical
Background: Single-Cell Fixed RNA Profiling (FLEX) is an advanced Data Analysis and Reporting System of the Hospital Authority, Hong
technology enabling single-cell resolution RNA expression analysis Kong. An active comparator new-user design was adopted with
from frozen tissues. This study aimed to utilize FLEX technology to angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II
investigate molecular and cellular dynamics during the progression receptor blockers (ARB) users as the control group. Inverse probability
and regression of liver fibrosis in human and experimental models, of treatment weighting (IPTW) was applied to balance the baseline
with the objective of identifying novel therapeutic targets for antifibrotic characteristics. Patients with prior history of VH were excluded.
treatment. Patients were censored upon discontinuation, addition, or switch in
Method: Liver fibrosis was induced in mice through intraperitoneal the medication. The incidence of VH in patients with cirrhosis was
administration of thioacetamide (TAA) at escalating doses (50–400 mg/ assessed from 90 days after drug initiation to 30 days post-cessation.
kg) over 10 weeks. Control mice received saline. Fibrosis regression Result: The cohort comprised 1,792 CCB users and 765 ACEI/ARB
was assessed two weeks after TAA cessation. Frozen liver tissues from users, each initiating a single antihypertensive drug. In IPTW-weighted
both murine models and human samples were fixed, dissociated into analyses, the VH incidence[WS2] rates during follow-up period were
single cells, and analyzed via single-cell RNA sequencing (scRNA- comparable between CCB and ACEI/ARB users (3.3% vs. 2.9%; P =
seq) following the 10X Genomics protocol. Validation of key findings 0.592), with a 5-year cumulative incidence of 3.36% (95% confidence
was performed using immunoblotting, immunohistochemistry, gene interval (CI) 2.20%–4.50%) for CCB users and 3.07% (95% CI 1.20%–
silencing, overexpression studies, and mouse cytokine arrays. 4.91%) for ACEI/ARB users. In the weighted Cox regression model,
Result: FLEX technology preserved whole liver cells, enabling single- CCB use was not associated with increased risk of VH (hazard ratio:
cell resolution analysis of ~40,000 cells, which were classified into 1.13; 95% CI 0.60–2.13).
10 major cell types using transcriptomic profiles and lineage marker Conclusion: CCB use did not significantly increase risk of VH in
signatures. Cellular composition analysis revealed a 30–50% reduction patients with cirrhosis compared to ACEI/ARB use. These findings
in hepatocytes and liver sinusoidal endothelial cells (LSECs) in cirrhotic suggested that CCBs may be a safe option for patients with cirrhosis
livers, accompanied by a 150–200% increase in immune cells, hepatic and hypertension, offering a new reference on medication selection in
stellate cells (HSCs), and biliary epithelial cells (BECs) compared to this vulnerable population.
healthy livers. Notably, a subpopulation of hepatocytes localized in Table and Figure:Figure 1.Comparison of 5-Year Cumulative Incidence
the pericentral region, identified by immunofluorescence staining, and Hazard Ratios of Variceal Hemorrhage Between CCBs and ACEI/
was enriched during the regression phase. These hepatocytes ARB in Hypertensive Cirrhosis Patients
expressed high levels of Cyp1a2, Cyp2e1, and Tnx1, and showed
increased activity in antioxidant and xenobiotic metabolism pathways. AA0015
Cell-cell interaction analysis using MultiNichenetR demonstrated
Exosomal miR-499a-5p from Human Umbilical Cord Mesenchymal
strong interactions between these hepatocytes and HSCs during the
Stem Cells Attenuates Liver Fibrosis via Targeting ETS1/GPX4-
regression phase via the Rarres2-Cmklr and Rarres2-Ccrl2 signaling
Mediated Ferroptosis in Hepatic Stellate Cells
axes. RARRES2 was highly expressed in healthy murine and human
HSCs but was significantly downregulated during spontaneous Zheng Wang1, Yingan Jiang1
activation or TGF-β treatment. Pharmacological induction of RARRES1/2
1
Department of Infectious Diseases, Renmin Hospital of Wuhan
expression in human hepatic stellate cells (HHSteCs) using all-trans University, Wuhan, China
retinoic acid, adapalene, bexarotene, or tazarotene dose-dependently Background: Liver fibrosis is a major contributor to liver-related
suppressed HSC activation by downregulating COL1A1 and α-SMA mortality worldwide, yet effective therapeutic options remain limited.
Mesenchymal stem cells (MSCs) have shown promise in alleviating to be highly expressed in FRC of cirrhotic MLN compared to control
liver fibrosis due to their anti-inflammatory and anti-fibrotic effects. FRC. In vitro, cirrhotic FRC had reduced bacterial phagocytosis activity
However, the molecular mechanisms underlying their therapeutic than control FRC and Vcan-siRNA treated cirrhotic FRC. Coculture of
potential remain unclear. This study aimed to investigate the role of T cells with cirrhotic FRC resulted in increased T cell clumping and
human umbilical cord-derived MSCs (hUC-MSCs) in liver fibrosis, attachment, reduced T cell migration, and Th cell activation compared
focusing on ferroptosis as a key regulator of hepatic stellate cells to when cultured with control FRC. In vivo inhibition by Vcan siRNA
(HSCs) activity. in CCl4 rats led to increased Th cell migration in systemic blood with
Method: To investigate the therapeutic potential of MSCs and MSC- reduced BT compared to that in control siRNA treated CCl4. Plasma
derived exosomes (MSC-Exos), liver fibrosis models were established Vcan levels were higher (by 35%) in cirrhotic patients with bacterial
in mice using CCl4 and TAA. MSCs and MSC-Exos were administered sepsis than in non septic cirrhotics. Patients with high Vcan levels had
via tail vein injection, and their effects on inducing ferroptosis in hepatic reduced activated Th cells than those with low Vcan levels.
stellate cells (HSCs) were evaluated in vivo. In vitro, a Transwell co- Conclusion: In cirrhosis, ECM remodeling and elevated Vcan
culture system was employed to examine the impact of MSCs and expression in MLN cause impaired bacterial clearance, reduced
MSC-Exos on mHSCs and LX-2 cells, revealing ferroptosis induction activation, and migration of Th cells from MLN to systemic circulation,
mediated by GPX4 downregulation. Subsequent miRNA sequencing fostering systemic bacterial dissemination. Targeting Vcan in MLN
of co-cultured mHSCs highlighted hsa-miR-499a-5p as a key regulator. presents a potential therapeutic target to treat systemic bacterial
Bioinformatics analyses further identified ETS1 as a transcriptional infections. Also, plasma Vcan may serve as biomarker for MLN
regulator of GPX4. Functional validation of the miR-499a-5p/ETS1/ dysfunction and bacterial sepsis in cirrhosis
GPX4 axis was conducted through dual-luciferase reporter assays, Table and Figure:Figure 1.MLN as a critical barrier in bacterial
ChIP-qPCR, and rescue experiments using ETS1 overexpression. translocation
Result: MSC-derived exosomes promoted ferroptosis in HSCs by Figure 2.effective immune response in MLN of control with LPS and
delivering hsa-miR-499a-5p, which suppressed the transcription cirrhotic rats, with reduced immune response in blood of cirrhotic rats
factor ETS1, subsequently downregulating GPX4. This suppression
reduced the fibrogenic activity of HSCs. ETS1 overexpression in HSCs
AA0018
counteracted the pro-ferroptotic effects of miR-499a-5p, underscoring
the pivotal role of the miR-499a-5p/ETS1/GPX4 axis. Molecular The Role of the Non-Invasive Diagnostic Method - FibroScan in
docking simulations further revealed optimal ETS1-GPX4 binding sites, Liver Diseases
providing structural insights into the regulatory mechanism. Saltanat Efendiyeva Maharramzade1, Gulnara Aghayeva1
Conclusion: This study elucidates a novel mechanism by which hUC- 1
Referans polyclinic - Liver disease department
MSCs alleviate liver fibrosis through MSC-Exos-mediated delivery Background: Non-invasive methods, such as FibroScan, have proven
of miR-499a-5p, targeting the ETS1-GPX4 axis to induce ferroptosis to be a reliable tool for assessing liver fibrosis and steatosis, offering
in HSCs. These findings advance our understanding of MSC-based significant advantages over traditional invasive methods like liver
therapies and ferroptosis pathways, paving the way for innovative biopsy. This study aims to analyze the relationship between gender,
treatments for liver fibrosis. liver diagnoses, co-existing conditions, and the degree of fibrosis and
Table and Figure:Figure 1.Graphical abstract steatosis across different liver diseases using FibroScan.
Method: In this study, a total of 171 patients were analyzed, each
AA0017 diagnosed with various liver diseases, including MAFLD (Metabolic
Associated Fatty Liver Disease), hepatitis B (HBV), hepatitis C (HCV),
Versican Upregulation and Matrix Remodeling in Mesenteric
alcohol related liver disease, and others. FibroScan by echosens
Lymph Nodes Hinder CD4+ T Cell Migration, Driving Systemic
(compact 530) was used to assess both liver stiffness (fibrosis) and
Infections in Cirrhosis
the degree of steatosis. The data was analyzed based on the following
Pinky Juneja1, Aarti Sharma2, DEEPIKA JAKHAR1, Shiv Sarin1, key variables: gender distribution, the age of patients, diagnoses, co-
Savneet Kaur1 existing conditions, fibrosis and steatosis stages.
1
Institute of liver and biliary sciences, 2Institute Of Liver And Biliary Result: During period since July 2024 to November 2024, 171
Sciences,New Delhi patients (43% males and 57% females, mean age 34 years±6.5) were
Background: Mesenteric lymph nodes (MLN) act as critical barrier included to our study ,while 66 (37,8%) with MAFLD , 42 (24.5%) with
against bacterial dissemination. In cirrhosis, enhanced gut bacterial Hepatitis C ,29 (17%) with Hepatitis B, 6 (3.5%) with Alcohol related
translocation (BT) through MLN promotes systemic inflammation. Here, liver disease , 29 (17,2%) with Hepatitis B and D and others (including
we investigated mechanisms underlying failure of MLN to effectively combinations like HCV+HBV,HBV+HDV , PBC , Talassemia, etc.).
contain bacteria in cirrhosis. MAFLD: In MAFLD patients (mean age: 46 years, 58.9% male),
Method: Cirrhosis was induced in rats using 12 wk CCl4-treatment. advanced fibrosis (F3-F4) was observed in 50% of those with co-
Endogenous bacterial load and exogenous BT using GFP-bacteria existing diabetes mellitus, emphasizing the interplay between
were assessed in MLN, lymph, blood, and other organs. MLN proteome metabolic disorders and liver disease progression.
profile and immune response to infection were analyzed. The role of HCV: In the HCV group (mean age: 55 years, 59.5% female), advanced
one of the extracellular matrix proteins (ECM), versican (Vcan), was fibrosis (F3-F4) was identified in 54.8% of patients, reflecting a
deciphered using CD45- CD31- Pdpn+ fibroblastic reticular cell (FRC). significant burden of progressive liver disease.
Effects of FRC on bacterial phagocytosis, T cell migration, and function HBV and HBV+HDV: Among HBV patients (mean age: 41 years, 79.3%
were studied in vitro. Effect of in vivo siRNA-mediated Vcan inhibition male), 31% exhibited advanced fibrosis, with a mean age of 50 years
in CCl4 models was delineated. Plasma Vcan levels and T cells were in this subgroup. In the HBV+HDV group, 75% of patients had F3-F4
quantified in cirrhotic patients with and without bacterial sepsis fibrosis, with a mean age of 30 years, underscoring the severity of co-
Result: High endogenous bacterial load was present in cirrhotic rats’ infection at a younger age.
MLN, efferent lymph, portal blood, and all organs vs none in control. In Alcohol related liver disease: In the Alcohol related liver disease group,
control, GFP bacteria were retained in MLN; in cirrhotic rats, bacteria 66.7% of patients had advanced fibrosis (F3-F4), with a mean age of
were translocated from MLN (3-fold high vs control) to lungs, liver, 53 years. This highlights the high prevalence of severe liver damage
spleen, lymph, and blood. In cirrhotic MLN, CD134+ activated Th in this cohort.
cells and antigen-presenting CD80+ DC were significantly higher than Conclusion: These results emphasize the necessity of timely diagnosis,
control. Conversely, in systemic circulation, activated Th cells and DC particularly through non-invasive methods such as FibroScan, to
were reduced in cirrhosis vs control. Proteome analysis of MLN from identify high-risk groups at an early stage. The use of this method not
healthy and cirrhotic rats revealed 73 differentially expressed proteins only avoids the need for liver biopsy but also allows accurate disease
(DEP), of which many ECM proteins were upregulated in cirrhotic MLN. staging, facilitating personalized treatment approaches and preventing
From top 10 upregulated DEP, we selected Vcan, which was found disease progression.
 AA0019 Method: Expressions of genes in glutaminolysis pathways were
Distinct molecular pathways regulated by activated AKT and YAP compared between normal bile ducts and CCA using public
signaling during intrahepatic cholangiocarcinoma progression databases from The Cancer Genome Atlas (TCGA) and GEO dataset.
The key differentially expressed were validated in CCA cell lines and
Jinqiu Zhao1, Xin Chen2
immortalized cholangiocyte cell lines using Western blot. Glutaminase
1
The First Affiliated Hospital of Chongqing Medical University, 1 (GLS1) was knocked down using siRNA, CCA cell proliferation was
Chongqing, China, 2university of Hawaii
then determined using an MTT assay. The combination of knocked-
Background: Activated AKT and YAP signaling cascades have down GLS1 and low-dose metformin treatment was used to assess
key roles in intrahepatic cholangiocarcinoma (iCCA) pathogenesis. their effects on mitochondrial energy production, and the consequence
However, how these pathways modulate iCCA progression, especially on cell growth was examined using a clonogenic assay.
how they regulate tumor microenvironment remains unclear. Result: From transcriptomic analysis, GLS1 is significantly upregulated
Method: We engineered two doxycycline (doxy) conditional iCCA in CCA compared with normal bile duct in both liver fluke-associated-
murine models using hydrodynamic injection to deliver transposon and non-liver fluke-associated CCA. Two CCA cell lines (KKU-213A and
plasmids encoding inducible activated YAP or AKT into the mouse KKU-213B) showed upregulated GLS1 compared with immortalized
liver, AKT/TRE-Yap or TRE-AKT/Yap, respectively. Mice were fed cholangiocytes. Silencing GLS1 in KKU-213A and KKU-213B by
doxy water to induce the expression of the corresponding gene, and siRNA reduced cell proliferation in both cell lines. The combination of
the gene was turned off when the mice were switched to the regular silencing GLS1 and low-dose metformin, a mitochondrial complex I
water. Histological and molecular analyses were used to investigate inhibitor, treatment significantly reduced clonogenicity of CCA cells
the phenotypes, specially tumor microenvironment, as well as genes compared with either silencing GLS1 or metformin treatment alone.
and pathways which are regulated by AKT and/or YAP during iCCA Western blots reviewed that knocking down GLS1 or metformin
progression. treatment led to increased phosphorylation levels of AMP-activated
Result: We found that suppression of YAP in AKT/TRE-Yap iCCA protein kinase (AMPK), suggesting a disturbance of ATP production, in
model led to tumor regression initially. However, livers eventually which the combination of GLS1 knockdown and metformin additionally
progress in the liver, leading to HCC-like lesions in mice due to the increased AMPK phosphorylation.
activated AKT signaling. In striking contrast, suppression of AKT in Conclusion: Glutamine metabolism has crucial roles in CCA
TRE-AKT/Yap iCCA model lead to a more profound regression of iCCA progression, at least in the energy metabolism of the mitochondria.
lesions with limited tumor burden over long term AKT suppression. Targeting GLS1, a key enzyme in glutaminolysis, is potentially
Histologically, we found that YAP inhibition led to the elimination of promising for therapeutic development of CCA
the neutrophils in CCAs with the infiltration of CD4(+) and CD8(+),
whereas AKT suppression has limited impacts on immune cells.
The data suggest that YAP, but not AKT, is the major driver of tumor
AA0021
immune microenvironment in iCCA. The immune phenotypes were Single-cell Spatial Proteomic Landscape of Intrahepatic
consistently observed in human iCCAs with nuclear/activated YAP. Cholangiocarcinoma Immune Microenvironment Reveals Immune
Using gene expression analysis, we discovered that AKT and YAP Evasion via FSTL1-negative Macrophage
largely modulated distinct pathways during iCCA pathogenesis with Wenzhu Li1,2, Yongquan Chi1,2, Junda Li1,2, Haipeng Jiang1,2, Wei Xu1,2,
limited overlapping genes. Furthermore, we identified RNF125 as a Shanke Sun1,2, Jianhua Rao1,2
tumor suppressor whose expression is inhibited by YAP in iCCA cells. 1
Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical
Overexpression of RNF125 inhibited iCCA tumor and cell growth both University, 2Research Unit of Liver Transplantation and Transplant
in vivo and in vitro. Finally, while YAP off leads to increased T-cell Immunology, Chinese Academy of Medical Sciences
infiltration, these T cells express PD1. Combined YAP-off with anti- Background: Intrahepatic cholangiocarcinoma (ICC), an aggressive
PDL1 treatment resulted in increased tumor regression. biliary malignancy, is usually diagnosed at advanced or metastatic
Conclusion: Our studies, for the first time, systematically analyzed stages, resulting in poor prognosis with five-year survival rate less
the molecular signature of AKT and YAP during CCA progression. than 5%, significantly lower than many other cancers. The incidence
Our studies identified novel targets for YAP and discovered activated of ICC has risen steadily, yet effective treatments remain scarce.
YAP as the major regulator of the suppressive tumor immune- Understanding the ICC immune landscape while preserving the tumor
microenvironment in iCCA, supporting the combined targeting of YAP microenvironment (TME) architecture could reveal potential targets for
with immune checkpoint inhibitor for iCCA treatment. innovative therapies to improve patient outcomes.
Method: An imaging mass cytometry (IMC) panel was designed to
AA0020 analyze 36 biomarkers across 36 tissue regions from 12 each ICC
Targeting glutamine metabolism is a potential strategy for patients, including tumor tissue, adjacent tumor and non-tumor tissue,
cholangiocarcinoma treatment and normal tissue. This approach produced single-cell resolution
histology images, enabling cell-type clustering and assessment of
Kullanat Khawkhiaw1,2,3, Padcharee Yuengchantuek1,2,3, Kanyarat
spatial distribution and functional changes with subsequent in vivo and
Thithuan1,2,3, Ching Wen Chang4, Ching Feng Chiu4, Seiji Okada5,
in vitro experiments.
Sopit Wongkham1,2, Charupong Saengboonmee1,2,3
Result: A comprehensive analysis of the ICC immune
1
Department of Biochemistry, Faculty of Medicine, Khon Kaen microenvironment was performed. In the tumor region, immune cell
University, Khon Kaen 40002, Thailand, 2Center for Translational numbers decreased, while an unusual significant positive interaction
Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen
between M1-phenotype macrophages and tumor cells were observed.
40002, Thailand, 3Cholangiocarcinoma Research Institute, Khon
At the tumor margin, an accumulation of M2 macrophages, CD4+ T
Kaen University, Khon Kaen 40002, Thailand, 4Graduate Institute
cells, CD8+ T cells, Treg cells, and neutrophils was identified. M2
of Metabolism and Obesity Sciences, College of Nutrition, Taipei
macrophages showed positive correlations with Kupffer cells and
Medical University, Taipei, 5Division of Hematopoiesis, Joint Research
Center for Human Retrovirus Infection, Kumamoto University, negative correlations with fibroblasts and endothelial cells, while
Kumamoto, Japan neutrophils exhibited significant positive correlations with Treg cells.
To further investigate, macrophages were re-clustered into seven
Background: Metabolic reprogramming is one of the cancer hallmarks subsets (C1–C7). Among M1 macrophages, only the FSTL1-negative
needed for cancer progression. Despite the glucose dependency, Mac C6 subset demonstrated a positive correlation with tumor cells,
cancer cells also need glutamine to provide the building blocks suggesting its role in altering the tumor microenvironment, while Mac
and precursors for their rapid proliferation. This study then aims to C1 and Mac C2 subsets were negatively correlated. Additionally, 8
investigate the roles of glutamine metabolism in the progression of cellular neighborhoods were defined, including an immune “barrier
cholangiocarcinoma (CCA) and examine whether targeting glutamine zone” at the tumor margin, primarily composed of neutrophils and
metabolism is a promising strategy for CCA treatment. Treg cells, which restricted the infiltration of tumor-killing immune cells.
The Mac C6 subset was closely associated with this immune barrier. AA0023
Functional validation using macrophage with characteristic proteins of Diagnostic Performance of Tumor Markers DCP and AFP in
the Mac C6 confirmed these findings through co-culture with tumor Patients With Hepatocellular Carcinoma and High-Risk Individuals
cells and immune cells. in Mongolia
Conclusion: Our study reveals for the first time a distinct immune
Barkhas Batkhuu1,2, Munguntsetseg Batkhuu2,1, Nomuunaa
landscape in ICC, highlighting the role of Mac C6 macrophage subset
Bayarbat2,1, Ganbolor Jargalsaikhan2, Oyungerel Lkhagva-Ochir2,
in immune regulation, promoting immune evasion and immune barrier.
Tuvshinjargal Ulziibadrakh2, Khandmaa Narantsetseg2, Purevjargal
Targeting Mac C6 or disrupting the immune barrier may enhance anti-
Bat-Ulzii2, Zolzaya Doljoo2, Bekhbold Dashtseren2, Baigal Narantuya2,
tumor immunity, offering new therapeutic strategies for ICC.
Erdenechuluun Sainbayar2, Sharawdorj Gur2, Uurtsaikh Baatarsuren1,
Table and Figure:Figure 1.Graphical Abstract
Enkhtuvshin Khorolgarav1, Sumiya Byambabaatar2, Byambasuren
Ochirsum2, Enkhnomin Ochirbat2, Orkhonselenge Davaadamdin1,
AA0022 Badamsuren Mend-Amar2, Munkhzaya Munkhbaatar2, Anujin
Coordination of Solute Carrier Family 39 Member 1 and Dynamin- Batkholboo2, Tuvshinzaya Purevdorj2, Enkhjargal Tsogtoo2, Altankhuu
related Protein 1 Facilitates Hepatocellular Carcinoma Recurrence Murdorj2, Dahgwahdorj Yagaanbuyant1, Naranbaatar Dashdorj2,
by Impairing Mitochondrial Quality Control Naranjargal Dashdorj2
RUI LI1, ZHE WANG1, LI XIN CHENG2, ZHI QIANG CHENG3, QIONG
1
Onom Foundation, 2The Liver Center
WU4, FENG JUAN CHEN5, QING XIAN CAI3, Yijin Wang1 Background: Hepatocellular carcinoma (HCC) is a leading
1
Southern University of Science and Technology, 2the First Affiliated cause of cancer-related deaths in Mongolia, with 72.2% of cases
Hospital of Southern University of Science and Technology, 3The diagnosed at advanced stages in 2022. Early detection is vital, but
Second Affiliated Hospital of Southern University of Science and the effectiveness of tumor markers like Alpha-fetoprotein (AFP) and
Technology, 4North Sichuan Medical College, 5The Eighth Affiliated Des-γ-carboxyprothrombin (DCP) in high-risk populations, particularly
Hospital of the Guangzhou Medical University those with hepatitis delta virus (HDV) infection, is not well understood.
Background: Despite rapid advances in HCC therapy, surgical This study evaluates the diagnostic performance of AFP and DCP in
resection is still one of the most effective treatment. However, detecting HCC in these high-risk individuals.
postoperative relapse develop in a large population and the mechanism Method: Data from 1,100 subjects (male n=517; female n=544) enrolled
remains to be explored. in the DETECT-HCC study between September 2023 and December
Method: HCC resection samples were retrospectively collected from 2024 were analyzed. HCC was diagnosed by gadoxetate disodium
12 non-relapsed and 15 relapsed HCC patients for RNA sequencing. contrast-enhanced MRI using LI-RADS classification. Hepatitis
Liver-specific SLC39A1 knockout mice were generated by crossing infection status and serum levels of DCP and AFP were measured
Alb-Cre mice and SLC39A1flox/flox mice. Liver samples from mice using a HISCL5000 analyzer, and cirrhosis was assessed using
were analyzed for inflammation, fibrosis and proliferation. Mitochondrial Fibrocan (Echosens) and CTP scores. Participants were divided into
dynamics, autophagy, ROS and mitochondrial membrane potential 4 cohorts: confirmed HCC (n=421), liver cirrhosis (n=175), chronic
(MMP), were detected. Co-immunoprecipitation and molecular hepatitis (n=268), and healthy controls (n=197). Diagnostic accuracy
docking were used to identify protein interactions. was evaluated using receiver operating characteristic (ROC) curves,
Result: SLC39A1, a Zn2+ transporter, is highly expressed in with sensitivity (Sens.) and specificity (Spec.) calculated for AFP and
relapsed HCC patients and negatively correlated with overall survival. DCP.
Knockdown of SLC39A1 inhibited cell proliferation by arresting cell Result: For the HCC group compared to the non-HCC group (all
cycle and promoted cell apoptosis, accompanied by suppressing cohorts), the optimal AFP threshold was 5.8 ng/ml (Spec. 81.2%, Sens.
autophagic flux. Zn2+ deficiency suppressed cell proliferation and 73.1%) and DCP was 44.5 mAU/ml (Spec. 87.3%, Sens. 86%). The
migration, however, knockdown of SLC39A1 elevated cellular Zn2+ AUCs for AFP and DCP were 0.84 and 0.925, respectively (p<0.001).
levels, suggesting alteration of Zn2+ is not a primary mechanism of Using these thresholds, elevated DCP was observed in 4.56% of
SLC39A1 mediated cell proliferation. We and others demonstrated healthy controls, 4.47% with chronic hepatitis, 34.28% with cirrhosis,
that SLC39A1 interacts with a member of the dynamin superfamily of and 85.98% with HCC. Elevated AFP levels were found in 3.04%,
GTPases dynamin-related protein 1 (DRP1), followed by facilitating 15.67%, 70.85%, and 81.23%, respectively.
mitochondrial fission and MMP reduction. Further, we found genetic For the HCC group compared to the risk group (cirrhosis and chronic
or pharmacological inhibition of DRP1 potently abolished SLC39A1- hepatitis), AFP had a threshold of 8.0 ng/ml (Spec. 71.6%, Sens.
induced mitochondrial division and MMP depolarization, while 74.6%) and DCP was 49.5 mAU/ml (Spec. 86%, Sens. 83.8%). The
overexpression DRP1 partially reversed SLC39A1 silence induced AUCs for AFP and DCP were 0.798 and 0.915, respectively (p<0.001).
mitochondrial fusion and MMP hyperpolarization, accompanied by For early-stage HCC (T-stage 1,2), AFP was 5.8 ng/ml (Spec. 62.6%,
recuperative cell proliferation. Liver specific SLC39A1 knockout mice Sens. 72.8%) and DCP was 36.5 mAU/ml (Spec. 77.2%, Sens. 82.1%).
displayed fewer tumor number and less liver damage compared with The AUCs for AFP and DCP were 0.728 and 0.847, respectively
wide type mice, evidenced by reduced liver damage, hepatocyte (p<0.001). In cirrhotic HCC, AFP was 69.0 ng/ml (Spec. 48.4%, Sens.
proliferation (Ki-67), inflammation (TGF-β), and fibrosis (Masson), 86.1%) and DCP was 72.5 mAU/ml (Spec. 80.1%, Sens. 79.8%). AUCs
accompanied by increased ROS accumulation and decreased for AFP and DCP were 0.724 and 0.872, respectively (p<0.001).
LC3 and BNIP3. Targeting SLC39A1 by specific peptide efficiently When comparing the HCC and risk group by etiology, DCP
prevented HCC progression, evidenced by reduced hepatocyte demonstrated superior performance across all groups (HBV, HCV,
proliferation (Ki-67), inflammation (TGF-β), accompanied by increased HBV/HDV, Non-viral), with statistical significance in the HCV and HBV/
caspase-3 level and decreased LC3 and BNIP3. HDV groups.
Conclusion: SLC39A1 was significantly upregulated in HCC relapsed Conclusion: AFP and DCP are reliable biomarkers for detecting HCC
patients. SLC39A1 interacted with DRP1 to impair mitochondrial quality in high-risk populations in Mongolia. DCP showed superior diagnostic
control, thereby promoting cell proliferation and inhibiting apoptosis. performance, particularly in individuals with liver cirrhosis and chronic
Targeting SLC39A1 may open an avenue for intervention of HCC hepatitis. These findings highlight the need for further validation
recurrence. to refine screening protocols for early HCC detection in high-risk
Table and Figure:Figure 1.Graphical abstract: Schematic depiction populations.
of the coordination mechanism of SLC39A1 and DRP1 to facilitate Table and Figure:Figure 1.Image 1: Diagnostic performance of AFP and
hepatocellular carcinogenesis by impairing mitochondrial quality DCP across different groups using Receiver Operating Characteristic
control. (ROC) analysis
Figure 2.Coordination of SLC39A1 and DRP1 contributes to MMP Figure 2.Table 1: Diagnostic performance of AFP and DCP in Different
reduction and mitochondrial fragmentation. Hepatitis Groups
 AA0024 in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn
University, Bangkok, Thailand.
Improved glycemic control over time in patients with type 2
diabetes mellitus (T2DM), with and without cirrhosis: a territory- Background: We conducted a systematic review and meta-analysis to
wide cohort study in Hong Kong SAR of China from 2000-2023 comprehensively evaluate the factors influencing the heterogeneous
Mary Yue Wang1,2, Sherlot Juan Song1,2, Grace Wong1,2, Vincent HBsAg seroclearance rates among patients who stopped nucleos(t)
Wong1,2, Terry Yip1,2 ide analogues (NAs) after long-term therapy. Our goal is to provide
1
Medical Data Analytic Center, Department of Medicine and evidence for designing future clinical trials aimed at achieving high
Therapeutics, The Chinese University of Hong Kong, Hong Kong, HBsAg seroclearance rates across different populations.
China, 2State Key Laboratory of Digestive Disease, Institute of Method: We conducted a comprehensive literature search in databases
Digestive Disease, The Chinese University of Hong Kong, Hong from inception to July 2024. This systematic review and meta-analysis
Kong, China followed the Preferred Reporting Items for Systematic Review and
Meta-analysis (PRISMA) guidelines. Two investigators (STM and PD)
Background: We aimed to compare the secular trends of glycemic
independently extracted data using a predefined template within the
control in patients with T2DM and no cirrhosis, compensated cirrhosis,
COVIDENCE software. Subgroup analyses and meta-regression were
or decompensated cirrhosis, and to determine factors associated with
performed to determine factors associated with HBsAg seroclearance,
the trends.
including ethnicity, HBV genotype, NA therapy duration, end-of-
Method: We identified adult patients aged ≥18 years at the time of
treatment (EOT) qHBsAg levels, HBeAg status, cirrhosis status, and
T2DM diagnosis retrospectively in a territory-wide registry in Hong
follow-up duration. We assessed the credibility of observed subgroup
Kong and excluded those with type 1 diabetes. Cirrhosis was defined
effects using the Instrument to assess the Credibility of Effect
by diagnosis/procedure codes, Fibrosis-4 index >3.25 or aspartate
Modification Analyses (ICEMAN) criteria. Additionally, we used Egger’s
aminotransferase-to-platelet ratio index >2, and cirrhosis-related
test and funnel plot asymmetry to assess potential publication bias.
death. Patients with cirrhosis were further categorized as compensated
Result: We included 73 studies, consisting of 6 RCTs, 39 prospective
and decompensated cirrhosis group based on the presence of
observational cohort studies, and 28 retrospective cohort studies,
hepatic decompensating events by diagnosis/procedure codes. Serial
involving 14,169 CHB patients who stopped long-term NA therapy. The
laboratory measurements in each period were summarized by time-
pooled cumulative HBsAg seroclearance rate over the follow-up period
weighted average. The percentage of patients who achieved time-
was 10% (95%CI: 8–12%, I²=92%). Of the included studies, 20 studies
weighted average hemoglobin A1c (HbA1c) <7% was compared in
including 2,388 patients, provided data on HBsAg seroconversion,
five consecutive periods (2000-2004, 2005-2009, 2010-2014, 2015-
with a pooled seroconversion rate of 6% (95%CI: 3–10%, I²=80%).
2019, and 2020-2023). Mixed effects logistic regression was used to
Caucasians had significantly higher seroclearance rates compared to
quantify the period effect on achieving HbA1c <7%.
Asians (16% vs. 8%, p=0.004). Patients with EOT qHBsAg ≤ 2.0 log
Result: Of 1,206,233 patients with T2DM from 2000-2023 (mean
IU/mL had a higher seroclearance rate than those with levels >2.0 log
age 63.1 years, 52.0% males), 63,200 (5.2%) had cirrhosis, among
IU/mL (24% vs. 8%, p=0.028). Among those with EOT qHBsAg ≤100
whom 17,992 (28.5%) patients had decompensated cirrhosis. The
IU/mL, Caucasians showed higher rates than Asians (73% vs. 33%,
proportion of patients achieving HbA1c <7% increased over time
p=0.001). Studies with >5 years of follow-up reported the highest rate
regardless of cirrhosis. Patients with compensated cirrhosis had the
(18%, 95%CI: 11–26%, I²=88%), while studies with <1 year had the
best glycemic control with HbA1c <7% (from 2000-2004 to 2020-2023,
lowest rate (6%, 95%CI: 2–11%, I²=90%). Meta-regression identified
49.7% to 77.7% in compensated cirrhotic group vs 50.3% to 68.9%
ethnicity, NA therapy duration, and follow-up duration as key factors
in decompensated cirrhotic group vs 40.1% to 66.6% in non-cirrhotic
for HBsAg seroclearance, while study design, HBeAg status, cirrhosis
group, p<0.001) (Figure 1). The probability of achieving glycemic
status, and NA type had no significant effect.
targets increased over time in all 3 groups (2020-2023 vs. 2000-2004,
Conclusion: Our meta-analysis highlights the role of ethnicity,
non-cirrhotic group: OR = 2.47, 95% CI = 2.44–2.51; compensated
EOT qHBsAg levels, NA therapy duration, and follow-up duration
cirrhotic group: OR = 3.56, 95% CI = 3.27–3.87; decompensated
in determining HBsAg seroclearance rates. These findings stress
cirrhotic group: OR = 2.24, 95% CI = 1.96–2.56, for all comparisons
the need for personalized NA discontinuation strategies and further
between the 2 periods). This improving trend remained robust after
research on HBV genotypes and biomarkers to improve treatment
adjustment for age, gender, comorbidities, etiologies of liver disease,
outcomes, predict seroclearance more accurately and to refine
use of antidiabetic medications and other relevant medications (Table
treatment guidelines.
1).
Table and Figure:Figure 1.Table 1
Conclusion: From 2000 to 2023, patients with T2DM in Hong Kong
Figure 2.Tables 2 and 3
showed improving HbA1c control irrespective of their cirrhosis status,
suggesting a positive shift in glycemic management across different
cirrhosis conditions. This result remains robust after adjustment AA0026
for potential confounding factors. Further exploration is needed to CLINICAL EFFICACY AND SAFETY OF LONG-TERM TREATMENT
elucidate the significance of sustained glycemic control in improving OF TENOFOVIR ALAFENAMIDE VS. TENOFOVIR DISOPROXIL
hepatic and extrahepatic outcomes, as well as to determine the optimal FUMARATE FOR CHRONIC HEPATITIS B IN VIETNAM
glycemic target in population with both T2DM and cirrhosis. Thong Duy Vo1,2, Thao HP Nguyen2
Table and Figure:Figure 1.Figure 1 1
University Medical Center Ho Chi Minh City, Vietnam, 2University of
Figure 2.Table 1 Medicine and Pharmacy at Ho Chi Minh City, Vietnam
Background: Hepatitis B virus (HBV) infection is a contagious condition
AA0025 posing a major public health risk in various nations including Vietnam.
Hepatitis B surface Antigen Seroclearance Rate after Stopping In 2019, the Ministry of Health introduced tenofovir alafenamide (TAF)
Nucleos(t)ide Analogues in Chronic Hepatitis B – A Systematic to treat patients with chronic HBV infection and reduce the long-
Review and Meta-Analysis term toxicity of tenofovir disoproxil fumarate (TDF). This study aimed
Soe Thiha Maung1,2, Pakanat Decharatanachart 1,3, Roongruedee to assess the effectiveness and safety of these two medications in
Chaiteerakij1,4 individuals with HBeAg-positive chronic HBV.
1
Division of Gastroenterology, Department of Medicine, Faculty Method: This retrospective cohort study included data collected
of Medicine, Chulalongkorn University and King Chulalongkorn from the medical records of patients with chronic HBV who visited the
Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand., Liver Clinic at University Medical Center HCMC between 2018 and
2
Ma Har Myaing Hospital, Yangon, Myanmar, 3Division of Academic 2020.
Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Result: After two years of treatment, the proportion of HBeAg loss in
Thailand., 4Center of Excellence for Innovation and Endoscopy the TAF group was twice that of the TDF group (22.4% vs. 11.2%),
indicating a statistically significant difference in the probability of different CLDs.
HBeAg loss (adjusted hazard ratio = 2.22; 95% CI 1.43 to 3.42; p < Method: This study was based on 5 datasets including one from a
0.01). Additionally, there was a statistically significant difference in the randomised controlled trial [China REALM trial with chronic hepatitis
rate and ability of antiviral response between patients treated with TAF B (CHB) patients], three prospective cohorts [Search-B CHB cohort,
and TDF (65% vs. 54.5%, respectively; adjusted hazard ratio = 1.34; UK biobank CLD cohort, Wenzhou metabolic dysfunction-associated
95% CI 1.08 to 1.69; p < 0.01). 93.9% of patients achieved the goal of fatty liver disease (MAFLD) cohort], and a territory-wide retrospective
restoring ALT to normal, a higher percentage compared to the 81.2% cohort (Hong Kong CDARS CLD cohort). The derivation cohort
in the TDF group, and the likelihood of achieving normal ALT levels with (Search-B CHB cohort) was used for model training, hyperparameter
TAF was greater compared to those on TDF (adjusted hazard ratio = tuning, and internal cross-validation. Other four cohorts were used
1.67; 95% CI 1.38 to 2.01; p < 0.01). Moreover, there was a statistically for external validation. Twenty machine learning algorithms were
significant difference in the variation in renal function between the TAF tested, including 10 binary classifiers for predicting the occurrence
and TDF groups. Serum creatinine levels in the TAF group increased of LREs in 5 years, and 10 survival algorithms for predicting time-to-
less than those in the TDF group by 0.03 mg/dL every 6 months (95% LREs in 5 years. An exhaustive ten-fold cross-validation, grid search
CI -0.04 to -0.01, p < 0.01), and the eGFR in the TAF group was higher was used to optimise hyperparameters for different algorithms. The
than that in the TDF group every 6 months by 2.78 mL/min/1.73 m² Harrell’s c-index and time-dependent area under receiver operating
(95% CI 0.98 to 4.57, p < 0.01). However, there was no statistically characteristic curve (AUROC) were used for the assessment of the
significant difference in the likelihood of HBeAg seroconversion discrimination of different algorithms.
between chronic hepatitis B patients treated with TAF or TDF (adjusted Result: A total of 268,251 patients with CLD (85,371 chronic viral
hazard ratio = 1.79; 95% CI 0.91 to 3.53; p = 0.09), nor in the risk hepatitis, 179,291 MAFLD, 563 alcohol-related liver disease, 3,026
of adverse events between the two groups (adjusted odds ratio = other chronic liver disease) were included in the final analysis and 5,659
1.34; 95% CI 0.88 to 2.05; p = 0.17). Additionally, although the HBsAg patients developed LREs. Seven features including age (years), sex,
concentration in the TAF group was lower than in the TDF group by an albumin (g/L), total bilirubin (μmol/L), platelet (×109/L), ALT (IU/L), and
average of 0.05 log10 IU/mL every 6 months (95% CI -0.15 to 0.05), creatinine (μmol/L) were selected by the machine learning algorithms.
this difference also did not reach statistical significance (p = 0.35). The best-performing algorithm with the highest c-index and AUROC for
Conclusion: TAF has been demonstrated to achieve some therapeutic 5-year LREs in the derivation cohort was Gradient Boosting Machine
efficacy goals and reduce nephrotoxicity better than TDF. However, no (GBM) (Figure 1). Survival SHAP analyses illustrated the importance
differences were found in seroconversion or adverse events between of the 7 features on the prediction of LREs (Figure 2). The top three
the patient groups. most significant features were platelets, age, and albumin. In validation
Table and Figure:Figure 1.Figure 1. Viral suppression and ALT cohorts, the c-index of GBM risk score was 0.84 in the China REALM
normalization by visit month. (A) shows the cumulative probability of trial CHB cohort, 0.80 in Hong Kong CLD cohort, 0.69 in Wenzhou
patients with HBV DNA < 29 IU/mL. (B) shows the cumulative probability MASLD cohort and 0.64 in UK biobank CLD cohort.
of patients with ALT normalization. TAF, tenofovir alafenamide; TDF, Conclusion: The score has good overall accuracy in predicting liver-
tenofovir disoproxil fumarate; ALT, alanine aminotransferase; HBV, related events in CLD patients.
hepatitis B virus. Table and Figure:Figure 1.Figure 1. The performance of different
Figure 2.Figure 2. HBeAg loss and seroconversion by visit month. (A) algorithms in the evaluation cohort by 5-year AUROC of LREs and
shows the cumulative probability of patients with HBeAg loss. (B) shows c-index. LREs, liver related events; AUROC, area under the receiver
the cumulative probability of patients with seroconversion to anti-HBe. operating characteristic curve; CatBoost, Categorical Boosting;
TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; HBeAg, RF, Random Forest; plsRcox, Partial Least Squares Regression for
hepatitis B e antigen; anti-HBe, anti hepatitis B e. Cox Models; XGBoost, eXtreme Gradient Boosting; RSF, Random
Survival Forest; Lasso, Lasso Regression; ENet, Efficient Neural
Network; CoxBoost, Cox Model with Likelihood-based Boosting;
AA0027
NB, Naive Bayes; StepCox, Step Cox Regression Model; Ridge,
A novel machine learning model to predict liver-related events Ridge Regression; GBM, Gradient Boosting Machine; LR, Logistic
(LREs) in patients with chronic liver disease (CLD) Regression; GNB, Gaussian Naive Bayes; CNB, Complement Naive
Guanlin LI1,2, Terry CF Yip3,4,5, Rong Fan1,2, Grace LH Wong3,4,5, Bayes; kNN, k-Nearest Neighbor; superPC, Supervised Principal
Minghua Zheng6,7, Vincent WS Wong3,4,5, Jinlin Hou1,2,5 Component; AdaBoost, Adaptive Boosting; SVM, Support Vector
1
Department of Infectious Diseases, Nanfang Hospital, Southern Machines; survivalSVM, Survival Support Vector Analysis.
Medical University, Guangzhou, China., 2State Key Laboratory of Figure 2.Figure 2. Time-dependent SHapley framework for features
Organ Failure Research; Key Laboratory of Infectious Diseases in GBM risk score. Cr, creatine; PLT, platelet; Tbil, total bilirubin; Alb,
Research in South China, Ministry of Education; Guangdong albumin; ALT, alanine transaminase;
Provincial Key Laboratory of Viral Hepatitis Research; Guangdong
Provincial Clinical Research Center for Viral Hepatitis; Guangdong
Institute of Hepatology, Guangzhou, China., 3Medical Data Analytics AA0028
Center, Department of Medicine and Therapeutics, The Chinese PD-1 is required for the early expansion of HBV-specific CD8+
University of Hong Kong, Hong Kong SAR, 4State Key Laboratory T cells and does not suppress their effector function during the
of Digestive Disease, Institute of Digestive Disease, The Chinese acute phase of HBV infection.
University of Hong Kong, Hong Kong SAR, 5Department of Medicine Xiaoqing Zeng1, Wen Pan1, Mengxiao Zhao1, Liwei Chen1, Ziwei
and Therapeutics, Faculty of Medicine, The Chinese University of Li1, Hongming Huang1, Xuecheng Yang1, Mengji Lu2, Ulf Dittmer2,
Hong Kong, Hong Kong SAR, 6MAFLD Research Center, Department Gennadiy Zelinskyy2, Xin Zheng1, Dongliang Yang1, Jia Liu1
of Hepatology, The First Affiliated Hospital of Wenzhou Medical 1
Department of Infectious Diseases, Union Hospital, Tongji Medical
University, Wenzhou, Zhejiang, China, 7Institute of Hepatology,
College, Huazhong University of Science and Technology, Wuhan
Wenzhou Medical University, Wenzhou, Zhejiang, China.
430022, China, 2Institute for Virology, University Hospital of Essen,
Background: Predicting the risk of disease progression in patients University of Duisburg-Essen, Essen 45147, Germany
with different CLDs is important to inform clinical management. Existing
Background: PD-1 is one of the key inhibitory receptors regulating
non-invasive tools for identifying patients with CLD at risk for developing
CD8+ T cell exhaustion during chronic viral infection. However, the role
LREs including hepatic decompensation, hepatocellular carcinoma,
of PD-1 in modulating effector T cell differentiation and function during
and liver-related death have limited accuracy. Several studies applied
acute HBV infection is not well defined.To address these questions, we
machine learning approaches to predict LREs, but they were confined
examined the impact of genetic depletion of PD-1 from HBV-specific
by small sample size, restriction to a specific CLD, and thus limited
CD8+ T cells on their differentiation and function in acute self-resolving
generalisability. This study aimed to develop and validate a machine
and persistent HBV replication mouse models.
learning model to predict LREs in Asian and European patients with
Method: Wild type (WT) or PD-1 knockout (KO) HBcAg-specific TCR
transgenic (C93-TCRtg) CD8+ T cells were transferred to naïve mice, stemness and drug resistance of HCC, which provides a strong
and the mice were then challenged with HBV, resulting in either self- theoretical basis for development of specific and efficient treatment of
resolving or persistent replication. HBV-infected HCCs.
Result: In the acute self-resolving HBV replication model, the early Table and Figure:Figure 1.Figure 1. Correlation of CSCs markers and
expansion of transferred PD-1 KO C93-TCRtg CD8+ T cells was HBV related markers.
significantly compromised compared to WT C93-TCRtg CD8+ T cells Figure 2.Figure 2. HBV replication affects stemness of HCCs in
after HBV exposure. PD-1 KO C93-TCRtg CD8+ T cells also showed HepG2.2.15 cells.
significantly decreased granzyme B expression compared to WT C93-
TCRtg CD8+ T cells. However, the ability to produce effector cytokines
AA0030
was unaffected in C93-TCRtg CD8+ T cells by PD-1 genetic depletion.
The absence of PD-1 also led to significant decreases in Tox, T-bet, Effect of Switching from Prior Nucleos(t)ide Analogue(s) to
and Eomes expression in C93-TCRtg CD8+ T cells in the liver at a late Tenofovir Alafenamide on Lipid Profile and Cardiovascular Risk in
stage during acute self-resolving HBV replication. In HBV persistent Patients with Chronic Hepatitis B
mice, the absence of PD-1 expression on C93-TCRtg CD8+ T cells Witchayaporn Praguylertluck 1, Apichat Kaewdech1, Naichaya
was insufficient to prevent the clone depletion of these cells but, in Chamroonkul1, Pimsiri Sripongpun1
contrast, led to significantly compromised early expansion of the cells. 1
Division of Internal Medicine, Faculty of Medicine, Prince of Songkla
Conclusion: Taken together, our data suggest that PD-1 is required University
for the early expansion of HBV-specific CD8+ T cells and does Background: Tenofovir alafenamide (TAF) is recommended as the 1st
not suppress their effector function during the acute phase of HBV line treatment of chronic hepatitis B (CHB). However, increased LDL-c
infection. Additionally, HBV-specific CD8+ T cell exhaustion and clone in those who were switched from Tenofovir disoproxil fumarate (TDF)
depletion can occur in the absence of PD-1. to TAF was observed. Whereas data regarding switching from other
antiviral agents to TAF are limited. We investigated how switching to
AA0029 TAF affected lipid and cardiovascular outcomes in CHB patients.
Method: We conducted a prospective observational study including
HBV replication facilitates drug resistance of hepatocellular
CHB patients who had to switch from their prior NUC to TAF according
carcinoma via CD133 regulating self-renewal of liver cancer stem
to the national reimbursement policy in late 2022. All enrolled patients
cells
had lipid tests and transient elastography (TE) done at 0 and 48-week
Kuanhui Xiang1, Xiangshu Jin1, Huijun Dong1, Yiwei Xiao1, Jie Li1, post-switch to TAF. Demographic data, prior NUC, liver biochemistry,
Tong Li1, Hui Zhuang1 controlled attenuated parameter (CAP) and liver stiffness (elastic
1
Department of Microbiology and Infectious Disease Center, School modulus; E) data measured by TE were collected. The changes in
of Basic Medical Sciences, Peking University Health Science Center, lipid, Thai cardiovascular (CV) risk score, and TE results between 0
Beijing, China and 48-week were compared.
Background: The presence of hepatic cancer stem cells (CSCs) plays Result: A total of 110 patients who were switched to TAF and
a crucial role in chemotherapy resistance and the recurrence of cancer completed 48-week follow-up were analyzed. The prior NUCs were
after treatment or surgery. However, the relationship between hepatitis as follows: 47 Lamivudine (LAM), 2 Entecavir (ETV), and 41 TDF-
B virus (HBV) replication and the stemness of hepatocellular carcinoma based. Baseline characteristics were similar between the three groups
(HCC) in HBV-related HCC patients remains poorly understood. In except for underlying hypertension was more frequent and baseline
this study, we aimed to investigate the impact of HBV infection on the total cholesterol were lower in the TDF-based group. At 48-week post-
stemness of HCCs, which is closely linked to drug resistance. switch, the median LDL-c changes (Figure 1) were -2.45, -5.9 and +8.8
Method: We collected tumor tissues (T), matched adjacent non-tumor mg/dL (p<0.001), and total cholesterol changes (Figure 2) were -4.5,
tissues (NT) and distal non-tumor tissues (FNT) from 55 HCC patients -4 and +17 mg/dL (p<0.001), in the ETV, LAM, and TDF-based group,
for analysis. To isolate and confirm CSCs, we performed sphere respectively. Whereas the changes in hepatic steatosis (measured by
formation assays and RT-qPCR. The IC50 values of sorafenib and CAP), and liver stiffness (measured by E) as well as Thai CV risk score
regorafenib were calculated and compared using the CCK-8 assay. were not significantly different. No cardiovascular events occurred
HBV infection was employed to assess the impact of HBV replication during follow-up.
on liver CSCs markers. Co-immunoprecipitation (CoIP) assays were Conclusion: Significant increase in LDL-c and total cholesterol after
conducted to investigate the interaction between CD133 and SRC. switching to TAF were observed only in patients with prior TDF, but
Additionally, the CRISPR-Cas9 system was used to knockout CD133 not in those with prior ETV or LAM. Careful monitoring of lipids after
expression in HepG2.2.15 cells. the switch may not universally needed. Data regarding long-term
Result: We found that HBV DNA levels were higher in T samples cardiovascular outcomes are warrant.
compared to NT and FNT samples. However, HBV pgRNA and total Table and Figure:Figure 1.Violin plot of the change in LDL level at 48
RNA expression were lower in T samples. In HBsAg-positive patients, weeks post switch
HBV pgRNA and total RNA showed stronger correlations with CSCs Figure 2.Violin plot of the change in Total cholesterol at 48 weeks post
markers in NT samples. The markers of CD133 and OCT4 were more switch
highly expressed in FNT samples, and the HBV replication marker
pgRNA was significantly positively correlated with these markers
AA0031
only in FNT samples. Detection of pgRNA and OCT4 in FNT was
associated with HCC recurrence following resection. Analysis of HBV The association between non‑alcoholic fatty liver disease and
receptor, sodium taurocholate co-transporting polypeptide (NTCP), chronic kidney disease in Egyptian patients
revealed a negative correlation between NTCP and CSCs markers Ahmed Mokhtar Yahia1
in T samples, excepted for the CD44 (Figure 1). In addition, Liver 1
Menoufia faculty of medicine
CSCs showed reduced sensitivity to sorafenib and regorafenib. HBV Background: NAFLD is a spectrum of disorders ranging from hepatic
replication promoted drug resistance and stemness in HCC cells steatosis to nonalcoholic steatohepatitis
(Figure 2). We identified that HBx protein in HepG2 cells up-regulated (NASH), NASH related cirrhosis and hepatocellular carcinoma (HCC).
the expression of CD133, EpCAM and CD24, thereby enhancing There is sparse data on the prevalence
resistance to sorafenib and regorafenib. CRISPR-Cas9 mediated CKD in Egyptian patients with NAFLD. The aim of this study is to
knockout of CD133 expression significantly inhibited drug resistance estimate the prevalence of CKD in the subjects
to both sorafenib and regorafenib in HepG2.2.15 cells. Mechanically, with NAFLD and to assess the risk factors of CKD among them.
HBV replication promotes CD133 expression, which interacted with the Method: A cross-sectional study was conducted on 430 patients from
SRC/STAT3 signaling pathway. the Internal Medicine Department, Menoufia
Conclusion: Our data found that HBV replication promotes the
University Hospitals, including 215 patients with NAFLD, and 215 Japan, 7Division of Endocrinology and Metabolism, Department of
patients without NAFLD. NAFLD was diagnosed Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan,
by abdominal ultrasonography. The liver fibrosis was assessed by 8
Medical Data Analytics Centre, Department of Medicine and
NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB- Therapeutics, The Chinese University of Hong Kong, Hong Kong,
4). CKD was defined as an estimated glomerular filtration rate (eGFR) China, 9State Key Laboratory of Digestive Disease, Institute of
< 60 ml/min/1.73 m2 and/or abnormal albuminuria Digestive Disease, The Chinese University of Hong Kong, Hong
(urinary albumin-to-creatinine ratio ≥ 30 mg/gm). The logistic regression Kong, China, 10Gastroenterology and Hepatology Unit, Department of
analysis was performed to examine Medicine, Faculty of Medicine, University of Malaya, Malaysia;,
the association between NAFLD and risk of CKD.
1
1Department of Endocrinology, First Affiliated Hospital of Wenzhou
Result: The prevalence of CKD was higher in individuals with NAFLD Medical University, Wenzhou, China, 12Liver Research Center, Beijing
Friendship Hospital, Beijing Key Laboratory of Translational Medicine
than in those without NAFLD (38.1% vs 7.4%,
on Liver Cirrhosis, National Clinical Research Center of Digestive
p < 0.001). Logistic regression analysis demonstrated that both NAFLD
Diseases, Capital Medical University, Beijing, China, 13Sezione di
and CKD were risk factors of each other.
Gastroenterologia, PROMISE, University of Palermo, Italy ,
The presence of hypertension, high levels of BMI and waist 1
4Hepatology Unit, Department of Infectious diseases, Nanfang
circumference were the other independent risk factors Hospital, Southern Medical University, Guangzhou, China, 15The First
of NAFLD. While the presence of DM, and the high level of BMI were Affiliated Hospital of Xinjiang Medical University, Urumqi, China,
the other significant risk factors of CKD 1
6Department of Hepatology, Clinical School of the Second People‘s
in the NAFLD group. Hospital, Tianjin Institute of Hepatology, Tianjin Medical University,
Conclusion: This study showed that the prevalence of CKD was Tianjin, China, 17Department of Infectious Disease, Qingdao
higher in individuals with NAFLD than in those without Municipal Hospital, Qingdao University, Qingdao, China,
NAFLD. Both NAFLD and CKD were risk factors 1
8Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine,
for each other. The presence of hypertension, and the Xiamen, China, 19Department of Medical Sciences, Division of
high levels of BMI and waist circumference were the Gastroenterology and Hepatology, A.O. Città della Salute e della
other independent risk factors of NAFLD. While the Scienza di Torino, University of Turin, Turin, Italy, 20Department of
presence of DM, and the high level of BMI were the Medicine, Huddinge, Karolinska Institutet, Sweden, 21Division of
other significant risk factors of CKD in the NAFLD Hepatology, Department of Upper GI Diseases, Karolinska University
group. And the presence and severity of NAFLD were Hospital, Huddinge, Stockholm, Sweden, 22Department of
associated with an increased risk of CKD. Gastroenterology and Hepatology, Hospital Universitario Puerta de
Table and Figure:Figure 1.Bar chart displaying the prevalence of CKD Hierro Majadahonda, Madrid, Spain, 23Department of
between subjects with non-NAFLD and NAFLD stratified by NAFLD Gastroenterology and Hepatology, Singapore General Hospital,
fibrosis score (NFS) Singapore, 24UCM Digestive Diseases. Virgen del Rocío University
Figure 2.Binary logistic regression analysis (inter method) for Hospital. CiberEHD, ISCIII. Institute of Biomedicine of Seville (CSIC/
independent risk factors for CKD in NAFLD cases HUVR/US). Department of University of Seville, Seville, Spain,
2
5Stravitz-Sanyal Institute of Liver Disease and Metabolic Health,
Department of Internal Medicine, VCU School of Medicine, Richmond,
AA0032 VA, USA, 26Department of Gastroenterology, Xinhua Hospital Affiliated
Fibrotic MASH resolutionVCTE index for the non-invasive to Shanghai Jiaotong University School of Medicine, Shanghai Key
diagnosis of fibrotic MASH resolution and prediction of liver- Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China,
related events: A global multicenter study
2
7Université Paris Cité, UMR1149 (CRI), INSERM, Paris, France;
Service d‘Hépatologie, Hôpital Beaujon, Assistance Publique-
Gong Feng1,2, Jerome Boursier3,4, Marc De Saint Loup3,4, Yusuf
Hôpitaux de Paris (AP-HP), Clichy, France, 28Division of
Yilmaz5, Hirokazu Takahashi6,7, Hiroshi Isoda6, Sherlot Juan Song8,9,
Gastroenterology & Hepatology, Beth Israel Deaconess Medical
Wah Kheong Chan10, Wen Yue Liu11, Hong You12, Xiaofei Tong12,
Center, Harvard Medical School, Boston, Massachusetts,
Salvatore Petter13, Grazia Pennisi13, Jinjun Chen14, Ling Zhou14, 2
9Department of Internal Medicine, Institute of Gastroenterology,
Fangping He15, Xiaotang Fan15, Yuqiang MI16, Liang Xu16, Yongning Yonsei University College of Medicine, Seoul, Republic of Korea,
Xin17, Huiqing Liang18, Man MI1, Elisabetta Bugianesi19, Hannes 3
0Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao
Hagström20,21, Jose Luis Calleja22, George Boon Bee Goh23, Rocio Tong University School of Medicine, Shanghai, China, 31Department
Gallego Durán24, Arun J Sanyal25, Jiangao Fan26, Laurent Castéra27, of Gastroenterology, The Fifth Affiliated Hospital, Guangzhou Medical
Michelle Lai28, Manuel Romero-Gomez24, Seung Up Kim29, Feng University, Guangdong, China, 32Department of Infectious Disease,
Ye2, Qing Xie30, Xiaolin Wang30, Chutian Wu31, Huiping Sheng32, General Hospital of Ningxia Medical University, Yinchuan, China,
Jing Wang33, Yongfeng Yang34, Xiaoling Chi35, Huanming Xiao35, 3
3The Affiliated Traditional Chinese Medicine Hospital of Southwest
Jing Zhang36, Bingyuan Wang37, Lang Bai38, Wen Xie39, Bihui Medical University, Luzhou, China, 34Department of Liver Disease, the
Zhong40, Junzhao Ye40, Junping Shi41, Yan Bi42, Jie Li43, Yongfen Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese
Zhu44, Mohamed El-Kassas45,46,47, Mohammed Emadeldeen48, Medicine, Nanjing, China, 35Guangdong Provincial Hospital of
Hong Deng49, S Halimar50, Sandeep Aggarwal51, Zhongtao Zhang52, Traditional Chinese Medicine, The Second Affiliated Hospital of
Mengyi Li52, Rixing Bai53, Jinghai Song54, Stergios Kechagias55,56, Guangzhou University of Traditional Chinese Medicine, Guangzhou,
Yoichi Hiasa57, Teruki Miyake57, Jacob George58, Keshni Sharma58, China, 36Unit Three, Department of Hepatology, Beijing Youan
Khalid Alswat59, Waleed K Al-Hamoudi59, Barham Abu Dayyeh60, Hospital, Capital Medical University, Beijing, China, 37Department of
Fateh Bazerbachi61, Leon A Adams62,63, Sanjaya K Satapathy64, Gastroenterology, the First Affiliated Hospital of China Medical
Bheesham Dayal64, Huapeng Lin8,9, Hye Won Lee65, Terry CheukFung University, Shenyang China, 38Center for Infectious Diseases, West
Yip8,9, Celine Fournier Poizat66, Grace Wong8,9, Angelo Armandi19, China Hospital, Sichuan University, Chengdu, China, 39Center of Liver
Ying Shang20, Elba Llop22, Kevin Teh23,9, Carmen Lara Romero24, Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing,
Amon Asgharpour25, Sara Mahgoub67, Mandy Chan66, Clemence M China, 40Department of Gastroenterology, the First Affiliated Hospital,
Sun Yat-sen University, Guangzhou, China, 41Department of
Canivet3,4, Giovanni Targher68,69, Christopher D Byrne70, Na He71,
Hepatology, Hangzhou Normal University Affiliated Hospital,
Vincent Wong8,9, Ming Hua Zheng72,73
Hangzhou, China, 42Department of Endocrinology, Drum Tower
1
Xi‘an Medical University, Xi‘an, China, 2Department of Infectious Hospital Affiliated to Nanjing University Medical School, Nanjing,
Diseases, The First Affiliated Hospital of Xi‘an Jiaotong University, China, 43Department of Infectious Disease, Drum Tower Hospital
Xi‘an, China, 3HIFIH Laboratory, SFR ICAT 4208, Angers University, Affiliated to Nanjing University Medical School, Nanjing, China,
Angers, France, 4Hepato-Gastroenterology and Digestive Oncology 4
4Department of Hepatology and Infection, Sir Run Run Shaw
Department, Angers University Hospital, Angers, France, 5Department Hospital, Affiliated with School of Medicine, Zhejiang University,
of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan Hangzhou, China, 45Endemic Medicine Department, Faculty of
University, Rize, Turkey, 6Liver Center, Saga University Hospital, Saga, Medicine, Helwan University, Cairo, Egypt, 46Liver Disease Research
Center, College of Medicine, King Saud University, Riyadh, Saudi 95%CI 0.012-0.156). Notably, the fibrotic MASH resolutionVCTE index
Arabia, 47Steatotic Liver Disease Study Foundation in Middle East and achieved an AUROC of 0.86 and 0.87, respectively, for predicting the
North Africa (SLMENA), Cairo, Egypt, 48Gastroenterology and 5-year and 10-year probability of not developing LREs.
Hepatology Department, National Hepatology & Tropical Medicine Conclusion: The fibrotic MASH resolutionVCTE index, developed and
Research Institute (NHTMRI), Cairo, Egypt, 49Department of Infectious validated with the largest sample size to date, is the first non-invasive
Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, tool specifically designed to accurately detect fibrotic MASH resolution
Guangzhou, China, 50Department of Gastroenterology and Human and the long-term risk of LREs.
Nutrition, All India Institute of Medical Sciences, Delhi, India, Table and Figure:Figure 1.Figure 1. Diagnostic performance of the
5
1Department of Surgical Disciplines, All India Institute of Medical fibrotic MASH resolutionVCTE index for the non-invasive identification
Sciences, Delhi, India, 52Department of General Surgery, Beijing of fibrotic MASH resolution in the derivation cohort.
Friendship Hospital, Capital Medical University & National Clinical Figure 2.Figure 2. Cumulative incidence rates of liver-related events
Research Center for Digestive Diseases & State Key Lab of Digestive
(LREs) stratified by the fibrotic MASH resolutionVCTE index and
Health, Beijing, China, 53Department of General Surgery, Beijing
change in liver stiffness measurement (LSM).
TianTan Hospital, Capital Medical University, Beijing, China,
5
4Department of General Surgery, Beijing Hospital, National Center of
Gerontology, Beijing, China, 55Department of Gastroenterology and AA0033
Hepatology, University Hospital, Linköping, Sweden, 56Department of a-ketobutyrate is a metabolite of transsulfuration pathway that
Health, Medicine, and Caring Sciences, Linköping University, activates autophagy and improves glucose tolerance and hepatic
Linköping, Sweden, 57Department of Gastroenterology and
steatosis in MAFLD
Metabology, Ehime University Graduate School of Medicine, Ehime,
Japan, 58Storr Liver Centre, The Westmead Institute for Medical Hepatology Branch of the Chinese Medical Association, Dan Zhang1,
Research, Westmead Hospital, University of Sydney, Sydney, NSW, Da Wang1, Mengwei Li1, Lanqing Ma1
Australia, 59Liver Disease Research Center, Department of Medicine,
1
The First Affiliated Hospital, Yunnan Institute of Digestive Disease,
College of Medicine, King Saud University, Riyadh, Saudi Arabia, Yunnan Clinical Research Center for Digestive Diseases, Kunming
6
0Division of Gastroenterology and Hepatology, Mayo Clinic, Medical University, Kunming 650032, Yunnan, China
Rochester, MN, USA, 61Division of Gastroenterology, Hepatology and Background: Metabolic dysfunction-associated fatty liver disease
Nutrition, University of Minnesota, Minneapolis, MN, USA, 62Medical (MAFLD) has become the most prevalent chronic liver disease, posing
School, The University of Western Australia, Perth, Australia, a significant threat to individuals’ health and well-being. Therapies are
6
3Department of Hepatology, Sir Charles Gairdner Hospital, Perth, limited. Weight loss is of benefit but is difficult to maintain. We aimed
Australia, 64Northwell Health Center for Liver Disease and at examining the effect of the a-ketobutyrate (a-KB), a metabolite of
Transplantation, North Shore University Hospital/Northwell Health, transsulfuration pathway, on autophagy, steatosis, glucose tolerance
Manhasset, NY, USA, 65Department of Internal Medicine, Yonsei and insulin sensitivity.
University College of Medicine, Seoul, Korea, 66Echosens, Paris,
Method: The serum samples of MAFLD patients and healthy people
France, 67National Institute for Health Research, Biomedical Research
was collected. The content of a-KB was detected using high-
Centre at University Hospitals Birmingham NHS Foundation Trust and
performance liquid chromatography, and the correlation between
the University of Birmingham, Birmingham, United Kingdom,
the level of a-KB and clinical parameters associated with MAFLD
6
8Department of Medicine, University of Verona, Verona, Italy,
6
9Metabolic Diseases Research Unit, IRCSS Sacro Cuore - Don was analyzed using Pearson’s method. The MAFLD cell model was
Calabria Hospital, Negrar di Valpolicella, Italy, 70Southampton established by sodium oleate and palmitic acid, and MAFLD animal
National Institute for Health and Care Research Biomedical Research model was induced by high-fat diet. the MAFLD model was interfered
Centre, University Hospital Southampton and University of by exogenous supplementation of a-KB, and corresponding control
Southampton, Southampton General Hospital, Southampton, UK, groups were designed. Glucose tolerance and insulin resistance
7
1Department of Gastroenterology, The First Affiliated Hospital of Xi‘an of mice in each group were detected by IGTT and IITT assays; The
Medical University, Xi‘an, China, 72MAFLD Research Center, degree of hepatic steatosis, fibrosis and inflammation were observed
Department of Hepatology, the First Affiliated Hospital of Wenzhou by histopathological staining; Serum lipid metabolism indexes and
Medical University, Wenzhou, China, 73Key Laboratory of Diagnosis indicators of hepatic injury were detected by biochemical analyzer;
and Treatment for The Development of Chronic Liver Disease in Western blot detected the expression of lipid metabolism genes. The
Zhejiang Province, Wenzhou, Zhejiang, China number of autophagosomes in the liver tissues was assessed using
Background: Fibrotic metabolic dysfunction-associated transmission electron microscopy; the expression levels of autophagy-
steatohepatitis (MASH) presents a challenge due to its risk of liver related proteins in liver tissues and hepatocytes were detected by
disease progression. We aimed to develop and validate the fibrotic Western blot. In order to further investigate the potential mechanism of
MASH resolutionVCTE index, a novel tool for non-invasive identification a-KB in improving MAFLD, transcriptomic analysis revealed that a-KB
of histological fibrotic MASH resolution and predicting liver-related can activate the AMPK signaling pathway and enhance the expression
events (LREs). of SIRT1. Furthermore, the observed effects of a-KB on steatosis and
Method: We collected data from 2,017 individuals, who had two liver autophagy in MAFLD were confirmed by inhibiting the AMPK signaling
biopsies separated in time, across 40 centers in the first dataset. pathway or downregulating SIRT1, thereby elucidating the potential
This dataset included two independent cohorts, which were used to mechanism of a-KB in MAFLD.
develop and externally validate the fibrotic MASH resolutionVCTE index Result: 1. a-KB in the serum of MAFLD patients was significantly lower
(including the baseline and change in acFibroMASH index compared to the control group. Furthermore, a-KBexhibited negative
plus change in serum alanine aminotransferase levels). The second correlations with BMI, WC, CAP, LSM, HOMA-IR, ALT, GGT, and TG;
independent dataset, consisting of 17,949 patients who underwent while showing positive correlations with HOMA-ISI and HDL-C.
vibration-controlled transient elastography (VCTE) at 16 centers, was 2. a-KB could activates autophagy and improves glucose tolerance
used to examine associations between this developed index and the and hepatic steatosis in MAFLD.
risk of incident LREs. 3. a-KB upregulated SIRT1 expression, increased NAD+-
Result: After applying the inclusion and exclusion criteria, 252 mediated SIRT1 activity and upregulated pAMPK expression in
and 8,752 patients were included in the first and second datasets, MAFLD. a-KB activates autophagy and improves glucose tolerance
respectively. The fibrotic MASH resolutionVCTE index accurately and hepatic steatosis through the AMPK-SIRT1 signaling pathways.
identified fibrotic MASH resolution with an AUROC of 0.82 (95%CI Conclusion: In vitro and in vivo studies have confirmed
0.74-0.90) in the derivation cohort and 0.80 (95%CI 0.72-0.88) that a-KB activates autophagy and improves glucose tolerance and
in the validation cohort. Moreover, patients with a fibrotic MASH hepatic steatosis through the AMPK-SIRT1 signaling pathways. a-KB is
resolutionVCTE index >0.61 had a substantially lower risk of incident expected to be a potential drug for MAFLD treatment.
LREs than those with the index <0.24 (adjusted-hazard ratio 0.043,
 AA0034 sensitive analyses were used to determine robustness of our findings.
TNFRSF12a Potentially Represents a Common Mechanism Result: This cross-sectional study analyzed data from 17,195 adults,
Linking Metabolic Dysfunction-Associated Fatty Liver Disease among whom MAFLD was identified in 9,110 participants (53.0%).
(MAFLD) and Heart Failure Weighted logistic regression indicated that dietary intake in the third
tertile, indicative of highest vitamin B1, B2, niacin, B6, folate, B12 and
Fan Du1, Yunfeng Fu1, Xiaodong Zhou1
C levels, was negatively associated with MAFLD risk fully adjusting
1
Department of Gastroenterology, the First Affiliated Hospital, Jiangxi for confounders. RCS analysis showed all dietary water-soluble
Medical College, Nanchang University
vitamins except for B1 intake represented a nonlinear relationship with
Background: MAFLD is a type of fatty liver closely associated with the outcome. In the WQS model, vitamin B12 and folate became the
metabolic disorders, and cardiovascular diseases are important main contributors. Subgroup analysis implicated the protective effect
complications in patients with MAFLD. Recent epidemiological against MAFLD concerning vitamin B12 levels were consistent, while
investigations have found that patients with MAFLD are more prone to higher dietary folate intake was associated with decreased MAFLD
developing heart failure (HF), leading to increased mortality. However, risk in the participants without dyslipidemia. Sensitive analysis further
the specific mechanisms underlying their interaction remain unclear, validated the association between dietary water-soluble vitamins
and further elucidation of the specific pathophysiological reasons is intake and MAFLD.
crucial for guiding the diagnosis and treatment of MAFLD. Conclusion: Our findings suggested that higher dietary water-soluble
Method: In this study, transcriptomic data related to MAFLD and heart vitamins intake was associated with a decreased risk of MAFLD, with
failure from 5 HF datasets and 4 MAFLD datasets in the GEO database the most influential component referring to vitamin B12 and folate.
were analyzed using Weighted Gene Co-expression Network Analysis Future studies are required to refine therapeutic courses and optimal
(WGCNA). Eighteen genes with differential expression in both diseases dosages, taking into account various dose-response relationships.
and closely related to the disease phenotype were identified. The Table and Figure:Figure 1.Table I. Weighted Odds Ratios (95% CI) for
representative gene TNFRSF12A was further analyzed using single- MAFLD according to the tertiles of dietary vitamin intake in NHANES
gene Gene Set Enrichment Analysis (GSEA) to explore its function. from 2003 to 2018.
Mouse models of MAFLD and HF were established, and PCR and WB Figure 2.Figure 1. Restricted cubic spline fitting for the association
were used to verify the expression of TNFRSF12A, investigating its between dietary vitamin intake and MAFLD Figure 2. Weights of WQS
potential connection between MAFLD and HF. index of seven dietary vitamins in MAFLD
Result: Through WGCNA analysis, 18 genes with differential
expression in MAFLD and HF were identified, including CD163,
AA0036
P2RY13, MARCO, LYVE1, FPR1, VSIG4, ANKRD13A, CCR1, HK2,
ABCA9, CD44, SLC43A2, HAAO, RGS7BP, SLC16A9, TNFRSF12A, Unsupervised partitional clustering of hemoglobin A1c (HbA1c)
LTBP4, and CDKN3. Among them, TNFRSF12A showed an increasing level and trajectory stratify the risk of liver-related complications
trend in 5 datasets, suggesting its potential importance. Single-gene in patients with type 2 diabetes (T2D)
GSEA analysis indicated that the CYTOKINE-CYTOKINE RECEPTOR Nana Peng1,2,3, Sherlot Juan Song1,2,3, Mary Yue Wang1,2,3, Jimmy CT
INTERACTION and TNFR2 NON CANONICAL NF-KB PATHWAY Lai1,2,3, Grace LH Wong1,2,3, Vincent WS Wong1,2,3, Terry CF Yip1,2,3
may be important pathways for TNFRSF12A. Animal experiments 1
Medical Data Analytics Centre, 2Department of Medicine and
demonstrated significantly elevated mRNA and protein levels of Therapeutics, 3Institute of Digestive Disease, The Chinese University
TNFRSF12A in the liver and heart of mouse models of MAFLD and HF. of Hong Kong, Hong Kong, China
Conclusion: This study posits that TNFRSF12A may serve as a pivotal Background: The relationship between glycemic control indicated
molecular target in the progression of MAFLD and HF, holding promise by HbA1c levels and trajectories and liver-related complications in
for both diagnostic and therapeutic interventions. patients with T2D remains unclear. We aimed to examine whether
Table and Figure:Figure 1.WGCNA results in HF dataset: A) HbA1c level and early-stage trajectories impact the risk of liver-related
hierarchical clustering tree; B) Heat map showing the correlation of complications, including hepatic decompensation, hepatocellular
different modules with phenotypes; C) the intersection of the module carcinoma, and liver-related death in patients with T2D, and to what
genes and differential genes obtained in the dataset; D) TNFRSF12A extent optimal glycemic control would benefit patients at high risk of
representation in the HF dataset. liver outcomes.
Figure 2.WGCNA results in MAFLD dataset: A) hierarchical clustering Method: A territory-wide retrospective cohort of patients with T2D
tree; B) Heat map showing the correlation of different modules with from 2000-2016 was identified in Hong Kong. Patients with type
phenotypes; C) the intersection of the module genes and differential 1 diabetes, chronic viral hepatitis, excessive alcohol use, or liver-
genes obtained in the dataset; D) TNFRSF12A expressed in the related complications before baseline or follow-up <5 years were
MAFLD dataset. excluded. Unsupervised partitional clustering was applied to identify
trajectories by testing the number of clusters (k) from 1 to 6. Various
AA0035 distance measures with centroid calculation were employed, including
Euclidean distance, dynamic time wrapping (DTW) and move-split-
Association of dietary water-soluble vitamins with MAFLD among
merge (MSM) with arithmetic mean, DTW with DTW barycenter
adults: evidence from NHANES 2003-2018
averaging (DBA), and MSM with MSM barycenter averaging (MBA).
Jia Li1, Jie Zhang1, Chao Sun1
Cluster validity indices were summarized to determine the optimal k
1
Tianjin Medical University General Hospital and the best-performing algorithm. The association between HbA1c
Background: Current evidence concerning interplay between dietary level and trajectories with liver-related complication risk was evaluated
water-soluble vitamins and metabolic dysfunction-associated fatty liver using cause-specific hazards models, with non-liver-related death as
disease (MAFLD) is inconclusive. Moreover, comprehensive research competing risk. Variation of each trajectory stratified by HbA1c level
on their single and combined impact has not been conducted was quantified by linear mixed models.
considering intimately pathophysiological links. This study aimed to Result: Among 240,076 patients (Figure A), MSM-MBA identified
explore the association of vitamin B group/vitamin C dietary intake, 3 robust HbA1c trajectories in the first 5 years after T2D diagnosis:
both singly and jointly, on the advent of MAFLD among adults. mild decreasing (n=103,659[43.2%]), increasing (n=94,738[39.5%])
Method: Data from a cohort study designated as the National Health and rapid decreasing (n=41,679[17.4%]). (Figure B) Patients with
and Nutrition Examination Survey 2003-2018 were analyzed. The baseline HbA1c ≥ 9% had a higher risk (hazard ratio [HR], 1.42 [95%
diagnosis of MAFLD was built according to the US fatty liver index CI, 1.23-1.64]) compared to those with HbA1c ≤ 7%. Compared to
(US-FLI) or fatty liver index (FLI). Weighted logistic regression analysis mild decreasing, patients with rapidly decreasing HbA1c showed a
(linear), weighted quantile sum (WQS) (combined) and restricted lower risk (HR, 0.80 [95% CI, 0.69-0.92]), while those with increasing
cubic spine (RCS) (nonlinear) were applied to investigate the impact of HbA1c had a higher risk (HR, 1.10 [95% CI, 1.01-1.20]). (Table A)
water-soluble vitamins intake levels on MAFLD. Multiple subgroup and Compared to a mild decreasing trajectory with HbA1c ≤ 7%, patients
with HbA1c levels of 7-9% with an increasing trend, or ≥ 9% with either lymphangiocrine secretory proteins like Wnt7a in hepatic LyEC,
a mild decreasing or increasing trend, had higher risks of liver-related that facilitate biliary cell proliferation. Our study highlights a novel
complications (HR, 1.20 [95% CI, 1.03-1.40], 1.44 [95% CI, 1.21-1.71], contribution of hepatic lymphatic vessels and LyECs during liver
and 1.55 [95% CI, 1.16-2.05], respectively), while notably, those with regeneration.
HbA1c ≥ 9% and a rapid decreasing trend did not show increased risk Table and Figure:Figure 1.Increased number of Lymphatics and Bile
(HR, 1.12 [95% CI, 0.97-1.30]). (Figure C and Table B) ducts are observed after PHx and Ischemia/Reperfusion injury
Conclusion: Higher baseline HbA1c levels and increasing trajectory Figure 2.Wnt7a regulates the proliferation of cholangiocytes via binding
are associated with a higher risk of liver-related complications in T2D, to frizzled 7a receptor
while rapid decreasing trajectory is associated with a lower risk. Good
glycemic control over time mitigates the risk associated with higher
AA0039
baseline HbA1c levels.
Table and Figure:Figure 1.Figure. (A) Patient characteristics, study Single cell RNA-sequencing delineates CD8+ tissue resident
design, and definitions of exposures, covariates, and outcomes memory T cells maintaining rejection in liver transplantation
(B) HbA1c trajectories across the first 5 years after T2D diagnosis Xinqiang Li1, Jinzhen Cai1
identified by MSM-MBA. 1
The Affiliated Hospital of Qingdao University
Figure 2.Table. (A) Association between baseline HbA1c level and Background: Understanding the immune mechanisms associated
HbA1c trajectories on the risk of liver-related complications. (B) Slope with liver transplantation (LT), particularly the involvement of tissue-
and 95% CI of trajectories stratified by baseline HbA1c level group. resident memory T cells (TRMs), represents a significant challenge.
Figure. (C) Joint association between baseline HbA1c level and HbA1c Method: This study employs a multi-omics approach to analyse liver
trajectory and liver-related complications risk in patients with T2D. transplant samples from both human (n=17) and mouse (n=16),
utilizing single-cell RNA sequencing, bulk RNA sequencing, and
AA0038 immunological techniques.
Result: Our findings reveal a comprehensive T cell-centric landscape
Wnt7a from Hepatic LyEC facilitates cholangiocyte proliferation
in LT across human and mouse species, involving 235,116 cells.
during liver regeneration
Notably, we found a substantial increase in CD8+ TRMs within
Aarti Sharma1, Pinky Juneja1, DEEPIKA JAKHAR1, Ashwini rejected grafts compared to stable ones. The elevated presence of
Vasudevan1, Archana Rastogi1, Dinesh Mani Tripathi1, Shiv Kumar CD8+ TRMs is characterised by a distinct expression profile, featuring
Sarin1, Savneet Kaur1 upregulation of tissue-residency markers (CD69, CXCR6, CD49A and
1
Institute Of Liver And Biliary Sciences,New Delhi CD103+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic
Background: Background: The angiocrine proteins of liver sinusoidal markers (GZMB and IFNG) and proliferative markers (PCNA and
endothelial cells (LSEC) supporting hepatocyte proliferation during TOP2A) during rejection. Furthermore, there is a high expression of
liver regeneration are well-known. Liver also contains a network of transcription factors such as EOMES and RUNX3. Functional assays
lymphatic capillaries lined by lymphatic endothelial cells (LyEC), which and analyses of cellular communication underscore the active role of
however remain less studied. We characterized LyEC and studied their CD8+ TRMs in interacting with other tissue-resident cells, particularly
proteome during liver regeneration. Kupffer cells, especially during rejection episodes.
Method: Methods: 70% partial hepatectomy (PHx) was developed Conclusion: These insights into the distinctive activation and
as a model of liver regeneration and compared with sham at different interaction patterns of CD8+ TRMs suggest their potential utility as
time points. FACS analysis and imaging of hepatic LyECs was done. biomarkers for graft rejection, paving the way for novel therapeutic
Lymphatic functionality was assessed by FITC dextran. Primary strategies aimed at enhancing graft tolerance and improving overall
LyEC were sorted using CD31+ and podoplanin (PDPN+)CD31+ for transplant outcomes.
proteome analysis at D2 post-PHx. Co-cultures of cholangiocytes- Table and Figure:Figure 1.Single-Cell Atlas of Human Liver
organoids (Chol-org) were done in presence of LyEC-CM (conditioned Transplantation
media). In some studies, lymphangiogenesis was inhibited by ip Figure 2.Identifying CD8+ T Cell Subsets in Human Transplanted Liver
injection of VEGFR-3 inhibitor (MAZ51:10mg/kg) for 3 days along with and Blood
PHx. The findings were validated in ischemia/reperfusion injury (IRI)
model.
AA0040
Result: Results: Proliferating hepatocytes (Ki67+HNF4a+) were
maximally observed at 1D and 2D post-PHx. An increase in intrahepatic PINK1/Parkin inhibits hepatocyte succinate accumulation and
CK19+ cholangiocytes was seen between 2–3D post-PHx in portal promotes liver regeneration by mediating the ubiquitination and
areas. Increased lymphangiogenesis and percentage of PDPN+LyEC degradation of Sigma-1 protein
was observed at 2D and 5D post-PHx compared to sham prominently Jian Xu1, Haoran Hu1, Yuecheng Wang1, Ping Wang1, Haoming
in portal areas. Hepatic lymphatic drainage was increased by 20% in Zhou1
2D PHx compared to sham. In proteome analysis, about 500 significant 1
The First Affiliated Hospital of Nanjing Medical University
differentially expressed proteins were identified. Compared to sham, Background: The liver exhibits remarkable regenerative capacity in
pathways like MAPK and Hedgehog were upregulated in PHx-LSEC response to injury or viral infection. Hepatocyte energy supply and
while AMPK, MAPK, and IL17 were upregulated in PHx-LyEC. Among various growth factors and cytokines in the microenvironment play
secreted proteins, PHx-LSEC showed increased expression of crucial roles in regulating liver regeneration. We aim to investigate the
hepatocyte mitogen angiocrine factors like, Wnt2 and oncostatin-M interaction between PINK1/Parkin and Sigma-1, and their roles in liver
while in LyEC, expression of secreted factors like Wnt7a and FGF20, regeneration.
involved in proliferation of cholangiocytes was upregulated. Expression Method: We established 2/3 partial hepatectomy (PHx) model
of Wnt7a gene was also found to be upregulated in LyECs isolated for liver regeneration in wild-type (WT) mice, hepatocyte-specific
from IRI models at 72h post-IRI. Also, expression of Wnt7a receptor, Pink1 knockout mice (PINK1fl/flAlbCre), hepatocyte-specific Pink1
Frizzled 7a (FZD7a) was upregulated in cholangiocytes in both PHx overexpressing mice (PINK1HKI), and macrophage-specific SUCNR1
and IRI models. An in vivo MAZ51 treatment, significantly decreased knockout mice (SUCNR1fl/flLyz2Cre).
intrahepatic CK19+ cells at 2D post-PHx and also in IRI models as Result: Following partial hepatectomy, PINK1 expression was
compared to untreated ones. Furthermore, chol-org treated with LyEC- significantly upregulated in liver samples. Hepatocyte-specific PINK1
CM and Wnt7a showed a considerable increase in their proliferation knockout inhibited liver regeneration after partial hepatectomy.
as compared to untreated controls, which however decreased in Additionally, the hepatocyte-specific deletion of PINK1 during
presence of FZD7a inhibition. regeneration disrupted the hepatocyte tricarboxylic acid cycle,
Conclusion: Conclusion: Hepatic lymphangiogenesis is a leading to a decrease in ATP production. PINK1-deficient hepatocytes
characteristic feature during liver regeneration. We identified
exhibited mitochondrial calcium overload, which inhibited the activity Figure 2.Figure 2
of succinate dehydrogenase and resulted in the accumulation of
succinate in hepatocytes. Furthermore, hepatocyte-derived succinate
AA0042
acted on macrophages in a paracrine manner, suppressing the pro-
regenerative phenotype of macrophages. Macrophage-specific Challenges of Rapid Scale-Up of Laboratory Capacity to Respond
SUCNR1 knockout promoted liver regeneration. Mechanistically, during to the Emerging Hepatitis C Crisis Among Refugees in Cox’s
liver regeneration, Parkin functions as an E3 ubiquitin ligase, binding Bazar, Bangladesh
to Sigma-1 and promoting its ubiquitination and degradation, which Debashish Paul1, SM Niaz Mowla1, Polin Chan2, Jorge Martinez1, Md
further inhibits the calcium transport from the endoplasmic reticulum Shahidul Islam1, Farhad Hussain3,4, Tahmina Shirin5, Nawsher Alam5,
to mitochondria across the mitochondria-associated endoplasmic Abdullah Omar Nasif5, Umme Salma Amin3, Abu Toha Bhuiyan6,
reticulum membranes. In contrast, PINK1 deficiency promotes calcium Tahsina Jainab1, Charles Erik Halder7, Abdullah Al Noman8,9, Aarti
transport from the endoplasmic reticulum to mitochondria, leading to Shrikrishana Singh1,10
mitochondrial dysfunction in hepatocytes. Moreover, hepatocyte- 1
World Health Organization, Cox‘s Bazar Sub-Office, Cox‘s Bazar,
specific PINK1 overexpression promoted liver regeneration after Bangladesh, 2World Health Organization, Southeast Regional
partial hepatectomy. Office (SEARO), Delhi, India, 3Cox‘s Bazar Medical College, Cox‘s
Conclusion: We demonstrated that conditional PINK1 knockout in Bazar, Bangladesh, 4Directorate General of Health Services, Dhaka,
hepatocytes impedes Sigma-1 ubiquitination and degradation, leading Bangladesh, 5Institute of Epidemiology Disease Control And Research
to mitochondrial calcium overload, impaired succinate dehydrogenase (IEDCR), Dhaka, Bangladesh, 6Office of the Refugee Relief and
activity, and succinate accumulation. This paracrine signaling Repatriation Commissioner, Cox‘s Bazar, Bangladesh, 7International
subsequently inhibits liver regeneration by modulating macrophage Organization for Migration, Cox‘s Bazar, Bangladesh, 8Save the
activity. Our findings identify PINK1 as a potential therapeutic target Children, Cox‘s Bazar, Bangladesh, 9Umeå University, Sweden
(Course), 10World Health Organization, Eastern Mediterranean
for liver regeneration.
Regional Office (EMRO), Cairo, Egypt
Table and Figure:Figure 1.
Background: The 2017 humanitarian emergency in Cox’s Bazar left
nearly 1 million Rohingya refugees residing in 33 overcrowded camps
AA0041 with limited healthcare access. In March 2024, the World Health
NAT10 promotes liver regeneration via mRNA ac4C modification Organization (WHO) and partners initiated hepatitis C (HCV) testing and
in a mouse model of hepatectomy treatment services across 110 primary care facilities and two treatment
Qingjing Wang1, Qianren Zhang1, Yuqin Wang1, Tianyi Ren1, Feng sites. Screening at the primary level used WHO-prequalified rapid
Shen1 diagnostic tests (RDTs), with positive cases referred to the Institute of
1
Department of Gastroenterology, Xinhua Hospital Affiliated to Epidemiology Disease Control and Research (IEDCR) field laboratory
Shanghai Jiao Tong University School of Medicine placed distantly at Cox’s Bazar for confirmation via reverse transcription
Background: The unique regenerative ability of liver ensures that polymerase chain reaction (RT-PCR). The aminotransferase-to-platelet
its vital functions remain intact, crucial for the success of most ratio index (APRI) liver staging was conducted at camp-level treatment
organ surgeries. Accumulating evidences suggest that epigenetic centres.
alterations, including several types of post-transcriptional modification Method: Between April and November 2024, 9,599 individuals were
contribute to liver regeneration. This study aims to elucidate the role of screened for HCV using Abbott SD Bioline RDTs. The IEDCR field
N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C), a laboratory utilized Rotor-Gene Q (Qiagen) and QuantStudio 5 PCR
novel post-transcriptional modification in liver regeneration. System (Applied Biosystems) with the HCV Real-TM Quant DX assay
Method: 8-week-old male C57BL/6J mice were performed partial (Sacace Biotechnologies). RNA extraction employed QIAamp Viral
hepatectomy (PH) or sham surgery, and then NAT10 expression in RNA Mini Columns (QIAGEN), followed by amplification with optimized
liver tissue was evaluated at 24h, 48h and 72h after surgery. Male thermal cycling. APRI staging included biochemical pre-assessments
hepatocyte-specific NAT10 knockout (CKO) and overexpression (serum bilirubin, serum glutamic-oxaloacetic transaminase, serum
(HOE) mice were generated using a Cre-LoxP system. PH was glutamic pyruvic transaminase, alkaline phosphatase, creatinine,
performed in male CKO and HOE mice, as well as their WT littermates. urea, and platelet counts) to classify disease severity as non-cirrhotic
Liver regeneration of mice was evaluated through detecting the or cirrhotic. Blood samples were collected at 18 sentinel primary
increase of liver index, as well as the expression of Ki67, BRDU and healthcare centers.
proliferating cell nuclear antigen (PCNA). Furthermore, mammalian Result: Of 9,599 individuals screened, 42.8% tested positive for
target of rapamycin (mTOR) signaling was assessed in mouse livers HCV antibodies by RDTs and 4.6% for hepatitis B. RT-PCR on 1,748
after PH by Western Blot and qRT-PCR. Transcriptomic-wide mapping RDT-positive cases confirmed active HCV infection in 67.4%, with an
of ac4C modification (acRIP-seq) was performed on mRNA samples average RNA viral load of 5.96 × 106 copies/mL. Turnaround time for
in primary hepatocytes from CKO and WT littermates at 48h after PH. RT-PCR reporting was 48–72 hours. Out of a total of 723 APRI results,
Target genes regulated by NAT10 were further identified by mRNA 86 indicate cirrhosis at stages F3 and F4. After 12 weeks of treatment,
stability assessments and RNA immunoprecipitation (RIP) in vitro. all 122 monitored patients achieved sustained virologic response
Result: After PH, NAT10 expression in mouse hepatocytes was (SVR12). The rapid scale-up of refugee screening encountered
significantly upregulated at 24h and 48h, whereas downregulated at significant challenges, including funding constraints, prolonged
72h. Hepatocyte-specific NAT10 knockout in mice notably inhibited procurement process drugs, shortages of reagents and consumables,
liver regeneration after PH, manifested as decrease in liver index and transportation issues for sample collection from the camps to IEDCR
downregulation in Ki67, BRDU and PCNA expression. However, NAT10 lab, high staff turnover requiring constant retraining, and concerns
overexpression in hepatocytes exerted significant pro-regenerative regarding the mobilization of patients to treatment centers.
effects in mouse livers. Moreover, mTOR signaling was inhibited in Conclusion: The scale-up of hepatitis testing and treatment services
CKO mouse livers, whereas enhanced in HOE mouse livers. Combined in Cox’s Bazar is anchored on assuring a good quality and response
analysis of acRIP and RNA-seq exhibited mTOR signaling-associated laboratory network, which includes the capacity to screen at primary
genes, Mtor and 4ebp1 were hypoacetylated and downregulated. In care facilities, supported centrally by the IEDCR field laboratory. Going
vitro experiments further demonstrated NAT10 interacted with mRNA forward, with the huge unmet need in the refugee camps for screening
of Mtor and 4ebp1 and enhanced their stability. and treatment, strategic planning for scaling up testing and treatment
Conclusion: NAT10 promotes liver regeneration by upregulating capacity to ensure equity and access would be crucial.
mTOR and 4EBP1 expression in an ac4C-dependant way. This
suggests NAT10 may be a potent biomarker for the prognosis of AA0043
patients undergoing hepatic resection or transplantation.
Table and Figure:Figure 1.Figure 1
Real-World Experience of Lenvatinib Monotherapy in Advanced kinase inhibitors (TKIs) and immunotherapies are widely utilized.
Hepatocellular Carcinoma Patients: A Study from Bali Nonetheless, the impact of treatment modality on healthcare burden
Dwijo Anargha Sindhughosa1,2, Ni Nyoman Gita Kharisma Dewi2, Ni in HCC patients has not been well-evaluated. We utilized days at
Luh Putu Yunia Dewi2, Putu Itta Sandi Lesmana Dewi2, Kadek Mercu home (DAH), a patient-centered metric, to assess the comparative
Narapati Pamungkas2, I Ketut Mariadi2,3 disease time burden between patients with advanced HCC on TKIs
1
Division of Gastroenterology and Hepatology, Department of Internal and immunotherapies.
Medicine, Udayana University, Bali, Indonesia, 2Centre Research for Method: Patients with advanced HCC receiving systemic therapy
Alimentary and Hepatobiliary System, Denpasar, Bali, Indonesia, from 1st January 2003 – 31st December 2023 were identified from a
3
Division of Gastroenterology and Hepatology, Department of Internal population-based cohort in Hong Kong. Patients were classified into the
Medicine, Udayana University/Prof. Dr. I.G.N.G. Ngoerah Hospital, TKI group (received sorafenib, lenvatinib, cabozantinib, regorafenib)
Bali or immunotherapy group (received nivolumab, pembrolizumab,
Background: Hepatocellular carcinoma (HCC) is the most common atezolizumab, durvalumab, tremelimumab, ipilimumab; including
form of liver cancer, with treatment strategies guided by the Barcelona monotherapies or combinations). Patients who received both types
Clinic Liver Cancer (BCLC) staging system. Patients frequently already of therapies were excluded. Healthcare utilization including inpatient
in advanced stage in which several treatment options are not effective. stay, accident and emergency (A&E) attendance, day procedures
This study aimed to assess the efficacy of lenvatinib as a therapeutic (liver biopsy, endoscopy, drug infusion, abdominal paracentesis
agent in the treatment of advanced HCC within the Indonesian and transjugular intrahepatic portosystemic shunt), blood tests, and
population. imaging were recorded. Primary outcome was DAH – defined as the
Method: This retrospective observational cohort study was conducted days alive without spending on healthcare utilization, within the first year
on patients with HCC. Data were obtained from medical records, of treatment. Subgroup analyses stratified by age, etiology of HCC,
including laboratory results and imaging studies. Laboratory parameter albumin-bilirubin (ALBI) grades and MELD score were performed.
differences between patients treated with lenvatinib and those not Result: This study included 3784 patients on TKIs (mean age 61.4
receiving lenvatinib were analyzed using an independent sample t-test years, 85.4% male) and 621 patients on immunotherapies (mean age
or the Mann-Whitney test. In patients receiving lenvatinib, changes 62.1 years, 85.4% male). The median overall survival was 7.5 (IQR
in laboratory parameters before and after treatment initiation were 2.6-24.1) months in the immunotherapy group and 6.6 (IQR 2.8-15.4)
analyzed using paired sample t-tests or Wilcoxon tests, depending on months in the TKI group, without reaching statistical significance
the data distribution. (p=0.331). The mean DAH was 225.8 (95%CI 215.3-236.3) days in
Result: The study involved 81 participants. The lenvatinib group had the immunotherapy group, which was significantly higher than the
significantly better outcomes than the non-lenvatinib group, as reflected TKI group [183.6 (95%CI 179.5-187.7) days; p<0.001], with patient
by improvements in the CTP score, aspartate aminotransferase (AST), distribution according to range of DAH shown in Figure 1. The
alanine aminotransferase (ALT), total bilirubin, AST to platelet ratio index difference in DAH was mainly driven by mortality days (immunotherapy:
(APRI), neutrophil-lymphocyte ratio (NLR), and albumin-bilirubin index 104.4days vs TKI: 149.4days) and in-patient stay (immunotherapy:
(ALBI) (p < 0.05). Additionally, a comparison of laboratory parameters 13.3days vs TKI: 16.2days), in the first year of treatment (all p<0.001).
before and after lenvatinib administration demonstrated significant Conversely, immunotherapy patients spent significantly more time
differences in MELD score, CTP score, activated partial thromboplastin on day procedures (immunotherapy: 5.4days vs TKI: 0.5days) and
time (APTT), international normalized ratio (INR), total bilirubin levels, blood tests (immunotherapy: 13.5days vs TKI: 12.1days) in the first
ALBI, AST/ALT ratio (De Ritis), and neutrophil-lymphocyte-albumin ratio year of treatment (both p<0.001) (Figure 2). Most results of subgroups
(NLA). Radiological evaluation using a 128-slice contrast-enhanced analyses were consistent with the main results, except the subgroups
abdominal CT scan revealed that, based on the modified Response of ALBI grade 3 and MELD score ≥ 15.
Evaluation Criteria in Solid Tumors (mRECIST), 20 out of 23 patients Conclusion: Immunotherapy, when compared with TKI, is associated
achieved stable disease, while 3 patients experienced progressive with significantly reduced disease time burden in advanced HCC
disease following at least three months of lenvatinib therapy. patients in this real-world cohort. Our data has important quality-of-life
Conclusion: Lenvatinib therapy in patients with advanced HCC shows implications and may influence the choice of oncological therapy for
potential in slowing disease progression. However, additional clinical patients with advanced HCC.
studies are required to further confirm and validate these findings. Table and Figure:Figure 1.Distribution of Days at Home
Table and Figure:Figure 1.Table 1. Comparative Analysis of Clinical Figure 2.Distribution of days spent in the first year of treatment
and Laboratory Parameters Before and After Lenvatinib Treatment
AA0045
AA0044 Exploring Immune Checkpoint Inhibitor Rechallenge of
Disease time burden in patients with advanced hepatocellular Durvalumab plus Tremelimumab in Advanced Hepatocellular
carcinoma receiving systemic therapy Carcinoma: Analysis of post-imAE Readministration and
Sequential Treatment after Atezolizumab plus Bevacizumab
Matthew ShingHin Chung1,2, Rex WanHin Hui1, ChiLeung Chiang3,
Carlos KingHo Wong2,4,5, Ian ChiKei Wong2,4,6, ManFung Yuen1,7, Takuya Yonemoto1, Sadahisa Ogasawara1, Chihiro Miwa1, Makoto
WaiKay Seto1,7, LungYi Mak1,7 Fujiya1, Takahiro Tsuchiya1, Midori Sawada1, Teppei Akatsuka1, Ryo
Izai1, Sae Yumita1, Miyuki Nakagawa2, Tomomi Okubo3, Keisuke
1
Department of Medicine, School of Clinical Medicine, LKS Faculty
Koroki1, Masanori Inoue1, Masato Nakamura1, Naoya Kanogawa1,
of Medicine, The University of Hong Kong, Hong Kong SAR China,
2
Centre for Safe Medication Practice and Research, Department Takayuki Kondo1, Shingo Nakamoto1, Norio Itokawa3, Masanori
of Pharmacology and Pharmacy, LKS Faculty of Medicine, The Atsukawa3, Ei Itobayashi2, Michihisa Moriguchi4, Naoya Kato1
University of Hong Kong, Hong Kong SAR China, 3Department
1
Department of Gastroenterology, Graduate School of Medicine,
of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Chiba University, Chiba, Japan, 2Department of Gastroenterology,
Medicine, The University of Hong Kong, Hong Kong SAR China, Asahi General Hospital, Chiba, Japan, 3Division of Gastroenterology,
4
Laboratory of Data Discovery for Health (D24H), Hong Kong Science Department of Internal Medicine, Nippon Medical School Chiba
and Technology Park, Hong Kong SAR China, 5Department of Family Hokusoh Hospital, Chiba, Japan, 4Department of Gastroenterology
Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing and Hepatology, Kyoto Prefectural University of Medicine, Kyoto,
Faculty of Medicine, The University of Hong Kong, Hong Kong SAR Japan
China, 6Aston Pharmacy School, Aston University Birmingham, Background: We aimed to investigate the safety of re-administering
Birmingham, United Kingdom, 7State Key Laboratory of Liver immune checkpoint inhibitor after immune-mediated adverse events
Research, The University of Hong Kong, Hong Kong SAR China (imAEs) in durvalumab plus tremelimumab (Dur/Tre), which frequently
Background: Systemic therapy options for advanced hepatocellular causes imAEs. Additionally, we explored the safety, efficacy, and
carcinoma (HCC) have expanded in recent years, and both tyrosine immunologic responses by cytokine and chemokine analysis in
advanced hepatocellular carcinoma (HCC) patients previously treated findings.
with atezolizumab plus bevacizumab (Atez/Bev).
Method: We retrospectively analyzed data from patients with advanced
AA0047
HCC treated with Dur/Tre at four Japanese institutions. We evaluated
the occurrence of imAEs, subsequent readministration of durvalumab, A retrospective study of immune checkpoint inhibitors-based
and recurrence of imAEs. We focused on patients previously treated combination therapy in patients with HCC for liver injury
with Atez/Bev, assessing clinical outcomes, imAEs development, Luping Lin 1, Huaying Lai1, Sha Huang1
tumor growth dynamics, and serum cytokine and chemokine levels. 1
Fujian Cancer Hospital
Result: Dur/Tre was administered to 68 patients, with an objective Background: Checkpoint inhibitors account for increasing numbers of
response rate of 10.3% and a disease control rate of 58.8% (RECIST drug-induced liver injury cases.We aimed to evaluate the incidence of
v1.1). Median progression-free survival was 3.1 months (95% liver injury caused by immune checkpoint inhibitors-based combination
confidence interval: 2.0-4.9). ImAEs occurred in 50.0% of patients, therapy in HCC patients.
with 27 patients requiring systemic steroids. Some cases required Method: The patients were divided into two groups: 1) the group that
biological agents: infliximab was administered to 3 patients with colitis, developed drug-related liver injury; 2) no drug-related liver injury ;
and tocilizumab was given to 1 patient with cytokine release syndrome. Demographic characteristics such as gender, age, and body mass
Durvalumab was readministered in 14 patients after recovery from index were collected, as well as clinical manifestations, blood routine,
imAEs, though 5 experienced recurrence. Among 33 patients (48.5%) liver biochemistry, coagulation function, abdominal imaging and
previously treated with Atez/Bev, 9 had experienced imAEs during other indicators. The similarities and differences in clinical outcomes
Atez/Bev, and 4 of these patients developed imAEs during subsequent of patients in each group were compared. Grade of liver injury after
Dur/Tre. In patients previously treated with Atez/Bev, Dur/Tre showed treatment was assessed according to CTCAE V5.1 criteria
an objective response rate of 9.1% and a disease control rate of Result: 1. Incidence of liver injury: 449 patients were finally included,
54.5%. Among patients who directly transitioned from Atez/Bev to Dur/ including 124 in the liver injury group and 325 in the no liver injury
Tre, 60.0% demonstrated decreased tumor growth dynamics. Analysis group. The incidence of liver injury was 27.6%.
of serum samples revealed elevated levels of CXCL9 and CXCL10 2. The incidence of liver injury in the HBsAg-negative group and the
following Dur/Tre administration, regardless of previous Atez/Bev. To positive group were 12.8% and 23.4% (P=0.009), and the incidence
identify potential biomarkers of treatment response, we analyzed the of liver injury in the fatty liver group and the non-fatty liver group were
correlation between elevated CXCL9 and CXCL10 levels and the best 4.0% and 0.6%,(P=0.029). The incidence of liver injury in the group
overall response to Dur/Tre. However, no clear correlation was found. with other IRAEs and without IRAEs was 31.7% and 6.2%(P<0.001).
Conclusion: Readministration of durvalumab after imAEs in Dur/Tre The incidence of liver injury in the group that therapies include TKIs
is feasible with appropriate imAE management and patient selection. or not are 64.5% and 75.7% (P=0.024), and the ORR was 62% and
Dur/Tre may demonstrate clinical efficacy in patients previously treated 40.8% in the liver injury group and no liver injury group(P<0.001). The
with Atez/Bev. Analysis of serum chemokine dynamics in these patients baseline white blood cell count [5.98*10^9 (3.63-8.33, P=0.039)],
suggests that Dur/Tre administration may induce immune responses. absolute neutrophil value [3.94*10^9 (1.81-6.07, P=0.039)], platelets
However, no correlation was found between chemokine dynamics and [170.6*10^9 (86.27-254.93, P=0.032)] and PLR (platelet-lymphocyte
treatment efficacy, indicating the need for further biomarker research. ratio) [132.58 (67.91-197.25, P=0.038)] in the liver injury group Lower.
3. There were no significant differences in Child-Pugh grade (p=0.338),
AA0046 liver cirrhosis (p=0.163), hepatitis B DNA positivity (P=0.149), cancer
thrombus PVTT classification (p=0.945), first-line treatment and first-
Efficacy of N-acetylcysteine in Preventing Anti-Tuberculosis Drug-
line post-treatment (p=0.945), ICI type (P=0.06), gender (p=0.24), and
Induced Liver Injury: A Meta-analysis
age (P=0.46) between the two groups.
Kristian Orap Orante1, Dwight Bumanglag Fernandez1, Mark De Conclusion: 1. Patients with ECOG score of 0-1, HBsAg negative, and
Lusong1, Ma Anonuevo Cruz1 fatty liver have a higher incidence of liver injury.
1
University of the Philippines - Philippine General Hospital 2. The incidence of liver injury is higher in TKI-containing treatment
Background: Tuberculosis (TB) remains to be a major health problem regimens; The effect was better in the group without liver injury; The
in most developing countries. Anti-TB drug-induced liver injury proportion of irAEs in other organs was significantly increased in
(ATDILI), which remains to be the most common adverse effect of anti- patients with liver injury, and multi-organ injury was alert. 3. Patients
TB therapy, could lead to treatment interruption, failure or in severe with low baseline leukocytes, neutrophils, platelets, and platelet-
cases, hospitalizations, or even death. This study aimed to examine lymphocyte ratio had a higher incidence of liver injury.
the efficacy of N-acetylcysteine (NAC) in preventing ATDILI through
outcomes such as incidence of ATDILI, elevation of liver markers, and
quality of life. ELIMINATION FORUM
Method: Electronic databases were searched for relevant literature
from inception until October 2024. All randomized controlled trials
(RCT) assessing the efficacy of NAC for prevention of ATDILI were PLENARY SESSION
included. Meta-analysis was performed to analyze the evidence using
random-effects model. PL0001
Result: Three RCTs were included examining a total of 183 patients.
Differential impacts of age and sex on diagnostic rates and
Compared with placebo or no treatment, NAC reduced the incidence
incidences of hepatic events in patients with chronic viral hepatitis
of ATDILI (OR 0.04; 95%CI 0.01 to 0.32). Patients given with NAC also
Grace Wong1, Vicki VK Hui1, Terry CF Yip1, Jimmy CT Lai1, Vincent
had significantly lower serum aspartate aminotransferase compared
WS Wong1
to control after 2 weeks (MD -12.44; 95%CI -18.76 to -6.11), 4 weeks
(MD -17.43; 95%CI -28.92 to -5.94), and 8 weeks of treatment (MD
1
The Chinese University of Hong Kong
-13.37; 95%CI -22.95 to -3.78). Moreover, patients given with NAC Background: Health inequalities related to age and sex significantly
had significantly lower serum alanine aminotransferase compared to impact diagnosis and management for patients with chronic viral
control after 2 weeks (MD -14.17; 95%CI -26.09 to -2.26) and 4 weeks hepatitis. This study evaluated the secular trends of diagnostic rates
of treatment (MD -9.68; 95%CI -18.83 to -0.53) but had no significant of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection,
difference after 8 weeks of treatment (MD -4.89; 95%CI -13.62 to 3.84). and the incidences of hepatic events stratified by age and sex over
Conclusion: NAC appears to be effective in preventing ATDILI two decades.
among TB patients. These findings, however, were limited by the Method: Patients were identified from a territory-wide database in Hong
variable definition of ATDILI, short study duration, and limited number Kong. Age- (18-30, 30-40, 50-60, 60-70, 70-80, >80 years) and sex-
of participants. Further research is necessary to strengthen these stratified diagnostic rates of HBV in 2000-2020 were calculated based
on the number of individuals tested annually, while HCV rates were 2.82]), hepatocellular carcinoma (3.92 [3.10–4.95]), intrahepatic
determined using population data from census records. Incidences cholangiocarcinoma (1.64 [1.12–2.39]), leukemia (1.90 [1.67–2.17]),
of hepatic event (hepatocellular carcinoma, decompensating events, and non-Hodgkin lymphoma (1.37 [1.23–1.53]). TyG index was
and liver transplantation) among HBV or HCV-infected patients were positively associated with pancreatic cancer (1.19 [1.02–1.39]),
determined. lung cancer (1.14 [1.04–1.24]), kidney cancer (1.35 [1.20–1.53]),
Result: A total of 234,865 individuals were diagnosed with HBV. Newly bladder cancer (1.20 [1.07–1.36]), leukemia (1.22 [1.09–1.37]), and
diagnosed HBV rates increased over time across all age groups, with non-Hodgkin lymphoma (1.16 [1.06–1.27]). For CVD, higher FIB-4
the most dramatic increase from 0.49% [0.46%-0.51%] in 2000 to 5.23% index was associated with all types of CVD outcomes except for the
[4.99%-5.47%] in 2020 in patients of 40-49 years old; the diagnostic hypertension with a HR ranged from 1.11 [1.04–1.19] for ischemic
rates increased from 0.57% [ 0.54%-0.60%] in 2000 to 3.57% [3.38%- stroke to 1.36 [1.24–1.49] for hemorrhagic stroke. Similarly, TyG index
3.75%] in 2020 in patients of 30-39 years old. Men had consistently was associated with higher risk of all types of CVD outcomes with a HR
higher diagnostic rates for HBV than women: it peaked in 2020 for ranged from 1.06 [1.02–1.10] for atrial fibrillation to 1.51 [1.43–1.59]
both sexes - 4.05% [3.94%-4.15%] in men and 3.33% [3.24%-3.42%] for myocardial infarction. Those associations remained essentially
in women. Diagnostic rates for HCV remained low throughout the two unchanged in sensitivity analyses including excluding cases that
decades, with highest rate of 0.03% [0.028%-0.034%] in patients of occurred in the first two years of follow-up.
60-69 years old in 2019. Men had consistently higher diagnostic rates Conclusion: Liver fibrosis and insulin resistance, as assessed by
for HCV than women; though it was always low (peaked at 0.03% in readily available measures such as the FIB-4 and TyG index, are
2012 for men; stayed at or below 0.01% for women). Incidence of associated with elevated risks of specific cancers and most CVD
hepatic event increased significantly with age over time; it was highest outcomes. Further studies in other populations are needed to confirm
in patients of 70 years or older, rising from 15.15% [14.44%-15.87%] our findings.
in 2000 to 32.19% [30.96%-33.42%] in 2020. Men had consistently Table and Figure:Figure 1.Figure 1. Prospective associations of
more hepatic events than women; it peaked in 2020 for both sexes Fibrosis-4 index and triglyceride glucose index with cancer outcomes
- 17.49% [16.89%-18.09%] in men and 11.45% [10.95%-11.96%] in in the Mass General Brigham Biobank
women (Figure). Figure 2.Figure 2. Prospective associations of Fibrosis-4 index and
Conclusion: Newly diagnosed HBV rates showed substantial triglyceride glucose index with cardiovascular outcomes in the Mass
increases, particularly among middle-aged males, while HCV rates General Brigham Biobank
remained low. Hepatic event rates rose with age, especially in older
males. Addressing these disparities is crucial to reduce health
PL0003
inequalities and support hepatitis elimination efforts.
Founding: This work was supported by the Investigator Sponsored Novel MAF6 risk score outperforms non-invasive scores for early
Research of Gilead Sciences (Reference: IN-HK-987-7181). MAFLD detection – A study of 33,255 residents from India’s capital
Table and Figure:Figure 1.Newly diagnosed hepatic events rate in city
Hong Kong from year 2000 to year 2020 stratified by age. Kanica Kaushal1, Sumridhi Gautam2, Guresh Kumar2, Shantanu
Figure 2.Newly diagnosed hepatic events rate in Hong Kong from year Dubey2, Shiv Kumar Sarin2
2000 to year 2020 stratified by gender. 1
Assistant Professor Clinical Research and Epidemiology Institute of
Liver & Biliary Sciences (ILBS), 2Institute of Liver & Biliary Sciences
(ILBS)
PL0002
Background: This study aimed to determine the prevalence of
Readily Available Indices of Liver Fibrosis and Insulin Resistance
MAFLD, often undiagnosed but leading to severe liver complications,
Associated With Cancer and Cardiovascular Disease Outcomes
in the Delhi NCR population and to develop and validate non-invasive
Longgang Zhao1, Xinyuan Zhang2, Diego Martínez Urbistondo3, risk scores for early detection.
Miguel Martínez-González3, Frank Hu4, Xuehong Zhang1 Method: A 2017-2023 Delhi cross-sectional survey used two-stage
1
Yale School of Nursing, 2Brigham and Women’s Hospital and Harvard sampling of Mohalla Clinics to gather anthropometric, biomedical,
Medical School, 3Clínica Universidad de Navarra, 4Harvard T.H. Chan and fibro-scan data for CAP and LSM. Logistic regression identified
School of Public Health MAFLD-associated parameters, developing and testing the MAF6
Background: Liver fibrosis and insulin resistance are known drivers score in two cohorts. The study validated noninvasive risk scores like
of cancer and cardiovascular disease (CVD) outcomes through FIB 4, HSI, APRI, and AST/ALT ratio in a large community cohort.
metabolic dysfunction and inflammation. However, gold standard Result: This study analyzed 33,255 residents across 161 campsites
measurements, e.g., imaging and hyperinsulinemic-euglycemic in 11 districts of Delhi. The prevalence of MAFLD was 57.65% (95%
clamp test, are often costly and impractical in large population-based CI: 57.1-58.1%), and lean MAFLD 4.39% (95% CI: 4.16 – 4.61).
studies or resource-constrained settings, making surrogate markers Multivariate analysis identified sex, age, log (GGT), log (platelet), and
as appealing alternatives. We aimed to evaluate the prospective ALT/AST ratio as significant predictors of MAFLD. Based on these six
associations of commonly used liver fibrosis (Fibrosis-4, FIB-4) and variables, a novel MAFLD risk score (MAF6) was developed, which
insulin resistance measurement (triglyceride glucose index, TyG) with demonstrated superior performance (AUROC 0.84, 95% CI: 0.844-
cancer and CVD risk. 0.852) compared to existing noninvasive scores such as FIB-4 (63.5),
Method: We developed a prospective cohort based on data from the APRI (60), HSI (74.5), and ALT/AST ratio (61). Both the derivative and
Harvard Mass General Brigham Biobank. We excluded those with validation cohorts had significant p-values (<0.05), and AUROC values
cancer or CVD diagnosis at baseline and without biomarker data and were comparable (AUROC 84.7 and 84.8, respectively).
integrated data on demographics and lifestyles (analysis sample: Conclusion: India leads the global fatty liver preparedness index
N=66,015 for cancer and 62,747 for CVD). FIB-4 was derived using with established national guidelines. The innovative MAF6 risk score
age, aspartate aminotransferase, alanine aminotransferase, and (AUROC 0.84) demonstrated superior performance compared to
platelet count, with a cutoff of 1.3. TyG was derived using fasting existing non-invasive scores for early community-based MAFLD
blood glucose and triglyceride, with a cutoff of 8.8. Health outcomes detection and has the potential for incorporation into national NCD
were collected via electric medical records. We used Cox models prevention guidelines, including NAFLD. Furthermore, this risk score
to estimate hazard ratios (HRs) [95% confidence intervals (CIs)] for may be evaluated and implemented by other countries.
disease outcomes adjusting for potential confounding factors including Table and Figure:Figure 1.Figure 1: Performance characteristics of the
demographics and lifestyles factors. MAF6 score in the derivative cohort using ROC curves and comparison
Result: With a median follow-up of 14.6 years for cancer and 6.5 with other noninvasive risk scores.
years for CVD analyses, we identified 25,407 cancer and 46,488
CVD outcomes. A higher FIB-4 index was associated with elevated
PL0004
risk of digestive cancers (1.13 [1.04–1.22]), liver cancer (2.34 [1.94–
Prognostic Value of Polymeric Immunoglobulin Receptor in to validate findings from liver biopsy samples. The levels of cytokines
Patients with Primary Biliary Cholangitis and chemokines in plasma from different groups were measured using
Faling Wu1,2, Yujuan Shen1, Tongtong Pan1, Xiaozhi Jin1,2, Yu liquid-phase array technology.
Huang1,2, Xiaodong Wang1, Dazhi Chen1,3, Yongping Chen1,2 Result: After rigorous quality control, all cells were categorized into
1
Zhejiang Provincial Key Laboratory for Accurate Diagnosis and CD8+T, CD4+T, γδT, NK, NKT-like, myeloid, B, plasma, parenchymal
Treatment of Chronic Liver Diseases, The First Affiliated Hospital of and proliferating cells. Cell proportion analysis revealed a decrease
Wenzhou Medical University, Wenzhou 325035, China, 2Department of in innate immune cells and an increase in adaptive immune cells,
Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical particularly CD8+ T cells, in the AIH group. 77 distinct clusters were
University, Wenzhou 325035, China, 3Hangzhou Medical College, identified. Notably, AIH group exhibited an elevated proportion of naïve
Hangzhou 310053, China CD8+ T cells in peripheral blood, as well as an increased proportion
Background: Primary Biliary Cholangitis (PBC) is a chronic of CTLA4+ CD8+ T cells within the liver. this subset of immune
autoimmune cholestatic liver disease with variable outcomes. Existing checkpoint-expressing T cells exhibited high expression of GZMK
prognostic models have limited predictive value for patients with PBC. and IFNG, as well as the highest inflammatory scores, indicating their
This study aims to identify new prognostic indicators to enhance model cytotoxic activity. Single-cell immune profiling confirmed that these cells
performance in identifying high-risk PBC patients. underwent TCR clonal expansion. mIHC staining further demonstrated
Method: Data were collected from enrolled PBC patients. TMT-labeled the presence of this cluster and revealed their close association with
proteomics identified serum differentially expressed proteins (DEPs). macrophages. Additionally, we identified a CXCL13+CXCR5- Tph
Patients were categorized into high- and low-expression groups based cluster, the proportion of which was specifically increased in the livers
on the median level of the most significantly upregulated DEP. Kaplan- of AIH group. Cytokine and chemokine analysis confirmed elevated
Meier survival curves and multivariate Cox proportional hazards serum CXCL13 levels in AIH group, which may be associated with the
analyses were used to assess the association between DEP levels accumulation of plasma cells in the liver.
and outcomes. Model performance was analyzed by incorporating the Conclusion: These findings present a comprehensive single-cell
DEP, and correlations between the DEP and key histological features immune atlas of peripheral blood and liver cells in AIH, emphasizing
of PBC were evaluated in liver biopsy samples. the cytotoxic CTLA4+CD8+T and the distinct CXCL13+CXCR5- Tph
Result: A total of 296 PBC patients and 30 healthy individuals were clusters. Our results provide new insights into AIH pathogenesis and
included, with 227 female patients (76.7%) and a median age of 55.5 potential therapeutic targets.
years (15). Proteomic analysis identified polymeric immunoglobulin Table and Figure:Figure 1.Intrahepatic and Peripheral scRNA-seq
receptor (pIgR) as the most significantly upregulated protein in the atlas in Autoimmune Hepatitis Patients
PBC group. Kaplan-Meier analysis showed that elevated pIgR levels Figure 2.Characters of cytotoxic CTLA4+CD8+T and CXCL13+CXCR5-
significantly predicted death or liver transplantation (LT) (p<0.001). Tph clusters in AIH group
Cox regression analysis confirmed that pIgR was an independent
predictor of death or LT (hazard ratio: 3.32; 95% CI: 1.92-5.72, PL0006
p<0.001). Incorporating pIgR increased the area under the curve of Improved ursodeoxycholic acid response with corticosteroid
the Mayo risk score from 0.848 (95% CI: 0.777-0.920) to 0.899 (95% CI: in primary biliary cholangitis with moderate-to-severe interface
0.845-0.953) and the area under the curve of the model for end-stage hepatitis
liver disease score from 0.734 (95% CI: 0.642-0.826) to 0.839 (95%
Linhua Zheng1, Bo Li1, Yansheng Liu1, Yulong Shang1, Ying Han1
CI: 0.756-0.921), with improved net reclassification improvement and 1
Xijing Hospital of Digestive Diseases
integrated discrimination improvement. Immunohistochemical staining
indicated that high pIgR expression was associated with severe bile Background: The moderate-to-severe interface hepatitis is frequently
duct injury in PBC, leading to higher rates of death or LT. observed in patients with primary biliary cholangitis (PBC) and may be
Conclusion: Serum pIgR may serve as a potential prognostic marker left out/under-served by the current definition of overlap. In this study,
in PBC and could support early risk stratification in patients. we aimed to investigate the clinical characteristic and therapeutic
Table and Figure:Figure 1.Figure 1. The differentially expressed pIgR in responses of PBC patients with moderate-to-severe interface hepatitis.
the PBC and control groups. a All the differentially expressed proteins. Method: In total, 544 treatment-naïve patients with PBC were enrolled
b The heat map results for pIgR expressions. c The expression level of in this retrospective study. Complete clinical data were obtained and
pIgR in enrolled individuals analyzed. The prognosis was assessed based on biochemical and
Figure 2.Figure 2. The performances of the new models by adding histological response to treatment. Univariate and multivariable binary
pIgR to the Mayo risk score and MELD score. a The AUC of MRS, logistic regression analyses were used to identify prognostic variables
MRS+pIgR, MELD, MELD+pIgR. b The IDI of the new Cox model for treatment response according to the ALP1.67 criteria (that was
compared to the MRS. c The IDI of the new Cox model compared to defined as ALP <1.67×ULN level after 12 months of treatment), and
the MELD score. then the area under the curves (AUC) was internally validated by
bootstrapping with 1000 resamples to evaluate the predictive ability.
Prognostic variables for changes of histological stage during follow-
PL0005
up were evaluated using univariate and multivariable-adjusted Cox
Single cell RNA sequencing reveals intrahepatic and peripheral proportional-hazards regression models. The absolute clinical benefit
immune landscapes related to autoimmune hepatitis patients of combined therapy over ursodeoxycholic acid (UDCA) alone was
Xinghuan Fu1, Yuan Hong1, Jiandan Qian1, Chi Zhang1, Long Xu1, evaluated using the number-needed-to-treat (NNT) to prevent one
Guiqiang Wang1 case of incomplete response or histological progression.
1
Department of Infectious Disease, Center for Liver Disease, Peking Result: In total cohort, 249 patients (45.8%) exhibited moderate-to-
University First Hospital, Beijing, 100034, China severe interface hepatitis, which was independently associated with
Background: The pathogenesis of autoimmune hepatitis remains biochemical incomplete response to UDCA monotherapy (OR 2.86,
unclear. The aim of this study is to establish a single-cell atlas of 95%CI 1.63-5.00, p<0.001) and the internally validated AUC was 0.72
immune cells both within and outside the liver in autoimmune hepatitis, (95%CI 0.65-0.81). Within this subgroup, progression in histological
in order to identify novel diagnostic and therapeutic targets. stage was noted in 42.2% of the biopsy samples, significantly
Method: Cells were extracted from the livers and peripheral blood of exceeding 14.4% rate observed in patients with exclusive PBC
9 patients with autoimmune hepatitis (AIH) and 3 patients with primary (p<0.001). Multivariable-adjusted Cox regression model showed
biliary cholangitis (PBC) for single-cell RNA sequencing, with healthy that moderate-to-severe interface hepatitis was an independent
control (HC) samples from public databases included for comparison. predictor of progression in histological stage (HR 2.24, 95%CI 1.19-
All bioinformatics and statistical analyses were performed using R and 4.19, p=0.012). Interestingly, the administration of UDCA combined
Python tools. Multiplex immunohistochemistry (mIHC) was employed corticosteroids resulted in significant improvements in biochemical
responses (OR 0.39, 95%CI 0.18-0.84, p=0.016) and histological
staging (HR 0.14, 95%CI 0.03-0.65, p=0.012) within this subgroup. metabolic stress of AFL with the ultimate goal of defining novel and
According to the NNT, 5 (95%CI 3–34) and 3 (95%CI 2–9) patients unique therapeutic targets of ARLD.
receiving UDCA alone would need to be given prednisolone to prevent Method: Primary human hepatocytes (PHH) or humanized-liver
one incomplete responder and one histological stage progression, chimeric mice-derived human hepatocytes (HLCM-HH), hereafter
respectively. referred to as human hepatocytes (HH), were cultured in vitro as two-
Conclusion: Our findings suggest that patients with PBC and dimensional monolayers for 7 days using our recently refined culture
moderate-to-severe interface hepatitis are at an increased risk of strategy, allowing HH to establish a steady state that preserves the
adverse clinical outcomes and potentially benefit from a combined characteristics of terminally differentiated hepatocytes. The HH were
treatment of UDCA and corticosteroids. subsequently incubated for an additional 7 days in the presence
ethanol (EtOH) or a fatty acid-carbohydrate cocktail to establish in
vitro models of AFL and Metabolic Dysfunction-Associated Fatty
PL0007
Liver (MAFL), respectively. These models underwent comparative
an unique childhood liver disease – analysis of role of autophagy characterization using mRNA-seq, ribosome profiling, and quantitative
in disease pathobiology proteomics analyses. The in vivo relevance of insights gleaned through
Kim Vaiphei1 in vitro studies were further evaluated with using HLCM.
1
Punjba ILBS Result: The in vitro cultured HH at baseline were confirmed to express
Background: - A rare and fatal cholestatic liver disease - Indian all key metabolic enzymes relevant to steatotic liver diseases at
Childhood Cirrhocis (ICC), is selectively described in India. Majority levels comparable to those observed in healthy human liver tissue.
of these children have history of intake of cow milk boiled in copper Incubation of HH with ethanol or the fatty acid-carbohydrate cocktail
utensils. And this condition has not been reproducible. Serum resulted in significant lipid droplet accumulation within the cytoplasm,
ceruloplasmin levels in these children are within normal limits. Liver at with the degree of steatosis being morphologically indistinguishable
autopsy in this fatal disease has distinctive pathological features. Lately, between the two treatments. Notably, EtOH treatment of HH led to
this condition is observed less frequently and molecular pathways the biogenesis of acetate, the final metabolite of alcohol, at a rate
have not been studied. Autophagy is a subcellular mechanism to comparable to that of the human liver. More importantly, it induced a
deliver cytoplasmic component to lysosome with formation of isolation pronounced upregulation of CYP2E1, a biomarker of chronic alcohol
membrane. Ubiquitin-proteasome plays crucial role in selective abuse and an indicator of metabolic stress. Multiomics analyses
degradation of short-lived regulatory proteins to be eliminated from a revealed substantial between HH models of AFL and MAFL, with only
cell. In lysosomal pathway, degradation of plasma membrane proteins minimal overlap, underscoring the distinct metabolic stress responses
and extra-cellular proteins is mediated by endocytosis. between these entities. Polysome profiling demonstrated significant
Method: Aims - to analyse role of autophagic proteins associated translatome repression in HH of AFL, which is mediated by ribosome
with two protein degradation pathways - ubiquitin-proteasome and dissociation from mRNAs due to ribosome collisions. Lastly, we found
lysosomal pathways. Control- liver biopsies from extrahepatic biliary that the translatome perturbation in AFL-HH underlies the sublethal
tract atresia (EHBTA) cases. Methodology– liver from 61 ICC cases; activation of cell death pathways, sensitizing the cells to apoptosis
25 EHBTA cases and 25 normal age matched autopsy liver tissues. upon exposure to inflammatory cytokines.
Immunohistochemistry (IHC) was used to study marker proteins and Conclusion: Our work uncovered a previously unrecognized
interpretations were observational. Markers used – i) autophagomal pathophysiology of ALD: the activation of sublethal levels of
membrane related proteins - LC3, LAMP-2, Ctr1, PI3K and beclin1; ii) programmed cell death pathways driven by persistent translatome
hepatocyte growth factor (HGF), HGF activator inhibitor type 1, tumor suppression caused by ribosome collisions.
necrosis factor α, Fas ligand and Bax. Protein degradation products -
p62, ubiquitin and KI67. PL0009
Result: age ranged 24 to 65 months, M:F= 45:16. History of
Comparison of pharmacological therapies for metabolic
growth retardation, anaemia, hepatosplenomegaly, jaundice and
dysfunction-associated steatohepatitis: systematic review and
encephalopathy, leafy firm palpable liver, protruding abdomen, minimal
network meta-analysis
ascites. Liver showed classic histological features. IHC- increased
expression for autophagy proteins, copper transporter, ubiquitin and Matheus Henrique1, Lubna Al-Sharif2, Vanio Antunes3, Daniel Huang4,
p62, increased Ki67. Similar positivity streams observed in EHBTA. Rohit Loomba5
Conclusion: Proteins associated with autophagy and copper
1
Department of Internal Medicine, Federal University of Rio de
transporters were increased both in ICC >EHBTA suggesting Janeiro, 2An-Najah National University, 3Federal University of Health
association with the disease pathobiology. However, the underlying Sciences of Porto Alegre, 4National University of Singapore, 5University
of California San Diego
aetiology of ICC still remains to be defined beyond its association with
intake of contaminated cow milk. Background: Background and Aims: Metabolic dysfunction-
associated steatohepatitis (MASH) is a leading cause of chronic
liver disease. With the advent of multiple therapeutic targets in late-
PL0008
phase clinical drug development, there’s a knowledge gap to better
Metabolic Stress in Alcoholic Fatty Liver Drives Sublethal Cellular understand the comparative efficacy of various pharmacological
Toxicity via Protein Translation Machinery Perturbation Induced agents for improving liver histology in MASH. We conducted an
by Ribosome Collisions updated systematic review and network meta-analysis to evaluate the
Go Sugahara1,2, Masashi Okawa1,2, Yuji Ishida1,2, Chise Tateno2, Meng relative rank-order of the different pharmacological agents for both
Li3, Muranaka Hayato4, Zhenghui Jiang5, Hyungjin Eoh1, Takeshi fibrosis regression and MASH resolution.
Saito1 Method: Methods: We searched PubMed and Embase databases
1
Keck School of Medicine, University of Southern California, from 2020 to June 10, 2024, for published randomized-controlled
2
PhoenixBio, Co., Ltd, 3University of Southern California, 4Cedars-Sinai trials (RCTs) comparing pharmacological interventions in patients
Medical Center, 5Beth Israel Deaconess Medical Center with biopsy-proven MASH. The co-primary endpoints were fibrosis
Background: Alcoholic fatty liver (AFL) represents the initial stage of improvement ≥1 stage without MASH worsening and MASH resolution
alcohol-related liver disease (ARLD). AFL is generally regarded as a without worsening fibrosis. We conducted surface under the cumulative
benign and reversible condition with sustained abstinence; however, ranking (SUCRA) curve analysis.
it also serves as a precursor for the progression to advanced stages Result: Results: A total of 27 RCTs (n=8356) were included. For the
of ARLD. Despite its significance, the molecular-level pathophysiology co-primary endpoint of fibrosis improvement without MASH resolution,
underlying AFL remains poorly understood. This study, therefore, is pegozafermin, cilofexor + firsocostat, survodutide, obeticholic acid,
designed to comprehensively decipher hepatocellular response to the tirzepatide, and resmetirom were significantly better than placebo in
improving ≥ 1 fibrosis stage without worsening MASH. Pegozafermin
(SUCRA: 90.18), cilofexor plus firsocostat (SUCRA: 82.82), and Method: A total of 600 NAFLD adults were prospectively recruited
cilofexor plus selonsertib (SUCRA: 79.62) were ranked the most from Beijing Friendship hospital. Carotid ultrasounds were performed
effective interventions. For the co-primary endpoint of MASH resolution on all participants, and plasma ADMA concentrations were measured
without worsening fibrosis, pegozafermin, survodutide, tirzepatide, at baseline and after 1 year of follow-up using enzyme-linked
efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, immunosorbent assay. The SCA was defined as the presence of
semaglutide, pioglitazone, and lanifibranor were significantly better carotid intima-media thickness (CIMT) and carotid plaque. A logistic
than placebo. Pegozafermin (SUCRA: 93.76), survodutide (SUCRA: regression model was used to assess the association between baseline
92.25), and tirzepatide (SUCRA: 86.52) were ranked the most effective ADMA levels, changes in ADMA, and the risk of SCA, adjusting for
interventions for achieving MASH resolution without worsening fibrosis. multiple variables.
Conclusion: Conclusion: This study provides updated rank-order Result: The baseline ADMA level was 23.30 (13.90, 40.95) ng/ml. The
efficacy of MASH pharmacological therapies for fibrosis regression risk of SCA significantly increased as ADMA level increased (P<0.001).
and MASH resolution. These data are helpful to inform practice and Compared with participants in the lowest quartile of baseline ADMA
clinical trial design. level, the multiple variables-adjusted odds ratios were 0.989 (95%
confidence interval, CI: 0.580-1.687), 1.853 (1.112-3.088) and 3.810
PL0010 (2.055-7.063) for participants in the Quartile 2, Quartile 3 and Quartile
4, respectively. At the 1-year follow-up, SCA progression occurred in
Pan-PPAR Agonist Chiglitazar for the Treatment of High-Risk 65 (12.45%) participants, including 18 who had CIMT at baseline and
Metabolic Dysfunction-Associated Steatohepatitis Coexisting 47 who were free of SCA at baseline. Both absolute and percentage
with Type 2 Diabetes: A Randomized, Double-Blind, Phase 2 Trial changes in ADMA from baseline to 1 year were significantly associated
Zhiyan YU1, Zhoujunhao Zhou1, Ruixiao Shi2, Yue Li1, Tiange Sun1, with SCA progression, with adjusted relative risks being 1.056 (95% CI:
Yueyue Wu1, Li Sheng1, Zhe Huang3, Jun Liu1, Shufei Zang1 1.042-1.069) and 1.014 (95% CI: 1.011-1.018), respectively. This trend
1
Department of Endocrinology, The Fifth People’s Hospital of was consistent in both NAFLD participants without SCA at baseline
Shanghai, Fudan University, 2Department of Traditional Chinese and those with SCA at baseline.
Medicine, Maqiao Community Health Service Center,, 3Department of Conclusion: ADMA levels may improve risk assessment in adults
Genetics and Developmental Science, School of Life Sciences and with NAFLD, while dynamic changes in ADMA could help predict the
Biotechnology, Shanghai Jiao Tong University, progression of SCA in these individuals.
Background: Pan-PPAR (peroxisome proliferator–activated receptor) Table and Figure:Figure 1.Figure 1. The association between baseline
agonist Chiglitazar has demonstrated a good safety and tolerability ADMA and subclinical carotid atherosclerosis in participants with
profile and promising effects as an insulin-sensitizing antidiabetic agent NAFLD. Multivariable model: adjusted for age, gender, smoke, disease
in China. However, its efficacy and safety in the treatment of metabolic history of hypertension and diabetes, body mass index, platelet
dysfunction-associated steatohepatitis (MASH) remain unclear. counts, ALT, AST, TC, Triglyceride, HDL, LDL, and glucose.
Method: This phase 2, multicenter, randomized, double-blind, Figure 2.Figure 2. The association between ADMA changes and
placebo-controlled study was conducted among patients with T2DM progression in subclinical carotid atherosclerosis. Multivariable model:
at high risk of MASH. Participants were randomly assigned in a 2:1 adjusted for age, gender, smoke, disease history of hypertension and
ratio to receive oral Chiglitazar (48 mg) or placebo once daily for diabetes, body mass index, platelet counts, ALT, AST, TC, Triglyceride,
24 weeks. The primary endpoint was a decrease of at least 0.22 in HDL, LDL, and glucose.
FibroScan-AST (FAST) scores, assessed in the intention-to-treat (ITT)
population. Secondary endpoints included liver enzyme levels, fibrosis PL0012
markers, and metabolic parameters. Safety indices (hemoglobin,
kidney function, bone turnover, and pro-brain natriuretic peptide) were Intestinal TM6SF2 protects against metabolic dysfunction-
evaluated in all patients. (ChiCTR2200064367). associated steatohepatitis through the gut–liver axis
Result: A total of 60 patients were randomly assigned to receive Xiang Zhang1, Harry Lau1, Suki Ha1, Chuanfa Liu1, Chichun Wong1,
chiglitazar (40 patients) or placebo (20 patients). After 24 weeks of Vincent Wong1, Jun Yu1
treatment, the improvement rate of FAST score in the chiglitazar 1
Department of Medicine and Therapeutics, Institute of Digestive
group was significantly higher than that in the placebo group (67.5% Disease, State Key Laboratory of Digestive Disease, Li Ka Shing
vs. 30.0%, P = 0.006). Liver enzymes decreased, insulin resistance Institute of Health Sciences, The Chinese University of Hong Kong,
improved in the chiglitazar group Chiglitazar was well-tolerated, with Hong Kong SAR, China.
only a small number of non-serious adverse events, occurring at a Background: Transmembrane-6 superfamily member 2 (TM6SF2)
rate similar to that of the placebo group. All safety indexes were similar regulates hepatic fat metabolism and is associated with metabolic
between two groups. dysfunction-associated steatohepatitis (MASH). TM6SF2 genetic
Conclusion: Chiglitazar demonstrated a favorable efficacy and safety variants are associated with steatotic liver disease. The pathogenesis
profile in the treatment of T2DM patients at high risk of MASH. These of MASH involves genetic factors and gut microbiota alteration, yet
findings support its further evaluation in a phase 3 trial. the role of host–microbe interactions in MASH development remains
Table and Figure:Figure 1.Primary endpoints of the study unclear.
Figure 2.Changes in clinical characteristics from baseline to week 24 Method: Mice with systematic, liver-specific, or intestine-specific
Tm6sf2 knockout (Tm6sf2ΔIEC) were fed with normal chow, high
PL0011 fat high cholesterol (HFHC), or choline-deficient high fat diet (CD-
HFD) for 2 months. Gut microbiota and metabolites were profiled by
Association between asymmetric dimethylarginine, its change metagenomic and metabolomic analysis. To determine the role of gut
and subclinical carotid atherosclerosis in non-alcoholic fatty liver microbiota of Tm6sf2ΔIEC mice, fecal microbiota transplantation was
disease performed in germ-free mice. Tm6sf2ΔIEC mice were co-housed with
Min Li1, Wei Wang1, Xintian Ren1, Pengfei Sun1, Tingting Lv1, Xinyan wildtype (WT) mice to evaluate the therapeutic potential of microbiota
Zhao1 manipulation.
1
Beijing Friendship Hospital, Capital Medical University Result: Mice with Tm6sf2ΔIEC develop MASH, accompanied by
Background: Asymmetric dimethylarginine (ADMA) is a promising impaired intestinal barrier and microbial dysbiosis. Transplanting
marker for assessing cardiovascular disease risk; however, it is unclear stools from Tm6sf2ΔIEC mice induces steatohepatitis in germ-free
whether ADMA can predict subclinical carotid atherosclerosis (SCA) in recipient mice, whereas MASH is alleviated in Tm6sf2ΔIECmice
individuals with non-alcoholic fatty liver disease (NAFLD). This study co-housed with wild-type mice. Mechanistically, Tm6sf2-deficient
aimed to investigate the association between baseline ADMA levels, intestinal cells secrete more free fatty acids by interacting with
changes in ADMA, and the risk of SCA in NAFLD adults. fatty acid-binding protein 5 to induce intestinal barrier dysfunction,
enrichment of pathobionts, and elevation of lysophosphatidic acid
(LPA) levels. LPA is translocated from the gut to the liver, contributing Cui4, Nanya Wang4, Xiujuan Qu5, Cheng Huang2, Chongyuan Xu3,
to lipid accumulation and inflammation. Pharmacological inhibition of Xueshuai Wan1, Hongyan Liu3, Naifei Chen4, Zan Teng5, Karin
the LPA receptor suppresses MASH in both Tm6sf2ΔIEC and wild-type Wisskirchen6, Xiaorui Wang6, Ke Zhang6, Ulrike Protzer7, Shukui Qin8,
mice. Hence, modulating microbiota or blocking the LPA receptor is a Jia Fan2
potential therapeutic strategy in TM6SF2 deficiency-induced MASH. 1
Peking Union Medical College, 2Zhongshan Hospital, Fudan
Conclusion: Intestinal TM6SF2 deficiency induces gut dysbiosis University, 3Nanfang Hospital, Southern Medical University, 4The
and barrier dysfunction, leading to increased translocation LPA to First Bethune Hospital of Jilin University, 5the First Affiliated Hospital
liver to promote MASH progression. Microbiota manipulation may of China Medical University, 6SCG Cell Therapy Pte Ltd, 7Institute of
be an effective strategy for the prevention of NASH driven by down- Virology, Helmholtz Munich, 8Nanjing TianYinShan Hospital
regulation of TM6SF2. Background: SCG101, a first-in-class autologous T cell receptor
Table and Figure:Figure 1.Graphical abstract (TCR)-T cell therapy targeting HBV, utilizes a natural, high-affinity
TCR and is being evaluated for its safety and efficacy in patients with
PL0013 HBV-related HCC in a Phase I IND study (NCT06617000). Here, we
summarize the antiviral outcomes of the trial.
Durability of response in Chinese responders from the global
Method: The trial enrolled 12 HLA-A*02:01(+), serum HBsAg(+), and
phase 2b study of bepirovirsen in participants with chronic
HBV-DNA≤1000 IU/mL patients with advanced HBV-related HCC
hepatitis B
(BCLC B/C, Child-Pugh≤7) who had received ≥ 2 prior systemic anti-
Man Fung Yuen1, Qing Xie2, Qin Ning3, Chuan Gu4
cancer therapies, including anti-PD-(L)1. Patients received a single
1
Queen Mary Hospital, The University of Hong Kong, 2Ruijin Hospital intravenous infusion of SCG101 at 5x107 or 1x108 cells/kg after
affiliated to Shanghai Jiao Tong University, 3Tongji Hospital, Tongji lymphodepletion. Key outcomes reported here are safety/tolerability
Medical College, Huazhong University of Science and Technology, and changes in HBV markers.
4
GSK
Result: Of the 12 patients, 11 were on antiviral treatment before and
Background: Bepirovirsen is an antisense oligonucleotide being throughout the study, and all had underlying liver cirrhosis. Baseline liver
investigated in participants with chronic hepatitis B virus (HBV) biopsies from all patients showed no detectable HBcAg, suggesting
infection. In a phase 2b study (B-Clear; NCT04449029), participants that a substantial part of HBsAg was derived from integrated HBV-DNA.
who achieved a complete (CR) or partial (PR) response following Following SCG101 infusion, 11 patients achieved a 1.0~4.6 log10 drop
bepirovirsen treatment, and who were maintaining this response of serum HBsAg within the first month, which persisted below 100 IU/
at the end of the B-Clear study (sustained response for at least 24 mL for up to 1 year. 4 patients (33%) achieved HBsAg loss. The 1x108
weeks following the end of treatment) were enrolled in a long-term cells/kg group showed a trend of faster HBsAg decline compared with
durability study (B-Sure; NCT04954859). Here we report the results of 5x107 cells/kg group. SCG101 was well-tolerated. The most common
a subgroup of Chinese participants in the B-Sure study who were ‘on’ treatment-related adverse events included elevated liver enzymes,
or ‘not-on’ nucleos(t)ide analog (NA) therapy in B-Clear. cytokine release syndrome, and cytopenia. One patient experienced
Method: CR was defined as hepatitis B surface antigen (HBsAg) <0.05 a dose-limiting toxicity of grade 3 acute kidney injury, which resolved
IU/mL and HBV DNA <lower limit of quantification (LLOQ), and PR as within 8 days with supportive care. One serious adverse reaction of
HBsAg <100 IU/mL and HBV DNA <LLOQ. If eligible, participants who disseminated intravascular coagulation was reported in 1 patient on
were on NA therapy at the start of B-Sure, discontinued NA treatment day 2 post-infusion, from which the patient recovered within 14 days
at month 3, and functional cure (FC) was defined as HBsAg and HBV without sequelae. ALT elevations (Grade ≥3 in 9/12 patients, lasting
DNA < LLOQ 6 months after NA cessation (month 9). Participants who 3~9 days) correlated with HBsAg reduction was observed, suggesting
were not on NA would be considered as FC if CR was maintained at on-target activity. Ten patients had HBV-DNA below LOD at baseline;
month 3 of B-Sure (9 months off bepirovirsen). 8 of them maintained HBV-DNA suppression throughout the study,
Result: 6 Chinese participants with a response (3CRs, 3 PRs) at the and 2 exhibited a transient elevation for 2-3 days post-infusion, which
end of B-Clear study were enrolled into B-Sure and included in this may have resulted from the killing of HBV+ hepatocytes and the
analysis. Baseline characteristics at the entry of B-Clear: male 4/6 subsequent release of HBV-DNA-containing capsids and integration
(66.7%), median age 44.5 years (range 24 – 56); all 6 were HBeAg fragments. Among the 2 patients with detectable baseline HBV-DNA,
negative, 3/6 were HBsAg ≤ 1000 IU/ml, and 3/6 were on-NA. Among one achieved suppression post-infusion, while the other experienced
the 1 CR and 2 PRs who were on NA, NA was discontinued in all a 0.9log10 increase.
3 participants at month 3 of B-Sure. FC was achieved in the 1 CR Conclusion: SCG101 demonstrated a rapid and sustained serum
participant and the response was maintained up to 9 months post-NA HBsAg reduction in advanced HBV-HCC patients that can be
cessation. For the 2 on-NA PRs, 1 maintained response through to attributed to its cytolytic activity targeting hepatocytes and HCC cells
6 months post NA cessation (the latest timepoint for which they had with integrated HBV-DNA. The sustained reduction in HBsAg, along
data available at the time of the data-cut), and 1 lost PR following NA with the >30% HBsAg loss observed in this difficult-to-treat population,
cessation and restarted NA due to virologic breakthrough. The 2 not- demonstrates SCG101’s potential to be a curative treatment option for
on-NA CR’s who entered B-Sure maintained a CR at 3 months follow- chronic HBV infection.
up in B-Sure, and therefore achieved FC. They were still maintaining Table and Figure:Figure 1.
this response at 9 months follow-up in B-Sure. The 1 not-on-NA PR
who entered B-Sure did not maintain PR and demonstrated HBV DNA
reversion before 3 months of follow-up in B-Sure. None of the not-on-
PL0015
NA participants had started on NAs, and no safety signals related to Combination treatment of TLR7 agonist and anti-PD-L1
the use of bepirovirsen were observed. reconstitute protective immunity in virally suppressed chronic
Conclusion: This interim analysis of the B-Sure study provides hepatitis B patients
evidence of durability of functional cure by bepirovirsen in a subset Yuying Chen1, Ting Wu1, Di Wu1, Zhize Yuan1, Da Huang1, Wei Yuan1,
of Chinese participants with chronic HBV infection especially in those Yizhi Wu1, Jiang Chang1, Weiming Yan1, Qin Ning1
with CR. The study is ongoing for recruitment and follow-up. 1
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic
Funding: GSK sponsored study 206882 Infectious Diseases, Department and Institute of Infectious Disease,
Tongji Hospital, Tongji Medical College, Huazhong University of
Science and Technology
PL0014
Background: The combination treatment of Toll-like receptor
SCG101 TCR-T Therapy Achieves Rapid and Sustained HBsAg
(TLR) 7 agonist TQ-A3334 and PD-L1 inhibitor TQ-B2450 has been
Reduction with >30% HBsAg Loss in HBV-Related Hepatocellular
demonstrated to induce a remarkable decline of HBsAg in viral-
Carcinoma Patients
suppressed chronic hepatitis B (CHB) patients with good safety and
Shunda Du1, Huichuan Sun2, Jinlin Hou3, Xiaowu Huang2, Jiuwei
tolerability in a pilot RCT phase II study (OCEAN cure05 Study). In were quantified and sequenced using inverse PCR coupled with digital
this study, we aimed to characterize the immunological features droplet PCR or targeted sequencing. Expression of HBx transcripts
responsible for the efficacy of combination therapy. was measured using quantitative 5’ rapid amplification of cDNA ends
Method: Totally 24 nucleos(t)ide analogues (NUCs)-treated CHB (5’RACE). HBx function was analyzed using western blot to quantify
patients were randomized to receive Entecavir (ETV) monotherapy SMC5/6 and γ-H2AX (marker for DNA damage). The functional
(n=6), ETV+TQA3334 dual therapy (n=9) or NA+TQA3334+TQB2450 consequences of HBx were also determined by infecting the clones
triple therapy (n=9) for 24 weeks and then followed up for 24 weeks. with wild-type HBV and quantifying integration rates using inverse PCR.
Serum and Peripheral Blood Mononuclear Cells (PBMCs) were Result: The HepG2-NTCP clones each contained 1-2 copies of
collected at indicated timepoints. The levels of Interferon Stimulating integrated HBV DNA and the sequence for SMC5/6 degradation (amino
Genes (ISGs) and cytokines were analyzed by Quantitative Polymerase acids 45 to 140) was present in >85% of integrations. Quantitative
Chain Reaction (qPCR) and electrochemiluminescence assay, 5’RACE revealed that HBx expression in the clones ranged from
respectively. Hepatitis B virus (HBV) specific CD8+T cell responses 3 - 518 copies/1000 ng RNA, on average ~4-fold lower than HBV-
were determined by flow cytometry. Then in vitro conditioned culture infected cells expressing HBx from cccDNA. The integration-derived
system was conducted for further validation. HBx appeared to be functional: compared to parental cells, SMC5/6
Result: Compared to NA monotherapy and dual therapy, triple therapy (DNA stabilizer complex) was reduced by 1.7-fold (p=0.0013, a one-
was associated with greater HBsAg reduction at the end of treatment sided t-test) and γ-H2AX (DNA damage marker) was increased by
(EOT). After 12 weeks of treatment, expression level of MX1 and ISG15 3.6-fold (p=0.0024, a one-sided t-test) in cells with transcriptionally-
significantly elevated among patients received triple therapy. The active integrations. These changes were not as marked in clones with
patients receiving triple therapy displayed significantly higher level of low HBx expression [no reduction in SMC5/6 and 2.9-fold increase
IFN-α, IFN-γ, IP-10 and soluble PD-1 as well as lower soluble PD-L1 at in γ-H2AX (p=0.0259, a one-sided t-test)] showing dependence of
week 12. While after 24 weeks of treatment, the IL-21 level in patients these changes on HBx. This increased DNA damage had functional
with triple therapy significantly increased and was the highest among consequences: cells with integrations were 2-12-fold more susceptible
the three treatment groups, the sPD-L1 level reduced to the lowest. In to additional integrations after a new HBV infection.
terms of HBV specific CD8+T cells, patients receiving triple therapy Conclusion: Cells with HBV integrations can express functional HBx
demonstrated significantly increased production of IFN-γ, TNF-a, and may be more susceptible to additional integrations, promoting a
degranulation specific for core peptides, and polymerase peptides self-amplifying process (Figure 1). The resultant exponential increase
specific IFN-γ, degranulation as well as envelope peptides specific in genomic instability then fuels accelerated acquisition of cancer
IFN-γ at EOT. And the elevation of core specific CD8+T IFN-γ remained driver mutations. Ongoing work will determine the role of HBx in this
significantly at 24w after treatment. Using a primary PBMCs culture process.
system in the presence of HBV peptides, co-stimulation of TQ-A3334 Table and Figure:Figure 1.Figure 1 A hypothetical model with feed-
and TQ-B2450 resulted in a significant increase in the frequency of forward loops
core and polymerase pentamer specific CD8+T cell in HLA-A2 positive
CHB patients. In a co-culture system containing PBMCs and HepAD38
PL0017
cell line, TQA-3334 in combination with TQB-2450 triggered obviously
higher lysis rate of HepAD38, accompanied with a accelerated HBV HBsAg loss in Inactive Chronic Hepatitis B Carriers is dependent
DNA level decline. on level of qHBsAg and interferon response: A Randomised
Conclusion: The combination of TLR7 agonist and anti-PD-L1 could Control Trial
reconstitute antiviral immunity in virally suppressed CHB patients by Seng Gee Lim1,2, Guan Huei Lee1, Yock Young Dan1,2, Yin Mei Lee1,
inducing the production of ISGs, antiviral cytokines, and reinvigorating Htet Htet ToeWaiKhine2, Amy Tay2, Cindy XiaYih Seah1, Shem Liang3,
HBV-specific CD8+T cell response, thus potentially favoring improved Edwin Chan4,5, Martin L Hibberd6
clinical outcome. 1
Division of Gastroenterology and Hepatology, National University
Table and Figure:Figure 1.Dual or Triple therapy altered cytokines and Health System, Singapore, 2Dept of Medicine, 3Biostats Unit, Yong Loo
ISGs level Lin School of Medicine, National University of Singapore, Singapore,
Figure 2.Triple therapy induces broader and stronger HBV specific
4
Singapore Clinical Research Institute, Singapore, 5Duke-NUS Medical
CD8+T cells respons School, Singapore, 6Faculty of Infectious and Tropical Diseases,
London School of Hygiene and Tropical Medicine, London, United
Kingdom
PL0016
Background: Peginterferon therapy of Chronic Hepatitis B (CHB)
Investigating HBV DNA integration and its role in genomic carriers how mixed results for HBsAg loss, but its unclear whether
instability through HBx expression low qHBsAg(<1000IU/ml) or low HBV DNA (<2000IU/ml) are more
Dong Li1, Vikki Ho1, Jochen M Wettengel2, Sarah Bae1, Henrik important
Zhang1, Harout Ajoyan1, Delgerbat Boldbaatar1, Gabriela Wu1, Ulrike Method: This was a 3-arm RCT of peginterferon alpha2a (PEG)
Protzer2, Jacob George1,3, Mark W Douglas1,3, Thomas Tu1,3 (pegasys, Roche) 180mcg weekly randomised 1:1:1 to 24
1
Westmead Institute for Medical Research, 2Institute of Virology, weeks(PEG24), 48 weeks(PEG48) or no treatment(C) in CHB
Technical University of Munich, 3Sydney Infectious Diseases Institute carriers(clinicaltrials.gov:NCT02992704). Patients were randomly
Background: Hepatitis B virus (HBV) infection causes >60% of assigned based on: HBsAg(+)>6months, HBeAg(-), normal ALT,
primary liver cancer (hepatocellular carcinoma, HCC), resulting in over HBV DNA ≤2x104IU/ml or qHBsAg≤1000IU/ml; absence of cirrhosis,
1 million deaths annually. Most HCC contain HBV DNA integrations, treatment naive, absence of HCV/HDV/HIV coinfection. The primary
suggesting they are linked, but the mechanism remains unknown. HBV endpoint was HBsAg loss 24weeks after treatment, and study size of 90
integration occurs at double stranded DNA breaks in the host genome patients had 80% power to detect a 25% difference between any PEG
in ~1/10,000 cells. A viral protein expressed by integrations is the HBV arm and control. Data analysis was performed using SPSSv20 based
X protein (HBx), which has been reported to induce genomic instability on ITT analysis. Baseline and on-treatment variables and multivariate
by degrading the structural maintenance of chromosome 5/6 (SMC5/6) analysis were used to predict HBsAg loss at end-of-treatment(EOT)
complex. However, integration-derived HBx often contains C-terminal and end of 24weeks followup(FU24). PAXgene transcriptome analysis
truncations, and the effects of these mutations are not known. We was performed on relevant patients.
hypothesise that integration-derived HBx enables increased DNA Result: Baseline characteristics were similar between groups.
damage (like wild type HBx), inducing more integrations, fostering a HBsAg loss occurred in a total of 7/30(23.3%) in PEG48, 9/30(30%)
feed-forward loop and HCC development. in PEG24 and 0/30(0%) in C at the EOT(p=0.007) but 5/30(16.7%) in
Method: We characterized integrated HBV DNA by generating 118 PEG48, 5/30(16.7%) in PEG24 and 1/30(3.4%) in C at FU24(p=0.169).
HepG2-NTCP-derived clones using a recombinant reporter HBV Baseline predictors of HBsAg loss at FU24 showed qHBsAg was the
expressing a Zeocin-resistance gene (in place of HBs). Integrations only significant factor by multivariate logistic regression (p=0.019).
ROC curve analysis showed baseline qHBsAg<88 IU/ml had groups. The ICG-HSA group had significantly higher fluorescence
AUROC of 0.896 for HBsAg loss at FU24. . There were four distinct imaging scores (4.78 ± 0.92 vs. 3.99 ± 1.01, P = 0.002), less
patterns(clusters) of interferon response despite qHBsAg<88IU/ml, intraoperative blood loss (100.0 [50.0-200.0] vs. 200.0 [100.0-350.0],
based on their HBsAg reduction at week 12. cluster 1 had  moderate P = 0.017), and lower ALT levels on postoperative day 3 (257.0 [201.0-
baseline qHBsAg (21.13 IU/ml minimal reduction in HBsAg (0.25 log) 370.0] vs. 113.0 [66.0-202.0], P < 0.005). No significant differences
and no HBsAg loss; cluster 2 had very low baseline HBsAg (0.38 were observed between groups for operative time, postoperative
IU/ml) and minimal reduction in HBsAg (0.34 log) with 4/6(66.7%) complications, or length of hospital stay.
HBsAg loss; cluster 3 also had low baseline HBsAg (7.35 IU/ml) Conclusion: The ICG-HSA complex demonstrated superior
but moderate reduction in HBsAg (1.66 log) with 6/10 (60%) HBsAg optical performance and stability compared to free ICG, improving
loss; and cluster 4 had the highest baseline HBsAg (43.49 IU/ intraoperative liver segment localization and reducing intraoperative
ml) and the greatest reduction in qHBsAg (2.55 log) with 4/5 (80%) blood loss. This novel complex offers a safe and effective alternative
HBsAg loss (fig 1). We examined responders and non-responders for fluorescence-guided laparoscopic anatomic liver resection, with
using PAXgene transcriptome analysis and found that responders potential to improve surgical outcomes and postoperative liver function.
had 55 differentially expressed genes of which 37 were upregulated Table and Figure:Figure 1.Method
(fig 2). The most significantly upregulated was MMP8 and a cluster Figure 2.Short-term Outcomes
of 13 genes which were enriched in the neutrophil degranulation
pathway (p=5.59x10-12).  There were 282 adverse events mostly
PL0019
interferon related(90%). There were 4 Serious Adverse Events but no
deaths. A novel HCV micro-elimination model: government-led hospital-
Conclusion: HBsAg loss with PEG in inactive carriers leads to 16.7% drug rehabilitation center cooperation (GHRC) in Southwest China
HBsAg loss with low baseline qHBsAg and interferon responsiveness Siyuan Gao1, Junyi Li1, Xiaodong Yang1, Fangrong Zhang1, Ting Jia1,
driving HBsAg loss but not HBV DNA. A novel neutrophil enriched Jia Xia1, Jiangyan Zhang1, Xiuling Zhang1, Zhengyou Li2, Li Li3, Qiu
pathway was found in responders based on transcriptome analysis Jin1, Xuan Yang1
Table and Figure:Figure 1. 1
The Third People‘s Hospital of Kunming, 2No. 5 Drug Rehabilitation
Figure 2. Center of Yunnan Province, 3Women‘s Drug Rehabilitation Center of
Yunnan Province
PL0018 Background: In China, achieving the WHO goal by 2030 remains a
significant challenge. Unlike other regions in the country, hepatitis C
Efficacy Analysis of a Novel Indocyanine Green-Human
transmission in Yunnan Province is predominantly associated with IV
Serum Albumin Complex (ICG-HSA) Assisted Near-Infrared
drug use. Consequently, it is crucial to promote effective screening
Fluorescence-Guided Laparoscopic Anatomic Liver Resection
algorithms and enhance treatment options for hepatitis C among
for Hepatocellular Carcinoma: A Single-Center, Double-Blind,
people who inject drugs (PWID). This study aims to investigate a co-
Prospective Randomized Contr
operation model for hepatitis C screening and treatment among PWID
Qingyun Xie1, Fengwe Gao1, Kun Li2, Hong Wu1 in Yunnan Province.
1
Liver Transplantation Center, State Key Laboratory of Biotherapy Method: A novel hepatitis C screening model, termed the government-
and Cancer Center, West China Hospital, Sichuan University and led hospital- drug rehabilitation center cooperation (GHRC), has
Collaborative Innovation Center of Biotherapy, 2Laboratory of Green been established in Kunming, Yunnan Province. Governments
Chemistry and Technology of Ministry of Education, College of funded, compiled lists of patients requiring screening, and facilitated
Chemistry, Sichuan University communication with hospitals. All patients in the drug rehabilitation
Background: Indocyanine green (ICG)-mediated near-infrared (NIR) centers would receive HCV-Ab screening. Those with HCV-Ab (+)
fluorescence imaging improves visualization of tumor lesions and would receive HCV RNA testing. HCV viremic patients would receive
liver anatomy during resection, reducing postoperative complications SOF/VEL±RBV treatment for 12 weeks. Throughout this process, a full
and enhancing tumor resection radicality. However, after intravenous time nurse at the drug rehabilitation centers collected blood samples
injection, ICG’s binding to vascular endothelium and degradation by free then subsequently sent to designated hospital for testing. Hepatology
radicals lead to fluorescence drift and reduced efficiency. Additionally, specialists at the hospital provided consultations and prescribe
ICG’s poor solubility, concentration-dependent aggregation, and DAAs . Hospital doctors offer guidance to drug rehabilitation centers
short liver retention time limit its use. To address these issues, we physicians during follow-up period. (Figure 1).
developed a novel ICG-human serum albumin (ICG-HSA) conjugate Result: From May 2023 to October 2024, The Third People’s Hospital
nanocomplex, designed to stabilize ICG in the bloodstream and of Kunming collaborated with five drug rehabilitation centers. A total
enhance liver-targeted uptake, minimizing fluorescence heterogeneity of 143 patients tested positive for HCV antibodies, among which data
and degradation. We conducted a prospective randomized controlled was complete for 138 patients. 84% (116/138) of patients were HCV
trial to compare the fluorescence navigation accuracy, success rate, RNA (+), and 86 completed treatment. 31 individuals (36.0%) achieved
and perioperative outcomes between ICG-HSA and conventional SVR24, while 40 patients (46.5%) attained SVR 12, and 15 patients
ICG in laparoscopic liver resection for hepatocellular carcinoma (17.4%) reached the end of treatment (EOT). There were 30 HCV RNA-
(NCT06219096). positive patients who either did not receive or did not complete DAAs
Method: The ICG-HSA complex was tested in vitro for absorbance treatment (Figure 2). In comparison to traditional hepatitis C screening
and stability under different solvents, concentrations, ratios, and methods employed in drug rehabilitation centers—where few patients
temperatures. After optimization, it was applied clinically. From were screened for HCV antibodies and subsequently received DAAs
January to September 2024, hepatocellular carcinoma patients treatment—the rates of HCV RNA testing among antibody-positive
eligible for fluorescence-guided laparoscopic anatomic liver resection patients and the overall treatment rate, have shown significant
were randomly assigned to either the ICG-HSA group or the free improvement. Most common adverse events (AEs) were fatigue and
ICG group (1:1 ratio). Both groups received Glissonean pedicle nausea due to ribavirin, which were effectively managed by dose
clamping with peripheral venous injection of either ICG or ICG-HSA, reduction. No serious adverse events (SAEs) were reported, and no
followed by fluorescence-guided liver resection. Surgical videos were patient discontinued treatment due to AE.
independently scored by three experts for fluorescence imaging Conclusion: In regions where PWID constitute the primary population
quality, and perioperative outcomes were compared between the of HCV patients, the GHRC model demonstrates a higher rate of HCV
groups. RNA testing and a greater treatment rate with DAAs compared to
Result: The ICG-HSA complex showed optimal stability and traditional HCV screening and treatment models. During DAAs antiviral
absorbance at a mass molar ratio of 1:6 and 37°C. A total of 62 patients therapy within the GHRC framework, adverse reactions[MY1] can be
were randomly assigned to the ICG-HSA group (31) and the free ICG more effectively monitored and managed, leading to an increased SVR
group (31). Baseline characteristics were comparable between the rate. This model merits promotion as a means to achieve enhanced
HCV clearance. in dietary lifestyle, the overlap between chronic hepatitis B (CHB) and
Table and Figure:Figure 1.Figure 1. A novel government-led hospital- metabolic dysfunction-associated steatotic liver disease (MASLD) has
prison/drug rehabilitation center cooperation (GHRC) model for HCV been growing. Our study aimed to explore the impact of HBV infection
micro-elimination on liver fibrosis progression in patients with MASLD.
Figure 2.Figure 2. Comparison of Traditional Model vs GHRC Model in Method: We enrolled MASLD patients who underwent liver biopsy at
Third People’s Hospital of Kunming- a single center practice 16 medical centers across China between April 2004 and April 2024.
Both univariable and multivariable logistic regression analyses were
conducted to examine the association between CHB and significant
PL0020
fibrosis, advanced fibrosis, and cirrhosis. Propensity score matching
Prospective observation of liver stiffness in SVR cases using (PSM) was used to adjust for potential confounders, ensuring a
Fibro-scan -Liver stiffness changes plateau after 5 years, but balanced comparison between patients with and without CHB.
carcinogenesis continues- Result: A total of 2,787 MASLD patients (Median age 43.5years,
Shuntaro Obi1,2, Yoshiki Asahina1, Kowa Nagasaka1, Tomoyoshi 58.9% male) were included in the study, with 1,811 (65.0%) having
Murata1, Hiroyuki Amano1, Shinya Takaoka1, Yuji Imai1, Yukiko DM. Multivariate regression analysis suggested that the combination
Asakawa1, Mizuho Hirose1, Youji Suzuki1, Hitoshi Mochizuki3, Yuichiro of CHB was an independent risk factor for significant fibrosis (before
Kojima1, Masao Omata1,4 PSM: OR 1.83, 95% CI: 1.52-2.20, p < 0.01; after PSM: OR 1.64, 95%
1
Gastroenterology, Yamanashi Central Hospital, 2Teikyo University CI: 1.26-2.15, p < 0.01), advanced fibrosis (before PSM: OR 1.63, 95%
Chiba Medical Center, 3Genome analysis Center, Ymanashi Centeral CI: 1.20-2.23, p < 0.01; after PSM: OR 1.75, 95% CI: 1.20-2.57, p <
Hospital, 4The University of Tokyo 0.01), and cirrhosis (before PSM: OR 2.18, 95% CI: 1.32-3.61, p <
Background: We have previously reported the fibrosis regression rate 0.01; after PSM: OR 2.46, 95% CI: 1.40-4.66, p < 0.01) in patients with
after HCV eradication using liver biopsy (Ann Intern Med 1999). In MASLD. In addition, sensitivity analyses were performed in different
this study, we prospectively observed changes in fibrosis due to DAA levels of HBeAg and HBV DNA and in HBV patients not receiving
treatment from 2015 using Fibro-scan (FS) stiffness as an alternative antiviral treatment previously, the conclusions were consistent with
index. previous findings.
Method: 689 cases that underwent HCV eradication using DAA from Conclusion: Our study demonstrated evidence that the combined
July 2013 to December 2023 were prospectively observed for an CHB was an independent risk factor for significant fibrosis, advanced
average of 6.1 years, with the longest observation period being 10.4 fibrosis and cirrhosis in patients with MASLD.
years. The progression of liver stiffness was observed by dividing the Table and Figure:Figure 1.Multivariable logistic regression for
patients into four groups based on the liver stiffness measured by the significant fibrosis, advanced fibrosis, and cirrhosis in MASLD patients
FS: Group I (stiffness of less than 4 kPa), Group II (stiffness of 4 to less with and without CHB after propensity score matching.
than 8 kPa), Group III (stiffness of 8 to less than 12 kPa), and Group
IV (stiffness of 12 kPa or more). The incidence of HCC was compared PL0022
between the groups.
TOX3 promotes liver fibrosis by regulation of hepatic immune
Result: The progress of 505/689 cases (77%) could be followed
microenvironment and crosstalk with hepatocyte
up using FS. A total of 3,006 FS procedures were performed, with a
median of 6.0 procedures per patient (maximum of 15). In Group I Shaoping She1,2, Yao Yang1,2, Liying Ren1,2, Xue Zhang1,2, Dongbo
(n=29), the change in liver stiffness was 0.34 at 1 year, 0.02 at 3 years, Chen1,2, Feng Liu1,2, Huiying Rao1,2, Hongsong Chen1,2
0.14 at 5 years, and 0.05 at 7 years, and the incidence of cancer was
1
Peking University People‘s Hospital, Peking University Hepatology
0%. Group II (n=206) had a change in liver stiffness of -0.29 at 1 year, Institute, 2Infectious Disease and Hepatology Center of Peking
-0.13 at 3 years, -0.11 at 5 years, and -0.17 at 7 years, with a cancer University People‘s Hospital, Beijing Key Laboratory of Hepatitis
rate of 6%. Group III (n=116) had a rate of -1.10 at 1 year, -0.28 at 3 C and Immunotherapy for Liver Diseases, Beijing International
years, -0.24 at 5 years, and -0.08 at 7 years, with a cancer rate of 9%. Cooperation Base for Science and Technology on NAFLD Diagnosis
Group IV (n=154) was -2.42 at 1 year, -1.09 at 3 years, -0.11 at 5 years, Background: Metabolic dysfunction-associated steatotic liver disease
and 0.13 at 7 years, with a cancer rate of 31%. (MASLD) is now the most common cause of chronic liver disease
Conclusion: In cases of mild liver stiffness (Groups I and II), there globally, affecting over 30% of adults.Thymocyte selection-associated
were only minor changes in liver stiffness and the incidence of cancer high mobility group box factor 3 (TOX3) is a member of an evolutionarily
was low. In cases of advanced liver stiffness (Groups III and IV), conserved DNA-binding protein family. Our previous study found
dynamic changes in liver stiffness were observed, but after 5 years that TOX3 could promote the progression of hepatocellular carcinoma
there was a tendency for the changes to plateau, and the incidence of (HCC) through the p53/p21 signaling pathway. However, the role
cancer continued. Therefore, it is necessary to continue to monitor the and mechanism of TOX3 in chronic liver disease have not yet been
progress of cancer. elucidated.
Method: The expression of TOX3 was detected in patients with chronic
liver diseases and several murine models of liver fibrosis induced
PL0021
by carbon tetrachloride (CCl4) injection, bile duct ligation (BDL),
THE ROLE OF CHRONIC HEPATITIS B IN ACCELERATING methionine-choline deficiency (MCD) diet or 5-diethoxycarbonyl-
FIBROSIS PROGRESSION IN METABOLIC DYSFUNCTION- 1,4-dihydrocollidine (DDC) diet. The role of TOX3 was evaluated
ASSOCIATED STEATOTIC LIVER DISEASE in heterozygous Tox3 gene knockout (Tox3+/-) mice and hepatocyte-
Fajuan Rui1, Yixuan Zhu1, Liang Xu2, Jing Zhang3, Qi Zheng4, specific Tox3 knockout (Tox3Hep) mice in vivo. Direct effects of
Minghua Zheng5, Haijun Huang6, Yongfeng Yang7, Youwen Tan8, TOX3 on hepatocytes (AML12 and THLE-2) and hepatic stellate cells
Chao Wu1, Yuemin Nan9, Qing Xie10, Junping Shi11, Jie Li1 (HSCs) (LX-2) were studied in vitro. Single-cell sequencing was used
1
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, to explore the molecular mechanism of TOX3 regulation of liver fibrosis
Nanjing University, 2Tianjin Second People‘s Hospital, 3Beijing Youan progression.
Hospital, Capital Medical University, 4The First Affiliated Hospital, Result: In this study, we found that TOX3 was significantly
Fujian Medical University, 5The First Affiliated Hospital of Wenzhou downregulated in fibrotic/cirrhotic tissues from patients with multiple
Medical University, 6Zhejiang Provincial People’s Hospital,, 7The etiologies and in mice treated with CCl4 injection, BDL, MCD diet
Second Hospital of Nanjing, 8The Third Hospital of Zhenjiang Affiliated and DDC diet. TOX3 deficiency resulted in a marked amelioration
Jiangsu University, 9The Third Hospital of Hebei Medical University, of of hepatic injury and fibrosis. At the same time, the secretion
1
0Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, of various proinflammatory cytokines in the serum and tissue
1
1The Affiliated Hospital and Institute of Hepatology and Metabolic of Tox3+/- and Tox3Hep mice was also significantly reduced. In vitro,
Disease of Hangzhou Normal University we found that the overexpression of TOX3 could directly promote
Background: With the increasing prevalence of obesity and changes the activation and survival of human LX-2 cells, while knockdown of
TOX3 inhibits the activation and survival of LX-2 cells. Single-cell Kappus116, Andrew Keaveny117, Andres Duarte Rojo118, Ricardo
sequencing showed that the proportion of hepatocytes in the liver Cabello Negrillo118, Elizabeth Verna119, Qing Xie59
decreased significantly due to TOX3 deficiency, while the proportion 1
University of Toronto, Toronto, Canada, 2Virginia Commonwealth
of neutrophils, mononuclear/macrophages, T lymphocytes and other University and Central Virginia Veterans Healthcare System,
immune cells increased significantly. Richmond, 3Department of Hepatology, ILBS, Delhi, 4Mayo Clinic
Conclusion: Taken together, TOX3 promotes hepatic injury and School of Medicine, Rochester, 5St Paul’s Hospital, Millenium Medical
fibrosis by regulation of hepatic immune microenvironment and College, Addis Ababa, Ethiopia, 6University of Edinburgh, Edinburgh,
crosstalk with hepatocytes. The results are expected to clarify the role UK, 7Instituto Nacional de Ciencias Médicas y Nutrición Salvador
and mechanism of TOX3 in the liver immune microenvironment for Zubirán, Mexico City, Mexico, 8Ankara University School of Medicine,
the first time, and indicate that TOX3 may be a potential therapeutic Ankara, Turkey, 9Department of Medicine, School of Clinical Medicine,
target for the treatment of MASLD. The University of Hong Kong, Hong Kong, China, 10Hospital de
Clínicas de Porto Alegre, Universidade Federal do Rio Grande
do Sul, Porto Alegre, Brazil, 11Storr Liver Centre, The Westmead
PL0023 Institute for Medical Research and Westmead Hospital, University
Chronic Kidney Disease in Hospitalized Patients with Cirrhosis, a of Sydney, Sydney, Australia, 12Virginia Commonwealth University,
Global Perspective Richmond, 13The Third People‘s Hospital of Guilin, 14The Fifth
Florence Wong1, Jasmohan S Bajaj2, Ashok K Choudhury3, Patrick S People‘s Hospital of Suzhou, 15The First Affiliated Hospital of Guangxi
Kamath4, Mark Topazian5, Peter C Hayes6, Aldo Torre7, Hailemichael Medical University, 16The First Hospital of Jilin University, 17The
Desalegn5, Ramazan Idilman8, Wai Kay Seto9, Mario Reis ALVARE- Second Xiangya Hospital of Central South University, 18The Third
DA-SILVA10, Jacob George11, Brian Bush12, Leroy R Thacker12, Affiliated Hospital of Hebei Medical University, 19Second Hospital
of Shandong University, 20The First Affiliated Hospital of Wenzhou
Yongchao Xian13, Jin Guan13, Chuanwu Zhu14, Yingling Wang14,
Medical University, 21Traditional Chinese Medicine Hospital of Xinjiang
Minghua Su15, Man Su15, Yanhang Gao16, Xinrui Wang16, Yongfang
Uygur Autonomous Region, 22Zhongshan Hospital, Fudan University,
Jiang17, Feng Peng17, Caiyan Zhao18, Wei Wang18, Lei Wang19, 2
3School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University,
Dedong Yin19, Ming Qin Lu20, Yijing Cai20, Xiaozhong Wang21, Feng 2
4Department of Infectious Disease, Union Hospital, Tongji Medical
Guo21, Ningping Zhang22, Wanqin Zhang22, Hai Li23, Fuchen Dong23, College, Huazhong University of Science and Technology, Wuhan,
Xin Zheng24, Jing Liu24, Hong TANG25, Libo Yan25, Bin Xu26, Linlin China, 25Center of Infectious Disease, West China Hospital of Sichuan
Wei26, Zhiliang Gao27, Zhen Xu27, Minghua Lin28, Haibing Gao28, University, 26Beijing Youan Hospital, Capital Medical University,
Xiaoping Wu29, Qunfang Rao29, Jinjun Chen30, Beiling Li30, Chenghai 2
7The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou,
Liu31, Yanyun Zhang31, Peng Hu32, Huan Deng32, Jie Li33, Jian Wang33, 2
8Mengchao Hepatobiliary Hospital of Fujian Medical University,
James Fung34, Abha Nagral35, Amey Sonavane35, Aabha Nagral36, 2
9The First Affiliated Hospital of Nanchang University, 30Nanfang
Ajay Jhaveri37, Anand Kulkarni38, Mithun Sharma38, Shiv K Sarin39, Hospital, Southern Medical University, 31Shuguang Hospital Affiliated
Ashish Goel40, C E Eapen40, Ajay Duseja41, Akash Gandotra41, to Shanghai University of Traditional Chinese Medicine, 32Second
Anoop Saraya42, Jatin Yegurla42, Dinesh Jothimani43, Mohammad Affiliated Hospital of Chongqing Medical University, 33Nanjing Drum
Rela43, Anil Arora44, Ashish Kumar44, Akash Roy45, R K Dhiman45, A C Tower Hospital, The Affiliated Hospital of Nanjing University Medical
Anand46, Dibyalochan Praharaj46, Radha VALSAN47, Akash Shukla48, School, 34School of Clinical Medicine, The University of Hong Kong,
Arun Vaidya48, Fiona Tudehope49, Scott Davison50, Tahrima Kayes50, 3
5Apollo Hospitals, Delhi, 36Jaslok Hospital, Mumbai and Apollo
Alexander Prudence51, Robert Gibson51, Amany Zekry52, Adam Hospital, Navi Mumbai, 37Jaslok Hospital, Mumbai, 38Asian institute
Doyle53, Hooi Ling Si53, Cameron Gofton54, Yu Sung Kim54, Stephen of Gastroenterology, Hyderabad, 39Institute of Liver and Biliary
Riordan55, Gerry MacQuillan56, Hala Al-Tamimi56, Fiona Tudehope57, Sciences, Delhi, 40Christian Medical College, Vellore, 41PGIMER,
Robert Feller57, Hiang Keat Tan58, Liou Wei Lun58, Zhujun Cao59, Wei Changdigarh, 42AIIMS, New Delhi, 43Dr. Rela Institute and Medical
Ling Danielle Ho60, Yu Jun Wong60, Kessarin Thanapirom61, Tongluk Centre, Chennai, 44Sir Ganga Ram Hospital, Delhi, 45Sanjay Gandhi
Teerasarntipan61, Busra Haktaniyan62, Coskun Ozer Demirtas63, Postgraduate Institute of Medical Research, Lucknow, 46KIMS,
Hasan Basri Yapici63, Sezgin Barutcu64, Alper Uysal65, Zeki Karasu65, Bhubaneswar, Odisha, 47AMRITA INSTITUTE OF MEDICAL SCIENCE,
Enver Ucbilek66, Tolga Kosay66, Dinc Dincer67, Haydar Adanır67, Shiva
4
8KEM hospital, Mumbai, 49Westmead Hospital, Sydney, 50Liverpool
Hospital, 51John Hunter Hospital, Newcastle, 52St George Liver
Kumar68, Adrian Gadano69, Sebastian Marciano69, Nargiz Afandi70,
Clinic, 53Royal Perth Hospital, Perth, 54Royal North Shore Hospital,
Sevda Agayeva70, Farhad Hossen71, Shahinul Alam71, Matheus 5
5Prince of Wales Hospital, Sydney, 56Sir Charles Gairdner Hospital,
Michalczuk10, Alberto Farias72, Patricia Zitelli72, Gustavo Pereira73, 5
7St Vincent‘s Hospital, Sydney, 58Singapore General Hospital,
Livia Victor73, JOAO ROGERIO OLIVEIRA74, LILIANA MENDES74, 5
9Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,
Chinmay Bera75, Nabiha Faisal76, Monica Dahiya77, Puneeta Tandon77, Shanghai, China, 60Department of Gastroenterology & Hepatology,
Marie Jeanne Lohoues78, Ponan Claude Regis Lah78, Carlos Changi General Hospital, Singapore, 61Chulalongkorn University and
Benítez79, Marco Arrese79, Dominik Bettinger80, Michael Schultheiß80, King Chulalongkorn Memorial Hospital, Bangkok, Thailand, 62Ankara
Christian Labenz81, Simon Johannes Gairing81, Hibat Allah Belimi82, University, School of Medicine, Ankara, 63Marmara University School
Nabil Debzi82, Alaa Mostafa83, Yasser Fouad83, Henok Fisseha84, of Medicine, Istanbul, 64Gaziantep University School of Medicine,
Abate Shewaye85, Abdullah Emre Yildirim64, Kaleb Berhane85, Gaziantep, 65Ege University School of Medicine, Izmir, 66Mersin
Aloysious D Aravinthan86, Suresh Vasan Venkatachalapathy87, Neil University School of Medicine, Mersin, 67Akdeniz University School
Rajoriya88, Rosemary Faulkes88, Damien Leith89, Ewan Forrest89, of Medicine, Antalya, 68Cleveland Clinic Abu Dhabi, 69Hospital
Danielle Adebayo90, James Kennedy90, Diana Yung91, Alexandra Italiano de Buenos Aires, Argentina, 70Azerbaijan, 71Bangabandhu
Alexopoulou92, Iliana Mani92, Dor Shirin93, Helena Katchman93, Edita Sheikh Mujib Medical University (BSMMU), 72Hospital das Clínicas
Kiudeliene94, Juozas Kupcinskas94, Araceli Bravo Cabrera95, Sarai da Faculdade de Medicina da Universidade de São Paulo,
Gonzalez Hueso95, Jose Luis Perez Hernandez96, Oscar Morales 7
3Hospital Federal de Bonsucesso, 74Hospital de Base do Distrito
Gutierrez96, Abraham Ramos-Pineda97, Godolfino Miranda Zazueta97, Federal, 75University of Toronto, 76University of Manitoba, Winnipeg,
Mauricio Castillo Barradas98, Lilian Torres Made99, Rene Male
7
7University of Alberta, Edmonton, 78CHU de Cocody, Abidjan,
Velazquez99, Francisco Félix-Tellez100, Jose Antonio Velarde-Ruiz100, Côte d‘Ivoire, 79Pontificia Catholic University of Chile, Santiago,
Jacqueline Cordova-Gallardo101, Nik Arsyad Nik Muhamad Afendi102,
8
0UMC Freiburg (University Medical Center Freiburg), 81University
Ruveena Rajaram103, Liana Mondlane104, Mussagy Tarmamade104, Medical Center Mainz, Germany, 82Mustapha Bacha University
David P Nyam105, Edith N Okeke106, Nazish Butt107, Eric Rutaganda108, Hospital, Algiers, 83Minia University, Egypt, 84St Paul‘s Hospital
Zainab Ingabire108, Dalia Allam109, Yashwi Haresh Kumar Patwa109, Millenium Medical College, Addis Ababa, Ethiopia, 85Adera Medical
Somaya Albhaisi12, Mohammad Amin Fallahadeh110, Sumeet Asrani110, and Surgical Center , 86NIHR Nottingham Biomedical Research
Centre, Nottingham University Hospitals NHS Trust and University
K Rajender Reddy111, Suditi Rahematpura111, Jawaid Shaw112, David
of Nottingham, Nottingham. Nottingham Digestive Diseases Centre,
Bayne113, Hugo Vargas113, Natalia Filipek114, Scott W Biggins114, Paul
Translational Medical Sciences, School of Medicine, University of
Thuluvath115, Somya Sheshadri115, Kara Wegermann116, Matthew
Nottingham, Nottingham., 87NIHR Nottingham Biomedical Research
Centre, Nottingham University Hospitals NHS Trust and University PL0024
of Nottingham, Nottingham, 88Queen Elizabeth University Hospitals,
Point-of-Care Ultrasound (POCUS) to assess impact of Dynamic
Birmingham, 89Glasgow Royal Infirmary, 90Royal Berkshire Hospital,
Cardiac Function, and Cirrhotic Cardiomyopathy in patients with
9
1Royal Infirmary of Edinburgh, 922nd Department of Medicine,
APASL defined Acute-on-Chronic Liver Failure
Medical School, Natinal & Kapodistrian University of Athens,
Hippokration General Hospital, Athens, Greece, 93Tel-Aviv Sourasky Madhumita Premkumar1, Kamal Kajal1, Prerna Sharma1, Anchal
Medical Center, Tel Aviv, Israel, 94Hospital of Lithuanian University Sandhu1, Sweta Rose1, C P Ganesh1, Ashwani Sood1, Ajay Duseja1
of Health Sciences Kauno klinikos, 95Centro Médico ISSEMYM, 1
Postgraduate Institute of Medical Education and Research
9
6Hospital General de México “Dr. Eduardo Liceaga“, 97Instituto Background: Background and Aims: Point-of-care echocardiography
Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán“, (POC-Echo) is used to determine left ventricular systolic and diastolic
Mexico City, 98Centro Médico la Raza, Mexico City, 99Instituto de la dysfunction (LVDD), inferior vena cava (IVC) dynamics and volume
Salud Digestiva, Guadalajara, 100Hospital Civil de Guadalajara Fray status in patients with acute-on-chronic liver failure (ACLF) accurately.
Antonio Alcalde, Guadalajara, 101Hepatology, Hospital General Dr. Cirrhotic Cardiomyopathy is a continuum that pertains to changes in
Manuel Gea Gonzlez, Mexico City, 102University of Malaya, Kuala
myocardial contractility, structure, response to stress, renal perfusion,
Lumpur, Malaysia, 103Universiti Malaya Medical Centre, Kuala
and tolerance for albumin and/or pressors which has prognostic
Lumpur, Malaysia, 104Maputo Central Hospital, 105Jos University
implications in ACLF.
Teaching Hospital Jos, Nigeria, 106Jos University Teaching Hospital,
Method: Methods: Point-of care ultrasound (POCUS) including
Jos, Nigeria, 107Jinnah Postgraduate Medical Centre, 108University
teaching hospital of Kigali, 109National Center for Gastrointestinal and echocardiography was done at presentation in patients with ACLF
Liver Disease, Khartoum, 110Baylor University Medical Center, Dallas, admitted to the Liver Intensive Care Unit at our centre. (Figure
1
11University of Pennsylvania, 112Richmond VA Medical Center, 1) Clinical, sepsis, acute kidney injury, and survival data were
1
13Mayo Clinic, Scottsdale, 114University of Washington, 115Mercy prospectively collected. POCUS IVC dynamics, LV systolic function [LV
Medical Center, Baltimore, 116Duke University, 117Mayo Clinic, ejection fraction (EF) & cardiac output (CO)], and diastolic dysfunction
Jacksonville, 118University of Pittsburgh, 119Columbia University variables (E/e’, e’ and E/A ratio) on mortality in patients with ACLF,
Medical Center which was defined per APASL criteria. Cirrhotic cardiomyopathy was
defined per AASLD CCM consortium 2020 criteria. Four variables
Background: Chronic kidney disease (CKD) in cirrhosis is becoming
were recorded to assess diastolic dysfunction: e′, E/e′ ratio, left
more common. Its impact on patient outcomes is unknown. We aimed
atrial volume index (LAVI), and tricuspid jet velocity. Based on tissue
to characterize on a global scale patients with cirrhosis and CKD and
Doppler imaging, the early diastolic annular velocity is often expressed
to assess its impact on patient outcomes.
as (e′) and the Late diastolic velocity as (a′) Systolic dysfunction was
Method: The CLEARED consortium is a global network that conducts
defined as an ejection fraction (EF) of 50% or less.
prospective studies on non-electively admitted patients with cirrhosis.
Result: Results: We enrolled 180 patients [(65.1% males, aged 46.6 ±
Participating centres from 6 continents all contributed 50 patients each.
13.1 years, 62% ethanol related, median MELD-Na 24.2 (18.7 - 26.3)].
Data collected included demographics, cirrhosis severity, admission
LVDD was present in 63.2% of patients with grade 1, 2 and 3 LVDD
details, laboratory results & admission outcomes. CKD was defined as
in 18.6%, 25.5% and 19.1% respectively. Systolic dysfunction with
GFR of <60ml/min/1.73m2 for >3 months. Patients with CKD (CKD+)
EF<50% was noted in just 8% of individuals. CCM was diagnosed in
were compared to those without (CKD-) for admission outcomes.
44.6% of patients. Overall mortality was 28.3% and 38.9% at 30 and 90
Result: 7040 patients from 127 centres in 35 countries were enrolled,
days, respectively. Low CO at 0h (HR 1.2, 95%CI 1.11-1.6, P=0.042),
2733 (38.8%) of patients had CKD. CKD+ patients were likely to be
E/e’ ratio(HR 1.8, 95%CI 1.2-3.6, P=0.012) and AARC score (HR 1.20
older (59±13 yrs vs. 54±13 yrs) women (40% vs.33%), with more
95%CI 1.10-2.99, P<0.001) new onset AKI. Survival based on LVDD
having MASH as an etiology of cirrhosis (25% vs. 12.5%) compared
grade and ACLF Grade is shown in Figure 2 A and B respectively.
to CKD- patients (p<0.0001 for all). CKD+ patients were more likely
Presence of CCM [HR 2.1, 95%CI 1.4-3.8, P=0.034) and circulatory
to have diabetes (38% vs 24%), hypertension (33% vs. 20%) and
failure[HR4.2, 95%CI 1.7-7.8, P=0.020) were independent predictors
hyperlipidemia (18% vs 10.5%) compared to CKD- patients (p<0.0001
of mortality in ACLF, adjusted for baseline MELDNa. Figure 2.
for all). Significantly more CKD+ patients had a history of ascites (74%
Conclusion: LVDD is common in patients with ACLF and is associated
vs. 58%), AKI (35% vs. 7%), hyponatremia (24% vs. 13%), infection
with survival independent of severity of Liver Disease. Assessment of
in the past 6 months (25% vs.17%) and therefore more admissions in
cardiac dysfunction using POC-Echo guides prognosis in ACLF.
past 6 months (56% vs. 45%) compared to CKD- patients (p<0.0001).
Table and Figure:Figure 1.Figure 2: POCUS assessment of patients
90% of both CKD+ and CKD- patients had a liver related reason for
with ACLF with Kaplan Meier curves for survival based on LVDD grade
admission, but significantly more CKD+ patients had infection as the
and AARC ACLF score
cause for admission (27% vs. 19%), especially for urinary tract infection
Figure 2.Figure 1 : Applications of POCUS algorithm in ACLF
(16% vs. 9%) (p<0.0001) but not for SBP (28% vs. 24%, p=0.11). The
major liver reasons for admission were related to renal and fluid issues
(AKI: 52% vs 5%; anasarca: 39% vs. 35%; electrolyte abnormalities:
30% vs. 17%), and encephalopathy (HE) (39% vs. 25%) (p<0.001 for
LATE BREAKER
all). There were more laboratory abnormalities in the CKD+ patients
on admission, with higher serum creatinine (1.7mg/dL vs. 0.74mg/dL) LB0001
white cell count (7.13 vs. 5.76 X109/L), lower serum Na (133mmlo/L C1ORF131 a novel target to enhance liver regeneration and protect
vs. 136mmol/L) and hence higher MELD score (25 vs.18) (p<0.0001 against chronic liver disease
for all). Table 1 shows the hospital course for both groups. Following Shainan Hora1, Amanpreet Kaur1, Rong Gao2, Jonathan Chee Chong
discharge, more CKD+ patients had readmission in 30 days (34% vs. Lek2, Agnes Bee Leng Ong1, Anna Potapova1, Torsten Wuestefeld2,1
26%), or had liver transplant (8.4% vs. 4.5%) or died (29% vs. 12%), 1
Genome Institute of Singapore, A*STAR, 2Lee Kong Chian School of
(p<0.0001). On multivariate analysis, having ascites with previous Medicine, Nanyang Technological University
paracentesis gave the highest odds ratio (OR) of 2.01X for having
CKD, followed by features of the metabolic syndrome (OR: 1.4X); prior Background: The liver has a remarkable regenerative capacity.
HE (OR:1.36X), residing in lower/lower middle-income countries (OR: Nevertheless, under chronic liver-damaging conditions, this capacity
1.34X). becomes exhausted, allowing the accumulation of fibrotic tissue
Conclusion: CKD in cirrhosis occurs mostly in patients with difficult- and leading to end-stage liver disease. Enhancing the endogenous
to control ascites, especially if they have features of the metabolic regenerative capacity by targeting regeneration breaks is a novel
syndrome. Improved management of these associated conditions may therapeutic approach. We conducted a genome wide in vivo functional
improve patient outcomes. genetic intervention screen to identify such regeneration breaks in a
MAFLD mouse model. C1ORF131 was one of the top hits. We proofed
that hepatocyte specific knockdown of C1ORF131 enhances the
endogenous regenerative capacity of the liver and counteracts chronic in the overall cohort. MASLD was found to be significantly associated
liver disease, defining for the first time a function for this gene in liver with renal graft dysfunction. Patients with MASLD had a 2.53-fold
biology. increased risk of renal graft dysfunction compared to those without
Method: We conducted a genome wide in vivo functional genetic MASLD (OR: 2.53, 95% CI: 1.83 to 3.50). Other factors associated with
intervention RNAi screen in the “Western Diet” driven chronic liver increased risk of renal graft dysfunction were hypertension (OR: 3.70,
disease model, screening nearly 80000 shRNAs. One of the top 95% CI: 2.56 to 5.35) and obesity (OR: 1.61, 95% CI: 1.18 to 2.21).
enriched shRNAs targets C1ORF131. We then tested the effect of Conclusion: This study identified a significant association between
C1ORF131 knockdown on mouse and human hepatocyte proliferation MASLD and renal graft dysfunction in adult renal transplant
in vitro. Furthermore, taking advantage of the FAH knockout mouse recipients. MASLD was associated with 2.53-fold increased risk of
model, we tested for C1ORF131 knockdown driven faster liver graft dysfunction. Hypertension and obesity were also significant
repopulation, enhanced regeneration after partial hepatectomy and risk factors, while no notable associations were found with age, sex,
fibrosis reduction in chronic liver damaging conditions, including diabetes, primary renal disease, or donor type. These findings highlight
“Western Diet” and choline-deficient L-amino acid defined high fat diet the need for careful management of MASLD and related comorbidities
(CDHFD) driven MAFLD. to improve graft outcomes.
Result: Knockdown of C1ORF131 in immortalized mouse as well as Table and Figure:Figure 1.Table 2. Outcome of adult patients who
human hepatocytes accelerates their proliferation and wound healing are renal transplant recipients at the National and Kidney Transplant
in vitro. In vivo knockdown of C1ORF131 in hepatocytes, accelerates Institute (NKTI) from January 2013 to December 2023. (n=2593)
their ability to repopulate the liver of FAH deficient mice. Furthermore, in Figure 2.Table 3. Factors associated with renal graft dysfunction among
fully repopulated mice, where every hepatocyte expresses the shRNA adult patients who are renal transplant recipients at the National and
targeting C1ORF131, liver regeneration upon partial hepatectomy is Kidney Transplant Institute (NKTI) from January 2013 to December
accelerated. The enhanced regenerative capacity also attenuated 2023.
TAA, CDHFD and “Western Diet” induced chronic damage. C1ORF131
knockdown not only reduced fibrosis but also steatosis in the MAFLD
LB0003
model. Transcriptomic analysis indicates that C1ORF131 knockdown
affects the Polo-like kinase 1 pathway, cell cycle and DNA replication. Durvalumab and Tremelimumab as First-line Treatment in Patients
Conclusion: We identified and validated C1ORF131 as a target with Unresectable Hepatocellular Carcinoma: Interim Analysis
for enhancing the endogenous regenerative capacity of the liver. of An Open-label, Multi-center Phase IIIb Study (TREMENDOUS
Enhancing the endogenous regenerative capacity attenuates chronic study)
liver disease. We for the first time define a biological function for Jia FAN1, Shukui QIN2, Huichuan SUN1, Yanqiao ZHANG3,
C1ORF131 in the liver. We are currently dissecting the underlying Zhenggang REN4, Yabing Guo5, Jia LUO6, Huikai LI7, Haitao ZHAO8,
mechanism and are in the process to translate our results into RNAi Yinying LU9, Hong ZHAO10, Minshan CHEN11, Xiujuan QU12, Hailan
therapeutics. LIN13, Jieer YING14, Baocai XING15, Yunfeng SHAN16, Zhixiang
ZHUANG17, Qiu LI18, Lunxiu QIN19, Xiaohui DUAN20, Kangshun
ZHU21, Haichuan SU22, Liyun FU23, Xianglin YUAN24, Feng ZHANG25,
LB0002 Hongtao HU26, Decai YU27, Xiaofeng SUN28, Weizhong ZHOU29, Jing
Association and Cumulative Incidence of Renal Graft Dysfunction ZHANG30, Xuetao SHI31, Lulu ZHANG32, Pu HUANG32, Zheng SU32
Among Patients with Metabolic Dysfunction-Associated Steatotic 1
Department of Liver Surgery & Transplantation Center, Liver Cancer
Liver Disease: A Single-Center, Single-Arm Retrospective Cohort Institute, Zhongshan Hospital, Fudan University, 2Nanjing TianYinShan
Study Hospital, 3Department of Oncology, Harbin Medical University
AIRENE PRE TENEDERO1, Jade Dequina Jamias1, Consesa Cancer Hospital, 4Liver Cancer Institute, Zhongshan Hospital, Fudan
Cabanayan Casasola1 University and National Clinical Research Center for Interventional
1
National Kidney and Transplant Institute Medicine, 5Department of Infectious Diseases and Hepatology,
Nanfang Hospital, Southern Medical University, 6Department of
Background: The importance of detecting MASLD in RTR cannot be
Hepatobiliary Surgery, Hunan Cancer Hospital, 7Department of Liver
overemphasized since these patients are prone for developing liver- Cancer, Tianjin Medical University Cancer Institute and Hospital,
related morbidity or mortality, and all-cause or cardiovascular mortality National Clinical Research Center for Cancer, Tianjin‘s Clinical
on top of underlying CKD and other related outcomes. MASLD is Research Center for Cancer, 8Department of Liver Surgery, Peking
already an established risk factor for the development of incident CKD. Union Medical College Hospital, 9Comprehensive Liver Cancer
Limited studies have been conducted dealing with its effect with renal Center, 5th Medical Center of PLA General Hospital, 10Department
graft function. Hence, this study aims to determine the association of of Hepatobiliary Surgery, National Cancer Center/National Clinical
metabolic dysfunction-associated steatotic liver disease with renal graft Research Center for Cancer/Cancer Hospital, Chinese Academy of
dysfunction among adult patients who are renal transplant recipients. Medical Sciences and Peking Union Medical College, 11Department
Method: The study is a retrospective cohort study of renal transplant of Liver Surgery, Sun Yat-sen University Cancer Center, 12Department
recipients (RTRs) in NKTI who were diagnosed with MASLD before of Medical Oncology, The First Hospital, China Medical University,
and/or after renal transplantation. All renal transplant patients were 1
3Department of Tumor Interventional Therapy, Fujian Cancer
included in the study; hence, the purposive sampling technique was Hospital, 14Department of Abdominal Oncology, Zhejiang Cancer
used. The patients’ charts were utilized to collect demographics and Hospital, 15Department of Hepatopancreatobiliary Surgery Unit
pertinent laboratory test results. MASLD was diagnosed based on I, Peking University Cancer Hospital & Institute, 16Department of
ultrasound findings and non-invasive indices such as hepatic steatosis Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou
index (HSI) and triglyceride-glucose-BMI (TyG-BMI) index. RTRs with Medical University, 17Department of Oncology, Zhangjianggang First
MASLD from 2013 to 2023 was followed up for five years and evaluated People’s Hospital, 18Department of Medical Oncology, Cancer Center,
for the presence of renal graft dysfunction, defined as an increase in West China Hospital, Sichuan University, 19Hepatobiliary Surgery,
serum creatinine of 15% from baseline. Descriptive statistics were used Department of General Surgery, Huashan Hospital, Fudan University,
to summarize the clinical and demographic profile and association
2
0Department of Hepatobiliary Surgery/Research Laboratory of
Hepatobiliary Tumour, Hunan Provincial People‘s Hospital, The
of having MASLD with renal graft dysfunction was determined by
First-Affiliated Hospital of Hunan Normal University, 21Department of
logistic regression analysis. Multivariable regression was performed to
Minimally Invasive Interventional Radiology, The Second Affiliated
account for other co-variates of interest. The magnitude of association
Hospital of Guangzhou Medical University, 22Department of oncology,
was reported as odds ratio and 95% confidence interval.
The Second Affiliated Hospital of Air Force Medical University ,
Result: A total of 2,593 adult RTRs at the National Kidney and Transplant 2
3Department of Hepatology, Ningbo Institute of Liver Diseases,
Institute (NKTI) from January 2013 to December 2023 were included in Ningbo No. 2 Hospital, 24Department of Oncology, Tongji Hospital,
this study. Among patients with MASLD (n=784), the incidence of renal Tongji Medical College, Huazhong University of Science and
graft dysfunction was 29.34% (95% CI: 26.17 to 32.66), higher than
Technology, 25Department of Hepatic & Biliary & Pancreatic Surgery, Background: In both the Phase 3, pivotal, placebo-controlled
Hubei Cancer Hospital, 26Department of Interventional Radiology, RESPONSE trial (NCT04620733) and the ongoing, open-label, long-
The Affiliated Cancer Hospital of Zhengzhou University & Henan term, Phase 3 ASSURE trial (NCT03301506), seladelpar, a first-in-
Cancer Hospital, 27Division of Hepatobiliary and Transplantation class delpar (selective PPARδ agonist), led to durable improvements
Surgery, Department of General Surgery, Nanjing Drum Tower in biomarkers of cholestasis and was overall safe and well tolerated
Hospital, Affiliated Hospital of Medical School, Nanjing University, in patients with primary biliary cholangitis (PBC). Here, we report the
2
8Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of efficacy and safety of seladelpar in the Asian subpopulation in both
Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical trials.
University, 29Department of Radiology, Interventional Radiology, The Method: Patients with PBC and inadequate response or intolerance to
First Affiliated Hospital of Nanjing Medical University, 30Department ursodeoxycholic acid received daily oral seladelpar 10 mg or placebo
of Minimally Invasive Intervention, Guangdong Provincial People‘s
(PBO; 2:1 randomization) for 12 months (M) in RESPONSE. Patients
Hospital (Guangdong Academy of Medical Sciences), Southern
with PBC who participated in earlier seladelpar studies (ENHANCE
Medical University, 31Department of Hepatobiliary Surgery, Shandong
[NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731
Cancer Hospital and Institute, Shandong First Medical University
[NCT03301506], or CB8025-21838 [NCT04950764]) and received
and Shandong Academy of Medical sciences, 32Medical Affairs,
Oncology, AstraZeneca open-label seladelpar 10 mg oral daily in ASSURE were also analyzed
(data cutoff date: January 31, 2024). Patients who self-identified as
Background: The global phase III HIMALAYA trial showed Asian were included in this subgroup analysis and compared to non-
unprecedented long-term overall survival (OS) benefit with STRIDE Asian patients. Key endpoints included composite response (alkaline
(single dose of tremelimumab added to regular durvalumab) as first- phosphatase [ALP] <1.67 × upper limit of normal [ULN], ALP decrease
line therapy in patients with unresectable hepatocellular carcinoma ≥15%, and total bilirubin ≤ULN), ALP normalization, and ALP change;
(HCC). This study aimed to evaluate the safety and efficacy of STRIDE safety was also assessed.
regimen in additional Chinese population beyond the HIMALAYA trial. Result: In RESPONSE, 7/128 seladelpar-treated and 4/65 PBO-treated
Here, we present the pre-planned interim analysis (IA) of cohort 1. patients were Asian; mean (SD) baseline ALP in Asian patients was
Method: This is an open-label, multi-center phase IIIb study in 241 (53) U/L for seladelpar and 324 (81) U/L for PBO compared to
which patients [Cohort 1: Child-Pugh A liver function and Eastern 319 (125) U/L and 313 (120) U/L, respectively, for non-Asian patients.
Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1, In ASSURE, 13/174 patients were Asian. Mean (SD) baseline ALP was
Cohort 2: Child-Pugh B or ECOG PS 2] received tremelimumab 300mg 296 (152) U/L in Asian vs 268 (122) U/L in non-Asian patients. At M12,
* 1 dose plus durvalumab 1500mg every 4 weeks until confirmed 7/7 (100.0%) seladelpar-treated and 0/4 PBO-treated Asian patients
disease progression or acceptable toxicities. The primary endpoints met the composite response in RESPONSE. In non-Asian patients,
were grade 3 or higher adverse event (AE) rate by CTCAE v5.0 72/121 (59.5%) receiving seladelpar vs 13/61 (21.3%) receiving PBO
and adverse events of special interest (AESI). Secondary endpoints met the composite endpoint. In ASSURE, 6/8 (75.0%) Asian patients
included objective response rate (ORR), disease control rate (DCR), and 98/140 (70.0%) non-Asian patients taking seladelpar also met this
progression-free survival (PFS) by investigator per RECIST 1.1, OS and endpoint at M12. At M12 in RESPONSE, ALP normalization occurred
safety. in 5/7 (71.4%) Asian patients and 27/121 (22.3%) non-Asian patients
Result: At data cutoff (May 31, 2024), 150 patients with unresectable treated with seladelpar, compared with no PBO patients. At M12 in
HCC, Child-Pugh A liver function and ECOG PS 0-1 were enrolled ASSURE, 2/8 (25.0%) Asian patients and 53/140 (37.9%) non-Asian
and received study treatment. Median follow-up was 9.3 (range, 0.5- patients reported ALP normalization with seladelpar. ALP was similarly
15.3) months. AE of grade 3 or higher occurred in 63 (42.0%) patients, reduced in all Asian and non-Asian patients receiving seladelpar.
49 (32.7%) were assessed to be treatment related by investigator. Overall, 6/7 (85.7%) Asian patients treated with seladelpar and 3/4
TRAEs leading to discontinuation occurred in 12 (8.0%) patients. (75.0%) Asian patients receiving PBO in RESPONSE and 7/13 (53.8%)
AESI occurred in 85 (56.7%) patients and most were grade 1-2. The seladelpar-treated patients in ASSURE experienced adverse events
confirmed ORR was 34.0% (51/150, 95% CI, 26.5-42.2). The DCR was (AEs). No serious AEs were reported among Asian patients.
65.3% (98/150, 95% CI, 57.1-72.9). The median PFS was 5.7 (95% Conclusion: Seladelpar reduced biomarkers of cholestasis among
CI, 4.7-9.4) months. The median OS is not reached. The 6-month and Asian and non-Asian patients in the RESPONSE and ASSURE trials.
9-month OS rate were 86.5% (95% CI, 79.8-91.0) and 80.7% (95% CI, Seladelpar was overall safe and well tolerated in Asian patients.
73.0-86.4). Table and Figure:Figure 1.Figure 1. (A) Composite Response Rate, (B)
Conclusion: STRIDE regimen displayed acceptable safety profile and Alkaline Phosphatase Normalization, and (C) Alkaline Phosphatase
promising efficacy at this IA in Chinese unresectable HCC patients as Percentage Change From Baseline Through Month 12 in RESPONSE
first-line systemic therapy, which are consistent with HIMALAYA study. Patients Receiving Seladelpar 10 mg or Placebo (Asian and Non-Asian
Long-term OS outcomes need further investigation with longer follow- Subgroups)
up (NCT05557838). Figure 2.Figure 2. (A) Composite Response Rate, (B) Alkaline
Phosphatase Normalization, and (C) Alkaline Phosphatase Percentage
LB0004 Change From Baseline Through Month 12 in ASSURE Patients
The Efficacy and Safety of Seladelpar in the Asian Subpopulation Receiving Seladelpar 10 mg (Asian and Non-Asian Subgroups)
of Patients With Primary Biliary Cholangitis: Results From the
RESPONSE and ASSURE Studies LB0005
Sook-Hyang Jeong1, Heo Jeong2, Won Young Tak3, Young Seok Kim4, Advancing Hepatitis B Elimination in New Zealand: Lessons from
Kang Mo Kim5, Jun Sik Yoon6, Christopher L. Bowlus7, Xin Qi8, Robert Community Engagement and Service Delivery Innovations
Kustra8, Catherine Frenette8, Susheela Carroll8, Daria B. Crittenden8, Hepatitis Foundation of New Zealand, Sarah Davey1, Amanda
Yoon Jun Kim9 Broxholme1, Ed Gane1, William Rainger1
1
Seoul National University Bundang Hospital, College of Medicine, 1
Hepatitis Foundation of New Zealand
Seoul National University, Seongnam, Republic of Korea, 2Department
of Internal Medicine, College of Medicine, Pusan National University Background: More than 35 years after the introduction of universal
and Biomedical Research Institute, Busan, Republic of Korea, neonatal vaccination in New Zealand, chronic hepatitis B virus
3
Kyungpook National University Hospital, Daegu, Republic of Korea, (cHBV) infection remains a leading cause of cirrhosis, liver cancer,
4
Soon Chun Hyang University Hospital Bucheon, Bucheon, Republic and liver-related death. Of the estimated 94,000 New Zealanders
of Korea, 5Asan Medical Center – PPDS, Seoul, Republic of Korea, with HBV, approx. 30,000 are registered with the national hepatitis B
6
Inje University Busan Paik Hospital, Busan, Republic of Korea, register maintained by Hepatitis Foundation of New Zealand (HFNZ)
7
University of California, Davis, Sacramento, CA, USA, 8Gilead a government-funded NGO with 19,206 actively monitored for
Sciences, Inc., Foster City, CA, USA, 9Seoul National University liver health. Priority populations include Māori, Pasifika, and Asian
Hospital, Seoul, Republic of Korea communities. However, only 8% of eligible individuals nationwide
currently receive antiviral treatment. This presentation highlights of all negative subjects with HBV vaccine and 28000 received three
HFNZ’s innovative strategies to address these challenges through doses of genetically engineered vaccine
enhanced partnerships, care navigation, and community engagement. Strategy 4: Family screening of all index HBV positive subjects in the
Method: 1. Resource and Expert Knowledge Hub two generations. 24% of the tested had positivity in the family.
- Centralised contact & coordination centre supporting patients and Strategy 5: Advocacy: Interactive sessions were conducted at three
healthcare professionals with nursing and clinical advice. levels of health care delivery and stakeholders for a preventive policy.
- Collaborative partnerships to improve HBV identification, Press briefings and media discussions in local and national Audio
management, and treatment initiation in primary care. visual channels were done periodically to increase awareness
- Development of simplified multi-language educational resources to Result: Strategy 1: 2012 to 2024 : Public awareness campaign had a
build capacity and confidence in HBV care. reach of 100,000 subjects.
2. Monitoring and Integrated Care Strategy 2: Screening for HBV: among 30000 subjects and prevalence
- Strengthening care pathways through improved navigation between of HBs Ag positivity was 2.4 % in 2012-2018 and 1.6 % in 2019-2024.  
healthcare settings, promoting equitable access to services. Strategy 3: Vaccination drive: HBV vaccine was administered
- Administering and monitoring blood tests and liver scans for early to 28000 with three doses of genetically engineered vaccine
disease detection. Strategy 4: Family screening :24% of the tested had positivity in the
3. Community Engagement in Elimination family.
- Partnering with Iwi Hauora (Māori health organisations) and Strategy 5: Advocacy: 22 press briefings and 30 discussions in  local
community groups to deliver awareness and outreach programmes, and national Audio visual channels
including point-of-care testing for priority populations. Conclusion: Community participation under a non governmental
- Launching culturally tailored campaigns to combat stigma, organisation, Population Health and Research Institute is a success
encourage early diagnosis, and support treatment adherence. story for preventive and promotive strategy to control HBV at the
Result: - Increased screening and diagnosis with significant provincial level and can be escalted to the state and national level.
engagement from priority populations. Table and Figure:Figure 1.HBV campaigns
- Increased treatment initiation in primary care facilitated by education, Figure 2.community camps on HBV
partnerships, and simplified resources.
- Strengthened integration between care settings, streamlining patient
LB0007
pathways and improving continuity of care.
Conclusion: HFNZ’s integrated approach demonstrates that Robust HBsAg loss after AHB-137 treatment in HBeAg-negative
partnerships supported by culturally appropriate resources can chronic hepatitis B patients on NA therapy: 24-week ON treatment
effectively overcome barriers to HBV elimination. While treatment and 8-week OFF treatment results from an ongoing multicenter,
rates are progressing toward the 80% target, results offer valuable randomized, open-label phase IIa study
insights for global efforts. Key achievements include reducing stigma, Yanhua Ding1, Xian Yu2, Xieer Liang3, Hong Ren2, Chongyuan Xu3,
enhancing equity and fostering collaboration across sectors to improve Wen Wang1, Zhihong Liu3, Yi Yang2, Hong Zhang1, Jinlin Hou3, Zhong
outcomes for priority populations. Shan2, Hong Chen1, Yilei Wen4, Tingting Lu4, Xiao Qiu4, Tianwen Lan4,
Table and Figure:Figure 1.Advancing Hepatitis B Elimination in New Lidan Wang4, Di Zhao4, Chen Yang4, Hao Wang4, Miao Wang4, Chris
Zealand: Lessons from Community Engagement and Service Delivery Yang4,5, Guofeng Cheng4,5, Junqi Niu6
Innovations - Poster 1
Phase I Clinical Trial Center, The First Hospital of Jilin University,
Changchun, China , 2The Second Affiliated Hospital, Chongqing
Medical University, Chongqing, China , 3Nanfang Hospital, Southern
LB0006 Medical University, Guangzhou, China, 4Ausper Biopharma Co. Ltd.,
Community participation as a strategy for Hepatitis B virus 5
AupserBio Therapeutics Inc., 6The First Hospital of Jilin University,
Prevention in Kerala, S India : A Success story Changchun, China
Leena Mohanan1, Shenoy Trivikrama Kotacherry2 Background: AHB-137 is an antisense oligonucleotide (ASO) that has
1
Senior Research Scientist Population Health and Research Institute, shown good tolerability and significant efficacy in reducing HBsAg
2
Sree Gokulam Medical College and Research Foundation ,Dept. of levels during the first 12 weeks of treatment with AHB-137 in HBeAg-
Gastroenterology negative chronic hepatitis B (CHB) patients in an ongoing phase
Background: Kerala in S India has high population density with IIa study. Here, we present the 24-week ON treatment and 8-week
excellent access to health care facilities and high social and health OFF treatment safety, efficacy, and pharmacokinetic profile from the
indicators. We implemented community based multilevel preventive ongoing phase IIa study.
and promotive strategies for public awareness on the implications of Method: HBeAg-negative CHB patients, with baseline HBsAg > 100
the disease and its prevention to 3,000 IU/mL (inclusive) and under stable nucleos(t)ide analogue
Method: We utilized five strategies for the control of HBV among (NA) treatment, were enrolled in the multicenter, randomized, open-
urban and rural subjects in Trivandrum district , with a population of label phase IIa study (NCT06115993). Patients were randomized to
2.8 M supported by the Grama Panchayats, the administrative base receive weekly subcutaneous doses of either 300 mg or 225 mg of
and under the guidance of Coalition to Eradicate Viral Hepatitis in Asia AHB-137, with two loading doses on Days 4 and 11. Following the
Pacific (CEVHAP). 24-week treatment, a 24-week follow-up with NA therapy alone and
Strategy 1: 2012 to 2024 : Public awareness campaign by trained an additional 24-week follow-up post NA cessation were scheduled.
social workers using pamphlets as well as face to face discussion The primary endpoint (virologic response) is the proportion of patients
using structured format in predesigned camps, each one with 1000 achieving HBsAg loss (HBsAg < limit of detection (0.05 IU/ml)) and
to 2000 subjects. HBV disease, mode of transmission, safe sex, use HBV DNA < lower limit of quantification (10 IU/ml), at the conclusion of
of safe blood and injection practices were discussed and there was the 24-week AHB-137 treatment.
question and answer session. We had such 55 camps in the community Result: To date, a total of 55 patients have enrolled and completed 24
among 30 panchayats and 15 school based campaign for teachers weeks of AHB-137 treatment, and 30 patients have completed W32 visit
and students and had a reach of 100,000 subjects. (8 weeks of OFF AHB-137 treatment phase). In the 300 mg and 225 mg
Strategy 2: Screening for HBV: We screened 30000 subjects   in these arms, respectively, 63% (20/32) and 57% (13/23) of patients achieved
camps using a detailed demographic profile and blood samples the primary endpoint, with most cases occurring within the initial 12-
were tested by ELISA . Prevalence of HBs Ag positivity was 2.4 % in week treatment (90% and 69% respectively; see figure). Among the
2012-2018 and 1.6 % in 2019-2024. All positive subjects had detailed patients who achieved the primary endpoint, 75% (15/20) in the 300
evaluation and received further treatment as per the National and mg arm and 62% (8/13) in the 225 mg arm achieved seroconversion
APASL guidelines. (HBsAg loss with detection of anti-HBsAg > 10 mIU/mL) by Week
Strategy 3: Vaccination drive: In these camps, we had vaccination 24. Furthermore, the rate of virologic response on Week 32 was 59%
(10/17) and 23% (3/13) of the patients in the 300 mg and 225 mg arms, visit points, patients with longer intervals between the two rounds of
respectively (see figure). There were no treatment-related serious interferon therapy had higher HBsAg loss rates, with 24-week rates of
adverse events (SAEs), and no AE led to drug discontinuations, early 12.5%, 16.3%, and 25.0% for intervals of 3-6, 6-12 and > 12 months,
study termination, or death. The most common treatment-related AEs respectively, for group A. All the patients were well tolerated despite
(TRAEs) were Grades 1-2. Grade 3 TRAEs included injection site commonly occurred adverse events in IFN-based treatment.
erythema and lab abnormalities (see table). No Grade 4 TRAEs were Conclusion: CHB patients with good and durable HBsAg responses
observed. Notably, ALT flare was highly associated with HBsAg loss. to initial interferon treatment and low baseline HBsAg levels currently
In addition, no significant accumulation was observed in plasma AHB- were an advantageous population for PEG IFNα-2b retreatment, with
137 exposure after 24 weeks of administration in CHB patients. HBsAg loss rate reaching 40% at 24 weeks of retreatment. PEG IFNα-
Conclusion: In this ongoing phase IIa trial, AHB-137 treatment was 2b retreatment is strongly recommended in these patients to achieve
well tolerated and led to rapid HBsAg reduction and loss. In the 300 FC.
mg arm, the rate of virologic response was 63% (20/32) at the end of Table and Figure:Figure 1.Table 1. Characteristics of baseline HBsAg
AHB-137 treatment and 59% (10/17) at 8 weeks of the OFF AHB-137 levels in different groups.
treatment phase. Current data support further development of AHB- Figure 2.Figure 1. Cumulative HBsAg loss rate at 12 and 24 weeks for
137 for HBV functional cure. different groups.
Table and Figure:Figure 1.Figure: Proportion of patients within each
HBsAg categories over time in the 225mg (A) and 300 mg (B) AHB-
LB0009
137 arms.
Figure 2.Table: Overview of adverse events in each arm of AHB-137 Higher end of treatment (EOT) HBsAg loss and seroconversion
treatment. rates in participants with chronic HBV infection receiving elebsiran
(BRII-835) and pegylated interferon alfa-2a (PEG-IFNα) compared
to PEG-IFNα alone: Week 48 results from ongoing ENSURE study
LB0008 Jidong JIA1, Bingliang LIN2, Peng HU3, Qing XIE4, Mark W
40% of interferon-experienced chronic hepatitis B patients DOUGLAS5, Fangfang LV6, Won Young TAK7, Ke CAO8, Chong ZHU8,
achieved HBsAg loss through 24 weeks of peginterferon alpha-2b Weihong LIU8, Yue WU8, Xiaofei CHEN8, David MARGOLIS9, Qing
retreatment: interim analysis from ongoing LEADING Study ZHU9
Qing Xie1, Chengrun Xu2, Xuehua Sun3, Jia Shang4, Yufeng Gao5, 1
Beijing Friendship Hospital, Capital Medical University, 2The Third
Haidong Zhao6, Liang Chen7, Haifang Cao8, Xiulan Xue9, Feng Liu10, Affiliated Hospital, Sun Yat-sen University, 3 The Second Affiliated
Yueyong Zhu11 Hospital of Chongqing Medical University, 4Ruijin Hospital, Shanghai
1
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Jiaotong University School of Medicine, 5The University of Sydney,
Tong University School of Medicine, Shanghai, China, 2The 909th Westmead Institute for Medical Research and Westmead Hospital,
hospital, 3Shanghai University of Traditional Chinese Medicine 6
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine,
Shuguang Hospital, 4He Nan Provincial people‘s Hospital, 5the First 7
Kyungpook National University Hospital, 8Brii Biosciences (Beijing)
Affiliated Hospital of Anhui Medical University, 6Xiamen chang gung Co. Limited, 9Brii Biosciences, Inc.
hospital, 7Shanghai Public Health Clinical Center, 8Qinghai Provincial Background: A previous study demonstrated potentially increased
Fourth People‘s Hospital, 9the First Affiliated Hospital of Xiamen hepatitis B surface antigen (HBsAg) loss rate in participants with
University, 10Tianjin Second People‘s Hospital, 11the First Affiliated chronic HBV infection, who received combination treatment with an
Hospital of Fujian Medical University HBV targeting, small interfering ribonucleic acid (siRNA) elebsiran
Background: Several existing clinical studies have shown that (BRII-835, VIR-2218) and PEG-IFNα. It also suggested that antibody
peginterferon alpha (PEG IFNα) retreatment facilitates functional cure to hepatitis B surface antigen (anti-HBs) at EOT was associated with
(FC) in some chronic hepatitis B (CHB) patients who responded well the off-treatment durability of HBsAg loss. The ongoing phase 2 study
to initial treatment but did not achieve FC. The purpose of this study ENSURE (BRII-835-002, NCT05970289) is the first randomized, PEG-
was to identify and validate potential candidates suitable for PEG IFNα IFNα controlled study to delineate the contribution of elebsiran and
retreatment and its efficacy. PEG-IFNα, respectively, in achieving HBsAg loss and functional cure.
Method: This was a multicenter, prospective, real-world study Method: Virologically suppressed non-cirrhotic participants with
(NCT06323681). Patients who had previously received interferon chronic HBV infection on nucleos(t)ide reverse transcriptase inhibitor
therapy (with a cessation period of ≥ 3 months) and demonstrated a (NRTI) therapy, with screening HBsAg > 100 and ≤ 3,000IU/mL, were
post-treatment HBsAg decline of ≥ 80%, had HBsAg ≤ 500 IU/mL at randomized at a ratio of 1:1:1 to one of three cohorts: PEG-IFNα
the current screening and experienced an HBsAg rebound of ≤ 50% of alone, elebsiran 200mg + PEG-IFNα, or elebsiran 100mg + PEG-IFNα.
the initial treatment baseline were enrolled and divided into two groups Elebsiran and PEG-IFNα were administered subcutaneously every 4
according to the patient’s willing. Patients in group A were treated weeks and weekly for 48 weeks, respectively. NRTI was given daily
with PEG IFNα-2b (Pegbing®, Xiamen Amoytop Biotech Co., Ltd.) until NRTI stopping criteria were met at Week (W) 72. Here, W48 EOT
monotherapy or combined with nucleos(t)ide analogues (NAs), and HBsAg loss and seroconversion results are summarized.
group B were treated with NAs monotherapy. The treatment period was Result: A total of 55 participants were enrolled. The baseline
48 weeks and the primary endpoint was HBsAg loss rate at week 48. characteristics were generally well balanced across the cohorts. At
Data were analyzed for those who completed 24 weeks of treatment. W48, HBsAg loss was observed in 5/19 (26.3%) and 6/18 (33.3%)
Result: A total of 266 patients from 11 centers (group A, n = 223; group participants from elebsiran 200mg or 100mg plus PEG-IFNα cohorts
B, n = 43) were included in this interim analysis. The mean age of all respectively, compared with 1/18 (5.6%) in the PEG-IFNα alone cohort
patients was 42.8 years and 75.9% were male. Mean HBsAg levels (Table). In the 12 participants who achieved HBsAg loss at EOT
in groups A and B were 3395.5 and 2835.7 IU/mL at the start of initial across the three cohorts, 10/12 (83.3%) had HBsAg seroconversion
interferon therapy and decreased to 69.4 and 227.0 IU/mL by the end defined as HBsAg loss with anti-HBs titer ≥ 10IU/L, with 8/12 (66.7%)
of treatment, with average reductions of 95% and 90%, respectively. having anti-HBs titer ≥ 100IU/L. Anti-HBs detection was observed
At the start of current treatment, mean HBsAg levels in groups A and concurrently with or after HBsAg loss in all 10 participants with HBsAg
B were 95.5 and 167.0 IU/mL, respectively, with an average interval seroconversion.
of 23.0 and 51.7 months between the two treatment rounds (Table 1). Conclusion: Compared with PEG-IFNα alone, the addition of elebsiran
Among those with available data, group A had HBsAg loss rates of resulted in greater HBsAg loss at EOT, with most HBsAg clearers also
19.4% at 12 weeks and 40.0% at 24 weeks, while group B had 0% achieving HBsAg seroconversion. This result suggests the potential
at both time points. In the total population that reached the treatment for a higher post-EOT sustained HBsAg loss rates in participants
point, group A had HBsAg loss rates of 13.8% and 19.7% at weeks 12 receiving elebsiran plus PEG-IFNα. The evaluation of 24-week post-
and 24, respectively, whereas group B still had no patients achieving EOT follow-up is ongoing.
HBsAg loss (Figure 1). Among those who reached the corresponding Table and Figure:Figure 1.Table. HBsAg loss and seroconversion rate
at W48 (EOT) world’s population. HCV infection is associated with several extra-
hepatic manifestations,some of which are neurological and mostly
related to immune mechanisms.Hepatitis C Virus (HCV) infection
LB0010
can affect the neurological system and neuropathy is one of these
Concurrent or sequential use of pegylated interferon alpha with manifestations. HCV infection is associated with diabetes mellitus
xalnesiran-based combination therapy in nucleos(t)ide analogue (DM) type II and diabetic patients are at higher risk of acquiring HCV
suppressed chronic hepatitis B patients: Results of 96 weeks of infection. Sweat function has been proposed to assess early autonomic
follow-up from a long-term observational study neuropathy.Aim:this study aimed to evaluate small fiber neuropathy in
Xieer Liang1, Zhihong Liu1, Qintao Lai1, Jie Peng1, Aili Lu1, Juanjuan asymptomatic HCV-related cirrhotic patients with or without diabetes
Chen1, Farouk Chughlay2, Qingyan Bo3,4, Cong Cheng5, Jinlin Hou1 mellitus through sweat function assessment by SUDOSCAN test.
1
Nanfang Hospital, Southern Medical University, 2F. Hoffmann– Method: three groups were involved: 47 healthy controls, 48 HCV-
La Roche, 3Takeda APAC Biopharmaceutical Research and related cirrhotic patients without DM (Group 1) and 49 HCV-related
Development, 4Former employee of Roche (China) Holding, 5Former cirrhotic patients with DM type II (Group 2). All participants were
employee of Roche R&D Center (China) Ltd subjected to liver panel tests, renal function tests, cell blood counts,
Background: A variety of new molecular entities (NMEs) including HbA1c, abdominal ultrasound. Sweat function was assessed in all
xalnesiran are being explored to achieve functional cure of chronic HBV patients and controls by measuring hand and feet Electrochemical
infection. This observational study (NCT05977283) aims to describe Skin Conductance (ESC, μS) using Sudoscan
the real-world treatment patterns and associated long-term outcomes Result: Peripheral neuropathy was detected in none of the controls,
after treatment with NMEs. This abstract focuses on participants (pts) 39% of Group 1 patients and in 62% of Group 2 patients (p< 0.0001).
treated with xalnesiran (a small interfering ribonucleic acid) - based The mean feet ESC (FESC) was 88.3 ±6.8 μS in controls, 67.2 ±19.2
therapy in the Piranga study (NCT04225715) and subsequently μS in Group 1 and 57.9 ±19.4 μS in Group 2 (p< 0.0001). A significant
enrolled into this study. correlation was observed between FESC and bilirubin, albumin,
Method: Pts who had an hepatitis B surface antigen (HBsAg) decline creatinine, international normalized ratio, transaminases and splenic
≥0.5 log10 IU/mL due to xalnesiran within 12 months before baseline size.
were enrolled and prospectively followed up every 12 weeks (wks) Conclusion: In conclusion, the mean FESC are decreased in HCV-
for 3 years at Nanfang Hospital. The baseline was the timepoint when related cirrhosis with or without DM when compared to the control
xalnesiran was discontinued. Three treatment patterns were observed group, suggesting small fiber autonomic neuropathy based on sweat
during follow-up (FU). Arm 1, 28 pts treated with a xalnesiran-based function assessment. SUDOSCAN seems a valuable noninvasive
therapy + nucleos(t)ide analogue (NUC) without pegylated interferon method for early detection of small fiber neuropathy in asymptomatic
alpha (IFN) in the Piranga study for a mean of 42 wks were subsequently HCV-related cirrhosis with or without DM. Long-term follow-up would
treated with NUC in this study. Arm 2, 9 pts treated with xalnesiran + be useful to evaluate the progression of neurological dysfunction in
NUC + IFN for 48 wks in the Piranga study were subsequently treated this population; and future studies are needed to confirm our results in
with NUC. Arm 3, 10 pts treated with a xalnesiran-based therapy + a larger population of hepatic patients with or without cirrhosis of any
NUC without IFN for an average of 26 wks in the Piranga study were etiologies, along with a clinical neurological examination.
switched to IFN + NUC for 24 to 48 wks in this study and then treated Table and Figure:Figure 1.Figure 1: Box-plots of feet ESC (FESC) in
with NUC. The primary endpoint is the proportion of pts with HBsAg controls, patients with HCV-related cirrhosis and patients with HCV-
loss (<0.05 IU/mL) at 48 wks of FU. The 96 wks of FU results were related cirrhosis as well as DM. FESC is decreased in HCV-related
reached at the time of this abstract. cirrhosis as compared to controls, and more profoundly decreased in
Result: Overall, 47 pts treated with 12 to 48 wks of xalnesiran-based patients with DM in addition.
therapy in the Piranga study were enrolled (characteristics before
treatment with xalnesiran: mean age 36.7 years, mean HBsAg 2.9 YI0002
log, 10.6% HBsAg <100 IU/mL, 42.6% HBeAg+, 100% previously on
Long-term dynamic changes of alanine aminotransferase levels
NUC). The proportion of pts achieving HBsAg loss in Arms 1 to 3 were
during nucleos(t)ide analogues treatment are associated with
10.7% (3/28), 55.6% (5/9) and 0% at the end of xalnesiran, 14.3%
liver-related events among patients with chronic hepatitis B in
(4/28), 22.2% (2/9) and 30% (3/10) at FU wk48, 0%, 22.2% (2/9) and
China
20% (2/10) at FU wk96, respectively. In Arms 1 to 3, 89.3% (25/28),
66.7% (6/9), and 80% (8/10) achieved HBsAg <100 IU/mL at the end Rong Fan1, Ning Yu1, Jimmy CheTo Lai2, Vicki WingKi Hui2, Jie
of xalnesiran, while these number were 28.6% (8/28), 55.6% (5/9), and Peng1, Yongpeng Chen1, Zhihong Liu1, Xieer Liang1, Henry LikYuen
70% (7/10) at FU wk96. Among all pts, 51.3% and 0% of those with Chan2, Junhua Yin1, Vincent WaiSun Wong2, Chunxiu Zhong1, Grace
HBsAg <100 IU/mL and >100 IU/mL at end of xalnesiran could maintain LaiHung Wong2, Jian Sun1, Terry CheukFung Yip2, Jinlin Hou1
or achieve HBsAg <100 IU/mL at FU wk96, respectively. HBsAg level
1
Department of Infectious Diseases, Nanfang Hospital, Southern
<1000 IU/mL before xalnesiran was associated with HBsAg <100 IU/ Medical University, Guangzhou, China; State Key Laboratory of
mL at FU wk96, but age, gender, or HBeAg status were not. Organ Failure Research; Key Laboratory of Infectious Diseases
Conclusion: Concurrent or sequential use of IFN in combination with Research in South China, Ministry of Education; Guangdong
finite treatment of xalnesiran resulted in prolonged effect on the HBsAg Provincial Key Laboratory for Prevention and Control of Major Liver
decline 96 wks after end of xalnesiran with over half of pts achieving Diseases, Guangzhou, China., 2Medical Data Analytics Centre, State
Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health
HBsAg <100 IU/mL. The durability of HBsAg loss after NMEs needs to
Sciences, The Chinese University of Hong Kong, Hong Kong SAR,
be confirmed in a long-term follow-up analysis.
China
Background: Alanine aminotransferase (ALT) is a widely used
YOUNG INVESTIGATOR SESSION indicator for initiating nucleos(t)ide analogues (NAs) treatment in
patients with chronic hepatitis B (CHB). However, the significance of
ALT levels during NAs therapy remains ambiguous. This study aims to
YI0001
assess the relationship between ALT dynamics and the occurrence of
Sudoscanfor Detection of Small Fiber Neuropathy Changes in liver-related events (LRE), and to determine the optimal ALT threshold
Hepatitis C Virus Infected Cirrhotics during NAs treatment.
Mohamed Abdel-Samiee1, Elsayed Tharwa 1, Mohsen Salama1, Method: We enrolled NAs-treated CHB patients based on a
Helmy M Elshazly1 Chinese prospective cohort (one centre from the Search-B study
1
National Liver Institute [NCT02167503]) and one real-world cohort in Hong Kong. The
Background: Worldwide,130-170 million people are infected latent-class mixed model (LCMM) was adopted to identify patients
withhepatitis C virus (HCV), which represents more than 3 % of the with similar ALT trajectory patterns during treatment. ALT value at
the 95th percentile of trajectory group with the lowest LRE risk was our validation cohort, the baseline random forest model achieved AUC
obtained as the optimal threshold. LRE were defined as hepatocellular 0.85 (specificity 98%, sensitivity 39%, PPV 80%, NPV 91%), and the
carcinoma, compensated/decompensated cirrhosis and liver-related longitudinal GRU model achieved AUC 0.87 (specificity 95%, sensitivity
death. 60%, PPV 68%, NPV 94%) for predicting HBsAg seroclearance.
Result: A total of 20,729 patients, comprising 3,104 patients from the The merging of both models appeared to be synergistic, and the
Search-B cohort and 17,625 patients from Hong Kong, were included combination model achieved AUC 0.91 (specificity 96%, sensitivity
in the analyses. The median ages for these cohorts were 39.0 years 52%, PPV 71%, NPV 92%). The performance of the models remained
(IQR: 32.0-46.0) and 57.0 years (IQR: 47.0-65.0), respectively. robust in various subgroup analysis after stratification by age, sex, HBV
During a median follow-up of 52.7 (IQR: 23.3-84.0) months, 1,478 treatment status, liver fibrosis, and baseline qHBsAg level respectively
patients developed LRE, resulting in a 7-year cumulative incidence (all AUC >0.8).
of 10.8% (Search-B cohort: 269 patients, 10.1%; Hong Kong cohort: Conclusion: We developed and validated machine learning models
1,209 patients, 11.0%). In the Search-B cohort, the LCMM identified for predicting long-term HBsAg seroclearance. The models can
3 trajectory groups with progressively increasing ALT levels, which accurately identify patients who are unlikely to achieve HBsAg
were positively associated with LRE risk (7-year: 7.3% vs. 11.5% vs. seroclearance, and can enable patient selection for novel HBV
16.6%, p <0.001 [men]; 0.0% vs. 3.2% vs. 16.5%, p <0.001 [women]). antivirals.
Subsequently, the optimal ALT thresholds were determined to Table and Figure:Figure 1.Area-under-curve of the developed machine
be 20 IU/L for men and 16 IU/L for women, respectively. The 7-year learning models
cumulative incidence of LRE was 4.5% among patients with ALT < 20
or 16 IU/L, significantly lower than that of patients with ALT ≥20 or 16
YI0004
IU/L but <40 IU/L (10.5%; aHR =2.2 [95% CI: 1.4-3.4], p =0.001), and
ALT ≥40 IU/L (17.6%; aHR =4.5 [95% CI: 2.7-7.5], p <0.001) (Figure The Genetic Blueprint of Paediatric Liver Disorders
A). When validated in Hong Kong cohort, ALT ≥20 or 16 IU/L but <40 Deepa Janakiraman1, NIRMALA DHEIVAMANI1, Sindhuja T A2,
IU/L, and ALT ≥40 IU/L also increased the LRE risk, with aHRs of Senthilkumar R2, Winston Thomas S2
2.3 (95% CI: 1.5-3.4, p <0.001) and 6.4 (95% CI: 4.3-9.6, p <0.001), 1
Institute of Child Health and Hospital for Children, Madras Medical
respectively (Figure B). The above findings were consistent across College , 2Institute of Child Health and Hospital for Children
subgroups with different disease states. Background: Inherited or monogenic liver disorders have narrowed
Conclusion: Long-term dynamic changes of ALT levels during down the spectrum of cryptogenic liver disorders in the recent past.
treatment were independent predictors of LRE in CHB patients. On- This study aimed to analyze the clinical and genetic spectra of
treatment ALT <20 IU/L for men and <16 IU/L for women presented a inherited liver disease in children in a paediatric tertiary care hospital
lower risk of LRE occurrence and were identified as the optimal in South India.
thresholds after initiation of NA, suggesting that CHB patients should Method: In this ambispective study between May 2022 to November
strive for lower ALT levels beyond the traditional normal range. 2024 in a tertiary care centre in South India, a total of 150 patients
Table and Figure:Figure 1.Cumulative incidences of LRE according to were classified into five groups according to their clinical presentation:
ALT levels during follow-up in the Search-B cohort (A) and the Hong Cholestasis (Group A), Chronic liver disease(Group B), and
Kong cohort (B) Hepatomegaly with or without splenomegaly (Group C) and Recurrent
Acute Liver Failure (Group D) and only Transaminitis (Group E). Next
YI0003 Generation Sequencing (NGS) was performed on all patients recruited
in this study.
Development and validation of machine learning models for
Result: The median age at enrollment of the 162 patients was
predicting long-term hepatitis B surface antigen seroclearance
20 months (IQR: 5.0, 43.5 months), with 59.3% males and 40.7%
Rex WanHin Hui1, Victor ChunLam Wong2, Karen CheukYing Ho1, females 60% consanguinity. The overall diagnostic rate was
Trevor KwanHung Wu1, Ryan HinMan Leung1, LungYi Mak1, Danny 78.3% (127/162) in this group. Overall 55 genes related to different
KaHo Wong1, James Fung1, WaiKay Seto1, ManFung Yuen1 phenotypes were indentified. In this study 59 novel variants were
1
The University of Hong Kong, 2OncoSeek Limited, Hong Kong SAR, identified and among them, 33 variants (55.9%) were identified as
China variants of uncertain significance and 26 variants 44% were novel
Background: Hepatitis B surface antigen (HBsAg) seroclearance disease related pathogenic variants. All the novel variants showed a
is an achievable yet rare outcome in chronic hepatitis B (CHB). phenotypic genotypic correlation. Among the already report variants,
Accurate prediction of HBsAg seroclearance has important prognostic variants of uncertain significance were observed at a lower frequency
implications, and may alter management decisions with the emergence 8/66 12.1%, compared to the novel variants group. The diagnostic rates
of novel antivirals. We aimed to develop and validate machine learning in the five groups: Cholestasis (Group A), Chronic liver disease(Group
models for predicting long-term HBsAg seroclearance. B), and Hepatomegaly with or without splenomegaly (Group C) and
Method: We included CHB patients with quantitative HBsAg (qHBsAg) Recurrent Acute Liver Failure (Group D) only Transaminitis (Group E)
data up till 15/5/2024 from Queen Mary Hospital, Hong Kong. Patients were 70.7%(46/65), 62.8% (22/35), 94.6% (53/56), 100% (4/4) and
were randomly divided into training and validation cohorts in an 8:2 100% (2/2) respectively. AGL, PYGL and ATP7B were the top three
ratio. A baseline random forest model was developed using routinely genes related to monogenic liver disease in this study. In 3 children
available baseline clinical data (Age, sex, HBV DNA, hepatitis B e monogenic origin of liver disease were established on reanalysis.
antigen status, HBV treatment status, liver function test, and complete Overall higher frequency of variants of uncertain significance was
blood count). A longitudinal gated recurrent unit (GRU) model seen 39/127 (30.7%). But all of them showed a phenotypic genotypic
was then developed using longitudinal qHBsAg trajectories. The correlation.
baseline random forest model and the longitudinal GRU model were Conclusion: This is the largest study till date in literature to report the
subsequently merged into a combined model for predicting HBsAg huge diversity of genes involved in inherited liver disorders from a single
seroclearance. Model performance was evaluated through area- centre. The higher number of variants of uncertain significance with
under-curve (AUC), positive and negative predictive values (PPV/ phenotypic genotypic correlations suggest that systematic approach
NPV), specificity, and sensitivity. to narrow down to a suspicion of inherited liver disorders after ruling out
Result: This study included 4,287 patients (62.5% male; mean all acquired causes significantly increases the yield of Next Generation
baseline age 48.0 +/- 12.8. years; baseline ALT 28.0 [20.0 – 42.0] U/L; Sequencing(NGS) in suspected monogenic cases and underutilization
24.9% baseline HBeAg positive; 45.2% on antivirals at baseline for of genetic testing till date. Compared to previous studies, this study
an average of 5.5 [3.6 – 8.1] years; baseline median qHBsAg 630.8 reports the highest yield of NGS and highlights the importance of
[117.1 – 1875.5] IU/ml). Patients were followed up for a median of 7.0 appropriate use of NGS in the algorithm to unravel the mystery behind
[6.1 – 15.6] years, with 12.3% (526 patients) of patients developing cryptogenic cirrhosis and also reiterates the importance of renalysis.
HBsAg seroclearance at a median time of 4.2 [3.0 – 9.3] years. In Table and Figure:Figure 1.
Figure 2. Results
Totally 103,652 MASLD individuals were identified with 6605 cases
diagnosed extrahepatic cancers. The primary outcome showed that
YI0005
the combination of abnormal blood pressure and hyperglycemia
Molecular Events Linked to Adverse Outcomes of Liver Fibrosis in significantly associated with extrahepatic malignancies in MASLD
Patients with Chronic Hepatitis B After Antiviral Treatment population (OR 1.33, 95%CI: 1.19,1.48). Aging, female gender,
Hong Li1, Yameng Sun2, Wen Zhang2, Wenyue Wu2, Shuyan Chen2, hypertension, type 2 diabetes mellitus, AST or ALT >40U/L, and
Ning Zhang2, Qi Han1, Xuzhen Yan1, Aiting Yang1, Hong You2, Wei chronic obstructive pulmonary disease associated with the risk of
Chen1 extrahepatic cancers respectively as well. Anti-metabolic dysfunction
1
Beijing Clinical Research Institute, Beijing Friendship Hospital, agents significantly protected MASLD population from non-hepatic
Capital Medical University, Beijing 100050, China, 2Liver Research malignancies. Age 35 to 65, FIB-4 over 1.3, between 1.3-2.67, over
Center, Beijing Friendship Hospital, Capital Medical University, Beijing 2.67, over 3.48 were associated with extrahepatic cancers compared
100050, China. with FIB-4 less than 1.3, which was consistent with aged over 65 whose
Background: Antiviral therapy (AVT) proves insufficient in alleviating FIB-4 over 2 associated with extrahepatic cancers risk in MASLD
liver fibrosis in all patients with chronic hepatitis B (CHB). Notably, population.
CHB patients with non-regressive liver fibrosis post-AVT frequently Conclusion
encounter a higher rate of adverse clinical outcomes. This study aims The combination of hypertension and hyperglycemia, and elevated
to investigate the molecular events that might explain or predict the FIB-4 associated with extrahepatic malignancies in MASLD population.
poor prognosis of liver fibrosis following AVT
Method: Transcriptomic gene expression profiles related to hepatitis YI0007
B virus (HBV)-related liver fibrosis and hepatocellular carcinoma
Fgl2-C3aR axis mediated NETs promote intravascular coagulation
(HCC) were retrieved from GEO, TCGA, and ICGC databases. Bulk
and liver fibrosis in MAFLD progression
RNA sequencing (RNA-seq) was performed on consecutive biopsies
from liver fibrosis patients with CHB at baseline and post-AVT. Xitang Li1, Junjian Hu1, Suping Hai1, Qiang Gao1, Wehui Wu1, Binghui
Comprehensive bioinformatics analyses were conducted to unveil Yu1, Xiaojing Wang1, Qin Ning1
the molecular events underlying adverse prognosis of liver fibrosis
1
Department and Institute of Infectious Disease, Tongji Hospital,
following AVT. Tongji Medical College and State Key Laboratory for Diagnosis
Result: A total of 466 genes were found to be dysregulated in HBV- and Treatment of Severe Zoonotic Infectious Diseases, Huazhong
related liver fibrosis. These genes were separated into six clusters with University of Science and Technology, Wuhan 430030, Hubei, China
consistent expression pattern during AVT, three of which (including Background: Procoagulant imbalance was observed in metabolic
228 genes) were resistant to recovery after 78 weeks of AVT. A dysfunction-associated fatty liver disease (MAFLD) patients with liver
comparative analysis between patients showing fibrosis regression fibrosis, but the role of coagulation in MAFLD remains largely unclear.
and those not, revealed a set of 9 genes (CCNA2, CDC20, ECT2, Neutrophil extracellular traps (NETs) served as an essential factor in
EZH2, MAD2L1, MCM6, NUSAP1, RACGAP1, and RRM2) that formed immuno-thrombosis. Here, we aim to study the role of NETs-mediated
a non-regression (non-RES) signature. Non-RES signature exhibited a complement and coagulation activation in MAFLD-fibrosis and the
higher expression level in patients at baseline who did not experience underlying mechanism.
fibrosis regression after AVT compared to those who experienced Method: NETs were depleted by intraperitoneal injection of DNase-1.
fibrosis regression, and did not reprogram after 78 weeks of AVT. Wild type (WT) and fgl2-/- C57BL/6 mice were treated either with 60%
Moreover, this non-RES signature was found to be upregulated in high fat diet (HFD) or methionine/choline-deficient (MCD) diet to induce
HBV-related HCC tumors, as per analyses from five independent MAFLD-fibrosis. RNA-Seq of hepatic tissues or liver leukocytes were
gene expression profiles in the GEO database. Additionally, the non- conducted in WT and fgl2-/- mice. Bone marrow neutrophils from WT
RES signature could stratify HBV-related HCC patients from the TCGA and fgl2-/- mice were subjected to palmitic acid (PA) and LPS in vitro.
and ICGC databases into low, intermediate, and high-risk subgroups, Result: Abundant neutrophil accumulation and NETs formation were
with the high-risk patients exhibiting a worse clinical prognosis. observed in MAFLD progression. NETs depletion improved liver
Conclusion: This study identifies a non-RES signature linked to fibrosis, inflammatory response and lipid accumulation both in HFD and
the non-regression of HBV-related liver fibrosis following AVT, as MCD models. Meanwhile, decreased coagulation activation, including
well as carcinogenesis and its poor prognosis. Our findings unveil lower level of plasma thrombin-anti-thrombin complex (TAT) and
the molecular events that probably contribute to the adverse hepatic fibrin deposition was observed following DNase-1 treatment.
outcomes of HBV-related liver fibrosis. Highly expressed on hepatic neutrophils, fibrinogen-like protein 2
Hypertension combined with Hyperglycemia Associated with the Risk (FGL2) colocalized tightly with NETs area. Fgl2 knockout inhibits NETs
of Extrahepatic Malignancies in MASLD population: a cross-sectional formation and coagulation activation in MAFLD progression. Combined
study in China. with RNA-Seq analysis, in vivo and in vitro experiment identified that
Xinyue Zhao1, Feng Xue1, Haiyun Ding2, Shanshan Wang2, NETs formation was regulated by FGL2-C3aR axis. Treatment with
Shuangqing Gao2, Lai Wei1 C3aR antagonist alleviated NETs formation, coagulation activation and
1Hepatopancreatobiliary Center, Beijing Tsinghua Changgung liver fibrosis in vivo.
Hospital, School of Clinical Medicine, Tsinghua University, Beijing Conclusion: NETs mediated coagulation dysregulation promotes
China., 2Beijing North Medical & Health Economic Research Center MAFLD-fibrosis progression. In depth, NETs formation was regulated
Background by FGL2-C3aR axis.
Extrahepatic cancers have been recognized as a significant outcome
of non-alcoholic fatty liver disease (NAFLD), which has been redefined
YI0008
as metabolic dysfunction-associated steatosis liver disease (MASLD)
with additional metabolic factors. We aimed to discover the association Gut microbiota predicts treatment response to empagliflozin
of hypertension, hyperglycemia, their combination, as well as liver among metabolic dysfunction-associated steatotic liver disease
fibrosis, and extrahepatic cancer in the MASLD population. patients without diabetes mellitus
Methods KaShing Cheung1, HoYu Ng2, Lina Zhang1, JingTong Tan1,
The MASLD population and those with comorbid extrahepatic cancers RexWanHin Hui1, ManFung Yuen1,3, WaiKay Seto1,3, WaiK Leung1
were derived from a hospital-based database across 11 centers in 1
Department of Medicine, School of Clinical Medicine, The University
Chinese nationwide, according to MASLD diagnostic criteria based on of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China, 2Li
keywords and ICD-10 codes. Logistic regression was used to estimate Ka Shing Faculty of Medicine, The University of Hong Kong, Queen
odd ratios (ORs) and 95% confidence interval (CI) between risk factors Mary Hospital, Hong Kong SAR, China, 3State Key Laboratory of Liver
and extrahepatic cancers. Research, The University of Hong Kong, Hong Kong SAR, China
Background: We aimed to investigate whether gut microbiota could specimens were included to evaluate clinical significance.
predict treatment response to pharmacological agents among Result: TM6SF2 was downregulated in tumours compared with
metabolic dysfunction-associated steatotic liver disease (MASLD) adjacent normal tissues from MASLD-HCC patients. Hepatocyte-
patients without diabetes mellitus (DM), as data is lacking. specific Tm6sf2 knockout exacerbated tumour formation in mice
Method: We prospectively followed up non-diabetic MASLD patients with diet-induced or diet-induced and carcinogen-induced MASLD-
who used empagliflozin 10mg daily. Clinical, anthropometric, HCC. The tumour-promoting effect of Tm6sf2 knockout was verified
laboratory assessments and magnetic resonance imaging-proton in orthotopic MASLD-HCC mice, while mice bearing Tm6sf2-
density fat fraction (MRI-PDFF) were performed from baseline to overexpressing tumours had opposite phenotypes. We observed the
week 52 (EOT). Baseline stool samples were collected, and shotgun reduction of interferon-gamma (IFN-γ)+CD8+ T cells in the tumours
DNA metagenomic sequencing performed to profile microbiome. of Tm6sf2∆hep mice and orthotopic Tm6sf2 knockout mice, while the
Primary outcome was treatment response to empagliflozin at EOT, tumour-suppressive effect of Tm6sf2 was abolished after depleting
defined as MRI-PDFF decline ³30% at EOT from baseline. Linear CD8+ T cells. The correlation between TM6SF2 and CD8+ T cells was
discriminant analysis [LDA] effect size analysis was used to identify confirmed in human MASLD-HCC tissues, inferring that TM6SF2 could
putative bacterial species. Multivariable logistic regression was used promote antitumour immunity. Mechanistically, TM6SF2 directly bound
to derive adjusted odds ratio (aOR) of outcome with bacterial species to IKKβ and inhibited NF-κB signalling pathway to reduce interleukin
by adjusting for clinical factors including body weight, diet and alanine (IL)-6 secretion, thereby activating cytotoxic CD8+ T cells. IL-6
aminotransferase (ALT). neutralisation abolished the tumour-promoting and immunosuppressive
Result: Twenty-two (48.9%) of 45 patients (median effects of Tm6sf2 knockout in mice. Moreover, introducing Tm6sf2 by
age:56.9y[IQR:51.0-63.2]; male:23[51.1%]) achieved treatment adenovirus improved immunotherapy response against MASLD-HCC
response at EOT. There was difference in alpha diversity (Shannon in mice.
index:p<0.001; Simpson index:p=0.001) and beta diversity Conclusion: Hepatic TM6SF2 protects against MASLD-HCC and
(p=0.048) in baseline microbiome between treatment response activates cytotoxic CD8+ T cells via NF-κB-IL-6 axis. TM6SF2 is a
and non-response groups. Faecalibacterium prausnitzii (log10LDA promising strategy for sensitising MASLD-HCC to immunotherapy.
score=4.27), Lachnospira pectinoschiza (log10LDA score=3.99), Table and Figure:Figure 1.Graphical abstract
Anaerostipes hadrus (log10LDA score=3.98), Roseburia faecis
(log10LDA score=3.97), Roseburia inulinivorans (log10LDA YI0010
score=3.58), and Agathobaculum butyriciproducens (log10LDA
score=2.77) were enriched in treatment response group (Figure 1). Detection and assessment of Antigen of hepatitis E virus in urine
L. pectinoschiza (aOR:34.1;p=0.015), A. hadrus (aOR:35.0;p=0.032) Haiying Zhang1, Yuyuan Jia1, Runling Zhang1, Huiying Rao2
and A. butyriciproducens (aOR:22.3;p=0.023) were associated with 1
Peking University People‘s Hospital,Peking University Hepatology
treatment response, but not clinical factors. These three species Institute,Infectious Disease and Hepatology Center of Peking
collectively distinguished treatment response from no response with University People‘s Hospital,Beijing Key Laboratory of Hepatits C and
AUROC of 0.89 (95% CI:0.80-0.99). A. hadrus significantly correlated Immunotherapy for Liver Diseases,Beijing International Cooperation
with pathways that produced metabolites beneficial to alleviating Base for Science and Technology on NAFLD Diagnosis,Beijing
hepatic steatosis, including acetyl-CoA fermentation to butanoate 100044,China, 2Peking University People‘s Hospital,Peking University
II pathway (r=0.47;p=0.024) as well as superpathway of L-lysine, Hepatology Institute,Infectious Disease and Hepatology Center
L-threonine and L-methionine biosynthesis II (r=0.44;p=0.035) (Figure of Peking University People‘s Hospital,Beijing Key Laboratory
of Hepatits C and Immunotherapy for Liver Diseases,Beijing
2). F. prausnitzii and A. butyricidproducens significantly correlated
International Cooperation Base for Science and Technology on
with L-arginine biosynthesis I and II pathway, and superpathway of
NAFLD Diagnosis,Beijing 100044,China
L-cysteine biosynthesis (mammalian) (Figure 2).
Conclusion: Baseline abundance of certain gut bacterial species, Background: Hepatitis E virus (HEV) is the main cause of acute and
particularly combination of A. hadrus, L. pectinoschiza and A. chronic viral hepatitis. Hepatitis E virus (HEV) is known to be excreted
butyriciproducens, may predict treatment response to empagliflozin in through feces, but there is little research on its presence in urine. This
MAFLD patients without DM. study investigated the presence and dynamic changes of antigens
Table and Figure:Figure 1.Baseline gut bacterial species enriched in (HEV Ag) in urine.
the empagliflozin response group and their relative abundances Method: Virus markers were detected in the urine and serum of acute
Figure 2.Spearman correlation between baseline metabolic pathways and chronic HEV patients to evaluate the diagnostic utility of HEV Ag in
and putative gut bacterial species predicting HEV infection outcomes.
Result: HEV RNA and HEV Ag were continuously detected in the blood
of 4 patients with chronic HEV infection, and HEV Ag was continuously
YI0009 detected in the urine. The dynamic change of HEV Ag in blood was
Hepatic TM6SF2 activates anti-tumor immunity to suppressed consistent with the dynamic change of HEV RNA in blood. Among 41
metabolic dysfunction-associated steatotic liver disease– patients with acute HEV, 97.56% (40/41) had HEV Ag detected in their
associated hepatocellular carcinoma and boosts immunotherapy urine, and the specificity of HEV Ag in urine was 100%. Among 63
Yating ZHANG1, Mingxu Xie1, Jun Wen1, Cong Liang2, Qian Song1, patients with acute HEV, 93.65% (59/63) had HEV Ag detected in their
Weixin Liu1, Yali Liu1, Harry Lau1, Jun Yu1, Xiang Zhang1 serum, although 2 cases were negative for anti HEV IgM.
1
Institute of Digestive Disease and Department of Medicine and Conclusion: Detecting HEV Ag in urine may have important value in
Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing diagnosing acute and chronic HEV infections and monitoring persistent
Institute of Health Sciences, CUHK Shenzhen Research Institute, The infections.
Chinese University of Hong Kong, Hong Kong SAR, China, 2Institute
of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen
YI0011
University, Guang Zhou, China
Study Of Infections in Hospitalized Patients With Liver Cirrhosis
Background: Transmembrane 6 superfamily member 2 (TM6SF2)
in mainland China: a prospective cohort study for the SONIC
has a protective role against metabolic dysfunction-associated
Consortium
steatotic liver disease (MASLD). We aim to investigate the mechanistic
role and therapeutic potential of hepatic TM6SF2 in MASLD-related Zhujun Cao1, Huadong Yan2, Yingling Wang3, Xiaoguang Dou4,
hepatocellular carcinoma (HCC). Xiaoguang Dou4, Qinghua Meng5, Wei Zhang5, Minghua Lin6, Haibin
Method: Hepatocyte-specific Tm6sf2 knockout (Tm6sf2∆hep) mice Gao6, Yongchao Xian7, Jin Guan7, Xiaoping Wu8, Xiaoping Lai8,
were fed with high-fat/high-cholesterol (HFHC) diet or diethylnitrosamine Yuerong Zhang9, Ning Zhou9, Caiyan Zhao10, Ziyue Li10, Honying
plus HFHC diet to induce MASLD-HCC. TM6SF2 function was also Pan11, Dujing Bao11, Yongping Chen12, Yi Chen12, Chenghai Liu13,
evaluated in orthotopic MASLD-HCC mice. Human MASLD-HCC Yongping Mu13, Peng Hu14, Huan Deng14, Xiaorong Mao15, Ni Jiang15,
Jiabin Li16, Yufeng Gao16, Xinsheng Xie17, Min Deng17, Lihua Huang18, infections before hospitalization, and UTI or bacteremia. Occurrence
Yiguang Li18, Minghua Su19, Huan Liang19, Yingren Zhao20, Taotao of infection significantly decreased 28-, 90-daytransplant-free survival,
Yan20, Longgen Liu21, Dongmei Zhu21, Qin Zhang22, Rongkun Yin22, leading to more ACLF, AKI and ICU transfer, longer hospital stay
Lijuan Ouyang23, Yuqian Hong23, Chuanwu Zhu3, Yaoren Hu2, Qing and more readmission after discharge. (Fig.1C). eABT were given
Xie1 promptly (within 24h of infection) in 76% and initiated with broad
1
Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao coverage in67% of infections, leading to an overall 81% of resolution.
Tong University School of Medicine, Shanghai, China , 2Department of Multivariable analysis demonstrated that infections with inefficient
Hepatology, Key Laboratory of Diagnosis and Treatment of Digestive eABT are associated with 7- and 4-fold risk of 28- and 90-day mortality,
System Tumors of Zhejiang Province, Hwamei Hospital, Ningbo respectively, independent of overt ascites, ACLF and AKI (Fig.1D).
No.2 Hospital, University of Chinese Academy of Sciences, Ningbo, Conclusion: MDR bacteria is emerging with regional variations within
China, 3Department of Infectious Diseases, the Fifth People‘s Hospital China and is underestimated by low cluture positiveness. Investigations
of Suzhou, Jiangsu, China , 4Shengjing Hospital of China Medical focusing on the enhancement of microbiology and drug resistance
University, Liaoning, China , 5Department of Critical Care Medicine diagnostics would be essential in guiding treatment while reducing
of Liver Disease, Beijing You‘an Hospital, Capital Medical University, MDR burden.
Beijing, China , 6Department of severe Liver Diseases, Fuzhou Table and Figure:Figure 1.
Municipal Infectious Disease Hospital, Mengchao Hepatobiliary
Hospital of Fujian Medical University, Fujian, China , 7The Third
People‘s Hospital of Guilin, Guilin, Guangxi, China, 8The First Affiliated YI0012
Hospital of Nanchang University, Nanchang, Jiangxi, China, 9The Development and Validation of a Home-based (LiverHome) Score
First People‘s Hospital of Lanzhou City, Lanzhou, Gansu, China , to Predict Advanced Fibrosis and Liver-related Outcomes in the
1
0Department of Infectious Diseases, Third Affiliated Hospital of General Population
Hebei Medical University, Shijiazhuang, Hebei, China , 11Department Shanghao Liu1, Jie Shen2, Jingli Gao3, Xuanwei Jiang4, Heng Wan2,
of Infectious Diseases, Zhejiang Provincial People‘s Hospital, Xingdong Chen5, Chuan Liu1, Qinglei Zeng6, Shuairan Zhang7, Yilin
Zhejiang, China , 12First Affiliated Hospital, Wenzhou Medical
Zhang1, Chengfu Xu8, Zhenqiu Liu5, Xiaozhong Jiang9, Jiawei Zhang1,
University, Zhejiang, China , 13Department of Cirrhosis, Institute of
Yuping Chen1, Ling Yang1, Lan Liu2, Hua Liang2, Xuan Liang10,
Liver Disease, Shuguang Hospital, Shanghai University of Traditional
Zhenyu Dai11, Yijun Tang12, Yang Bo13, Min Zhao14, Yong Zhou15,
Chinese Medicine, Shanghai, China, 14Second Affiliated Hospital of
Jiajun Zhao16, Junming Han17, Jitao Wang18, Dongfang You19, Minghua
Chongqing Medical University, Chongqing, China, 15Department of
Infectious Disease, The First Hospital of Lanzhou University, Lanzhou, Zheng20, Wanguang Zhang21, Junliang Fu22,23, Xiao Liang24, Hui Shi25,
Gansu, China , 16First Affiliated Hospital of Anhui Medical University, Jinhua Shao26, Wei Rao27, Shenghong Ju1, Jie Li28, Victor W Zhong4,
Hefei, Anhui, China, 17The first Hospital of Jiaxing, Zhejiang, China, Vincent WaiSun Wong29, Gaojun Teng30, Xiaolong Qi1, LiverHome
1
8The Fifth People‘s Hospital of Wuxi, Affiliated to Jiangnan University, study group
Wuxi, Jiangsu, China , 19Department of Infectious Disease, The First 1
Liver Disease Center of Integrated Traditional Chinese and
Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, Western Medicine, Department of Radiology, Zhongda Hospital,
China , 20Department of Infectious Diseases, First Affiliated Hospital Medical School, Southeast University, Nanjing, China, 2Department
of Xi‘an Jiaotong University, Shanxi, China , 21Department of Liver of Endocrinology and Metabolism, Shunde Hospital, Southern
Diseases, The Third People‘s Hospital of Changzhou, Changzhou, Medical University (The First People‘s Hospital of Shunde, Foshan),
Jiangsu, China , 22Department of Hepatology and Infection, Tongren Guangdong, China, 3Department of Intensive Care Unit, Kailuan
Hospital, Shanghai Jiao Tong University School of Medicine, General Hospital, Tangshan, China, 4Department of Epidemiology and
Shanghai, China, 23Xiamen Hospital of Traditional Chinese Medicine, Biostatistics, School of Public Health, Shanghai Jiao Tong University
Xiamen, Fujian, China School of Medicine, Shanghai, China, 5State Key Laboratory of
Genetic Engineering, Human Phenome Institute, and School of
Background: Multi-drug resistant (MDR) bacterial/fungal infection
Life Sciences, Fudan University, Shanghai, China, 6Department of
in patients with cirrhosis is high in previous multinational studies and
Infectious Diseases and Hepatology, The First Affiliated Hospital
increases overtime with regional variations at the country levels. We
of Zhengzhou University, Zhengzhou, China, 7Department of
aimed to investigate the prevalence, characteristics, microbiology,
Gastroenterology, The First Affiliated Hospital of China Medical
empirical antibiotic treatment (eABT) of infection and impact of regional University, Shenyang, China, 8Department of Gastroenterology, the
variations on outcome across China. First Affiliated Hospital, Zhejiang University School of Medicine,
Method: We collected data from pts non-electively admitted with Hangzhou, China, 9Department of Digestive, Kailuan General
cirrhosis at 23 centers in China from November 2018 through July Hospital, Tangshan, China, 10Department of Infectious Disease,
2019. Data were collected for demographics, comorbidities, etiology The Sixth People‘s Hospital of Shenyang, Shenyang, China,
of cirrhosis, cause of admission, medical history, vital signs, lab data 1
1Department of Radiology, The Yancheng School of Clinical
and hospital course. All infections were confirmed with prespecified Medicine of Nanjing Medical University (Yancheng Third People‘s
standard criteria and clinically suspected Is without evidence were Hospital), Yancheng, China, 12Regulatory Mechanism and Targeted
excluded. Once infection was diagnosed, the characteristics, Therapy for Liver Cancer Shiyan Key Laboratory, Hubei provincial
microbiology, antibiotic data and outcome data of infection were Clinical Research Center for Precise Diagnosis and Treatment of Liver
collected. Patients were followed until death, liver transplantation, or Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China,
90-day post-discharge. 1
3Department of Hepatobiliary Surgery, People‘s Hospital of Ningxia
Result: Infection was confirmed in 342 of 1294 pts (26%) from 6 Hui Autonomous Region, China, 14Department of Outpatient, The
administrative regions. A total of 372 episodes (#) of infection were Third People‘s Hospital of Taiyuan, Taiyuan, China, 15Department of
confirmed with balanced source of acquisition (31% community, Gastroenterology, Qingdao Sixth People‘s Hospital, Qingdao, China,
39% health-care, 30% nosocomial). No.1 type was pneumonia
1
6Key Laboratory of Endocrine Glucose & Lipids Metabolism and
(45%) followed by SBP (23%)and spontaneous bacteremia (11%). Brain Aging, Ministry of Education; Department of Endocrinology,
Organisms were identified in 106 # (29%)with 62% GNB, 20% GPC Shandong Provincial Hospital Affiliated to Shandong First Medical
and 9% fungi. MDR was confirmed in 14% of all # and57% in # with University, Jinan, China, 17Department of Endocrinology, Shandong
isolated organisms. EastNorth sites had the highest infection rate, yet Provincial Hospital Affiliated to Shandong First Medical University,
Jinan, China, 18Hebei Provincial Key Laboratory for Liver Cirrhosis
lowest rate of organism isolation and MDR infection than other sites,
and Portal Hypertension, Xingtai People’s Hospital, Xingtai, China,
whereas WestNorth sites were literally the opposite (Fig.1A). Despite 1
9Department of Biostatistics, School of Public Health, Nanjing
of the highest rate of MDR infection in WestNorth sites, the resolution
Medical University, Nanjing, China, 20MAFLD Research Center,
of infection was highest with the highest rate of eABT efficacy (44 vs
Department of Hepatology, the First Affiliated Hospital of Wenzhou
26% in WestSouth and <20% in the rest regions).Infection type and Medical University, China , 21Hepatic Surgery Center, Tongji Hospital,
pathogens varied significantly across regions (Fig.1B). Independent Tongji Medical College, Huazhong University of Science and
risk factors for MDR infection were infection in WestNorth China, prior
Technology, Hubei, China, 22Medical School of Chinese PLA, Beijing, YI0013
China, 23Senior Department of Infectious Diseases, The Fifth Medical
Construction of a Combined Predictive Model for Liver Fibrosis
Center of Chinese PLA General Hospital, National Clinical Research
Staging in Chronic Hepatitis B patients based on Capsid-Antibody-
Center for Infectious Diseases, Beijing, China, 24Department of
Complexes.
General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University
School of Medicine, Hangzhou, China, 25Department of Neurosurgery, Li Ting Ting1,2, Li Jin2, Wu Xun Xun2, Chen Fan2, Li Yang2, Zhu Chuan
The First People‘s Hospital of Liangyungang, Lianyungang, China, Wu2, Zhang Xiao Nan3, Zhu Li1,2
2
6Wuxi Hisky Medical Technologies Co.,Ltd, Wuxi, China, 27Chairman 1
The Affiliated Infectious Diseases Hospital, Suzhou Medical College,
& President, Shenzhen New Industries Biomedical Engineering Co., Soochow University, Suzhou, Jiangsu 215123, China, 2Department
Ltd., Shenzhen 518118, China, 28Department of Infectious Diseases, of Infectious Diseases, The Affiliated Infectious Disease Hospital,
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing Suzhou Medical College, Soochow University (Suzhou Fifth People‘s
University Medical School, Nanjing, China, 29Department of Medicine Hospital), Suzhou, Jiangsu 215131, China, 3Shanghai Public Health
and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Clinical Centre, Fudan University, Shanghai 200083, China
China , 30Basic Medicine Research and Innovation Center of Ministry Background: Hepatitis B virus infection represents a significant
of Education, Zhongda Hospital, Southeast University; State Key public health challenge globally, as it can lead to the progressive
Laboratory of Digital Medical Engineering, Nanjing, China development of liver fibrosis. There exists a significant lack of effective
Background: Liver fibrosis is a common condition leading to noninvasive predictive models for liver fibrosis staging assessment
tremendous disease burden, and the prevalence is high in the general in chronic hepatitis B (CHB) patients. Our previous studies identified
population. A fundamental shift must occur with health promotion, that circulating CACs display significant positive correlation with liver
proactive case-finding, and early recognition of advanced fibrosis. To fibrosis staging. This paper aims to establish a combined predictive
drive the paradigm shift, we aimed to develop and validate a home- model for liver fibrosis staging of chronic hepatitis B patients based on
based tool to predict advanced fibrosis and liver-related outcomes in circulating capsid-antibody-complexes (CACs) and to facilitate clinical
the general population. implementation.
Method: The LiverHome score was derived from a prospective Method: A total of 161 treatment-native CHB patients who underwent
Chinese cohort, to detect advanced fibrosis (i.e. liver stiffness liver biopsy were enrolled and divided into two groups: 64 individuals
measurement >= 10 kPa in transient elastography), then validated with no or mild fibrosis (S<2) and 97 individuals with advanced fibrosis
in two prospective cohorts. Moreover, we determined the prognostic (S≥2). The expression levels of circulating CACs were determined by
value of the LiverHome score for liver-related outcomes, including liver enzyme-linked immunosorbent assay (ELISA) techniques. Univariate
cancer and liver-related mortality, in two prognosis cohorts. and multivariate logistic regression analysis was used to screen the
Result: The cross-sectional cohorts included 15,457 individuals key factors for liver fibrosis staging of CHB patients. Receiver operating
(Chinese derivation cohort: 6,120; Chinese test cohort: 2,624; characteristic curve (ROC) was used to evaluate the diagnostic
American validation cohort: 6,713). The prognostic cohorts consisted efficiency of the combined prediction model.
of the Chinese prognostic cohort with 96,869 participants (median Result: The expression levels of CACs (P=6.19E-11), M30
follow-up time: 10.2 [10.2–10.2] years) and the UK prognostic cohort (P=1.60E-13), M65 (P=6.79E-11), ALT (P=2.20E-5), AST (P=6.16E-8),
with 454,621 participants (median follow-up time: 14.7 [14.6–14.8] GGT (P=0.0009), ALB (P=0.0120), PLT (P=9.62E-7), APRI
years). The LiverHome score (free online calculator: https://sourl.cn/ (P=1.54E-11) and FIB-4 (P=6.19E-8) scores displayed statistically
ED9GSD) included waist circumference, diabetes, and viral hepatitis differences between the S < 2 group and the S ≥ 2 group. Importantly,
history, and low-risk (LiverHome score < 0) and high-risk (LiverHome circulating CACs exhibited the most significant positive correlation with
score >= 0) groups were created. In the three cross-sectional cohorts, liver fibrosis staging (r=0.5253, P=3.3E-3). Through univariate and
the prevalence of advanced fibrosis exceeded 10% in the high-risk multivariate logistic regression analysis, circulating CACs, M30 and
group but remained below 1.5% in the low-risk group (Figure 1A- PLT were identified as independent key factors for liver fibrosis staging
B). The LiverHome score significantly outperformed fibrosis-4 index of CHB patients. Furthermore, a combined prediction model was
in identifying advanced fibrosis as measured by area under the constructed as follows: logistic(p) = -1.976 + 3.701*CACs + 0.036*M30
receiver-operating characteristics curve (AUC), i.e., 0.77 (0.72-0.82) - 0.014*PLT, with an area under the ROC curve (AUC) of 0.923, a
vs. 0.64 (0.58-0.70), 0.76 (0.70-0.83) vs. 0.63 (0.55-0.71), and 0.84 sensitivity of 93.8% and a specificity of 81.2%. The performance of
(0.82-0.86) vs. 0.65 (0.62-0.68), in the derivation cohort, Chinese and our combined model was superior to APRI (AUC=0.814) and FIB-4
American validation cohorts, respectively. In the subgroup analysis score (AUC=0.752), and the differences were statistically significant
from American validation cohort (n = 3,304), the LiverHome score also between the ROC curves (P<0.05).
surpassed the LiverRisk score for detecting advanced fibrosis (0.84 Conclusion: In our study, it was identified that circulating CACs, M30,
[0.81-0.87] vs. 0.77 [0.73-0.81], p = 0.004). Furthermore, high-risk and PLT serve as independent predictors for liver fibrosis staging of
individuals demonstrated a significantly increased incidence of liver CHB patients. Based on these key biomarkers, a promising combined
cancer in both the Chinese (hazard ratio [HR] = 5.77 [4.58–7.26]) and model for liver fibrosis staging was constructed and evaluated.
UK prognosis cohorts (HR = 4.55 [3.84–5.38]) (both p<0.001, Figure This combined model based on circulating CACs demonstrated
2A-B); similarly, HRs for liver-related mortality were 6.02 (4.83–7.51) high predictive diagnostic efficiency for liver fibrosis staging. It may
and 5.27 (4.72–5.87) in the UK cohort compared to the low-risk group contribute to achieving more accurate liver fibrosis staging assessment
(both p<0.001, Figure 2C-D). in clinical, thereby facilitating precise treatment and functional cure for
Conclusion: The home-based (LiverHome) score can better assess CHB patients.
advanced liver fibrosis and liver-related outcomes in the general
population. The LiverHome score is suitable for universal fibrosis
YI0014
screening and has the potential to reduce the burden of chronic liver
disease. IFITM1 Aggravates ConA-Induced Autoimmune Hepatitis by
Table and Figure:Figure 1.Figure 1. Comparison of the screening Promoting NKT Cell Activation through Increased AMPK-
performance of the LiverHome score and FIB-4. The proportion of Dependent Mitochondrial Function
advanced fibrosis in the high-risk group by LiverHome >= 0 and FIB-4 Jie Sun1,2, Xiaotong Han1,2, Dong Zhang1,2, Guangyong Sun1,2
>= 1.3 (A). The proportion of advanced fibrosis in the low-risk group by 1
Medical Research Center, Beijing Institute of Respiratory Medicine
LiverHome < 0 and FIB-4 < 1.3 (B). Fibrosis-4 index, FIB-4. and Beijing Chao-Yang Hospital, Capital Medical University, 2
Figure 2.Figure 2. Cumulative incidence of liver-related outcomes by Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital
LiverHome score groups. Cumulative probability of liver cancer in the Medical University
Chinese prognosis cohort (A) and UK prognosis cohort (B). Cumulative Background: AIH is an immune-mediated liver injury driven by
probability of liver-related mortality in the Chinese prognosis cohort (C) autoantibodies, with an increasing incidence in the Asia-Pacific
and UK prognosis cohort (D). region. IFITM1, a member of the interferon-induced transmembrane
protein family, plays a crucial role in antiviral immunity, particularly in Result: Demographics: The mean age was 56.3 ± 16.7 years, with
promoting intrahepatic immunity against HBV and HCV.  This study 72% female predominance.
aims to investigate the expression of IFITM1 in various intrahepatic cell Clinical Features: Acute hepatitis (50%) and cirrhosis (35%)
subsets and its impact on ConA-induced immune hepatitis, as well as were the most common presentations, followed by cholestasis (11%),
to elucidate the underlying mechanisms for AIH. liver failure (7%), and hepatic encephalopathy (4%).
Method: We constructed IFITM1-KO mice and IFITM1-GFP mice, Autoantibody Prevalence: ANA (63%) and ASMA (44%)
and induced immune hepatitis through tail vein injection of ConA to were most frequent, followed by F-Actin (15%), AMA (7%), and LKM
determine the effect of IFITM1 on the progression of AIH. ScRNA- (3%). Single autoantibody positivity was observed in 72.2%, two
seq and flow cytometry were employed to assess IFITM1 expression. autoantibodies in 23.6%, and three in 4.2%.
Serum transaminase levels, liver HE staining, and intrahepatic pro- Paraclinical Findings: Elevated transaminase levels (AST:
inflammatory cytokine levels were analyzed to evaluate the impact of 105 [49–383] U/L, ALT: 109 [49.3–499] U/L) and bilirubin levels (total:
IFITM1 on ConA-induced liver injury. The proportions, survival, and 27.3 [13.8–126] µmol/L, direct: 26.1 [5.1–147.8] µmol/L) indicated
function of intrahepatic immune cell subsets were examined to clarify significant liver damage at diagnosis.
the pathways through which IFITM1 influences immune-mediated liver Conclusion: This study highlights the clinical and immunological
injury. Differential gene expression analysis of IFITM1+ and IFITM1- characteristics of AIH in Vietnamese patients, a condition frequently
NKT cells in the ConA model, followed by in vivo validation, was misdiagnosed due to the prevalence of viral hepatitis. AIH primarily
performed to explore the mechanisms by which IFITM1 regulates NKT affects middle-aged females and often presents with advanced
cell activation. liver injury. ANA and ASMA were the most prevalent autoantibodies,
Result: IFITM1 was primarily expressed in intrahepatic immune cells confirming their diagnostic utility.
rather than in hepatocytes, with further upregulated in NKT cells The observed liver damage at diagnosis underscores the need for
following ConA stimulation. In the ConA model, IFITM1-KO remarkably improved clinical awareness and early detection. Routine autoantibody
reduced serum ALT and AST levels, the area of liver necrosis, and testing in patients with unexplained liver disease and standardized
the expression of intrahepatic pro-inflammatory cytokines. In IFITM1- diagnostic protocols are essential in the Vietnamese context. Future
KO mice, the proportion and absolute number of intrahepatic NKT studies should explore long-term outcomes, genetic predispositions,
cells were significantly reduced, along with diminished proliferation, and environmental factors to enhance diagnosis and management,
decreased expression of the cytotoxic molecule FasL and GZMB, ultimately improving patient outcomes in resource-limited settings.
lower levels of the pro-inflammatory cytokines IFN-γ and TNF-α. Table and Figure:Figure 1.Table 1: Demographic and Laboratory
These findings suggest that IFITM1 may exacerbate ConA-induced Characteristics of Patients with AIH
immune hepatitis by promoting NKT cell survival and function. Next,
scRNA-seq revealed that mitochondrial ATP synthesis and the AMPK
YI0016
signaling pathway were significantly upregulated in IFITM1+ NKT
cells compared to IFITM1- NKT cells. In vivo experiments further Prognostic Discordance Among Five Major Staging Systems
confirmed that IFITM1+ NKT cells exhibited higher mitochondrial for Early-stage Hepatocellular Carcinoma: A Multi-institutional
mass, membrane potential, and AMPKα levels. Analysis of 4,623 Patients
Conclusion: Our study demonstrates that IFITM1 expression is Lanqing Yao1, Shaodong Lv1, Junhong Chen2, Mingda Wang1, Han
upregulated in NKT cells during ConA-induced immune hepatitis. Wu1, Alfred WC Kow3, Yifan Li4, Yingjiang Liang5, Ziqiang Li6, Yongyi
IFITM1 enhances mitochondrial energy metabolism in NKT cells Zeng7, Qixuan Zheng8, Hong Wang9, Yahao Zhou10, Tinghao Chen11,
through the AMPK signaling pathway, leading to increased NKT cell Siyuan Wang12, Hongwei Guo13, Chao Li1, Lanqing Yao1, Yongkang
activation, cytotoxicity, and pro-inflammatory cytokine release, thereby Diao1, Jiahao Xu1, Lihui Gu1, Feng Shen1, Tian Yang1
exacerbating intrahepatic inflammation. This research unveils a novel 1
Eastern Hepatobiliary Surgery Hospital, Second Military Medical
mechanism of NKT cell activation in immune-mediated liver injury and University (Naval Medical University), 2Department of Hepatobiliary
provides new immunotherapeutic targets for AIH. and Pancreatic Surgery, General Surgery Center, First Hospital of
Table and Figure:Figure 1. Mechanism of IFITM1 regulation of NKT Jilin University, 3Division of Hepatopancreaticobiliary Surgery and
cells during ConA-induced immune hepatitis. Liver Transplantation, Department of Surgery, National University
Health System Singapore, 4Affiliated Hospital of Nantong University,
5
Department of Hepatobiliary Surgery, First Affiliated Hospital of
YI0015 Harbin Medical University, 6The First Affiliated Hospital of Shandong
Prevalence of Autoantibodies and Clinical Features in Patients First Medical University & Shandong Provincial Qianfoshan Hospital,
with Autoimmune Hepatitis at University Medical Center HCMC 7
Mengchao Hepatobiliary Hospital, Fujian Medical University,
Huy Huu Nguyen 1, Phong Kim Vi1, Suong Bang Nguyen Thi1, Bac
8
Shandong Provincial Hospital Affiliated to Shandong First Medical
Hoang Nguyen1, Nga Minh Cao1 University, 9Department of General Surgery, Liuyang People’s
Hospital, 10Department of Hepatobiliary Surgery, Pu’er People’s
1
University Medical Center HCMC
Hospital, 11Department of General Surgery, Ziyang First People’s
Background: Autoimmune hepatitis (AIH) is a chronic inflammatory Hospital, 12Beijing Tsinghua Changgung Hospital, Tsinghua University,
liver disease caused by an aberrant immune response targeting 1
3The Second Department of General Surgery, Second People’s
hepatocytes. It is characterized by elevated transaminases, Hospital of Changzhi
hypergammaglobulinemia, interface hepatitis, and specific Background: Multiple staging classifications for hepatocellular
autoantibodies, particularly antinuclear antibody (ANA) and smooth carcinoma (HCC) have created diverse definitions of “early-stage”
muscle antibody (SMA). If untreated, AIH can progress to cirrhosis disease, potentially leading to varied prognostic assessments and
and liver failure, with a five-year mortality rate of up to 50%. Although treatment strategies. This study aimed to evaluate the long-term
widely studied in Western populations, AIH remains underdiagnosed in survival and recurrence patterns among patients with “early-stage”
Vietnam due to its clinical overlap with viral hepatitis and limited local HCC, as defined by five widely-adopted staging systems, after
epidemiological data. curative hepatectomy.
Method: A cross-sectional study was conducted on 72 patients Method: This retrospective multicenter study enrolled 4,623 patients
diagnosed with AIH at the University Medical Center HCMC who underwent curative hepatic resection for newly diagnosed HCC
between January 2018 and April 2023. Diagnosis was based on the between 2014 and 2023 at 11 tertiary hospitals in China. Early-stage
simplified AIH scoring system (Hennes EM, 2008) and the revised disease was classified according to: 1) AJCC-TNM stage I, 2) BCLC
1999 International AIH Diagnostic Criteria. Data collected included stage 0/A, 3) within Milan criteria, 4) HKLC stage I/IIa, and 5) CNLC
demographics, clinical presentations, biochemical and immunological stage I. Overall survival (OS), time to recurrence (TTR), and prognostic
parameters, and histopathological findings. Autoantibodies were performance were analyzed using Kaplan-Meier method, competing
detected using ELISA and indirect immunofluorescence. Statistical risk analysis, and C-index calculation. The Akaike information criterion
analyses were performed using SPSS version 20.0.
was employed to assess model fitness. YI0018
Result: Marked variations were observed in the proportion of patients Serine/threonine kinase 39 contributes to the progression of liver
classified as early-stage: TNM stage I (49.3%), BCLC stage 0/A fibrosis to cancer and is promising drug target
(71.4%), within Milan criteria (49.3%), HKLC stage I/IIa (53.1%), and
Hongping Xia1
CNLC stage I (76.3%). After a median follow-up of 63.1 months,
significant differences emerged in survival outcomes. The 5-year
1
Cancer & Stem Cell Program, SingHealth-Duke-NUS Medical School
OS rates exhibited substantial variation, ranging from 67.4% (CNLC Background: Protein kinases are critical therapeutic targets for curing
stage I) to 74.9% (within Milan criteria), demonstrating a notable 7.5% hepatocellular carcinoma (HCC). As a serine/threonine kinase, the
difference. Similarly, 5-year cumulative recurrence rates showed potential roles of serine/threonine kinase 39 (STK39) in liver fibrosis
considerable disparity, from 39.5% (TNM stage I) to 46.3% (BCLC and cancer remains to be explored.
stage 0/A), revealing a 6.8% difference. Prognostic performance Method: We profile the whole kinome expression in clinical liver cancer
analysis indicated modest variations among staging systems, with samples and identify the overexpression of STK39. Then we established
C-indices ranging from 0.651 to 0.678 for OS prediction and 0.679 to the STK39 knockout mice using the CRISPR/Case9 technology and
0.715 for TTR prediction. The BCLC system demonstrated marginally following investigated the role of STK39 in different liver fibrosis and
superior discriminatory ability, although differences in prognostic cancer models. The expression of STK39 was examined by RT-qPCR,
performance were not statistically significant. western blotting and immunohistochemistry. The cell proliferation
Conclusion: This comprehensive analysis reveals substantial and apoptosis was detected by CCK8 and TUNEL kit. Cell migration
heterogeneity in long-term outcomes among patients with “early- and invasion assay were performed using a transwell system with or
stage” HCC across different staging systems, with clinically significant without Matrigel. RNA-seq, mass spectrometry and luciferase reporter
variations in both survival and recurrence rates. The findings highlight assay was used to identify STK39 binding proteins.
an urgent need for a more unified and precise definition of early-stage Result: We firstly report that STK39 is highly overexpressed in clinical
HCC. Such standardization would enhance prognostic assessment HCC tissues compared with adjacent tissues, high expression of
accuracy and optimize treatment decision-making in clinical practice. STK39 was induced by transcription factor SP1 and correlates with a
These results also suggest that current staging systems might benefit poor patients’ survival. Gain and loss of function assays revealed that
from refinement to better stratify early-stage HCC patients and predict overexpression of STK39 promotes HCC cell proliferation, migration
their outcomes more accurately. and invasion. In contrast, the depletion of STK39 attenuated the
Table and Figure:Figure 1.Virtual Abstract growth and metastasis of HCC cells. Moreover, knockdown of STK39
induces the HCC cell cycle arrested in the G2/M phase and promotes
apoptosis. In mechanistic studies, RNA-seq revealed that STK39
YI0017
positively regulates the ERK signaling pathway. Mass spectrometry
Plasma Exchange (PLEX) does not improve post-transplant identified that STK39 binds to PLK1. STK39 promotes HCC progression
survival and increase risk of sepsis in patients with acute on and activates ERK signaling pathway that was dependent on PLK1. In
chronic liver failure the STK39 knockout mice model, we found the critical role of STK39 in
Raghuram Nelluri, Karan Kumar1, Vivek Anand Saraswat1, Naimish N viral infection and the progression of liver fibrosis and cancer.
Mehta1 Conclusion: Our study uncovers a novel role of STK39 in viral infection
1
Mahatma Gandhi Medical College and Hospital and the progress of liver fibrosis and cancer and suggests STK39 as
Background: Plasma exchange (PLEX) is commonly used as a bridge an prognosis biomarker and a promising drug target of liver fibrosis
to liver transplantation (LT) in patients with severe acute-on-chronic and cancer.
liver failure (ACLF). However, the impact of pre-transplant PLEX on Table and Figure:Figure 1.Establishment of the STK39 knockout mice
post-transplant survival remains unclear. This study evaluates whether and induced liver injury and fibrosis models
the use of PLEX before LT affects post-transplant outcomes in ACLF Figure 2.The different induced liver cancer models in the STK39
patients. knockout mice
Method: This retrospective cohort study included patients who
underwent LT for ACLF between January 2022 and September 2024. YI0019
Patients were divided into two groups: those who received PLEX prior Development of a CT radiomics and clinical feature combined
to LT (Group 1) and those who underwent LT without PLEX (Group 2). model for predicting early recurrence of surgical resected
The primary outcomes were 90-day survival, incidence of sepsis, and Hepatocellular Carcinoma
length of hospital stay.
Minjun Liao1, Naying Liao2, Shengjun Huo3, Xiaoxiao Wang1, Zilong
Result: A total of 34 patients (mean age: 40 ± 4 years, 94.1% male)
Wang1, Baiyi Liu1, Xin Ai1, Feng Liu1, Yuanping Zhou2, Huiying Rao1
underwent LT for ACLF. The most common cause of ACLF was
alcohol-associated hepatitis (26/34, 76.47%), followed by Hepatitis B
1
Peking University People‘s Hospital, Peking University Hepatology
Institute, Infectious Disease and Hepatology Center of Peking
flare (3/34, 8.8%). Eight patients (Group 1) received PLEX before LT.
University People‘s Hospital, Beijing Key Laboratory of Hepatitis
The mean Model of end stage liver disease (MELD) score (33.5±5.26
C and Immunotherapy for Liver Diseases, Beijing International
v/s 32.35±5.18), APASL ACLF research consortium (AARC) score
Cooperation Base for Science and Technology on NAFLD Diagnosis,
(11.13±0.83 v/s 10.88±1.24), and CLIF-C ACLF score (43.25±2.12 v/s 2
Department of Gastroenterology, Nanfang Hospital, Southern
42.77±2.32) were comparable between the two groups [p value-not Medical University, 3General Surgery, Dongguan Liaobu Hospital
significant]. In group 1, 75% (6/8) of patients had ACLF grade II, while
25% had grade III. In contrast, in group 2, 26.92% (7/26) of patients Background: Recurrence rate remains unsatisfactory among surgical
had ACLF grade III. After liver transplant, the 90-day survival was 50% resected hepatocellular carcinoma (HCC) patients even with radical
for Group 1 compared to 73.1% in Group 2 (p-value: 0.005). Group 1 intention, and effective surveillance methods are lacking for post-
had a significantly higher incidence of sepsis compared to Group 2 operative recurrence. In this study, we constructed a noninvasive
(50% vs. 34.61%, p-value: 0.005). The average length of hospital stay and simple prediction model based on quantified subvisual features
was comparable between the two groups (19 ± 6.89 vs. 20 ± 8.78 extracted from contrast enhanced Computer Tomography (CECT)
days; p-value: 0.770). (Figure-1) images and clinical features of HCC patients, intending to illuminate
Conclusion: Pre-transplant plasma exchange does not improve post- the underlying correlation between CT image features and post-
transplant survival in patients with ACLF. In fact, it is associated with operative early recurrence (≤ 2 years) of HCC.
an increased risk of sepsis and mortality, suggesting limited benefit of Method: A total of 436 HCC patients were selected for analyses.
using PLEX as a bridge to liver transplantation. Semi-automatic segmentation method was used to outline the
Table and Figure:Figure 1.Table-1 favorable ROIs in the CECT images, and significant features were
extracted and selected by LASSO method to construct the radiomics
signature. According to univariate and multivariate Cox regression
analyses, a novel CT radiomics and clinical feature-based prediction Background: Hepatocellular carcinoma (HCC) treatments being
model was constructed to evaluate 2 year- RFS of resected HCC. guided a multi-disciplinary tumour board (MTB) is standard of care.
Model discrimination was evaluated by area under the ROC curve However, MTB decisions are complicated due to the interplay of
and the calibrated curves, and decision curve analysis was applied tumour, patient and MTB characteristics, local expertise and treatment
to assess clinical utility. Gene expression of FAM83D, RECQL4 etc. access. This study investigated the extent of clinical variation in
were assessed by q -PCR for 48 randomly selected HCC patients, and decision-making in MTBs.
correlation between image features and genomic characteristics was Method: Ten tertiary hospital MTBs that manage HCC independently
investigated. reviewed standardized imaging and clinical information from twenty
Result: Radiomics signature was established based on the 20 de-identified cases randomly selected from the participating MTBs.
early recurrence-related CECT features. Multivariate Cox regression The outcomes reported by the MTBs were assessment of BCLC
analysis selected microvascular invasion (MVI) status, serum alpha- stage, recommended treatment, and intent of treatment. The strength
fetoprotein (AFP) level, gamma-glutamyl transpeptidase to lymphocyte of agreement between the MTBs for these outcomes was analysed
ratio (GLR) level and radiomics signature as independent predictors for multi-rater reliability using Fleiss’ Kappa (κ). These were reported
of early recurrence of HCC after surgery, and the four factors were using 95% confidence intervals (CI) and deemed significant if p<0.05.
incorporated in the novel nomogram which predicted 2-year RFS for Factors that may have influenced treatment recommendations were
HCC, with radiomics signature accounting for the highest proportion. analysed using 2-sided Chi squared tests.
In training cohort, the radiomics and clinical combined model revealed Result: The multi-rater reliability for the BCLC stage assessment of
favorable prediction ability with AUC of 0.744 to predict 2-year RFS; disease was rated overall as ‘Good’ (κ 0.72, CI 0.69-0.76, p<0.001).
and validation cohort further verified the results with AUC of 0.821. The highest level of BCLC stage agreement was in BCLC D disease
The calibration curve and DCA curve either confirmed model potential rated as ‘Perfect’ (κ 0.72, CI 0.94-1.00, p <0.001). When the BCLC
in predicting early recurrence and clinical significance. HCC patients could not be determined, the multi-rater reliability was ‘Poor’ (κ
were successfully divided into the low-, intermediate- and high-risk 0.07, CI 0.002–0.14, p = 0.04). Disagreement often occurred when
groups, with the RFS difference between groups statistically significant there were differences in the imaging interpretation, e.g. whether an
(p < 0.01). Similar results were either observed in sub-group of AFP adrenal nodule indicated metastatic disease. The overall agreement
level ≤ 20 ng/ml. Additionally, Pearson correlation analyses revealed for recommended treatment was only ‘Fair’ (κ 0.39, CI 0.36- 0.41, p
favorable relationship between radiomics signature and BCAT1 as well <0.0001). However, when the intent of treatment was analysed as either
as CENPA gene expression level. curative or non-curative, the level of agreement improved to ‘Moderate’
Conclusion: The novel predictive model based on quantified CECT (κ 0.53, CI 0.50–0.62, p < 0.001). There was ‘Moderate’ agreement
radiomics features and clinical variables could evaluate post-operative for surgery (κ 0.54, CI 0.47-0.60, p <0.01) and Y90 (κ 0.56, CI 0.49-
early recurrence for HCC, and its clinical significance remained even in 0.62, p<0.01). There was ‘Poor’ agreement for combination TACE and
AFP-negative HCC patients. ablative therapy (κ 0.07, CI 0.01-0.135, p=0.04). This therapy was not
recommended in local HCC guidelines but supported by literature.
YI0020 Other non-guideline treatment strategies differed between MTBs, e.g.
combination locoregional and systemic therapies. There was a strong
Variation in Clinical Decision Making across Tertiary Hospital association between concordant BCLC stage and treatments.When
Hepatocellular Carcinoma Multidisciplinary Tumour Boards there was concordance on BCLC stage, agreement on treatment was
Anna Elizabeth Di Bartolomeo1, Cameron Gofton2,1,3, Rose Boutros1, 68.2%, however agreement was only 38% when BCLC assessment
Winston Liauw4, Karen Waller5,6, Amany Zekry7,8, Scott Anthony differed (p=0.006).
Davison9, Stephen Riordan10,11, Geoffrey William McCaughan12,13,14, Conclusion: Whilst BCLC stage assessment achieved ‘Good’
Stephen Clarke2,15, Emily He16,6, Martin Weltman17, Ken Liu13,18, Steven consistency across the MTBs, there was evidence of some inconsistent
Bollipo19,20, Mark Danta21,22, Miriam T Levy9, Simone I Strasser13, interpretation of imaging findings. Treatment recommendations also
Jacob George1 differed, despite agreement on stage, often relating to use of emerging
1
Storr Liver Centre, The Westmead Institute for Medical Research evidence, or aggressive strategies, outside of standard guidelines.
and Westmead Hospital, University of Sydney, 2Royal North Shore Clinical variation in HCC decision making is multifactorial in its aetiology
Hospital, St Leonards, Australia. , 3Hepatology Services, NSLHD, and impact, the causes and effects on patient outcomes warrants
St Leonards, Australia., 4School of Clinical Medicine, Faculty of further investigation.
Medicine and Health, University of New South Wales, Kensington,
5
Collaborative Centre for Organ Donation Evidence, Sydney School of
Public Health, Faculty of Medicine and Health, University of Sydney, YI0021
Camperdown, 6Gastroenterology and Liver Services, Concord Noninvasive prediction of liver inflammation grades in chronic
Hospital, Sydney, NSW, Australia., 7St George and Sutherland hepatitis B patients based on DWI combined with T2WI signal
Clinical Campuses, University of New South Wales, 8Department intensity index
of Gastroenterology and Hepatology, St George Hospital, Sydney, Yuan Liu1, Jinghui Dong1, Yanan Zhang2, Hongwei Ren1, Huiyi Ye3,
9
Department of Gastroenterology Liverpool Hospital, University of Jianming Cai1
New South Wales, Liverpool Australia., 10Gastrointestinal and Liver 1
Fifth medical centre of Chinese PLA general hospital, 2Third medical
Unit, The Prince of Wales Hospital, Sydney, 11Prince of Wales Clinical
centre of Chinese PLA general hospital, 3First medical centre of
School, University of New South Wales, Sydney, 12Centre for Organ
Chinese PLA general hospital
Assessment Repair and Optimisation, Royal Prince Alfred Hospital,
Sydney, NSW, 2050, Australia, 13AW Morrow Gastroenterology and Background: According to WHO, The number of People are living with
Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, NSW, hepatitis B worldwide is 296 million. Hepatitis B(HBV) also has a high
Australia., 14Faculty of Medicine and Health, The University of Sydney, prevalence in China. There are about 86 million HBV infected patients,
Sydney, NSW, 2006, Australia, 15University of Sydney, Sydney, NSW, which means about 1 in 15 Chinese carries HBV and there are about
Australia. , 16Daffodil Centre, The University of Sydney, a Joint Venture 20-30 million chronic hepatitis B (Chronic Hepatitis B, CHB) patients.
with Cancer Council NSW, Sydney, Australia., 17Hepatology Services, “Guidelines for the Prevention and Treatment of Chronic Hepatitis B”
Nepean Hospital, Sydney, Australia., 18Sydney Medical School, pointed out that when the liver inflammation grade greater than or
The University of Sydney, Sydney, NSW, Australia., 19Department equal to G2 can be used as indication for antiviral treatment.
of Gastroenterology, John Hunter Hospital, Newcastle, New South Biopsy is the gold standard for liver inflammation, but it has the following
Wales, Australia., 20Faculty of Health and Medicine, University of disadvantages, such as late reporting, Potential complications and
Newcastle, Newcastle, New South Wales, Australia., 21Department of so on. According to former studies, we can take diffusion‑weighted
Gastroenterology, St Vincent‘s Hospital Sydney, Darlinghurst, NSW, imaging (DWI) and T2WI signal intensity index (SII) as a potential non-
Australia., 22St Vincent‘s Clinical School, UNSW, Sydney, New South invasive method for liver inflammation.
Wales, Australia. Method: The research was designed by the method of diagnostic
test. Since May 2020-April 2024,we prospectively recruited 100 Public Health Clinical Center, 30Xiamen Humanity Rehabilitation
consecutive patients with CHB who underwent DWI (b = 800s / mm2) Hospital, 31The Second Affiliated Hospital of Xi‘an Jiaotong University,
and T2WI within 6 hours before liver biopsy at a GE 3.0T Signa HDxt 3
2Gan su Wu wei Tumour Hospital, 33Guangzhou Eighth People‘s
MRI scanner, the protocols were respiratory-triggered DWI(RT-DWI), Hospital,Guangzhou Medical University, 34West China Hospital
T2 FS and T1 DUAL.The apparent diffusion coefficient (ADC )values of Sichuan University, 35Department of Microbiology & Infectious
and SII values which were defined as the ratio of signal intensity of Disease Center, School of Basic Medical Sciences, Peking University
the liver to the right erector spinal muscle at the same level near the Background: Low-level viremia (LLV) is associated with increased risk
liver puncture site of the same patient were measured by using the of hepatocellular carcinoma. This study aimed to explore the optimal
delineation region of interest (ROI) method. With the pathological liver therapeutic strategy for LLV patients.
inflammation grade as the gold standard, the patients were divided Method: From October 2021 to October 2024, this multicenter,
into the case group (N=50,inflammation stage≥G2) and the control prospective, observational study enrolled CHB patients treated
group (N=50,inflammation stage≤G1), ROC was used to predict the with first-line nucleos(t)ide analogues (NAs) for ≥ 48 weeks at 44
diagnostic power for liver inflammation stages≥G2 of DWI,SII and DWI centers. The LLV patients and CVR patients (complete virological
combined with SII for the same CHB patient. response, HBV DNA < 10 IU/ml) receiving one of the following three
Result: The area under curve(AUC) of DWI in predicting liver therapeutic options: mono-NAs therapy, combination NAs (comb-NAs)
inflammation stages≥G2 was 0.860 in CHB patients, the sensitivity and therapy, or peginterferon α-2b (PegIFNα-2b) add-on therapy (add-
specificity was 84.0 % and 74.0 %, the cutoff value of ADC = 1.19×10- PegIFN) for 96 weeks.
3 mm2/s, the AUC of SII in predicting liver inflammation stages≥G2 Result: A total of 1,631 patients were enrolled (LLV, n=1,264;
was 0.812,the sensitivity and specificity was 76.0 % and 82.0 %, the CVR, n=367). PegIFNα-2b add-on therapy achieved higher
cutoff value of SII = 1.36.Meanwhile the AUC of DWI combined with HBV DNA undetectable rates compared to mono-NAs and
SII in predicting liver inflammation stages≥G2 was 0.904, the sensitivity comb-NAs at 48 weeks [mono-NAs: comb-NAs: add-PegIFN
and specificity was 87.8 % and 84.0 %, the cutoff value of ADC = 42.5% (54/127) vs. 48.7% (110/226) vs. 60.2% (115/191), P = 0.005]
1.19×10-3 mm2/s, the Youden index was 0.718. in LLV patients. Of the LLV patients, 80.7% were HBeAg-positive.
Conclusion: Both DWI and T2WI SII can predict liver inflammation Noticeably, in patients with high HBeAg levels (>100 COI or S/CO),
grade accurately, and the accuracy of DWI combined with SII to PegIFNα-2b therapy outperformed mono-NAs and comb-NAs at
predict G2 grade was higher. if the measured ADC values of DWI ≤ 48 weeks [mono-NAs: comb-NAs: add-PegIFN 26.8% (15/56) vs.
1.19×10-3 mm2/s or the measured SII values ≥ 1.36, it can be used as 33.1% (40/121) vs. 51% (51/100), P = 0.003].
an early predictive index of liver inflammation grade as G2 in patients Based on baseline HBV DNA levels, the LLV group was further divided
with chronic hepatitis B, which is conducive to the determination of into low (10–100 IU/ml) and moderate to high (≥100, but<2,000 IU/
treatment regimen and efficacy evaluation. ml) subgroups. At 48 weeks, PegIFNα-2b add-on therapy achieved
superior outcomes, particularly in patients with moderate to higher viral
YI0022 loads (Table 1). Though more than half of the LLV patients with low viral
load archived completed viral response at 48 weeks, in the moderate to
Therapeutic options for low-level viremia in patients with high viral load subgroup, the rates of HBV DNA undetectable dropped
chronic hepatitis B: adding on peginterferon α-2b as a potentially to about 30% for mono- and comb-NAs treated subgroups. Meanwhile,
superior option though the undetectable rate was also decline for PegIFNα-2b add-on
Suzhen Jiang1, Bo Feng2, Sujun Zheng3, Hao Wu4, Junliang Fu5, subgroup, it remains the highest among the three threat options (Table
Dong Ji5, Yinong Feng6, Juanhua Wang7, Rao Xie8, Xiaobo Lu9, Qing 1).
Mao10, Jie Qiu11, Tianyan Chen12, Qinghua Lu13, Jia Shang14, Xiaoping The consistency positive correlation relationships of serum HBV
Wu15, Chaoshuang Lin16, Lingyi Zhang17, Yueyong Zhu18, Liaoyun pgRNA level with HBeAg level (r = 0.844, P < 0.001) and HBV DNA
Zhang19, Qingfa Yuan20, Liting Zhang21, Zhengbin Zhao21, Hong Wan22, level (r = 0.566, P < 0.001) implicated that serum HBV pgRNA could
Jie Peng23, Zujiang Yu24, Haifeng Yu25, Guoxin Hu26, Haidong Zhao27, be a reliable indicator for the transcription activity of cccDNA pool
Qing Ye28, Xiaoying Li29, Wenqi Huang30, Shuangsuo Dang31, Wenling of the patients. As compared to that in CVR patients, a significantly
Jia32, Chunlan Zhang33, Xuezhong Lei34, Fengmin Lu35 higher HBV pgRNA levels [6.42 (4.71, 7.15) vs. 3.89 (3.47, 4.34),
1
Peking University People‘s Hospital, Peking University Hepatology P < 0.001] in LLV patients might reveal the underlined mechanism
Institute, Infectious Disease and Hepatology Center of Peking relevant to LLV occurrence. More than that, compared to CVR
University People‘s Hospital, Beijing Key Laboratory of Hepatitis patients, a significantly lower cumulative HBsAg clearance rate in LLV
C and Immunotherapy for Liver Diseases, Beijing International patients [14.6% (28/192) vs. 3.4%(13/384), P < 0.001]
Cooperation Base for Science and Technology on NAFLD Diagnosis, Conclusion: PegIFNα-2b add-on therapy appears to be a superior
Beijing 100044, China., 2Peking University People‘s Hospital, option for HBV DNA clearance in LLV patients, particularly in those
Peking University Hepatology Institute, Infectious Disease and patients with high HBeAg levels or moderate to high viral loads. High
Hepatology Center of Peking University People‘s Hospital, Beijing
HBV pgRNA levels in LLV patients suggest higher transcriptional
Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases,
activity of cccDNA. LLV status significantly impairs HBsAg clearance
Beijing International Cooperation Base for Science and Technology
compared to CVR patients.
on NAFLD Diagnosis, Beijing 100044, China., 3Beijing You‘an
Table and Figure:Figure 1.Table 1. Subgroup analysis of baseline HBV
Hospital,Capital Medical University, 4SHIHEZI UNIVERSITY, 5The
Fifth Medical Center of PLA General Hospital, 6the Third People‘s DNA levels in LLV patients
Hospital of Taiyuan, 7The Fifth People’s Hospital of Wuxi, 8Beijiing
Ditan Hospital Capital Medical University, 9The First Affiliated Hospital YI0023
of Xinjiang Medical University, 10The southwest hospita of AMU,
The validation of histological criteria from the IAIH-PG to
1
1The Second Hospital of Nanjing, 12The First Affiliated Hospital
distinguish AIH from drug-induced liver injury in China
of Xi‘an Jiaotong University, 13Qinghai Provincial Fourth People‘s
Hospital, 14Henan Provincial People‘s Hospital, 15The First Affiliated Zikun Ma1, Li Wang2, Jimin Liu3, Romil Saxena4, Zongming Eric
Hospital of Nanchang University, 16The Third Affiliated Hospital of Chen5, Xuchen Zhang6, Hanlin L.Wang7, Mukul Vij8, Mina Komuta9,
Sun Yat-sen University, 17The second hospital of lanzhou university, Gwyneth Soon Shook Ting10, Wei Zheng11, Jiping Zhang12, Bin
1
8the First Affiliated Hospital of Fujian Medical University, 19First Wang13, Min Li14, Yongfeng Yang15, Xinyan Zhao1
Hospital Of Shanxi Medical University, 20Xiamen Hospital of Traditional 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
Chinese Medicine, 21The First Hospital of Lanzhou University, 22The University, Beijing, China, 2Department of infectious disease and
NO.2 People‘s Hospital Of Lanzhou, 23nanfang hospital, 24The First liver Disease, the Second Hospital of Nanjing, Affiliated to Nanjing
Affiliated Hospital of Zhengzhou University, 25 Yantai Qishan Hospital, University of Chinese Medicine, 3Department of Pathology and
2
6Peking University Shenzhen Hospital, 27Xiamen Changgeng Laboratory Medicine, Mt Sinai Hospital, Toronto, ON, Canada,
Hospital Co., Ltd., 28Tianjin Third Central Hospital , 29Shandong 4
Department of Pathology and Laboratory Medicine, Mayo Clinic,
Rochester, MN, USA, 5Department of Pathology and Laboratory were identified during our MALRIC study (NCT06462742). Patients
Medicine, Indiana University School of Medicine, Indianapolis, IN, who underwent curative-intent MWA or rLR for recurrent tumors within
USA, 6Department of Pathology, Yale University School of Medicine, Milan criteria were included. One-to-many propensity score matching
New Haven, CT, USA, 7Department of Pathology and Laboratory (PSM) and overlap weighting (OW) was used to balance baseline
Medicine, University of California at Los Angeles, California, USA, characteristics. The primary outcome was overall survival (OS) and the
8
The Institute of Liver Disease & Transplantation, Dr. Rela Institute & secondary outcome was disease-free survival (DFS).
Medical Center, Bharath Institute of Higher Education and Research, Result: Finally, 494 first recurrent iCCA patients fulfilled enrollment
Chennai, India, 9Department of Pathology, International University criteria and underwent MWA (n=375) and rLR (n=119). Patient baseline
of Health and Welfare, School of Medicine, Narita Hospital, Chiba, characteristics were well balanced after either PSM or OW. Compared
Japan, 10Department of Pathology, National University Hospital, with rLR, MWA offered comparable OS (HR 0.89, 95%CI 0.68-1.17, P
National University Health System, Singapore, 11Department of =.31) and DFS (HR 0.78, 95%CI 0.61-1.00, P =.068) in primary cohort.
Pathology, Emory University School of Medicine, Atlanta, GA,
These results were also robust in PSM cohort and OW cohort, along
USA, 12Department of Pathology, Guangzhou KingMed Center for
with less complications after MWA. Stratification analysis showed that
Clinical Laboratory, Guangzhou, China, 13Department of Pathology,
rLR provided favorable DFS than MWA in the following four scenarios:
Mengchao Hepatobiliary Hospital of Fujian Medical University,
large duct subtype of primary tumor, complication-free during the initial
Diagnostic Pathology Center, Fujian Medical University, Fuzhou,
China, 14Department of Clinical Epidemiology and EBM, National resection, disease-free interval <12 months and margins of MWA/rLR
Clinical Research Center for Digestive Diseases, Beijing Friendship <5mm.
Hospital, Capital Medical University, Beijing, China., 15Department of Conclusion: Microwave ablation may be considered as a viable
infectious disease and liver disease, The Second Hospital of Nanjing, alternative option for selected patients with recurrent iCCA particularly
Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. for those unsuitable for general anesthesia or liver resection.
Table and Figure:Figure 1.Survival comparison between microwave
Background: To validate the applicability of the new histological
ablation (MWA) and repeat liver resection (rLR) in overall cohorts.
criteria of autoimmune hepatitis (AIH) proposed by the International
Overall survival (OS) and disease-free survival (DFS) were similar
AIH Pathology Group (IAIH-PG) in 2022 among Chinese patients with
between the MWA and rLR groups in primary cohort (A, D), propensity
drug-induced liver injury (DILI) and AIH.
score matched (PSM) cohort (B, E) and overlap weighting cohort (C,
Method: The diagnostic gold standard is based on a comprehensive
F). Hazard ratio (HR) was calculated by log-rank at rLR versus MWA.
analysis of clinical manifestations, laboratory tests, histopathological
Figure 2.Stratification analysis for overall survival (OS) and disease-
findings, and follow-up data. All patients from two hospitals
free survival (DFS) between microwave ablation (MWA) and repeat
were retrospectively retrieved from 2002 to 2023. The diagnostic
liver resection (rLR) in propensity matched (PSM) cohort.
performance was assessed by an area under the receiver operating
characteristic curve (AUROC).
Result: Out of 69 patients: AIH (41, 59.4%) and DILI (28, 40.6%). The YI0025
accuracy, sensitivity, and specificity of the new histological criteria for Outcomes of Conversion Surgery After Immune Checkpoint
likely and possible AIH were 69.6%, 97.6% and 28.6%, respectively, Inhibitor-Based Combination Therapy in Initially Unresectable
with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533- Hepatocellular Carcinoma: A Retrospective Cohort Study
0.8938]. For likely AIH, the accuracy, sensitivity and specificity were Mingjian Piao1, Chengjie Li1, Ziyue Huang1, Nan Zhang1, Jiongyuan
72.5%, 61.0% and 89.3%, respectively, with an AUROC of 0.9177 Li1, Ziyu Xun1, Shuofeng Li1, Haitao Zhao1
[95% CI: 0.8757-0.9596]. Moreover, for possible AIH, significant 1
Department of Liver Surgery, Peking Union Medical College Hospital,
differences found in serum alanine aminotransferase levels [178.4
Chinese Academy of Medical Sciences and Peking Union Medical
(87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear College (CAMS & PUMC)
antibody (ANA) ≥1:160 [10 (66.7%) versus 1 (5.9%)], as well as in
lobular lymphoplasmacytic infiltrate [15 (100.0%) versus 12 (70.6%)] Background: Hepatocellular carcinoma (HCC) has a high incidence
and more than mild inflammation [6 (35.3%) versus 13 (86.7%)] rate and is often asymptomatic in its early stages. Combination
between AIH and DILI (all P values were <0.05). therapies using immune checkpoint inhibitors (ICIs) have demonstrated
Conclusion: The new histological criteria can distinguish AIH from survival benefits and high objective response rates, offering hope for
DILI, with good diagnostic performance. In practice, for possible conversion surgery in patients with initially unresectable HCC. We
AIH, the presence of low aminotransferase, ANA ≥1:160, lobular aimed to investigate the oncological outcomes of conversion surgery
lymphoplasmacytic infiltrate, and more than mild inflammation are compared to those with continuing systemic treatment alone in patients
parameters in favor of AIH over DILI. who responded well to ICIs-based therapy, as well as the surgical
Table and Figure:Figure 1.The flowchart of patient enrollment. outcomes associated with conversion surgery.
Figure 2.ROC curves of the new histological criteria for AIH to distinguish Method: We consecutively enrolled patients diagnosed with HCC
between DILI and AIH. (A) Possible AIH and Likely AIH identified as between January 1, 2019 and April 1, 2024. These patients received
AIH, Unlikely AIH identified as DILI; (B) Likely AIH identified as AIH, treatment with ICIs combined with either anti-VEGF antibodies or
Possible AIH and Unlikely AIH identified as DILI. tyrosine kinase inhibitors. Tumor response and resectability were
assessed every 2 months. Patients who responded positively and met
the criteria for conversion surgery were included.
YI0024 Result: Among 613 patients with initially unresectable HCC, 136
Microwave Ablation versus Repeat Liver Resection for Recurrent achieved conversion and met the surgical resection criteria during
Intrahepatic Cholangiocarcinoma within Milan Criteria: A Long- combination therapy. The median follow-up time was 26.9 and 42.5
term Multicenter Cohort Study months for the surgery and non-surgery groups, respectively. The
Chuan Pang1, Jie Yu1, Ping Liang1 median PFS was 29.1 months in the surgery group versus 11.2
1
Department of Interventional Ultrasound, Chinese PLA General months in the non-surgery group (P<0.0001, hazard ratio [HR]=0.40
Hospital [0.25–0.63]). The median OS was 50.8 months in the surgery group,
compared to 25.8 months in the non-surgery group (P<0.0001,
Background: Only a minority of recurrent intrahepatic
HR=0.27 [0.15–0.47]). The median RFS was 18.7 months in the
cholangiocarcinoma (iCCA) patients are eligible for repeat resection.
surgery group. Multivariate Cox regression analysis indicated that
Whether they can benefit from the minimally invasive ablation treatment
conversion surgery was independently associated with improved OS
is worth defining. This study aims to compare the prognostic difference
and PFS (P<0.001), and continuing the original treatment post-surgery
of microwave ablation (MWA) and repeat liver resection (rLR) for the
significantly influenced OS and RFS.
first recurrent iCCA.
Conclusion: Conversion surgery after meeting the surgical criteria
Method: In this real-world multicenter cohort study from January
during immunotherapy provides significant prognostic benefits for
2009 to June 2022, 10,441 iCCA patients from ten tertiary hospitals
patients with initially unresectable HCC, demonstrating high safety
and R0 resection rates. For those specifically selected based on their biomarkers and developing targeted therapies.
response to immunotherapy and undergoing conversion surgery, Method: The association between liver cirrhosis and thyroid
promptly resuming the original treatment after surgery is necessary. dysfunction was analyzed using the MIMIC database. Genetic
Our results emphasize the importance of continuing immunotherapy correlation was assessed via linkage disequilibrium score regression
post-conversion surgery to prevent recurrence in patients who respond (LDSC), and bidirectional two-sample Mendelian randomization
to immunotherapy (MR) was used to explore causality. Candidate genes were identified
Table and Figure:Figure 1.(A) Kaplan-Meier analysis of OS of surgery through transcriptome-wide association studies (TWAS) under
group and no surgery group. (B) Kaplan-Meier analysis of PFS of the OTTERS framework, then prioritized using weighted gene co-
surgery group and no surgery group. (C) Kaplan-Meier analysis expression network analysis (WGCNA), differential gene expression
of RFS of surgery group. Abbreviations: OS, Overall Survival; PFS, (DEG) integration, and machine learning methods (LASSO and SVM-
Progression-Free Survival; RFS, Recurrence-Free Survival; HR, Hazard REF). Functional enrichment analyses (GO and KEGG) examined
Ratio. the biological significance of prioritized genes. Single-cell RNA
sequencing was used to investigate cell-specific expression dynamics
and intercellular communication. Finally, molecular docking identified
YI0026
therapeutic compounds targeting these genes.
FAK-TRIM25 Promotes Hepatic Stellate Cell Activation And Aerobic Result: A significant positive causal relationship between liver cirrhosis
Glycolysis By Inhibiting FBXW7-mediated c-Myc Ubiquitination and hypothyroidism was identified, suggesting hypothyroidism as
Lu Han1, Guo Yuan Lin1, Shao Jie Chen1, Tao Huang1, Hua Yue Wu1, a potential risk factor for cirrhosis progression. Multi-omics analysis
Xue Ke Zhao1 highlighted HLA-DQA1 as a key gene with dynamic expression in
1
Affiliated Hospital of Guizhou Medical University macrophages and monocytes during cirrhosis and hypothyroidism
Background: Chronic liver disease (CLD) affects over 800 million progression. CD27, co-expressed with HLA-DQA1, showed a
people globally, with liver fibrosis as a key reversible stage in its positive correlation and elevated expression in lymphocytes. Pathway
progression. Hepatic stellate cell (HSC) activation drives fibrosis by enrichment analysis implicated these genes in T cell activation,
enhancing aerobic glycolysis, regulated by focal adhesion kinase lymphocyte proliferation, and immune responses. Molecular docking
(FAK). This study investigates the molecular mechanisms linking FAK, identified glycyrrhizic acid as a promising therapeutic compound with
TRIM25, FBXW7, and c-Myc in liver fibrosis and explores FAK as a high binding affinity for HLA-DQA1 and CD27.
therapeutic target. Conclusion: This study suggests a potential causal relationship
Method: Human liver samples, mouse models, and LX-2 between liver cirrhosis and hypothyroidism, possibly mediated by
cells were analyzed. Techniques included Western blotting, immune dysregulation involving HLA-DQA1 and CD27. These findings
immunohistochemistry, RNA sequencing, Co-IP, and cycloheximide offer insights into the molecular mechanisms underlying disease
assays. Functional assays evaluated FAK’s impact on cell activation, progression and identify HLA-DQA1 and CD27 as potential therapeutic
migration, and glycolysis. Mouse models with FAK inhibition and targets, with glycyrrhizic acid showing promise as a candidate drug.
TRIM25 overexpression assessed the in vivo effects. Biochemical and
histological analyses were used to evaluate fibrosis and inflammation. YI0028
Result: FAK expression was elevated in fibrotic liver tissues and
Jieduan-Niwan Formula Alleviates Macrophage Pyroptosis in
correlated with increased HSC activation and aerobic glycolysis. FAK
Acute-on-Chronic Liver Failure through Modulation of the GSK-
inhibition reduced fibrosis, inflammatory cytokines, and glycolytic
3β/NLRP3/Caspase-1 Pathway
enzyme expression. Mechanistically, FAK stabilized TRIM25 via tyrosine
phosphorylation, suppressing TRIM25 auto-ubiquitination. TRIM25 Wenxin Zhang1, Kaidi Zhao1, Chognyang Ma1, Jiajun Liang 2, Yuqiong
enhanced FBXW7 ubiquitination, stabilizing c-Myc and promoting Du1, Qiuyun Zhang3, Peng Fang4
glycolytic enzymes. TRIM25 knockdown reversed these effects in LX-2
1
School of Traditional Chinese Medicine, Capital Medical University,
cells. In mice, TRIM25 overexpression aggravated fibrosis, which was
2
Integrated Hospital of Traditional Chinese Medicine, Southern
mitigated by FAK inhibitors. Histological analysis confirmed improved Medical University, 3Capital Medical University, School of Traditional
Chinese Medicine, 4Department of Infectious Diseases, The First
liver structure and reduced collagen deposition.
Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang
Conclusion: FAK plays a pivotal role in promoting liver fibrosis and
Provincial Hospital of Chinese Medicine)
aerobic glycolysis by stabilizing TRIM25 and modulating the TRIM25/
FBXW7/c-Myc pathway. This interaction enhances HSC activation and Background: Acute-on-Chronic Liver Failure (ACLF) is a syndrome
metabolic reprogramming, fueling the progression of fibrosis. FAK characterized by a high short-term mortality rate, for which effective
inhibitors demonstrated therapeutic potential in alleviating liver fibrosis interventions are still lacking.Systemic inflammation, characterized
and inflammation. by elevated circulating levels of inflammatory cytokines and
Table and Figure:Figure 1. increased infiltration of macrophages into tissues, represents the
core mechanism of ACLF. Macrophage pyroptosis serves as a critical
exacerbating factor in this process.The JDNW formula, derived from
YI0027 the academic insights of renowned Chinese national TCM masters,
Integrating Multi-Omics and Machine Learning to Uncover the has demonstrated significant therapeutic efficacy in long-term clinical
Causal Link Between Liver Cirrhosis and Hypothyroidism practice. This study aims to investigate the therapeutic mechanisms
Ziyang Yang1, Qi Zhang2, Weixuan Liang2, Hao Deng2, Can Weng2, of JDNW in ACLF and elucidate its potential effects on macrophage
Zhuofeng Wen2, Jingwen Deng2, Yi Wei Lin3, Hui Yang1, Jiyuan Zhou1 pyroptosis.
1
Department of Gastroenterology, the Second Affiliated Method: The ACLF rat model was developed through the administration
Hospital of Guangzhou Medical University, Guangzhou, China, of carbon tetrachloride (CCl4) , a chemical that induces chronic liver
2
Guangzhou Medical University, Guangzhou, China, 3Department injury, followed by the injection of lipopolysaccharide (LPS) and
of Ophthalmology, Nanfang Hospital, Southern Medical University, D-galactose (D-GalN), which induce acute liver injury. In vitro, THP-
Guangzhou, Guangdong, China. 1 cell pyroptosis was also induced in vitro with LPS and Nigericin
Background: Liver cirrhosis is a progressive chronic disease with sodium salt (Nig) . Rats in the intervention group were given JDNW
high morbidity and mortality, posing a global health challenge. gavage treatment 7 days before acute liver injury. Liver transcriptome
Evidence suggests thyroid dysfunction, particularly hypothyroidism, sequencing identified GSK-3β as a potential target of JDNW. Therefore,,
is linked to liver diseases. Hypothyroidism disrupts metabolism, a depletion of macrophages and an injection of GSK-3β siRNA (si-
immune homeostasis, and inflammatory pathways, processes central GSK) into the tail vein were performed prior to the induction of acute
to cirrhosis pathophysiology. However, its causal role and molecular injury. In this study, a combination of transcriptomics and proteomics
mechanisms remain unclear. Bridging this gap is vital for identifying was utilized. Observation of liver injury in rats by hematoxylin-eosin (HE)
staining and serum ALT, AST and TBIL level. IL-1β, IL-18 inflammatory
cytokines, macrophage pyroptosis and GSK-3β/NLRP3/Caspase-1 Health Clinical Trial Center, 5Humanity and Health Medical Group,
signaling pathway were observed by Western blotting, flow cytometry, 6
Humanity & Health Medical Group
immunofluorescence staining and ELISA. Background: Recurrence after hepatectomy presents a significant
Result: JDNW improved liver function and reduced mortality in ACLF challenge in the treatment of hepatocellular carcinoma (HCC). The
rats by inhibiting macrophage pyroptosis. It also inhibited LPS- and aim of this study was to investigate the risk factors associated with the
Nig -induced pyroptosis in THP-1 cells. This effect may be attributed to recurrence of HCC in patients with advanced tumor characteristics.
the ability of JDNW to inhibit GSK-3β, thereby reducing the activation Method: The study was conducted on patients who underwent
of NLRP3 inflammasomes. Additionally, JDNW was found to down- hepatectomy for HCC at our hospital between March 2019 and April
regulate the levels of pyroptosis-related proteins, including caspase-1, 2021. Based on whether there was recurrence, patients were divided
cleaved caspase-1, GSDMD, and GSDMD-N. Furthermore, JDNW was into two groups: those who experienced HCC recurrence and those
shown to inhibit the release of inflammatory cytokines, such as IL-18 who did not. COX regression analysis was performed to identify the
and IL-1β. risk factors for HCC recurrence.
Conclusion: JDNW may contribute to the treatment of ACLF by Result: This study included 144 patients with HCC who underwent
attenuating macrophage pyroptosis and alleviating the inflammatory liver resection at our hospital, with 24 women and 120 men, and the
response through the inhibition of the GSK-3β/NLRP3/Caspase-1 mean age was 53.0 ± 1.1 years. The median maximum tumor diameter
pathway. was 6.0 (4.0, 9.0) cm, and the median alpha-fetoprotein level was
21.7 (4.2, 505.0) ng/ml. Before liver resection, 2 patients took tyrosine
YI0029 kinase inhibitors and immune checkpoint inhibitors, 9 had experienced
transcatheter hepatic arterial chemoembolization, and 9 had the
Cancer Neutrophil Encyclopedia: A Deep Dive into Antigen-
history of microwave ablation. After liver transplantation, 43 patients
Presenting Warriors
had preventability transcatheter hepatic arterial chemoembolization. Of
Yingcheng Wu1
the144 patients, 78patients experienced HCC recurrence and 66 with
1
Fudan University Zhongshan Hospital non-recurrence, with a recurrence rate of 54.2% (78/144), and a median
Background: Neutrophils, the most efficient defenders against recurrence time of 4.8 (2.8, 10.4) months. Compared to patients with
pathogens, are essential for tumor microenvironment balance and non-HCC recurrence, those with HCC recurrence had a significantly
homeostasis. However, given their plasticity and short half-life which larger tumor size (P = 0.001), a higher prevalence of microvascular
made them too fragile to be profiled, it poses complex challenges invasion (94.9%, P = 0.001) and a higher percentage of positive ki67
regarding how neutrophils are imprinted and adapt specific fates (>60%, P = 0.045).There were no significance in whether if were a
across cancers. preventability had transcatheter hepatic arterial chemoembolization
Method: Here we designed a one-two-punch sorting strategy, (P = 0.054). After conducting univariate and collinearity analyses,
generated the neutrophil atlas from 225 samples of 144 patients from the eligible variables were included in a multivariate COX regression.
17 cancer types, and further developed a computational pipeline to Multivariate COX regression analysis revealed that patients who were
recover both shared and specific transcriptional programs. diagnosed with HCC based on histology and had positive expression
Result: Unexpectedly, neutrophils harbored extraordinary complexity of arginase (HR 0.52, 95%CI 0.27-0.99) were less likely to experience
composed of 10 cell states and showed sharp tissue or phenotypic recurrence. However, those with microvascular invasion (HR 1.72,
specialty. We observed and verified that cancer neutrophils are 95%CI 1.08-2.76), a maximum tumor diameter greater than 5.8cm (HR
dramatically arranged along tumor-specific terminal differentiation 1.11, 95%CI 1.03-1.20), and a BMI greater than 23.8kg/m2 (HR 1.11,
paths such as inflammation, angiogenesis and antigen-presenting. In 95%CI 1.02-1.20) were at higher risk for recurrence.
particular, the antigen-presenting program was associated with better Conclusion: Positive histological expression of arginase is associated
patient outcomes in the majority of cancers. Such a program can be with a lower risk of HCC recurrence, in contrast to those with negative
evoked by leucine metabolism and is dependent on mitochondrial expression of arginase.
remodeling, acetyl-CoA generation, and preferable epigenetic
histone H3K27ac modification. Functionally, antigen-presenting
YI0031
neutrophils invoked expanded T cell response and neoantigen-
specific reactiveness. We finally designed the antigen-presenting COSSH diagnostic framework outperforms in acute-on-chronic
neutrophil immunotherapy (adoptive transferring and leucine diet) liver failure: evaluation from a global aetiology cohort
which fine-tunes the microenvironment balance and fuels anti-PD-1 Jinjin Luo1, Meiqian Hu1, Tingting Feng2, Liyuan Zhang1,3, Yan
immunotherapy. Huang4, Yuxian Huang5, Feng Ye6, Jiang Li7, Ferran Aguilar8, Cristina
Conclusion: In summary, these data not only lay the groundwork Sánchez-Garrido8, Eva Maria Usón Raposo8, Bing Zhu9, Jinjun
for future neutrophil research, and open the black box of neutrophil Chen10, Shaojie Xin9, Xue Li11, Huazhong Chen12, Bingliang Lin13, Yu
state divergence across cancers, but also unravel minimally invasive Chen14, Shaoli You9, Xin Chen15,16, Alberto Queiroz Farias17, Jonel
therapeutic opportunities including adoptive transferring antigen- Trebicka8,18, Jing Jiang1, Richard Moreau8,19,20, Emad M El-Omar21,
presenting neutrophils. Jun Li1, Chinese Group on the Study of Severe Hepatitis B (COSSH)
Reference: 1
State Key Laboratory for Diagnosis and Treatment of Infectious
Wu Y, Ma J, Yang X, Nan F, Zhang T, Ji S, Rao D, Feng H, Gao K, Gu Diseases, National Clinical Research Center for Infectious Diseases,
X, Jiang S, Song G, Pan J, Zhang M, Xu Y, Zhang S, Fan Y, Wang X, National Medical Center for Infectious Diseases, The First Affiliated
Zhou J, Yang L, Fan J, Zhang X, Gao Q. Neutrophil profiling illuminates Hospital, Zhejiang University School of Medicine, 2Department
anti-tumor antigen-presenting potency. Cell. 2024 Mar 14;187(6):1422- of Infectious Diseases, The First Affiliated Hospital of Suzhou
1439.e24. University, 3Department of Infectious Diseases, The Second Affiliated
Table and Figure:Figure 1.Graphical Abstract Hospital of Hainan Medical University, 4Department of lnfectious
Diseases, Xiangya Hospital, Central South University, 5Department
of Infectious Diseases, Shanghai Key Laboratory of Infectious
YI0030 Diseases and Biosafety Emergency Response, National Medical
Positive histological expression of arginase is a favorable factor Center for Infectious Diseases, Huashan Hospital, Fudan University,
for hepatocellular carcinoma recurrence
6
Department of Liver and Infectious Diseases, the First Affiliated
Xi He1, Dali Zhang2, Zhijie Li3, Xiaofeng Niu3, Hui Ren3, Yudong Hospital of Xi’an Jiaotong University, 7Department of Infectious
Disease, The First Affiliated Hospital of Anhui Medical University,
Wang4,5, George Lau6,4, Zhenwen Liu3 8
European Foundation for the Study of Chronic Liver Failure (EF
1
the Fifth Medical Center of Chinese People‘s Liberation Army
CLIF), 9Senior Department of Hepatology, The Fifth Medical Center
General Hospital, 2 the Fifth Medical Center of Chinese People‘s
of Chinese PLA General Hospital, 10Hepatology Unit, Department of
Liberation Army General Hospital,, 3the Fifth Medical Center of
Infectious Diseases, Nanfang Hospital, Southern Medical University,
Chinese People‘s Liberation Army General Hospital, 4Humanity and
1
1Department of Big Data in Health Science, School of Public Health steatotic liver disease (MASLD) is on the rise within the chronic
and the Second Affiliated Hospital, Zhejiang University School of hepatitis B (CHB) population. This research is intended to delve into
Medicine, 12Department of Infectious Diseases, Taizhou Hospital of the influence of metabolic dysfunction (MD) on the risks of liver-related
Zhejiang Province, 13Department of Infectious Diseases, the Third events (LREs) in cirrhotic patients with CHB.
Affiliated Hospital of Sun Yat-sen University, 14Beijing Municipal Key Method: Patients with HBV-related compensated cirrhosis were
Laboratory of Liver Failure and Artificial Liver Treatment Research, consecutively recruited between April 2019 and April 2022 and followed
Fourth Department of Liver Disease, Beijing Youan Hospital, Capital until July 2023. The existence of MD was determined according to the
Medical University, 15Institute of Pharmaceutical Biotechnology five cardiometabolic criteria defined in the MASLD definition. Based on
and the First Affiliated Hospital Department of Radiation Oncology, these criteria, patients were separated into two groups: the MD group
Zhejiang University School of Medicine, 16Joint Institute for Genetics and the non-MD group. The primary outcome was LREs, defined as
and Genome Medicine between Zhejiang University and University hepatocellular carcinoma or hepatic decompensation (ascites, variceal
of Toronto, Zhejiang University, 17Department of Gastroenterology,
hemorrhage, hepatic encephalopathy, or hepatorenal syndrome) and
Hospital das Clínicas, University of São Paulo School of Medicine,
liver-related deaths.
1
8Department of Internal Medicine B University Clinic Münster,
Result: Overall, 873 patients with HBV-related cirrhosis under
Münster, Germany, 19Institut National de la Santé et de la
maintained viral suppression were enrolled with a median follow-up
Recherche Médicale, Université Paris Cité, Centre de Recherche
sur l’Inflammation, Paris, France., 20Assistance Publique-Hôpitaux of 30 months. 55 patients (6.3%) developed LREs. Patients in the MD
de Paris, Hôpital Beaujon, Service d’Hépatologie, Clichy, France, group (n = 580) were older (median age was 48 years) than non-MD
2
1UNSW Microbiome Research Centre, St George & Sutherland patients (n = 293, median age was 45 years). After adjustment of age,
Clinical Campuses, School of Clinical Medicine, University of New gender, FIB-4, hepatic steatosis, and ALT, MD patients had significantly
South Wales higher risks of LRE (adjusted ratio [aHR]: 3.07, 95% confidence
interval [CI]: 1.76-5.36, P = 0.002). Hepatic steatosis had no impact on
Background: Acute-on-chronic liver failure (ACLF) of various
the development of LREs (P = 0.448). Spleen stiffness measurement
aetiologies is a complicated syndrome with high short-term mortality.
(SSM) classified fewer patients between the low and high cutoffs than
A uniform diagnostic framework and a simple and accurate prognostic
Agile3+ and Agile4 scores and achieved the highest discriminatory
score for ACLF applicable worldwide are urgently needed.
power in predicting LREs (integrated area under the receiver-operating
Method: A total of 7388 hospitalized patients with acute deterioration
characteristic curve, 0.78).
of chronic liver disease with different aetiologies were prospectively
Conclusion: Concurrent MDs increase the risks of LREs in cirrhotic
screened and enrolled. Clinical data were used to evaluate the
patients under maintained viral suppression with CHB, independent
performance of European Association for the Study of the Liver
of hepatic steatosis. Single SSM is highly accurate in predicting
(EASL)-ACLF and Chinese Group on the Study of Severe Hepatitis B
LREs among these patients. Proactive investigation of metabolic
(COSSH)-ACLF criteria. Three non-Asian cohorts were performed to
comorbidities and SSM is of critical importance for stratifying the risk of
validate the results.
liver disease progression.
Result: Among 5288 enrolled patients, 844 patients were diagnosed
Table and Figure:Figure 1.The risk of LREs in cirrhotic patients with
as ACLF using EASL-ACLF criteria (321 with a non-hepatitis B virus
CHB. Those with MD had a higher risk of LREs than non-MD patients.
(HBV) aetiology and 523 with an HBV aetiology), while 2038 patients
Figure 2.AUROC for the Prediction of HCC and Hepatic Decompensation
were diagnosed as ACLF using COSSH-ACLF criteria (602 with a non-
Risk by LSM, SSM, Agile Scores and Other Non-Invasive Tests in the
HBV aetiology and 1436 with an HBV aetiology). COSSH-ACLF criteria
Baseline Model
diagnosed additional 22.6% patients as ACLF compared with EASL-
ACLF criteria, including an additional 14.2% in patients with non-HBV
aetiology. COSSH-ACLF criteria yielded a more reasonable diagnostic YI0033
distribution (COSSH-ACLF grades 1–3: 63.4%/27.5%/9.1%, EASL- Multi-omics analyses of the gut microbiota and metabolites in
ACLF grades 1–3: 25.8%/56.3%/17.9%). The 28-/90-day mortality children with metabolic dysfunction-associated steatotic liver
rates of ACLF patients under COSSH-ACLF criteria were significantly disease
lower than those under EASL-ACLF criteria (28-/90-day: 27.3%/41.0% Landuoduo Du1, Kaichuang Zhang1, Lili Liang1, Yi Yang1, Deyun Lu1,
vs. 40.7%/57.0%, both p<0.0001), which may help to identify more Yongchang Zhou1, Tianyi Ren1, Jiangao Fan1, Huiwen Zhang1, Ying
patients with a golden window receiving early treatment. COSSH-ACLF Wang1, Lu Jiang1
II score showed the highest predictive values for 28-/90-day mortality 1
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of
in both cirrhotic and all ACLF patients (n=844/2038) with various
Medicine
aetiologies, outperforming the CLIF-C ACLF and other scores. The
similar outperformance of China-CLIF score (renamed from COSSH- Background: The development and severity of metabolic dysfunction-
ACLF score) was validated in three non-Asian cohorts. associated steatotic liver disease (MASLD) in children are closely
Conclusion: COSSH-ACLF criteria and COSSH-ACLF II score can related to alterations of gut microbiota. This study aims to investigate
effectively diagnose and accurately prognose ACLF patients with all changes in the gut microbiota signature and microbial metabolites in
aetiologies. These findings provide a new insight on the diagnostic children with MASLD.
approach/classification of ACLF patients with all aetiologies, which Method: We collected fecal samples from children and adolescents
could improve global clinical management of ACLF. aged 6 to 16 years, and the presence of MASLD was diagnosed
by ultrasound. We performed 16S rDNA sequencing and targeted
metabolomics in 36 and 25 subjects, consisting of healthy controls,
YI0032 children with obesity, and children with MASLD.
Metabolic Dysfunctions Increase Liver-related Events in Patients Result: The microbial diversity was significantly lower in children with
with HBV-related Compensated Cirrhosis obesity and MASLD compared with healthy controls. Specifically, in
Ling Zhou1,2, Haiyu Wang1,2, Jiankang Song1,2, Jinjun Chen1,2 children with MASLD, the abundance of Anaerostipes and A. hadrus
1
Department of Infectious Diseases, Nanfang Hospital, Southern was significantly reduced compared with the obesity group. In MASLD
Medical University, Guangzhou, China, 2State Key Laboratory of patients with high ALT values (≥ 50 U/L for boys and 44 U/L for girls),
Organ Failure Research; Key Laboratory of Infectious Diseases we observed a decrease in the gut microbiota health index associated
Research in South China, Ministry of Education; Guangdong with a depletion of Anaerostipes, Peptoniphilus, Enterococcus, and
Provincial Key Laboratory for Prevention and Control of Major Liver Agathobaculum. MASLD patients with high shear wave elastography
Diseases; Guangdong Provincial Clinical Research Center for Viral (E) values (≥ 6.2 kPa) showed an increased abundance of
Hepatitis; Guangdong Institute of Hepatology; Guangdong Provincial Ruminococcus torques, which was positively correlated with the levels
Research Center for Liver Fibrosis Engineering and Technology of deoxycholic acid (DCA) and E values.
Background: The incidence of metabolic dysfunction-associated Conclusion: In conclusion, we showed that pediatric MASLD is
featured by the depletion of Anaerostipes and A. hadrus. Increased
R. torques could potentially lead to elevated levels of DCA and the underlying mechanisms remain unclear.
advancement of MASLD. Method: We employed metabolomics and scRNA sequencing to
Table and Figure:Figure 1.Decreased microbial diversity in children compare DNTregs with conventional T cells, identifying the main energy
with obesity and MASLD. metabolism pathway in DNTregs. We added specific metabolic enzyme
Figure 2.Correlations between the gut microbiota and metabolites in inhibitors to manipulate DNTregs energy metabolism and observed the
children with obesity and MASLD. impact on their immunoregulatory function. Then, we used CUT&Tag
and hypoxic culture assays to elucidate the mechanisms by which key
DNTreg metabolites affect immunoregulatory function. Finally, we used
YI0034
hypoxia probe to clarify the mechanism in MASLD mice.
Perspective on illness perception and self-management Result: Initially, we observed that during MASLD progression, the
behaviours from patients with metabolic dysfunction-associated mitochondrial function and oxidative phosphorylation (OXPHOS)-
steatotic liver disease and healthcare professionals: An related enzymes in DNTregs were significantly reduced, accompanied
exploratory qualitative study by a decline in their immunoregulatory function. Compared with
Ma Angel Cho Kan1,2, Tse William Wai Lin3,2, Chow Ka Ming2 conventional T cells, DNTregs in healthy livers exhibited stronger
1
Department of Medicine and Therapeutics, Prince of Wales Hospital, mitochondrial function and higher OXPHOS levels. Manipulating
2
The Nethersole School of Nursing, Faculty of Medicine, The Chinese OXPHOS in DNTregs significantly affected their immunoregulatory
University of Hong Kong, 3Department of Surgery, North District function, indicating that OXPHOS was essential for DNT cell
Hospital immunoregulatory function. DNTregs displayed higher enzyme activity
Background: Metabolic dysfunction-associated steatotic liver disease of mitochondrial electron transport chain complex II, leading to higher
(MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), levels of mitochondrial reactive oxygen species (mtROS). MtROS
is a prevalent condition associated with metabolic risk factors. Lifestyle generated by OXPHOS enhanced DNTreg cell immunoregulatory
modification, particularly diet and exercise, is the primary intervention function. Further analysis revealed that increased mtROS levels
to manage MASLD, yet patient adherence remains low. Limited illness promoted H3K9/H3K27 acetylation of key immunoregulatory molecules
perception and self-management challenges are contributing factors. in DNTreg cells, such as Prf1 and GzmB. The acetyltransferase HAT1
This study explores MASLD patients’ perceptions of their illness and played a crucial role by binding to the promoter regions of these
self-management practices, as well as healthcare professionals’ views immunoregulatory molecules. Meanwhile, using hypoxia probes in the
on the barriers and facilitators impacting effective care delivery. MASLD model, we confirmed that the OXPHOS levels were lower in
Method: A qualitative descriptive design was utilised, involving semi- a subset of DNTregs in hypoxic areas, which was accompanied by
structured interviews with MASLD patients and healthcare professionals reduced acetylation and impaired immunoregulatory function. Finally,
at a hepatology clinic of an acute publicly subsidised hospital in Hong we found that pretreatment of DNTregs with OXPHOS agonist or
Kong. A total of 22 MASLD patients and 10 healthcare professionals, administration dichloroacetate (an OXPHOS agonist) in MASLD mice
including doctors, nurses, dietitians, and physiotherapists receiving DNTregs could upregulate OXPHOS activity and increase
participated. Thematic content analysis was performed to identify key the immunoregulatory functions of DNTregs in vivo, thereby better
themes and subthemes, providing a comprehensive understanding suppressing MASLD development.
of their perspectives. Conclusion: During MASLD progression, the reduced mitochondrial
Result: Four themes were generated: (1) Poor illness perception, with OXPHOS in DNTregs led to a decrease in the mtROS-H3K9/
subthemes of asymptomaticnature of MASLD and limited patient H3K27 acetylation-Prf1/GzmB axis, which in turn impaired the
awareness; (2) Barriers to lifestyle modifications, with subthemes of time immunoregulatory function of DNTregs and weakened their suppressive
constraints, social and financial limitations, and confusion from effect on MASLD.
inconsistent information; (3) Facilitators for adherence, with subthemes
of perceived social support, motivational guidance from healthcare YI0036
professionals, and practical information; and (4) Expectations for
Cerium dioxide nanoparticles ameliorate steatohepatitis in rats
care, with subthemes of a need for structured, multidisciplinary, and
induced by high-fat, high-cholesterol diet by regulating the mTOR/
patient-centered approaches. These insights underscore the value of
SREBP-1 signaling pathway
continuous patient education, supportive environments, and regular
monitoring to enhance MASLD management. Jing Zeng1, Fengzhi Xin1, Liqun Huang2, Feng Shen1
Conclusion: This study highlights the critical role of personalised care
1
Shanghai Xinhua Hospital, 2Dongfang East Hospital
and targeted education in improving MASLD patients’ self- Background: Metabolic dysfunction-associated steatohepatitis
management and illness understanding. Healthcare professionals are (MASH) is a severe manifestation of metabolic dysfunction-associated
essential in encouraging adherence by providing consistent support, steatotic liver disease (MASLD), often linked with obesity, insulin
multidisciplinary care, and personalised lifestyle guidance. Bridging resistance, and metabolic syndrome. With limited effective treatments
the gap between guidelines and practice can foster better patient for MASH, Cerium dioxide nanoparticles (CeO2) are hypothesized to
outcomes in MASLD management. offer therapeutic benefits due to their antioxidative properties. This
study aims to evaluate the effects of glycol chitosan-coated CeO2 (GC-
YI0035 CeO2) on liver steatosis and inflammation in rats fed a high-fat, high-
cholesterol diet (HFHCD) and to elucidate the underlying mechanisms.
Impaired Mitochondrial Oxidative Phosphorylation in Hepatic
Method: GC-CeO2 were synthesized and their stability, antioxidative
DNTregs Leads to Reduced Immunoregulatory Function and
properties, and cytotoxicity were validated. Thirty SPF-grade male
Exacerbated MASLD Progression
Sprague-Dawley rats were randomly divided into a control group, a
Guangyong Sun1, Zihan Zhang1, Jingjing Zhu1, Dong Zhang1 HFHCD group, and a CeO2 group (n=10 each). The control group
1
Medical Research Center, Beijing Institute of Respiratory Medicine received a standard diet, while the HFHCD and CeO2 groups were
and Beijing Chao-Yang Hospital, Capital Medical University fed an HFHCD. From week 8, animals received thrice-weekly gavages
Background: Double-negative regulatory T cells (DNTregs) are a of saline (2 mL) for the control and HFHCD groups, and GC-CeO2 (1
subset of CD3+TCRαβ+CD4-CD8-NK1.1/CD56- T cells, which are mg/kg) for the CeO2 group. At week 16, rats were sacrificed to assess
highly enriched in liver and play crucial roles in maintaining liver gene expression via RT-PCR, and protein and regulatory pathway
immune homeostasis. Our previous studies found that adoptive expression via Western blot.
transfer of DNTregs from healthy livers could significantly inhibit Result: The synthesized GC-CeO2 were structurally stable, exhibited
hepatic inflammation and MASLD development. However, in MASLD significant antioxidative activity, and showed minimal cytotoxicity.
livers, DNTregs exhibited mitochondrial dysfunction, abnormal Treatment with GC-CeO2 significantly ameliorated liver steatosis
energy metabolism, and reduced immunoregulatory function, and the and inflammation induced by HFHCD, evidenced by decreased
histopathological lesions and reductions in serum liver enzymes,
glucose, and lipid levels (P<0.05). GC-CeO2 modulated lipid of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia,
metabolism by inhibiting de novo lipogenesis and enhancing fatty 1
3Hallym University Medical Centre, Chuncheon, Republic of
acid oxidation. Additionally, GC-CeO2 regulated the mTOR/SREBP Korea, 14302, Military Hospital, China, 15Dayanand Medical
signaling pathway, contributing to its hepatoprotective effects and College, Ludhiana, India, 16Department of Gastroenterology
amelioration of MASH pathogenesis. and Hepatology Sciences, IMS & SUM Hospital, Bhubaneswar,
Conclusion: CeO2 demonstrate antioxidative and anti-inflammatory Odisha, India, 17Division of Gastroenterology and Hepatology,
effects and can regulate liver lipid metabolism. These findings Department of Medicine, National University Health System,
provide a significant theoretical and experimental basis for developing Singapore, 18Department of Medicine, Chulalongkorn University,
therapeutic strategies for MASH. Bangkok, Thailand, 19Department of Hepatology, Global Hospitals,
Table and Figure:Figure 1.TEM Imaging and Redox Cycling of Mumbai, India, 20Digestive Disease and GI Oncology Centre,
Medistra Hospital, Jakarta, Indonesia, 21Department of Hepatology,
Synthesized GC-CeO2. A: Representative TEM images of GC-CeO2,
Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia,
shown with 500 nm and 200 nm scale bars. B: Histogram of GC-CeO2 2
2Department of Gastroenterology, VGM Hospital, Coimbatore,
size distribution, determined from particle statistics in TEM images. C:
India, 23Department of Medicine, Ankara University School of
Redox activity and recyclability of GC-CeO2 with hydrogen peroxide;
Medicine, Ankara, Turkey, 24Department of Medicine, University of
time-dependent color changes reveal the transition between Ce(III) and Santo Tomas, Manila, Philippines, 25Dr. Ziauddin University Hospital
Ce(IV). D: Cellular antioxidant capacity of nano-CeO2, assessed using Clifton Karachi Pakistan, 26Alka Hospital Pvt Ltd, 27Humanity &
the DCF assay to measure reactive oxygen species (ROS) levels. E: Health Medical Group, 28Fatima University Medical Center Manila,
Quantitative fluorescence analysis of nano-CeO2’s antioxidant effects, Manila, Philippines, 29Egyptian Liver Research Institute And Hospital,
with spectra of different groups after hydrogen peroxide treatment. Egypt., 30Asian Institute of Gastroenterology, Hyderabad, India, 31Sir
F: Cytotoxicity assessment of nano-CeO2, indicating minimal cellular Salimullah Medical College Hospital, Bangladesh, 32SGPGI, Lucknow,
toxicity after 24 hours at concentrations up to 80 μg/ml. India, 33Crescent Gastroliver and General Hospital, Bangladesh,
Figure 2.Impact of GC-CeO2 on Lipid Metabolism and Inflammatory 3
4Chiba University, Japan, 35CMOSH Medical College, Bangladesh,
Pathways in HFHCD-Induced MASH Mice. A: CeO2 suppresses the 3
6Global Hospitals, Hyderabad, 37Max Super Specialty Hospital,
expression of lipogenic genes in HFHCD-fed mice. B: Enhancement Saket New Delhi, India, 38Department of Gastroenterology and
of fatty acid oxidation and reduction in lipid uptake by CeO2 in MASH Hepatology, Sir Ganga Ram Hospital New Delhi, India, 39SKIMS,
mice. C: Modulation of the mTOR/SREBP-1c pathway by CeO2 in Srinagar, India, 40Lakeshore Hospital. Kochi , 41KGMC, Lucknow,
HFHCD-induced MASH. 4
2Mansoura University, Egypt, 43TN Medical College and BYL Nair
Hospital, Mumbai, 44SMS, Jaipur, 45IGIMS, Patna, India, 46Cipto
Mangunkusumo Hospital, Indonesia, 47Queen Mary Hospital, Honk
YI0037 Kong, China, 48Punjab Institute of Liver and Biliary Sciences, Mohali,
Regional and temporal disparities in the etiologies and outcomes India, 49SUM Ultimate Medicare, Bhubaneswar, India, 50Violeta
of acute-on-chronic liver failure: insights from two decades of the Medical Centre, Armenia, 51Linkou Chang Gung Memorial hospital,
APASL-ACLF Research Consortium Taiwan, China, 52Midas Multispeciallity Hospital Pvt. Ltd.-Nagpur,
Nipun Verma1, Ajay Duseja1, Sunil Taneja1, Rakhi Maiwall2, Ashok India, 53Medical school of Chinese PLA, China, 54University of Malaya
Choudhury2, Vinod Arora2, Mohamed Rela3, Dinesh Jothimani3, Medical Centre, Malaysia, 55Aster Medicity, Kochi, India , 56SMNC,
Mamun Al Mahtab4, Harshad Devarbhavi5, C E Eapen6, Ashish Jodhpur, India, 57G.B. Pant Hospital, New Delhi, India, 58SCB Medical
Goel6, Cesar Yaghi7, Q Ning8, Tao Chen8, Jidong Jia8, Jidong JIA9, College & Hospital, Cuttack (Odisha), India, 59Liaquat National
SS Hamid10, Amna Subhan Butt10, Wasim Jafri10, Akash Shukla11, Hospital, Pakistan, 60MIOT International Hospital, Chennai, India,
6
1Gleneagles Global Health City, Chennai, India, 62Zydus Hospital,
Soek Siam Tan12, Dong Joon Kim13, Anoop Saraya2, Jinhua Hu14,
Ahmedabad, India, 63Aster MIMS Hospital, Kannur, India, 64Medanta,
Ajit Sood15, Omesh Goyal15, Vandana Midha15, Manoj Sahu16, Guan
The Medicity Multispeciality Hospital, Gurgaon, India, 65Apollo
H Lee17, Sombat Treeprasertsuk18, Kessarin Thanapirom18, Ameet
Multispeciality Hospital, Kolkata, India, 66Nanavati Max Super
Mandot19, Samir Shah19, Ravi Kiran19, Laurentius A Lesmana20,
speciality Hospital, Mumbai, India, 67Government Medical College,
Hasmik Ghazinyan21, VG Mohan Prasad22, A Kadir Dokmeci23, Jose Trivandrum, 68Istanbul Umraniye Training and Research Hospital,
Sollano24, Zaigham Abbas25, Ananta Shrestha26, George LAU27, Istanbul, 69University of Kelaniya, Ragama, Srilanka
Diana Payawal28, Gamal Shiha29, PN Rao30, Anand Kulkarni30, Anand
Kulkarni30, Mithun Sharma30, Fazal Karim31, Radha Krishan Dhiman32, Background: Acute-on-chronic liver failure (ACLF) is a heterogeneous
Ajay Mishra32, Shahinul Alam33, Osamu Yokosuka34, Debashis syndrome with diverse etiologies and outcomes. Investigating regional
Chowdhury35, Chandan Kumar36, Sanjiv Saigal37, Anil Arora38, GN and temporal variations provides critical insights to inform global,
Yatto39, Abraham Koshy40, Abraham Koshy40, Ajay Kumar Patwa41, governmental, and local healthcare policies and practices to improve
Mohamed Kumar Elbasiony42, Pravin Rathi43, Sudhir Maharishi44, patient outcomes, and optimize resource allocation.
VM Dayal45, Ashish Kumar Jha45, Kemal Fariz Kalista46, Rino Gani46, Method: We analyzed data from 6319 ACLF patients across 15
MF Yuen47, Virendra Singh48, Ayaskanta Singh49, Sargsyan Violeta50, countries in the APASL-ACLF Research Consortium spanning 2004–
Chieu Hao Huang51, Saurabh Mukewar52, SHAOJIE XIN53, Xin 2024. Acute insults and chronic liver disease (CLD) etiologies and
Shaojie53, Ruveena Bhavani54, Charles Panackel55, Sunil Dhadhich56, mortality rates were assessed regionally and temporally using trend
Sanjeev Sachdeva57, Ajay Kumar57, Sanatan Behera58, Prabir Maji58, analyses and generalized mixed-effects models with cubic splines to
Lubna Kamani59, Hemamala VS60, Joy Varghese61, Pathik Parikh62, capture non-linear trends over time adjusting for regional variations.
Javed P63, Neeraj Saraf64, Akash Roy65, Chetan Kalal66, Krishnadas Result: The cohort comprised predominantly males (84.9%) with a
Devadas67, Gupse Adali68, H Janaka DeSilva69, Shiv K Sarin2, APASL median age of 45 years. The primary acute insults were alcohol-related
ACLF Working Party hepatitis (67.2%) and acute presentation of hepatitis B (HBV) (13.1%),
while the most common CLDs were alcohol-related liver disease (ALD:
1
Department of Hepatology, Postgraduate Institute of Medical
70.8%), HBV (9.3%), and ALD+HBV (11.8%). Overall, 30 and 90-
Education and Research, Chandigarh, India, 2Institute of Liver and
Biliary Sciences, New Delhi, India, 3Dr. Rela Institute, Chennai, India, day mortality rates were 45.5% and 54.3%, respectively. Significant
4
Department of Hepatology, Bangabandhu Sheikh Mujib Medical regional disparities were identified (Figure 1): Alcohol-related hepatitis
University, Dhaka, Bangladesh, 5Department of Hepatology, St John ranged from 20% in Singapore to 72.4% in India and >80% in Japan,
Medical College, Bangalore, India., 6Department of Hepatology, Egypt, and Turkey. Acute-HBV prevalence was highest in Bangladesh
CMC, Vellore, India, 7Saint Joseph University, Lebanon, Beirut, (46%) and Singapore (44%). ALD prevalence varied from 9% in China
8
Tongji Hospital, Wuhan, China, 9Hepatology Institute Capital Medical to 80% in India, Nepal, and Egypt. The highest 30-day mortality rates
University, China, 10Department of Medicine, Aga Khan University were observed in Singapore (80%) and Pakistan (65%), compared to
Hospital, Karachi, Pakistan, 11Department of Gastroenterology, India (47%) and Bangladesh (24%). Over time (Figure 2), alcohol-
Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak related hepatitis (β: +7.3) and acute-HBV (β: +6.1) increased
Municipal Medical College, (LTMMC), Mumbai, India, 12Department significantly, while prevalence of CLD due to HCV declined (β: -5.8).
The COVID-19 pandemic (2020–2021) saw a surge in autoimmune Conclusion: With the body composite parameters, BCOS effectively
hepatitis (AIH) flares and ALD+ MAFLD (metabolic dysfunction- predicts overall and liver-related mortality in cirrhosis patients, offering
associated fatty liver disease) cases. Mortality initially declined until improved stratification over MELD scores. This imaging-based tool
2019 (β: -0.7) but surged thereafter (β: +1.1), driven primarily by shows promise for prognose assessment in clinical practice.
patients with alcohol-related hepatitis (β: +1.3), AIH flares (β: +1.6), Table and Figure:Figure 1.Table 1
drug-induced liver injury (DILI, β: +2.5), ALD (β: +1.1), and ALD+HBV Figure 2.Figure 1
(β: +2.7) or ALD+MAFLD (β: +1.8) (p<0.05 for all).
Conclusion: Regional disparities and temporal perturbations in
YI0039
ACLF etiologies and outcomes highlight the influence of local disease
burdens, risk factors, and healthcare disparities. The increasing burden Baveno VII algorithm was able to stratify the risk of portal
of ALD, ALD+MAFLD, and HBV, alongside rising mortality in specific hypertension-related events in patients with HBV-related cirrhosis
etiologies-AIH and DILI, underscores the urgent need for region- Haiyu Wang1, Jinlin Hou and Jinjun Chen
specific, evidence-based clinical guidelines and need for change in 1
Hepatology Unit, Department of Infectious Diseases, Nanfang
national liver transplant priorities to mitigate ACLF-related mortality. Hospital, Southern Medical University
Table and Figure:Figure 1.Regional differences in the etiologies and Background: The Baveno VII algorithm has been proposed and
mortality in acute-on-chronic liver failure (ACLF) validated as an alternative to endoscopy screening in cirrhosis
Figure 2.Temporal differences in the etiologies and mortality in acute- patients; however, its prognostic value lacks prospective validation.
on-chronic liver failure (ACLF) Method: Patients with HBV-related compensated cirrhosis were
prospectively enrolled from April 2019 to April 2022 and
YI0038 followed until July 2023. All patients underwent liver stiffness
measurement (LSM), spleen stiffness measurement (SSM) and
A novel body composition score based on CT imaging in predicting
oesophagogastroduodenoscopy (EGD) screening for
all-cause and liver-related mortality in cirrhosis: a retrospective
oesophageal varices (EVs), and some were reassessed during follow-
cohort study
up.
Changjie Tie1,2, Tingyang Wei1,2, Yuteng Yang1,2, Shuo Yang3, Result: Overall, 1253 patients were enrolled, with a median
Chengwu Hong1,2, Zixing Wang4, Rui Huang4 follow-up of 29 months (IQR 20–42). One patient experienced
1
Peking University People’ s Hospital, No.11 Xizhimen South Street, decompensation among the 667 patients identified as low risk by the
Beijing 100044, China, 2School of Basic Medical Sciences, Peking Baveno VII algorithm, compared with 31 cases among the 586 high-
University Health Science Center, No.38 Xueyuan Avenue, Beijing, risk patients (0.6 vs. 20.8 per 1,000 person-years, p=0.0004). The
1
0038, China, 3Department of Radiology, Peking University People’ s Baveno VII algorithm identified more patients (53.2%) at low risk for
Hospital, No.11 Xizhimen South Street, Beijing 100044, China, 4Peking
decompensation than did the Baveno VII single cut-off model (47.2%,
University Hepatology Institute, Peking University People’ s Hospital,
p=0.003) and the Baveno VI criteria (33.8%, p<0.0001). Patients
No.11 Xizhimen South Street, Beijing, 100044, China
with high-risk varices diagnosed via endoscopy following Baveno VII
Background: CT-derived parameters offer valuable prognostic algorithm assessment had a greater probability of decompensation
insights into conditions such as sarcopenia, myosteatosis, and visceral than those identified by the Baveno VII single cut-off model did (43.2
obesity, which are prevalent among cirrhotic patients and correlate vs. 21.3 per 1,000 person-years, p=0.0093). Additionally, among
with poor prognoses. This study aims to explore the predictive value the 499 patients who underwent endoscopic reassessment, 242
of these body composition indices and develop a mortality prediction consecutively identified as low risk had a much lower incidence of EV
score for patients with cirrhosis. progression (2.6 vs. 106.3 per 1,000 person-years, p=0.0003) and a
Method: This retrospective study involved adult patients diagnosed lower risk of decompensation than the 144 consecutively identified as
with cirrhosis from November 2008 to September 2022 (NCT06531200). high risk by the Baveno VII algorithm (0 vs. 33.5 per 1,000 person-
We included patients with follow-up time over 6 months after baseline years, p=0.0266).
CT. The study was approved by the Ethics Committee of our hospital Conclusion: The Baveno VII algorithm could identify HBV-related
(No. 2023PHB214-001). Body composition parameters were assessed cirrhosis patients at low risk of decompensation, which was greatly
from L3-level CT scans. The primary endpoint was defined as the liver- improved upon Baveno VII algorithm reassessment.
related mortality. The secondary endpoints were defined as all-cause Table and Figure:Figure 1.
mortality and specific liver-related mortality (e.g. infections, portal
hypertensive, oncologic and others). Competing risks Cox regression
was employed to identify potential predictors of liver-related death YI0040
(and the specific causes), with stratified survival curves plotted and The diagnostic value of 26 fibrosis or cirrhosis models in
differences between strata assessed using the log-rank test. community-based patients with NAFLD
Result: A total of 769 patients with cirrhosis were analyzed, with 281 Xiajie Wen1,2,3, Boyi Chen4
(36.5%) having sarcopenia and 473 (61.5%) having myosteatosis (Table 1
National Key Laboratory of Intelligent Tracking and Forecasting for
1). 259(33.7%) patients died during the follow-up period. 216(83.4%) Infectious Diseases, Beijing Ditan Hospital, Capital Medical University,
deaths were liver-related, in which 22(2.9%), 86(11.2%), 43(5.6%) and Beijing,100015, China, 2HBV Infection, Clinical Cure and Immunology
65(8.5%) deaths were due to infectious, portal hypertensive, oncologic Joint Laboratory for Clinical Medicine, Capital Medical University,
and other liver-related conditions, respectively. Body composition 3
Beijing Institute of Infectious Diseases, Beijing, 100015, China,
metrics showed significant intercorrelation (spearman’s P > 0.5; P < 4
Baoding 1 Cent Hosp, Dept Gen Surg, Baoding 071000, Hebei,
0.05). Principal component analysis reduced these metrics to three BaoDing, Peoples R China
components (PC1, PC2, PC3), explaining 92% of variance. The Body Background: Non-alcoholic fatty liver disease (NAFLD) prevalence to
Composition Score (BCOS) was developed from these components be 38% in the general population, and it is an increased risk of liver
to predict mortality risk. Multivariable analysis identified MELD (HR fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma.
1.05; 95% CI 1.02–1.07; P < 0.001), PC2 (HR 1.17; 95% CI 1.04–1.32; A lot of models based on clinical test were built for screen risk of
P = 0.012), and BCOS (HR 1.01; 95% CI 1.00–1.02; P = 0.006) as fibrosis or cirrhosis nowadays, such as FIB-4, APRI, NFS, FLI, and FSI.
independent predictors of overall survival. For liver-free survival, However, the diagnostic value of these models in community based
MELD (HR 1.05; 95% CI 1.03–1.08; P < 0.001) and PC2 (HR 1.15; NAFLD patients still unclear.
95% CI 1.01–1.31; P = 0.040) were predictive of mortality. Kaplan- Method: Fourteen models based on viral hepatitis cohort and 12
Meier analysis confirmed that BCOS provided superior stratification for models based on NAFLD cohort were included through the literature
overall survival (P < 0.0001) compared to MELD alone, supporting its search. NHANES database cycle 2017-2020 were used in this study.
use in predicting all-cause and liver-related mortality among cirrhosis The diagnostic value of advanced fibrosis (≥F2, 9.6≤ LSM) or cirrhosis
patients (Figure 1). (≥F4, LSM≥13.6) was evaluated for these 26 scoring models by using
ROC curves. Subgroup analysis was also carried out seeking the most and validate robust, cost-effective diagnoses coupled with hospital
suitable target population in various models. 2542 NAFLD patients equipment and c) guarantee communication between all those
were diagnosed with Cap greater than 288db/m and included in the involved for the monitoring and control using state of the art and artifitial
final analysis. intelligence methodologies / informatic applications in municipalities of
Result: Among the 2542 NAFLD patients, 190 participants were the Havana City.
diagnosis as significant liver fibrosis and 157 were diagnosis as Result: Sanitary Intervention is expected to end in Havana City by
cirrhosis. The AUC and 95%CI of FLI, NFS, and FSI for significant 2025 and extend to the rest of the country subsequently, however, the
fibrosis diagnosing were 0.735(0.717, 0.752), 0.723(0.705, 0.741) and preliminary results of the Phase III and IV clinical trials conducted from
0.721(0.703, 0.738) (figure1.A-E) respectively, no statistical difference 2011 to 2024 in Cuba will be described in the presentation, in both
between any two groups for these three models were observed. cases presenting the five years follow-up results. In summary, several
The AUC and 95%CI of Hui score were 0.748(0.730, 0.765), and no clinical trials suggest that the HBsAg to anti HBsAg seroconversion
statistical difference was observed between the Hui score and models with HeberNasvac range is between 10 and 20%, increasing with the
mentioned above (FLI, NFS, and FSI). time. A generalized stability in all liver function tests has been achieved
APRI and FIB-4 were commonly used as the fibrosis risk evaluation, in long term follow-ups as well as a superior histological progress was
the AUC and 95% CI was 0.595(0.576, 0.614), and 0.593(0.573, 0.612) detected in HeberNasvac compared to PegIFN treatment. These
respectively, with no statistical difference between them (P=0.791). results were associated to a strong, sustained and increasing-on-time
The AUC of APRI and FIB-4 was lower than the Hui score, FLI, NFS, proportion of patients with undetectable HBV DNA levels above the
and FSI (P<0.001 for any comparison). 80% after five years of treatment-free follow-up. No severe adverse
NFS, FLI, SAFE showed better diagnostic value of cirrhosis, the events has been associated to HeberNasvac in the last 15 clinical
AUC and 95%CI were 0.763(0.746, 0.779), 0.742(0.725, 0.759), trials conducted with this product.
0.728(0.710, 0.710), respectively (Figure1. F-J). The AUC of NFS was Conclusion: HeberNasvac will be used as part of a large scale sanitary
significantly higher than SAFE (P=0.022), and no difference with FLI. intervention, this product will be used as part of a technological
The highest diagnostic value of models based on viral hepatitis was package comprising the vaccine, a cost effective diagnostic set
the Hui score with the AUC and 95%CI were 0.748(0.730, 0.765). No optimized for a massive introduction of the product, and with the use
statistical difference was observed between any two comparisons of of computing technology. This approach may be a suitable option to
the Hui score, NFS, and FLI. tackle chronic hepatitis B derived fatalities in Cuba and in future in other
The subgroup analysis results show that FIB-4(Figure2. A) and APRI countries as a method for CHB elimination strategy in Cuba as part of
(Figure2.B) might not be applicable in advanced fibrosis diagnosis the Cuban Health System efforts to accomplish WHO goals. Patients
of the non-Hispanic black population, with the AUC and 95%CI from all countries are also welcome in specialized Cuban hospitals to
0.521(0.476, 0.566) and 0.513(0.468, 0.558) respectively. The Hui receive the product as part of Health Services to be provided during
score (Figure2. C), NFS (Figure2. E), FLI (Figure2. F), and FSI (Figure2. the 2025-2030 campaign.
G) had relatively high diagnostic value in various subgroups. Table and Figure:Figure 1.Therapeutic Vaccine HeberNasvac.
Conclusion: The NFS were recommended as the screening model for
MAFLD patients with a high risk of fibrosis or cirrhosis in community
OP0002
compare with other 25 models included in this study.
Table and Figure:Figure 1.Figure 1. ROC curves for the 26 for advanced Social support for hepatitis C patients in two cities, China: a
fibrosis or cirrhosis. (A-E) Diagnosis of advanced fibrosis;(F-J) cross-sectional study
Diagnosis of cirrhosis. *Patients who can calculate both models Jiejun Yu1, Zhongfu Liu1, Jian Li1
the same time was used for the comparing of ROC and the P value 1
National Center for STD/AIDS Control and Prevention, Chinese
calculation. Center for Disease Control and Prevention
Figure 2.Figure 2. Forest plot of AUC and 95% CI for 7 models used for Background: Similar to HIV/AIDS, hepatitis C is transmitted through
advanced fibrosis/cirrhosis diagnosis. (A)FIB-4 for advanced fibrosis; sexual contact, blood, and mother-to-child transmission. These
(B) APRI for advanced fibrosis;(C) Hui score for advanced fibrosis; transmission routes lead to widespread social discrimination against
(D) S index for advanced fibrosis; (E) NFS for advanced fibrosis; (F) individuals with hepatitis C, which significantly impacts their mental
FLI for advanced fibrosis; (G) FSI for advanced fibrosis; (H) FIB-4 for health. Robust social support can enhance patients’ adaptability to
cirrhosis; (I) APRI for cirrhosis; (J) Hui score for cirrhosis; (K) S index for society, protect them from adverse social influences, and help maintain
cirrhosis; (L) NFS for cirrhosis; (M) FLI for cirrhosis; (N) FSI for cirrhosis. good physical and mental health, thereby enabling them to actively
engage in antiviral treatment and achieve faster recovery.
Method: From July to September 2022, a convenience sampling
ORAL PRESENTATION method was used to conduct a questionnaire survey among hepatitis
C patients in Wenshan Prefecture, Yunnan Province, and Xuzhou City,
OP0001 Jiangsu Province, using the Social Support Rating Scale. Statistical
Sanitary Intervention with HeberNasvac in Cuba to Treat all HBsAg analysis was performed using R version 4.1.3. Differences between
Positive Chronic Hepatitis B Patients Before 2027 groups were compared using the chi-square (χ²) test, and multivariate
analysis of social support scores was conducted using an ordinal
Gerardo Enrique Guillen1
logistic regression model.
1
Research Director Result: The social support score of hepatitis C patients was 38 (31,
Background: HeberNasvac is a therapeutic vaccine that is currently 43), with males scoring 38 (32, 43) and females scoring 38 (31, 42).
in use in Cuba as a monotherapy for chronic hepatitis B. This product The majority of patients (359, 74.33%) were in the moderate social
has been studied in a total of 15 clinical trials and received the support group, while 38 (7.87%) were in the low social support group
sanitary registration by the Cuban Regulatory Authority (CECMED; and 86 (17.80%) were in the high social support group. The results
https://www.cecmed.cu/sites/default/files/adjuntos/rcp/biologicos/ of the ordinal logistic regression model analysis showed that patients
rcp_hebernasvac_0.pdf). This product was obtained and developed aged ≥50 years had lower social support scores (OR=0.55, 95%CI:
in Cuba, with multiple assessments in Japan, Bangladesh, France and 0.35–0.87). Patients with high school education or above (OR=2.63,
Germany, evidencing the immunogenicity and safety of the product in 95%CI: 1.49–4.68), those who were married (OR=17.91, 95%CI: 6.94–
animal models and in human trials. 47.08), those who were divorced or widowed (OR=1.53, 95%CI: 0.59–
Method: The project aims to develop a sustainable and cost-effective 3.90), those with a per capita monthly household income of 1000–
health intervention (SI) in municipalities of the City of Havana, in 3000 yuan (OR=1.36, 95%CI: 0.83–2.27), and those with a per capita
particular: a) train health personnel during the recruitment, product monthly household income >3000 yuan (OR=2.57, 95%CI: 1.35–4.89)
administration and patient monitoring stages. in the context of an had higher social support scores.
IS under conditions of Good Clinical Practice (GCP); b) establish Conclusion: The overall social support status of hepatitis C patients
is relatively good. However, older patients, those with lower education South Wales, Australia, 2HepBCommunity.org, Sydney, New South
levels, unmarried individuals, and those with lower per capita monthly Wales, Australia, 3Hepatitis B Voices Australia, Melbourne, Victoria,
household incomes receive relatively lower levels of social support. Australia, 4Cooperman Barnabas Medical Center, Florham Park, New
Targeted care measures should be taken to improve their social Jersey, USA, 5Hepatitis B Foundation, Doylestown, Pennsylvania,
support levels. USA, 6ASHM Health, Sydney, Australia, 7Taiwan Hepatitis Information
& Care Association, 8The National Organisation for People Living
with Hepatitis B, 9Hep B Companion, London, UK, 10Hepatitis Patient
OP0003 Forum, Liver Foundation West Bengal, India., 11Inno Community
Advancing viral hepatitis B and C elimination in Bangladesh: Development Organisation, Guangdong, China, 12Yellow Warriors
achievements, challenges, and future directions Society of the Philippines, Philippines, 13European Liver Patients’
Md Ismail Gazi1, Hema Binte Hamid2 Association, Brussels, Belgium
1
National Gastroliver Institute and Hospital, Dhaka, 2Institute of Public Background: Strong and developed voices from the affected
Health, Dhaka community are crucial for designing, promoting, and advocating for
Background: Bangladesh has made notable progress against effective solutions in the health system. However, engagement with the
hepatitis B and C, yet these diseases remain a major public health affected community remains difficult in many instances due to variable
challenge. This study explores achievements, challenges, and future understanding of the roles, capacities, and expertise of people with
directions for HBV and HCV elimination in Bangladesh. lived experience.
Method: This study employed a systematic literature review and Method: Here, we argue for several guiding principles governing
key informant interviews (KIIs). The literature review analyzed peer- how public health, clinical, scientific, industrial, and policy-making
reviewed articles and government and NGO reports. Key informants bodies should engage with the affected community. We use here as a
included public and private healthcare providers and HBV and HCV case study chronic hepatitis B, a condition associated with significant
patients. stigma, informed by first-person experiences of the authors living with
Result: In 2019, Bangladesh reduced hepatitis B surface antigen hepatitis B and/or advocating for them.To address this, we the authors
(HBsAg) prevalence among children under five to below 1%, a (as people with lived experience of hepatitis B and representatives
milestone in the WHO South-East Asia region. Chronic HBV prevalence of patient advocacy groups) have developed a several consensus
is 5.5% and HCV 0.6%, with higher rates among Rohingya populations viewpoints summarised into 13 guiding principles to enable respectful
(7% for HBV, 22% for HCV). Annual mortality from HBV and HCV and effective partnership with communities affected by hepatitis B.
exceeds 16,000, highlighting the need for urgent action. Result: Our consensus best practices included:
The country faces several challenges in its elimination efforts. The lack Partner with advisors early and throughout the project
of a national action plan for HBV and HCV, weak surveillance systems, design, providing opportunities for actionable input into the process.
and insufficient funding hinder progress. Financial barriers persist, Budget for advisory time and remunerate advisors
with patients bearing out-of-pocket costs for diagnostic and treatment appropriately for their expertise.
services. Additionally, gaps in HBV birth dose coverage, limited Invite more than one advisor.
awareness, and poor coordination between public and private sectors Recruit lived experience advisors through established
exacerbate the issue. Despite these challenges, Bangladesh has community groups.
demonstrated significant innovations, including the introduction of the Provide contract agreements that are easy to understand
first generic direct-acting antiviral (DAA) sofosbuvir for HCV treatment and equitable.
in 2015. Tax waivers on antivirals further improve affordability. However, Choose the right level of engagement.
equitable access remains a challenge, particularly for marginalized Ensure accessibility of briefing information ahead of meeting.
groups such as people from low socioeconomic conditions, rural Recognise the technical support needed to optimally
communities, people who inject drugs, men who have sex with men, engage.
sex workers, and Rohingya refugees. Be mindful of advisors during a meeting, actively seek out
Key recommendations for achieving the WHO 2030 hepatitis their counsel, and engage with them.
elimination goals include strengthening national surveillance systems Ensure safety and respect boundaries regarding
to monitor incidence, prevalence, and mortality; developing and confidentiality, privacy, and disclosure.
disseminating comprehensive national guidelines for HBV and HCV Train staff working with communities in trauma-informed
management; removing financial barriers by providing free screening practices and cultural safety.
and treatment at the district and sub-district levels; and ensuring both Provide cultural and emotional support to lived experience
birth and adult HBV vaccinations through the national immunization advisors.
program. Additionally, implementing mandatory testing for all pregnant Debrief with advisors and include them in follow-up steps.
women during antenatal care is crucial to prevent vertical transmission, Conclusion: We argue that this list of 13 best practices should be
along with screening for adult hepatitis. Expanding public awareness incorporated into any engagements with communities affected by
campaigns to reduce stigma and improving healthcare provider hepatitis B, and that these practices can be generalisable to other
training at all levels are also critical. conditions.
Conclusion: A robust commitment to addressing the challenges,
coupled with strategic resource allocation, multi-sectoral collaboration, OP0005
sustained advocacy, policy development, and global partnerships, Launch of the first World Hepatitis Testing Week
is crucial for Bangladesh to achieve the WHO 2030 viral hepatitis
Cary James1, Jessica Hicks1, Alexandra Smith1
elimination goals. 1
World Hepatitis Alliance
Background: More than 300 million people are living with hepatitis
OP0004
worldwide, yet only very few know they have it. In Asia Pacific, only
Best practices for engaging with communities affected by 16.8% of people living with hepatitis B and 34.4% with hepatitis C
hepatitis B have been diagnosed. To combat the global rise of hepatitis cases,
Thomas TU1,2,3, Nafisa Yussf3, Lien Tran3, Kim Ngo3, Su Wang4,5, Adi the World Hepatitis Alliance (WHA) launched World Hepatitis Testing
Mondel6, Isabelle Purcell6, Jacki Chen7, Wendy Lo5, Bright Ansah5, Week (WHTW), an international campaign highlighting the urgent need
Fiona Borondy-Jenkins5, Yasmin Ibrahim5, Beatrice Zovich5, Kenneth to increase testing and diagnosis of viral hepatitis to reach elimination
Kabagambe8, Supa Chantschool 9, Soumen Basu10, Dee Lee11, Chris targets by 2030.
Munoz 12, Marko Korenjak13, Ivana Dragojevic 13, Chari Cohen5 Method: The first WHTW ran from 18 to 24 November 2024 and
1
Storr Liver Centre, The Westmead Institute for Medical Research, was promoted to individuals, organisations, partners, and 360 WHA
The University of Sydney at Westmead Hospital, Westmead, New members in over 100 countries, including 78 members in Asia Pacific.
As part of WHTW materials, WHA produced visual identity assets positives and treatment initiated in 51 HCV RNA positives. Portable
and created graphic design tools which could be translated into any fibroscan was used for fatty liver screening and AUDIT questionnaire
language. WHA also delivered two workshops giving practical advice for alcohol screening and quantification, for risk stratification, enabling
to community members on hepatitis testing so that they are better able early intervention. Integration with national programs has maximized
to conduct testing within their local settings. Additionally, WHA and resource utilization and program reach.
WHTW supported the delivery of testing by facilitating the donation Conclusion: The AIIMS Rishikesh preventive hepatology program is
testing kits to the Myanmar Liver Foundation (MLF). playing a vital role in India’s efforts to eliminate viral hepatitis. Through
Result: Individuals, organisations, and partners around the world community outreach, active case finding, research, micro-elimination
participated in the multi-channel communications campaign, raising projects, and integration with national programs, the initiative is
awareness online and in their communities. Through a mix of paid and contributing to improved access to care and reduced disease burden.
organic promotion, the WHTW campaign received over 6.2 million The program’s comprehensive strategy offers a valuable model for
impressions on social media channels X, LinkedIn and YouTube. The other institutions working towards viral hepatitis elimination.
hashtag #heptestweek had a combined reach of 7 million impressions Table and Figure:Figure 1.Fatty Liver Screening camp after HCV self
across social media platforms. MLF screened 2000 people for testing in Prison
hepatitis in 10 townships, with 2.45% testing positive for hepatitis B Figure 2.Health awareness activity for community mobilization
and 1.05% for hepatitis. MLF tracked next steps in care and reported
that 45 people with hepatitis B and 25 people with hepatitis C were
OP0007
referred for treatment. WHA members also embraced WHTW, with 214
registering for the educational workshops and many finding creative Hepatocellular carcinoma in Armenia: Liquid biopsies and primary
ways to promote WHTW’s message, from media engagements to assessment of molecular alterations prevalence
rallies, workshops, and testing services in their communities. Over Pascal Pineau1, Saro Khemichian2, Hasmik Ghazinyan3
90% of respondents to a WHA survey reported that WHTW increased 1
pasteur institute, 2Keck Medicine of USC , 3Yerevan MSC
awareness of hepatitis testing, with 87% reporting it increased the Background: Hepatocellular carcinoma (HCC) shows marked
number of people getting tested. geographical variation in incidence, influenced by environmental and
Conclusion: WHTW resonated globally with stakeholders at all levels. genetic risk factors. Armenia has one of the highest HCC incidence rates
Individuals and groups from public and private sectors, global health in a large region spanning Eastern Europe to China, yet the underlying
advocates, parliamentarians, individuals, and organisations engaged causes are not fully understood. Environmental contaminants, such as
with the resources and actively promoted and/or undertook testing. aflatoxin B1 (AFB1) and other mutagenic compounds, are suspected
The impact of the campaign was far reaching and demonstrates why contributors due to their ability to induce specific mutational signatures
it is a critical tool to raise awareness around testing for viral hepatitis in DNA.Hepatocellular carcinoma (HCC) shows marked geographical
and so accelerate progress towards achieving the hepatitis elimination variation in incidence, influenced by environmental and genetic risk
targets by 2030. factors. Armenia has one of the highest HCC incidence rates in a
large region spanning Eastern Europe to China, yet the underlying
OP0006 causes are not fully understood. Environmental contaminants, such as
aflatoxin B1 (AFB1) and other mutagenic compounds, are suspected
A Multifaceted Approach to Viral Hepatitis Elimination: The
contributors due to their ability to induce specific mutational signatures
Preventive Hepatology Initiative
in DNA.
Ajeet Singh Bhadoria1, Amrita Mehndiratta1, Rohit Gupta1, Meenu This study aims to investigate the mutagenic pressures in Armenian
Singh1, Samiran Nundy1 HCC patients by analyzing key mutations in the TP53 and TERT
1
ALL INDIA INSTITUTE OF MEDICAL SCIENCES RISHIKESH genes. By assessing mutation frequencies in patients with HCC and
Background: Viral hepatitis remains a significant public health liver cirrhosis (LC), we seek to understand the role of environmental
challenge in India. Achieving elimination requires comprehensive mutagens in the development of liver cancer in Armenia.
strategies encompassing prevention, early detection, and effective Method: We used droplet digital PCR (ddPCR) to analyze liquid
treatment. This abstract describes the multifaceted preventive biopsies from 100 Armenian patients, comprising 50 HCC and 50 LC
hepatology program at AIIMS Rishikesh and its contributions towards cases. Free-circulating DNA (fcDNA) was assessed for major mutations
national viral hepatitis elimination goals. in TP53 and TERT, both known to be associated with exposure to
Method: The AIIMS Rishikesh preventive hepatology program employs environmental mutagens. Mutation frequencies and mutation burdens
a multi-pronged approach: 1) Community-based screening camps for (mutated copies/mL) were compared between HCC and LC patients.
viral hepatitis and fatty liver disease, targeting both general populations Correlations between mutations and clinical factors, such as hepatitis
and high-risk groups (e.g., prison, contacts of known cases). 2) Active C virus (HCV) positivity and alpha-fetoprotein (AFP) levels, were also
case finding through family member screening of hepatitis B and C evaluated
patients. 3) Integration with the National Viral Hepatitis Control Program Result: The study found a high frequency of TERT promoter mutations
(NVHCP) to provide comprehensive, free care. 4) Implementation of (24%) and AFB1-associated TP53 mutations (3%) in HCC cases,
micro-elimination projects, such as targeted screening and treatment compared to lower mutation rates in LC patients. HCC patients also
within a district prison. 5) Cutting-edge research, including a cluster exhibited a significantly higher mutation burden than LC patients.
randomized controlled trial evaluating the effectiveness of hepatitis C Additionally, mutation prevalence was positively correlated with HCV
self-testing. 6) Screening and counseling for fatty liver disease and positivity and elevated AFP levels.
harmful alcohol consumption. 7) Collaboration with national programs, Conclusion: These findings suggest that AFB1 exposure may
including the NVHCP, the National Non-Communicable Disease (NCD) contribute to HCC development in a subset of Armenian patients,
program, and the immunization program. possibly through occasional contamination of food products by
Result: Since Dec 2021, preventive hepatology clinic has provided Aspergillus species. Further research with larger sample sizes is
care to 1500 patients (300 HBV, 200 HCV, 200 ALD and 800 NAFLD) necessary to confirm these findings and clarify the role of environmental
at the tertiary care center and screened 3500 individuals through mutagens in liver cancer risk among the Armenian population
numerous community screening camps, (900 in urban, 900 in rural,
500 in urban slum, and 1200 in a prison) and linked to care through the
OP0008
national programs. Screening of 4500 family member of 1500 patients
has proven highly effective in active case detection and linkage to care. Des-gamma-carboxy prothrombin: A crucial biomarker for
Over 40% family members had either HBsAg or Anti-HBc positivity predicting aggressive hepatocellular carcinoma in patients with
among family member of HBV patients. The prison micro-elimination normal alpha-fetoprotein
project among 1200 prison inmates has demonstrated the feasibility of Zaigham Abbas1, Darayus P Gazder1, Zeeshan Hyder1, Muhammad A
targeted interventions using HCV self-testing, identifying 72 Anti-HCV Qadeer1, Manesh Kumar1, Aasia Sabeen1, Shamim Nazir1
1
Dr. Ziauddin University Hospital Clifton Karachi Figure 2.
Background: The patients with hepatocellular carcinoma (HCC)
exceeding Milan criteria and those with portal vein tumor thrombosis OP0010
are usually dropped from the transplant list due aggressive nature
CXCL2 Potentiates Neutrophil-mediated Anti-tumor
and risk of recurrence. Though high values of alpha-fetoprotein
Immunity by Inhibiting Cholesterol Biosynthesis in Hepatocellular
(AFP) predict the aggressive behavior of tumors, little is known about
Carcinoma
the tumor behavior when AFP is normal and Des-gamma-carboxy
Xin Liu1, Danli Yang1, Lin Wang1, Xiangmei Chen1, Fengmin Lu1
prothrombin (DCP), also known as a protein induced by vitamin K
absence/antagonist-II (PIVKA-II) is elevated alone as this biomarker is
1
Department of Microbiology & Infectious Disease Research Center,
still not included in most HCC guidelines. We evaluated the prognostic School of Basic Medical Sciences, Peking University Health Science
Center, Beijing, China
value of DCP in patients of HCC with normal AFP.
Method: We retrospectively analyzed 101 HCC patients with normal Background: Hepatocellular carcinoma (HCC) remains a leading
AFP and known DCP values. Patients were divided into two groups cause of cancer mortality. Immunotherapy has proven to be a valid
based on whether they had aggressive behavior or not. For this treatment against malignancies. Nevertheless, a significant proportion
study patients who exceeded Milan criteria and/or had portal vein of HCC patients fail to derive benefit from these efficacious agents
tumor thrombosis were included in the aggressive tumor group. DCP due to the overwhelming immunosuppressive microenvironment.
levels were compared between the two groups. Receiver operating Consequently, there is an urgent need to identify key genes and
characteristic (ROC) curve analysis was performed to determine the effective strategies to reshape the HCC microenvironment.
optimal cut-off value of DCP for predicting HCC prognosis. Method: The array-comparative genomic hybridization (aCGH)
Result: This study included 67 males and 34 females. The mean age technique and public immunotherapy datasets from Gene Expression
of the patients was 58.6 ± 11.7 years. Etiology of liver disease was Omnibus (GEO) database were employed to identify the potential genes
hepatitis C in 46 (45.5%), hepatitis B in 25 (24.7%), fatty liver disease affecting pivotally the efficacy of immunotherapy in HCC. Clinical HCC
in 16 (15.8%), alcohol-related liver disease in 6 (5.9%), autoimmune specimens, in vitro experiments and in vivo animal models, including
liver disease in 4 (4.0%), hepatitis D 3 (3.0%) and cryptogenic in 2 chromatin immunoprecipitation (ChIP), coimmunoprecipitation (co-
(2.0%). Sixty-five (64.4%) patients had decompensated liver disease IP) and flow cytometry (FCM) were utilized to validate the expression
due to ascites or encephalopathy. Patients with aggressive tumors had status, functional roles and molecular mechanisms of chemokine C-X-C
significantly higher DCP levels (mean± SEM) 7776 ±1913 mAU/mL vs motif ligand 2 (CXCL2) in modulating the HCC microenvironment.
534 ±119, p<0.001. ROC curve analysis revealed AUROC of 0.723 Result: We observed a downregulation of CXCL2 in HCC, which
with an optimal cut-off value of 400 mAU/mL for DCP with a sensitivity was associated with poor prognosis and suboptimal responsiveness
of 68%. 21 patients had elevated DCP levels of ≥ 4000 mAU/L. A to immunotherapy. Overexpression of CXCL2 was found to recruit
level of 4000 mAU/mL had a maximum value of Youden’s Index and a considerable neutrophils into HCC and induce their N1 polarization,
precision of 1.000. thereby curbing HCC progression. Mechanistically, differing from the
Conclusion: DCP (PIVKA II) levels ≥ 400 mAU/mL are associated with prevailing notion that CXCL2 primarily exerts its effects extracellularly
aggressive HCC in patients with normal AFP. Our findings suggest as a chemokine, we identified that intracellular CXCL2 could bind to
that DCP may serve as a useful biomarker for risk stratification and Y-box binding protein 1 (YBX1) and prevent its nuclear translocation
treatment decision-making in HCC patients with normal AFP. to inhibit the transcription of sterol regulatory-element binding
transcription factor 2 (SREBF2) and cholesterol biosynthesis, which
subsequently reshapes the HCC microenvironment and retarding
OP0009 HCC progression.
Targeted Therapy with GPC3-Loaded Exosomes: IR780-Based Conclusion: We elucidate the unconventional role of CXCL2,
Thermotherapy and Lenvatinib Chemotherapy in Hepatocellular underscoring its critical function in modulating neutrophils polarization
Carcinoma and neutrophil-mediated immune responses in HCC, and highlighting
Shenan Huang1, Zhili Wen1, Binhai Zhou1, Xiaomei Huang1 its potential as a promising therapeutic target.
1
The Second Affiliated Hospital of Nanchang University
Background: Exosomes (EXOs) are considered natural nanoparticles OP0011
and have been widely used as carriers for the treatment and diagnosis A Multi-institutional Analysis of Risk Factors and Predictive Model
of various diseases. However, due to nonspecific uptake, unmodified for Distant Metastasis After Hepatic Resection for Hepatocellular
EXOs cannot effectively deliver the cargo to the target site. Carcinoma
Method: In this study, we utilized the pDisplay vector to decorate
Mingda Wang1,2, Yongkang Diao1,2, Jiahao Xu1,2, Fujie Chen3, Yuchen
the surface of exosomes with a single-chain scFv antibody against
Li3, Weimin Gu4, Hong Wang5, Yuze Yang6, Yongyi Zeng7, Yahao
Glypican-3 (GPC3). Through a series of in vitro experiments, we
Zhou8, Xianming Wang9, Jie Li10, Tinghao Chen11, Yingjiang Liang12,
assessed the impact of these modified exosomes on the proliferation
Lanqing Yao1,2, Lihui Gu1,2, Han Wu1,2, Xinfei Xu1,2, Chao Li1,2, Feng
and migration of hepatocellular carcinoma (HCC) cells. Additionally,
Shen1,2, Tian Yang1,2
we further validated our findings using mouse xenograft models and 1
Eastern Hepatobiliary Surgery Hospital, Second Military Medical
patient-derived xenograft (PDX) models. Furthermore, by designing a
University (Naval Medical University), 2Eastern Hepatobiliary Clinical
single-chain scFv antibody targeting GPC3 on the exosome surface,
Research Institute, Eastern Hepatobiliary Surgery Hospital, Naval
we improved the delivery system to more effectively target HCC.
Medical University, 3Department of Graduate, Bengbu Medical
Moreover, this delivery system was loaded with IR780 and lenvatinib
College, 4The First Department of General Surgery, the Fourth
for combined photothermal therapy and chemotherapy treatment. Hospital of Harbin, 5Liuyang People’s Hospital, 6General Surgery
Result: Our research findings indicate that antibody-decorated Centre, First Hospital of Jilin University, 7Mengchao Hepatobiliary
exosomes enhance the efficacy of IR780 in HCC xenograft models Hospital, Fujian Medical University, 8Pu’er People’s Hospital, 9The First
and exhibit notable antitumor photothermal therapy (PTT) effects Affiliated Hospital of Shandong First Medical University & Shandong
following irradiation. Provincial Qianfoshan Hospita, 10Department of Hepatobiliary
Conclusion: Due to the loading of IR780 and lenvatinib in exosomes, Surgery, Fuyang People’s Hospital, 11Department of General Surgery,
only a single injection is required for cancer cell treatment. Our results Ziyang First People’s Hospital, 12First Affiliated Hospital of Harbin
highlight the significant role of clinically applying exosomes modified Medical University
with GPC3 single-chain scFv antibodies and loaded with IR780 and Background: Distant metastasis after curative hepatectomy for
lenvatinib, which can simultaneously achieve imaging and treatment of hepatocellular carcinoma (HCC) is associated with poor prognosis, yet
HCC. Background: Medical English Literature. risk factors and predictive models remain underdeveloped. This study
Table and Figure:Figure 1. aimed to establish a nomogram for predicting distant metastasis at first
recurrence following HCC resection. Background: Given the high burden of hepatocellular carcinoma
Method: A multi-institutional retrospective cohort study was conducted, (HCC), identifying high-risk groups among cirrhosis patients is
including 2,705 patients who underwent curative hepatectomy for HCC essential, as cirrhosis is a well-established major risk factor for HCC
from 2013 to 2020. Independent predictors of distant metastasis were development. We aimed to develop and validate a non-invasive HCC
identified using univariable and multivariable Cox regression analyses. risk prediction model for cirrhosis patients by integrating liver and
A nomogram was constructed to predict the risk of distant metastasis, spleen CT image signatures into a clinical model.
and its performance was evaluated using the concordance index Method: Patients were from a Chinese multicenter, prospective,
(C-index) and calibration curves. Patients were classified into low-, observational, cirrhosis cohort, who underwent 3-phase contrast-
intermediate-, and high-risk groups based on nomogram scores, and enhanced abdominal CT scan at enrollment. aMAP score, as one of
survival analyses were performed. the most promising HCC prediction clinical models, was evaluated for
Result: Of the 2,705 patients analyzed, 342 (22.7%) developed each patient. Radiomic and deep learning features were extracted
distant metastasis at first recurrence. Independent predictors included from liver and spleen ROIs using PyRadiomics and ResNet-18
preoperative tumor rupture, tumor size >5 cm, presence of multiple architectures, respectively.
tumors, satellite nodules, macrovascular and microvascular invasion, Result: A total of 2411 patients were included in the analysis. Over
narrow resection margins, and intraoperative blood transfusion. The a median follow-up of 42.7 (IQR 32.9–54.1) months, 118 patients
nomogram demonstrated high predictive accuracy (C-index >0.85) developed HCC with a 3-year cumulative incidence of 3.59%. An
and effectively stratified patients into different risk categories, with advanced HCC prediction model, called aMAP-CT, was developed
significant differences in distant metastasis-free survival (P<0.001). and validated by integrating liver and spleen CT image signatures into
The 5-year overall survival rate was significantly lower in patients with the existing aMAP model. The inclusion of image features significantly
distant metastasis compared to those with intrahepatic recurrence or improved the model’s robustness and predictive power, with the AUC
no recurrence (9.1% vs. 41.1% vs. 90.8%, P<0.001). ranging from 0.809-0.869, which is notably higher than most existing
Conclusion: The nomogram developed in this study provides a HCC models. The aMAP-CT model effectively discriminated between
reliable tool for predicting the risk of distant metastasis after curative high- and low-risk patients, with 3-year HCC incidences of 26.3%
hepatectomy for HCC, facilitating tailored postoperative management and 1.7% (p < 0.0001). The inclusion of spleen features significantly
and potentially improving outcomes for high-risk patients. boosted the model’s robustness and predictive power. The overfitting
Table and Figure:Figure 1.Virtual Abstract observed in the model with aMAP and liver image signatures alone
(AUC 0.853 in the training cohort vs. 0.691 in the validation cohort) was
OP0012 mitigated by the inclusion of spleen image signatures (AUC 0.869 in
the training cohort vs. 0.809 in the validation cohort). Survival analysis
HCC risk stratification for cirrhosis patients: integrating radiomics further confirmed that the model incorporating spleen signatures more
and deep learning CT signatures of liver and spleen into clinical effectively classified patients into different risk groups, as the aMAP-
model CT model with spleen features showed a much higher hazard ratio (HR
Rong Fan1, Yaru Shi1, Lei Chen2, Chuanxin Wang3, Yunsong Qian4, 12.3) for high-risk patients compared to the aMAP+liver model (HR
Yanhang Gao5, Chunying Wang6, Xiaolong Liu7, Xiaotang Fan8, 4.0). Furthermore, the stepwise approach (aMAP --> aMAP-CT) further
Honglian Bai9, Dan Zheng10, Guoqing Jiang11, Yanlong Yu12, Xieer stratified patients into groups with 3-year HCC incidences of 1.8% and
Liang1, Jinjun Chen1, Weifen Xie13, Lutao Du3, Huadong Yan4, Yujin 27.2%, representing 93.0% and 7.0% of the cohort (p < 0.0001).
Gao6, Hao Wen14, Jingfeng Liu7,15, Minfeng Liang9, Fei Kong5, Jian Conclusion: Integrating liver and spleen image signatures into the
Sun1, Shenghong Ju16, Hongyang Wang2, Jinlin Hou1 aMAP model significantly enhances HCC risk prediction for cirrhosis
1
Department of Infectious Diseases, Nanfang Hospital, Southern patients, effectively identifying super high-risk individuals and
Medical University, Guangzhou, China; State Key Laboratory of Organ improving personalized surveillance to facilitate early detection for
Failure Research; Key Laboratory of Infectious Diseases Research better patient outcomes. The stepwise application identified a more
in South China, Ministry of Education; Guangdong Provincial Key focused group with higher-risk, prioritizing those requiring intensified
Laboratory for Prevention and Control of Major Liver Diseases, surveillance, which enhances resource optimization particularly in
Guangzhou, China, 2International Cooperation Laboratory on Signal resource-limited settings.
Transduction, National Center for Liver Cancer, Eastern Hepatobiliary Table and Figure:Figure 1.Figure 1 (A) ROC curves of aMAP-CT model
Surgery Institute/hospital, Shanghai, China, 3Department of Clinical (aMAP+liver+spleen), model with aMAP and liver image signatures
Laboratory, The Second Hospital, Cheeloo College of Medicine,
(aMAP+liver), and aMAP to predict HCC occurrence in the training
Shandong University, Jinan, China, 4Hepatology Department, Ningbo
cohort, validation cohort, and test cohort. (B) Cumulative incidence
Hwamei Hospital, University of Chinese Academy of Sciences,
of HCC in the training, validation, and test cohorts stratified by aMAP-
Ningbo, China, 5The First Hospital of Jilin University, Changchun,
CT model. ROC, receiver operating characteristic curve; HCC,
China, 6Xuzhou Infectious Diseases Hospital, Xuzhou, China, 7The
United Innovation of Mengchao Hepatobiliary Technology Key hepatocellular carcinoma.
Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Figure 2.Figure 2 Stepwise application of aMAP --> aMAP-CT. (A)
Fujian Medical University, Fuzhou, China, 8Department of Hepatology, Sankey plot for stepwise application. (B) Kaplan-Meier analysis of HCC
First Affiliated Hospital of Xinjiang Medical University, Urumqi, China, incidence of high and low risk groups among overall cohort classified
9
The Department of Infectious Disease, The First People’s Hospital by the stepwise application of aMAP --> aMAP-CT (compared using
of Foshan, Foshan, China, 10Department of Gastroenterology, The the log-rank test). HCC, hepatocellular carcinoma.
Central Hospital of Wuhan, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan, China, 11Department OP0013
of Hepatobiliary Surgery, Clinical Medical College, Yangzhou
University, Yangzhou, China, 12Chifeng Clinical Medical School of East Asian Sub-Analysis of a Phase 2 Trial of the Glucagon
Inner, Mongolia Medical University, Chifeng, China, 13Department of and GLP-1 Receptor Dual Agonist Survodutide in People with
Gastroenterology, Changzheng Hospital, Naval Medical University, Metabolic Dysfunction-Associated Steatohepatitis (MASH) and
Shanghai, China, 14State Key Laboratory of Pathogenesis, Prevention Fibrosis
and Treatment of High Incidence Diseases in Central Asia, First Lai Wei1, Samina Ajaz Hussain2, Mandy Fraessdorf3, Azadeh
Affiliated Hospital of Xinjiang Medical University, Urumqi, China, Hosseini-Tabatabaei4, Vincent Wai-Sun Wong5, Ramy Younes2,
1
5Department of Hepatopancreatobiliary Surgery, Clinical Oncology Atsushi Nakajima6
School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 1
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung
China, 16Nurturing Center of Jiangsu Province for State Laboratory Hospital, Tsinghua University, Beijing, 2Boehringer Ingelheim
of AI Imaging & Interventional Radiology (Southeast University); International GmbH, Ingelheim, Germany, 3Boehringer Ingelheim
Department of Radiology, Zhongda Hospital, Medical School of Pharma GmbH & Co. KG, Ingelheim, Germany, 4Boehringer
Southeast University, Nanjing, Chin Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United
States of America, 5Department of Medicine and Therapeutics, evaluating its potential as a therapeutic target in MAFLD.
Medical Data Analytics, Hong Kong Centre, State Key Laboratory of Method: Thirty healthy female Sprague-Dawley (SD) rats were used in
Digestive Disease, The Chinese University of Hong Kong SAR, China, this study. The rats were divided into control and high-fat diet groups
6
Department of Gastroenterology & Hepatology, Yokohama City to induce liver fibrosis. Liver tissues were analyzed using Masson’s
University School of Medicine, Yokohama trichrome staining to assess fibrosis staging. Immunohistochemistry
Background:We present data from an East Asian sub-analysis was performed to evaluate Gremlin1 expression. LX-2 hepatic
of a phase 2 trial of survodutide, a glucagon receptor/glucagon- stellate cells were exposed to oxidized low-density lipoprotein
like peptide-1 receptor dual agonist for the treatment of metabolic (OX-LDL) to induce fibrotic conditions, followed by treatment with
dysfunction-associated steatohepatitis (MASH) and fibrosis. varying concentrations of transforming growth factor-beta (TGF-β)
Method:In this multinational, double-blind, phase 2 trial for mechanistic studies. Additionally, siRNA-mediated knockdown
(NCT04771273), 295 people aged 18–80 years with biopsy-proven of Gremlin1 was used to assess its role. Cellular responses were
MASH (Non-alcoholic fatty liver disease Activity Score [NAS] ≥4), liver evaluated through CCK-8 assays, scratch assays, and Western
fibrosis (stage F1–F3), and body mass index (BMI) ≥25 kg/m2 were blot analysis to quantify fibrotic and mitochondrial markers such
randomised to once-weekly subcutaneous injections of survodutide as PGC-1α and TFAM. Electron microscopy was used to examine
2.4, 4.8, or 6.0 mg or placebo (PBO) (escalated over up to 24 microstructural changes, and Gremlin1 expression was confirmed
weeks). In this sub-analysis of participants from East Asia (N=61), we using immunofluorescence techniques.
evaluated the percentage of participants achieving >30% reduction in Result: The expression of Gremlin1 was significantly increased in
liver fat content (LFC) and relative change in LFC (both assessed by rats with MAFLD-induced liver fibrosis, correlating with progressive
magnetic resonance imaging proton density fat fraction [MRI-PDFF]), changes across fibrosis stages F1-F4. Elevated levels of Gremlin1
absolute change in enhanced liver fibrosis (ELFTM) score, relative were associated with substantial increases in collagen deposition
change in propeptide of type III collagen (PRO-C3), absolute change and the upregulation of fibrotic markers such as COL-1, TGF-β, and
in alanine transaminase (ALT) and aspartate transaminase (AST), and α-SMA, highlighting its integral role in fibrogenesis. Additionally,
relative change in FibroScan®-AST (FAST) score, from baseline (BL) to we observed mitochondrial dysfunction, evidenced by alterations
week 48. These parameters were analysed based on the actual dose in mitochondrial biogenesis markers PGC-1α and TFAM, along with
received at the start of the maintenance period. Survodutide treatment increased ROS production in hepatic stellate cells, further implicating
arms were pooled. Gremlin1 in the exacerbation of oxidative stress and the progression of
Result:Overall, the mean age (44.8 years), bodyweight (90.7 kg), BMI fibrosis. Furthermore, manipulation of Gremlin1 in LX-2 cells affected
(32.4 kg/m2), MRI-PDFF (21.1%), and NAS (5.4) of participants at cell viability and migration under OX-LDL treatment, suggesting its
BL were similar across treatment arms. 23 (37.7%) were female, 16 therapeutic potential in modulating fibrosis-related pathways.
(26.2%) had diabetes, 24 (39.3%) had F2 fibrosis, and 24 (39.3%) had Conclusion: Our findings indicate that Gremlin1 plays a pivotal
F3 fibrosis. The percentage of participants achieving >30% reduction role in the progression of liver fibrosis by modulating mitochondrial
in LFC was 62.5% for survodutide vs 23.1% for PBO. Relative reduction dysfunction and oxidative stress. This suggests that Gremlin1 may
in LFC was 58.5% for survodutide vs 17.8% for PBO. Absolute mean serve as a promising therapeutic target in MAFLD-induced liver
reduction in ELF score was 0.735 for survodutide (BL: 9.604) vs fibrosis.
0.159 for PBO (BL: 9.650). Relative reduction in PRO-C3 was 32.9% Table and Figure:Figure 1.Figure 1: The expression of Gremlin
for survodutide (BL: 44.55 µg/L) vs 3.6% for PBO (BL: 49.14 µg/L). was upregulated in MAFLD and fibrotic rats.(A) Representative
Absolute reduction in ALT was 53.1 U/L for survodutide (BL: 80.5 U/L) images of the expression of Gremlin in each group of rats detected
vs 27.3 U/L for PBO (BL: 111.8 U/L); absolute mean reduction in AST by IHC staining. (B)Bar plot of relative density of Gremlin in IHC.
was 31.2 U/L (BL: 54.0 U/L) vs 20.1 U/L (BL: 77.2 U/L), respectively. (C)WB detected the expression of Gremlin protein in each group.
Relative reduction in FAST score was 75.38% for survodutide (BL: (D)Quantification of interleukin-6(IL-6)and Gremlin1 mRNAlevels
0.60) vs 13.94% for PBO (BL: 0.62) (Table). Overall, adverse event by RT- PCR.*Note:Statistical significance is indicated as
(AE) incidence was similar between survodutide and PBO groups. follows:****p<0.0001,***p<0.001,**p< 0.01,p<0.05,ns =not significant
The most reported events were gastrointestinal disorders (75.5% and Figure 2.Figure 2: (A)Transmission electron microscopy images
33.3%, respectively). AEs leading to discontinuation for survodutide displaying the ultrastructural changes in mitochondria within
and PBO groups were 12.2% and 0.0%, respectively. No unexpected hepatic stellate cells across fibrosis stages from control to F4 (B)
safety issues were reported in this sub-population. The expression and quantitative analysis of Gremlin,PGC-1a
Conclusion:Overall, survodutide was generally well tolerated and and TFAM in fibrotic tissue of rats were detected by WB.(C)ROS
showed benefit compared with PBO in East Asian participants with detection by ROS assay.*Note:Statistical significance is indicated as
MASH and fibrosis. follows:****p<0.0001,***p<0.001,**p<0.01,p<0.05,ns =not significant
Table and Figure:Figure 1.Changes in parameters after 48 weeks of
treatment OP0015
Fatty liver exacerbates ischemia reperfusion injury by impairing
OP0014 hepatocyte Nrf2 activation and enhancing macrophage STING
Gremlin1 plays a pivotal role in the progression of liver fibrosis by signaling
modulating mitochondrial dysfunction and oxidative stress. Haoran Hu1, Dongming Wu1, Haoming Zhou1
Yonghong Guo1, Han Lin2,1, Lin Mei3, Mengmeng Liu1, Xue Li1, 1
The First Affiliated Hospital of Nanjing Medical University
Zhenghaoyu Huang2,1, Junhong Wang4 Background: Liver ischemia–reperfusion (IR) injury is an inevitable
1
Department of Infectious Disease,Shanghai Pudong New Area pathophysiological process in various liver surgeries. Previous studies
Gongli Hospital,219 Miaopu Road, Shanghai,200135,China, 2School have found that IR injury is exacerbated in fatty liver due to significant
of Gongli hospital Medical Technology,University of Shanghai for hepatocellular damage and macrophage inflammatory activation,
Science and Techonology, Shanghai 200093, China , 3Department though the underlying mechanisms are not fully understood. In this
of Gastroenterology,the Second Hospital, Medical College of study, we aim to explore the role and mechanism of Nrf2 (Nuclear
Xi‘an Jiao Tong University, Xi‘an,710004,China, 4Department of factor erythroid 2-related factor 2) signaling in regulating hepatocellular
Endocrine,Shanghai Pudong New Area Gongli Hospital,219 Miaopu damage and macrophage immune response in fatty liver IR injury.
Road, Shanghai,200135,China
Method: The study used high-fat diet-induced fatty liver mice to
Background: Metabolic-associated fatty liver disease (MAFLD) establish an IR model, alongside an in vitro co-culture system of primary
frequently progresses to liver fibrosis, yet the role of Gremlin1 in hepatocytes and macrophages. This approach was used to examine
this process remains insufficiently understood.This study aims to mitochondrial dysfunction, oxidative stress, mitochondrial DNA
investigate the effects of Gremlin1 on mitochondrial dysfunction and (mtDNA) release, and activation of macrophage STING (Stimulator of
oxidative stress during the progression of liver fibrosis, with the goal of interferon genes) signaling. We also conducted recovery verification
using H-151 (a STING in hibitor) and tBHQ (an Nrf2 activator). to appreciate its association with all-cause, cardiovascular and tumor
Result: Compared to the control group, mice on a high-fat diet mortality. Depression seriously harms the mental and physical health of
demonstrated more severe liver IR injury, as evidenced by increased patients. Previous studies have shown a high incidence of depression
histological damage, elevated liver enzyme levels, and heightened in some metabolic diseases such as diabetes, metabolic syndrome,
inflammatory markers. The HFD group showed significant oxidative and cardiovascular diseases, which are also risk factors for MAFLD.
stress and mitochondrial dysfunction and damage post-IR, as However, the incidence of depression in people with MAFLD is not
indicated by elevated levels of ROS and lipid peroxidation markers, clear.
and decreased antioxidant enzyme ac tivity. Elevated mtDNA release Method: This cross-sectional study was based on the data from
from hepatocytes post-IR activated macrophage STING signaling, the 2017–March 2020 cycle of the NHANES in the US. Transient
worsening inflammation and liver damage. However, STING signaling elastography was utilized to evaluate hepatic steatosis and fibrosis with
inhibition with H-151 in vivo or employing STING knockout macrophages controlled attenuation parameters and liver stiffness measurements,
significantly reduced these injuries. In-depth mechanism studies have respectively. Significant liver fibrosis was defined as LSM≥8. Health
found that the transfer of Nrf2 protein into the nucleus of liver cells Questionnaire-9 (PHQ-9) was used to assess the mental state. Major
after IR in fatty liver is reduced. Pre-treatment with tBHQ ameliorated depression was defined as PHQ-9 score >10.
liver oxidative stress, mitochondrial damage and suppressed the Result: Of the 6460 individuals (mean age 50.3 years, 49.6% male)
macrophage STING signaling activation. included, 36.7% had MAFLD. The incidence of major depression was
Conclusion: Our study reveals a novel mechanism where the significantly higher in patients with MAFLD than in the non-MAFLD
interaction between hepatocellular damage and macrophage population (9.8%vs8.1%, p=0.02). Among MAFLD patients with
inflammation intensifies liver IR injury in fatty liver. Enhancing Nrf2 depression, more were female, less than bachelor’s degree, state
activation to protect mito chondrial from oxidative stress damage of divorced/lived alone/unmarried and low income (all p<0.001),
and inhibiting macrophage STING signaling activation emerge as they. Individuals were more likely to have metabolic syndromes such
promising strategies for clinical intervention in fatty liver IR injury. as diabetes, hypertension, low HDL, Hs-CRP > 2, gout, history of
Table and Figure:Figure 1. Graphical abstract stroke (all p<0.05), were less likely to exercise and have more sleep
disorders(p<0.001). Logistic regression analysis showed that inactivity
exercise(OR 1.54, 95%CI: 1.13 -2.12,p=0.007 ), hypertension(OR
OP0016
1.43, 95%CI: 1.02-2.01 , p=0.038 ), Hs-CRP > 2 (OR 1.47, 95%CI:
Exploring the mechanism of anti-MAFLD liver fibrosis effect of 1.04-2.07, p=0.029), sleeping disorder (OR 4.52, 95%CI: 3.30-6.20,
Astragalus formula based on network pharmacology with RNA- p<0.001)history of gout (OR 1.52, 95%CI: 1.09-2.12, p=0.013) and
seq and experimental validation COPD (OR 1.75, 95%CI: 1.16-2.62, p=0.007) were risk factors for
JUNRAN YANG1, Zhenhua Hou1 depression, while being male(OR 0.70, 95%CI:0.51-0.94,p=0.02) and
1
Shanghai University of Traditional Chinese Medicine being married (OR 0.67, 95%CI:0.50-0.90,p=0.009) were protective
Background: Metabolic-associated fatty liver disease (MAFLD) is factors. The incidence of major depression was 8.1%, 9.5% and 10.7%
one of the most common chronic liver diseases worldwide. The global (p=0.014), respectively, in population of non-MAFLD, MAFLD with
prevalence is about 25%, 12-40% of MAFLD patients are accompanied LSM<8 and MAFLD with LSM>8 (with significant fibrosis).In population
by liver fibrosis, and 5-10% of patients will progress from MAFLD to among MAFLD with significant fibrosis, non-Hispanic White(OR 2.3,
advanced liver fibrosis (F3/F4) within 10 years. 95%CI:1.2-4.5,p=0.011), hypertension(OR 3.2,95%CI 1.27-8.10,
Method: To investigate the effect of QZF on NASH fibrosis, C57BL/6 p=0.014), and sleep disorder(OR 3.14,95%CI 1.61-6.10, p<0.0) was
mice were fed a high-fat diet (HFD) and intraperitoneally injected with risk factor of major depression.
CCl for 48 weeks, and QZF was administered by gavage. To elucidate Conclusion: In patients with MAFLD, the incidence of major depression
the underlying mechanisms, palmitic acid (PA) stimulation of AML12 increased significantly, especially in those with significant liver fibrosis.
cells induced a hepatocyte apoptosis model. The PA-stimulated Sleep disturbances and hypertension both play important role in the
AML12 cells were intervened with QZF-containing serum with or development of major depression in MAFLD patients with or without
without QZF-containing serum, respectively, and the cell supernatant significant liver fibros
of each group was aspirated to co-culture TGF-β induced LX2 cells. Table and Figure:Figure 1.
Result: The results showed that QZF exhibited dose-dependent anti- Figure 2.Odds ratios of factors for major depression among adults
hepatic fibrosis efficacy in HFD +CCl4-induced NASH mice. QZF according to the presence of MAFLD: NHANES 2017–2020
significantly inhibited PA-induced lipotoxic cell apoptosis, preventing
hepatic stellate cell activation. Mechanistically, network pharmacology OP0018
and RNA-seq analysis were co-enriched to the P53-related apoptotic
DC-SIGN+ Macrophages Mitigate Metabolic dysfunction-
pathway, and experiments verified P53-related apoptotic protein
associated fatty liver disease via Fine-Tuning TLR4 Signaling
expression Specifically, QZF reduced hepatocyte apoptosis by
Cascades and Modulating Inflammatory Secretory Profiles
modulating the expression of the P53-related apoptotic pathway,
which in turn reduced hepatic stellate cell activation. Jinxia Liu1, Haifeng Wu1,2, Lishuai Qu1, Chunhua Wan1,3
Conclusion: QZF has an inhibitory effect on NASH fibrosis. This effect
1
Department of Gastroenterology, Affiliated Hospital of Nantong
attenuated hepatocyte apoptosis by targeting the SIRT1/P53-related University, 2Affiliated Nantong Hospital of Shanghai University (The
pathway in hepatocytes, thereby indirectly inhibiting hepatic stellate Sixth People’s Hospital of Nantong)filiated Hospital of Nantong
University, 3School of public health, Nantong University, Nantong,
cell activation.
Jiangsu, China
Table and Figure:Figure 1.
Figure 2. Background: Innate immune receptors play a pivotal role in
modulating immune responses during the progression of metabolic
dysfunction-associated steatohepatitis (MASH). This study aims to
OP0017 comprehensively dissect the role of the C-type lectin receptor DC-
The incidence of depression is increasing in the population specific ICAM3-grabbing non-integrin (DC-SIGN) in modulating MASH
of MAFLD especially with liver fibrosis: Analysis of data from progression.
NHANES 2017-2020. Method: The expression profile of DC-SIGN in liver tissues from
Xiaohe LI1, Huiying RAO1, Nan Wu1 MASH patients and healthy subjects was examined using histological
1
Peking University People‘s Hospital analyses. Immunofluorescence was conducted to determine the
Background: Metabolic associated fatty liver disease (MAFLD) has distribution of DC-SIGN across different liver cell types. In vivo, adeno-
become the leading cause of chronic liver disease worldwide. As our associated virus (AAV)-mediated transduction of CD68 promoter-driven
understanding of NAFLD increased over the past years, we have come human DC-SIGN (hDC-SIGN) or a control construct was performed in
mice fed either a high-fat, high-cholesterol (HFHC) diet or a normal
chow diet (NCD). Additionally, THP1-differentiated macrophages were Garg1, Diana Lewis1, Siddharth Sood1
used as an in vitro model to investigate the molecular mechanisms by 1
Department of Gastroenterology, Northern Health, Epping, Victoria,
which DC-SIGN modulates Toll-like receptor 4 (TLR4) endocytosis and Australia
inflammatory cytokine secretion. Background: Liver At Home (L@H), a 12-week program offering
Result: The expression of DC-SIGN was significantly downregulated home-based care by hepatology nurses, was initiated in early 2023
in liver tissues from MASH patients and HFHC-fed mice, compared at a tertiary metropolitan health service in Melbourne, Australia.
to healthy human subjects and chow diet-fed mice, respectively. Through regular home visits and telehealth reviews, L@H facilitates
DC-SIGN predominantly co-localized with the macrophage marker the continued management of patients with cirrhosis in the community
CD68. Remarkably, the delivery of CD68 promoter-specific hDC- following inpatient admission under the Gastroenterology service. We
SIGN notably ameliorated HFHC-induced liver lipotoxicity, hepatic aimed to evaluate hospital readmission and mortality outcomes in
steatosis, inflammation, and fibrosis. Mechanistically, DC-SIGN patients enrolled to L@H.
facilitated macrophage TLR4 endocytosis via direct binding to TLR4, Method: Patients with cirrhosis enrolled to L@H between 01/03/2023-
leading to the suppression of MyD88-dependent pro-inflammatory 01/09/2024 (L@H group) were compared to patients who were referred
responses and the activation of TBK1-dependent IRF3 signaling. to L@H but not enrolled during the same time period (non-L@H group).
Accordingly, LewisX-DC-SIGN signaling reduced LPS-initiated pro- Reasons for non-enrolment included ineligibility based on home safety
inflammatory cytokine secretion, while simultaneously enhancing anti- screening, residence outside the hospital catchment, and patient
inflammatory IL-10 secretion. preference. Readmission was defined between 8-90 days, and failed
Conclusion: Overall, our findings underscore a crucial role of discharge between 0-7 days of initial hospitalisation. Differences
macrophage-expressed DC-SIGN in fine-tuning TLR4-dependent between the L@H and non-L@H groups were evaluated using intention-
inflammatory responses via endocytic pathways during MASH to-treat analysis, and Cox proportional hazards regression was used to
progression. Collectively, this study highlights a promising potential of compare survival and readmission.
manipulating macrophage DC-SIGN as a novel therapeutic strategy Result: 61 index patients enrolled to L@H were compared to 50 non-
for MASH. L@H patients (n=21 declined participation, n=15 out of catchment, n=9
Table and Figure:Figure 1. known to another service, n=5 other). The L@H and non-L@H groups
were similar in median age [59 (interquartile range (IQR) 45-69) vs.
OP0019 57 (IQR 53-72), p=0.31] and proportion of females [29.5% (n=18) vs.
Very low dose continuous infusions of terlipressin is not inferior 42% (n=21), p=0.17]. The non-L@H group had a significantly higher
to intermittent infusion of terlipressin for the control of acute proportion of patients who were living alone [42% (n=21) vs. 13 %
variceal bleeding in patients with portal hypertension. (n=18), p <0.001]. Compared to L@H patients, median MELD-Na was
significantly lower in the non-L@H group [17 (IQR 11-19) vs. 19 (14.5-
MOHAMMED FORHAD ABEDIN1, MOHAMMAD ABDULLAHAL
22), p=0.02]. Whilst the proportion of failed discharges was similar
FARUQUE1, MOHAMMAD IZAZUL HOQUE1, MOHAMMAD IZAZUL
between the L@H and non-L@H groups [6.6% (n=4) vs. 10% (n=5),
HOQUE1
p= 0.52], 12-week follow-up demonstrated significantly reduced liver-
1
Comilla Medical College
related hospital readmission in the L@H group [hazard ratio (HR) 0.39
Background: The most dangerous side effect of decompensated (0.19-0.8), p=0.01] (Figure 1). During extended follow-up (final censor
liver cirrhosis is acute variceal hemorrhage.Periodic infusion of very date 01/12/2024), a statistically significant mortality benefit associated
low dose terlipressin is not less effective than continuous infusion in with the L@H program was observed [HR 0.41 (0.18-0.92), p=0.03]
controlling variceal hemorrhage.The study’s objective was to evaluate (Figure 2).
the effectiveness of terlipressin continuous infusion versus intermittent Conclusion: L@H significantly reduced liver-related readmission to
boluses in treating acute venous hemorrhage (AVB) in patients with hospital at 12 weeks in patients with cirrhosis compared to the non-
portal hypertension. enrolled group. Further, we demonstrate a significant reduction in
Method: Forty consecutive patients with portal hypertension and AVB all-cause mortality associated with enrolment to L@H that was seen
were randomized to receive either continuousintravenous infusion well beyond the program’s completion, despite higher MELD-NA
(Group A, n = 20) or intravenous boluses of terlipressin (Group B, n = scores compared to non-L@H patients. Our findings suggest that liver-
20). Group A received 1 mg intravenous bolus of terlipressin followed focused transitional care programs such as L@H may have enduring
by a continuous infusion of 2 mg in 24 h. Group B received 2mg morbidity and mortality benefits for patients with cirrhosis following
intravenous bolusofterlipressin followed by 1 mg intravenous injection hospitalisation.
every 6 h. Upper gastrointestinal (UGI) endoscopy was done within12 Table and Figure:Figure 1.Figure 1. Comparison of liver-related
h of admission. Endoscopic variceal ligation (EVL) was done using a readmissions at 12 week follow-up between L@H and non-L@H
multi-band ligator. In both groups, treatment was continued up to 5 patients
days. The primary endpoint was rebleeding or death within 5 days of Figure 2.Figure 2. Comparison of all-cause mortality on extended
admission follow-up between L@H and non-L@H patients
Result: There is no significant difference between two groups in
respect of treatment failure, rebleeding within 6 weeks, hospital stay
(days) and death within 6 weeks.But adverse effect of terlipressin is
OP0021
significantly higher in group B (45%) than group A (10%)respectively Arginine glutamate injection for the treatment of mild hepatic
(p = 0.003). encephalopathy: an open?label, randomized, controlled, non-
Conclusion: Continuous infusion of low dose terlipressin may be as inferiority trial
effective as intermittent infusion to control acute varicealbleeding. Haibo Zhang1, Huaibin Zou2, Yuan Gao2, Li Wang3,4, Ming Kong2,
Terlipressin related adverse effect is significantly lower in low dose Weiwei Kang2, Rui Zhong2, Xianshan Yang2, Yan Ren2, Lili Feng2,
continuous infusion group. Lu Li2, Shuang Li2, Yunyi Gao5, Zhongping Duan2, Yutao Zhan6, Yu
Table and Figure:Figure 1.Table 1. Patient characteristics at baseline Chen2
(n=40) 1
Department of Emergency, Beijing Tongren Hospital, Capital Medical
Figure 2.Table 2. Outcome of treatment University, 2Fourth Department of Liver Disease, Beijing Youan
Hospital, Capital Medical University, 3Department of Epidemiology
and Biostatistics, Institute of Basic Medical Sciences Chinese
OP0020
Academy of Medical Sciences, 4School of Basic Medicine Peking
A hepatology home-based care program for patients with cirrhosis Union Medical College, 5School of Basic Medicine Qingdao University,
improves readmissions and mortality. 6
Department of Gastroenterology, Beijing Tongren Hospital, Capital
Leya Nedumannil1, Catherine Yu1, Kristen Peake1, Kendall Medical University
Fitzpatrick1, Vanessa Lowen1, Mustafa Mohamedrashed1, Mayur
Background: Decompensated cirrhosis commonly triggers serious validation cohort. The initial period prediction score, PPS-1, was
complications including ascites, hepatic encephalopathy, and developed to forecast 28-day outcomes, using variables including
bleeding.Hepatic encephalopathy significantly impacts patient health total bilirubin (TB),international normalized ratio (INR), age, trends in
and healthcare costs, linked to cognitive decline and ammonia bilirubin and INR over the first week, and the presence of extrahepatic
toxicity.L-ornithine-L-aspartate helps reduce ammonia but can cause organ failure during this period. PPS-1 achieved an impressive
gastrointestinal side effects.Arginine glutamate is a promising treatment area under the receiver operating characteristic curve (AUROC) of
for hepatic encephalopathy, though its comparative effectiveness is 0.83/0.90 for predicting recovery or death/liver transplantation (LT)
understudied. within 28 days, markedly outperforming established scoring systems
Method: Participants aged 18-75 years with cirrhosis and mild hepatic such as COSSH-II ACLF, CLIF-C ACLF, CLIF-COF, MELD-Na, and
encephalopathy were included in the study, having received treatment MELD. For longer-term prognosis, the second score, PPS-2, was
at our hospital. Stratified blocks were formed using the West-Haven formulated, incorporating TB, INR, bilirubin and INR trends over 28
grading method, and patients were then randomized into either the days, and underlying liver disease, to predict 90-day outcomes. PPS-
arginine glutamate injection group or the L-ornithine-L-aspartate 2 also demonstrated strong predictive power, achieving AUROC
injection group. Treatment lasted for 7 days. The primary endpoint values of 0.81/0.92 in forecasting recovery or death/LT within 90 days.
was the clinical improvement of HE symptoms. Secondary endpoints Across external validation cohorts as well as EASL-ACLF and COSSH-
included improvements in blood ammonia levels and time to complete ACLF subgroups, our models maintained high diagnostic accuracy.
the number connection test, and the comparison of these changes Calibration plots, clinical decision analysis (DCA), and risk stratification
between the arginine glutamate and L-ornithine-L-aspartate groups confirmed the models’ superior predictive capacity, providing reliable
to establish non-inferiority. tools for optimal outcome prediction.
Result: From March 2020 to October 2021, 132 patients were assessed Conclusion: Phased multi-outcome predictive scores (PPS-1/PPS-2)
for eligibility, with 108 qualifying for random assignment to receive were proposed for the first time, demonstrating strong accuracy in
either arginine glutamate (n=54) or aspartic acid ornithine (n=54). In predicting short- and medium-term clinical outcomes in ACLF patients,
the intention-to-treat (ITT) analysis, on day 8, clinical improvement of with significant potential to inform clinical management strategies.
HE was observed in 48 (88.9%) of 54 patients in the arginine glutamate Table and Figure:Figure 1.Graphical abstract-1
group and 49 (90.7%) of 54 in the L-ornithine-L-aspartate group. Figure 2.Graphical abstract-2
The between-group difference was -1.9% (95% CI -13.3% to 9.6%),
indicating non?inferiority. Per-protocol (PP) analysis similarly suggested OP0023
non-inferiority at the primary endpoint. Post-treatment, both groups
exhibited reductions in blood ammonia levels and improvements in Long-term prognosis and survival benefits of liver transplantation
number connection test scores. Arginine glutamate was non?inferior to in acute-on-chronic liver failure: results of a cohort study
aspartic acid ornithine injection in these secondary endpoints. Peng Li1, Xi Liang2, Jinjin Luo2, Jun Li2, Hongtan Chen1
Conclusion: Both arginine glutamate injection and L-ornithine- 1
Department of Gastroenterology, The First Affiliated Hospital,
L-aspartate injection effectively alleviated clinical symptoms and Zhejiang University school of Medicine, 2The First Affiliated Hospital,
reduced blood ammonia levels in patients with cirrhosis and mild HE, Zhejiang University school of Medicine
with the clinical improvement rate of arginine glutamate being non- Background: Acute-on-chronic liver failure (ACLF) is a life-threatening
inferior to that of L-ornithine-L-aspartate. Compared to L-ornithine-L- clinical syndrome characterized by hepatic and/or extra-hepatic organ
aspartate, arginine glutamate also achieved non-inferiority in reducing failure and high short-term mortality. Liver transplantation (LT) is an
blood ammonia and improving number connection test scores, with no effective method for the treatment of ACLF. However, the long-term
appreciable adverse effects.(ChiCTR2300068160) post-LT prognosis and survival benefits remain limited. We aimed to
Table and Figure:Figure 1.Figure1. Primary outcome of clinical evaluate the long-term prognosis and survival benefits of ACLF after
improvement of hepatic encephalopathy in the intention-to-treat and LT in a large clinical cohort of COSSH, and to identify the risk factors
per-protocol population. affecting the prognosis.
Figure 2.Talbe 1. Adverse events and adverse events associated with Method: Based on the multicenter, prospective and open COSSH
the study treatment cohort, 2307 patients diagnosed with ACLF between January 2015
and March 2023 were enrolled, including 518 patients who received
OP0022 LT. Detailed clinical data and long-term prognosis information were
collected. The survival was assessed by Kaplan-Meier analysis, and
Phased prediction scores of clinical multiple outcomes in
independent prognostic risk factors were determined by logistic
Acute-on-Chronic Liver Failure (ACLF) patients: A prospective
regression analysis. The last follow-up time of this study was March
multicenter study
31, 2024.
Wenling Wang1, Manman Xu1, Yu Wu1, Huaibin Zou1, Yu Chen1 Result: Among the enrolled 2307 patients with ACLF, 518 patients
1
Beijing You‘an Hospital Affiliated to Capital Medical University received LT. The mean age was 48.0±11.0 years old, and male
Background: Acute-on-chronic liver failure (ACLF) presents as accounted for 85.2%. Patients were followed up for a median of 1762
a highly dynamic clinical syndrome with variable outcomes. Early (1672-1851) days after LT. The median waiting days before LT was
determination of the prognosis of ACLF patients is important to guide 9 (5-19) days. The proportions of ACLF-1, -2 and -3 grades were
clinical management. The objective of this study is to construct 32.4% (168), 33.2% (172) and 34.4% (178), respectively. The most
phased prediction scores (PPS) incorporating both static and dynamic common type of organ failure was liver failure (92.7%), followed by
variables to forecast 28-day and 90-day multi-outcome scenarios. coagulation failure (55.3%), and circulatory failure accounted for the
Method: In a national multicenter prospective cohort study conducted least (4.9%).The proportion of patients with ≥4 organ failure was 11.6%
across four centers, patients were monitored through two progression (60).The 1-year, 5-year, and 8-year overall survival rates (OS) post-LT
phases: from baseline to day 28 and from day 28 to day 90. Each of ACLF patients were 76.8%, 73.1%, and 67.4%, respectively. Among
phase was further stratified into three distinct outcomes. A stepwise them, the 1-year, 5-year, 8-year OS of patients with grade 1/2/3 were
prognostic scoring system was constructed using both static and 95.0%/93.1%/89.7%, 79.8%/76.9%/72.8%, and 56.8%/50.0%/41.0%,
dynamic variables, named phase prediction scores (PPS-1 and PPS-2), respectively. Univariate and multivariate analysis showed that
and their performance was assessed against established prognostic COSSH-ACLF IIs>10, CLIF-C ACLFs>56, preoperative infection and
models. External validation was conducted in an independent cohort preoperative circulatory failure were independent risk factors of death
as well as in subgroups meeting COSSH-ACLF and EASL-ACLF for ACLF patients after LT.
criteria. Patients were stratified into improving, stable, and critical Conclusion: This study provides the long-term survival data of LT in
categories based on these prognostic models. patients with ACLF from a large multicentre cohort study. The higher
Result: We analyzed prospective clinical data from 1,046 hospitalized severity score before transplantation, the existing of infection and
ACLF patients, with 739 in the derivation cohort and 215 in an external circulatory failure before transplantation predicted poor prognosis.
 OP0024 and Treatment of Infectious Diseases, TangDu Hospital, The Fourth
Military Medical University, 11Department of Infectious Diseases,
Unveiling the continuum of acute-on-chronic liver failure:
Santai County People‘s Hospital, 12Department of Hepatology,
phenotypic insights into severity and outcomes
Maanshan Fourth People‘s Hospital, 13Department of Infectious
Qian Zhang1,2, Jiaxuan Hu3, Shaotian Qiu3, Jiale Bian3, Aimin Gao2, Diseases, Shishou People‘s Hospital, 14Department of Infectious
Fang Liu4, Caiyan Zhao5, Liaoyun Zhang6, Wanhua Ren7, Shaojie Diseases, Taishan People‘s Hospital, 15Department of Infectious
Xin8, Yu Chen9, Zhongping Duan9, Tao Han3 Diseases, Central People‘s Hospital of Zhanjiang , 16Department
1
Tianjin Union Medical Center, Tianjin, China, 2Tianjin Medical of Infectious Diseases, Songzi People‘s Hospital, 17Department of
University, Tianjin, China, 3Tianjin Union Medical Center Affiliated to Hepatology, Shanghai Public Health Clinical Center, 18Center for
Nankai University, Tianjin, China, 4The Third Central Clinical College Liver Disease, Guangzhou Eighth People‘s Hospital of Guangzhou
of Tianjin Medical University, Tianjin, China, 5The Third Hospital of Medical University, 19Peking University People‘s Hospital, 20Institute
Hebei Medical University, Shijiazhuang, China, 6First Hospital of of Hepatology Peking University, 21HPB Center, Beijing Tsinghua
Shanxi Medical University, Taiyuan, China, 7Shandong First Medical Changgung Hospital affiliated to Tsinghua University
University Affiliated Shandong Provincial Hospital, Jinan, China,
Background: Pan-genotypic direct-acting antivirals (DAAs) have
8
The Fifth Medical Center of Chinese PLA General Hospital, Beijing,
revolutionized the management of hepatitis C virus (HCV) infection
China, 9Beijing You’an Hospital Affiliated to Capital Medical University,
by simplifying treatment regimens and achieving cure rates >95%.
Beijing, China
However, large-scale, multicenter studies on the use of the NS5A
Background: Recently, Kulkarni and Sarin introduced a novel inhibitor coblopasvir remain limited in China. This study aims to
framework for the Acute-on-Chronic Liver Failure (ACLF) continuum, assess the efficacy and safety of coblopasvir (CLP) in combination
ranging from the European Association for the Study of the Liver with sofosbuvir (SOF) for the treatment of chronic HCV infection from
(EASL) pre-ACLF stage to the more severe EASL-Chronic Liver Failure multiple hospitals across China.
(EASL-CLIF) ACLF stage, illustrating progressive severity. This study Method: This multicenter, retrospective study included treatment-
aims to evaluate and validate phenotypic classifications and outcomes naive patients with chronic HCV infection who received coblopasvir
across the ACLF spectrum, focusing on Hepatitis B Virus (HBV) and (60 mg) and SOF (400 mg) at multiple hospitals in China. Baseline
alcohol-related aetiologies. characteristics were recorded. Cirrhosis was defined as liver stiffness
Method: A multi-center retrospective analysis of 955 patients classified measurement (LSM) ≥14.6 kPa or as documented from clinical
into EASL pre-ACLF and EASL-CLIF ACLF subgroups was conducted. records. Diagnoses of fatty liver disease and hepatocellular carcinoma
Clinical features, outcomes, and prognostic accuracy of scoring (HCC) were based on medical records. Estimated glomerular
systems for 28-day and 90-day mortality were compared. filtration rate (eGFR) was calculated with MDRD formula. The primary
Result: Of 955 enrolled patients, 659 (69.01%) had HBV-related and endpoint was sustained virologic response (SVR), defined as RNA
296 (30.99%) had alcohol-related chronic liver disease. Across the <50 IU/mL. Secondary endpoints included rapid virologic response
entire study population and within HBV and alcohol stratified groups, (RVR) and changes in alanine aminotransferase (ALT), aspartate
28-day and 90-day mortality rates were significantly higher in EASL- aminotransferase (AST), total bilirubin (TBIL), LSM, and eGFR before
CLIF ACLF patients compared to EASL pre-ACLF patients. The MELD- and after DAAs treatment.
sodium (MELD-Na) score was a more accurate predictor of 28-day Result: A total of 1219 patients (median age 55 years; range 19~89;
and 90-day mortality for EASL pre-ACLF patients, whereas the Chronic 40.4% female) were included. Among 1092 patients with available
Liver Failure-Consortium ACLF (CLIF-C ACLF) and Chinese Group on HCV genotype data, genotypes mainly consists of 2a (37.4%), 1b
the Study of Severe Hepatitis B-ACLF II (COSSH-ACLF II) scores were (22.2%), 3b (10.3%), 3a (7.6%), 6a (7.0%) and genotype 6 (excluding
superior for EASL-CLIF ACLF patients. 6a) (12.0%). Among the patients, 84 and 50 had compensated and
Conclusion: The proposed phenotypic classification for the ACLF decompensated cirrhosis, respectively. Comorbidities included fatty
continuum, stratified by severity stages, effectively distinguishes liver disease (3.4%, n=42), HCC (1.5%, n=18), and moderate to
clinical features and prognosis across different aetiologies. Distinct severe renal injury (2.8%, n=34). Overall SVR rate at 12-week
prognostic scoring systems demonstrated different emphases at each follow-up after end of therapy was 99.7% (660/662). High SVR rates
stage of ACLF, thereby enabling more accurate prognostic predictions were observed in patients with compensated or decompensated
and advancing treatment strategies. cirrhosis (97.3%, 36/37), genotype 3 (98.6%, 145/147), genotype 6
Table and Figure:Figure 1.Flowchart of the study group selection (100.0%, 118/118), age ≥70 years (100.0%, 72/72), and moderate to
process severe renal injury (100.0%, 24/24). After 12 weeks of treatment, the
Figure 2.Comparison of 28-day and 90-day survival between EASL RVR12 rate was 99.8% (889/891). ALT and AST levels decreased
pre-ACLF stage and EASL-CLIF ACLF stage in the entire cohort (a,d), significantly, with median (IQR) ALT dropping from 58 (32~100) to 19
the HBV-aetiology cohort (b,e) and the alcohol-aetiology cohort (c,f) (13~26) U/L and median (IQR) AST from 52 (34~82) to 25 (20~32) U/L.
Median TBIL decreased from 14.1 to 12.3 μmol/L and LSM from 9.3
OP0025 to 8.6 kPa after 12-week therapy. No clinically significant changes in
median eGFR were observed (98.6 vs 95.7 ml/min/1.73m2). No drug-
Efficacy and safety of coblopasvir plus sofosbuvir treatment
related adverse events were reported.
for Chinese patients with chronic HCV infection: a large-scale,
Conclusion: The 12-week regimen of coblopasvir in combination with
multicenter retrospective study
sofosbuvir displayed high efficacy and a favorable safety profile
Fangfang WEI2, Yang WANG1, Zhiyong HUANG2, Zhiyan PEI3,
in Chinese patients with chronic HCV infection, including those with
Rongquan FU4, Xing CHEN5, Yaocai LI6, Nongwei LUO7, Yuanwang
genotype 3 or 6, advanced age, compensated or decompensated
QIU8, Wei DENG9, Hong JIANG10, Hui XU11, Ming WEI12, Yaoming
cirrhosis and moderate to severe renal injury.
YUAN13, Qinghui HE14, Zeng PANG15, Sheng HUANG16, Liang
Table and Figure:Figure 1.Table 1 Baseline characteristics and
CHEN17, Lingyi ZHANG3, Jianping LI18, Huiying RAO19,20, Lai WEI21,
virological response after treatment of coblopasvir with sofosbuvir
Yunsheng LONG2
among multi-center Chinese patients with chronic HCV infection
1
Department of Infectious Diseases, Yingjiang County People‘s
Hospital, 2Department of Infectious diseases, Xinyi People‘s Hospital,
3
Department of Hepatology, Lanzhou University Second Hospital, OP0026
4
Department of Hepatology, People‘s Hospital of Yangjiang, Coblopasvir and sofosbuvir treatment for Chinese patients with
5
Department of Hepatology, Yangjiang Public Health Hospital, chronic HCV infection is safe and efficacious: a real-world study
6
Department of Infectious Diseases, Maoming People‘s Hospital, Zhiyan Pei1, Aidi Ma1, Yuanyuan Liu1, Tianfu Liu1, Yaping Zhang1,
7
Department of Infectious Diseases, Yangxi General Hospital People‘s Longquan Li1, Yongfang Li1, Yin Kong1, Juan Li1, Jie Ding1, Jingjing
Hospital, 8Department of Hepatology, Wuxi Fifth People‘s Hospital,
He1, Guangming Li1, Rui Zhao1, Lingyi Zhang2
9
Department of Infectious Medicine and Tropical Medicine, Affiliated
Hospital of Guangdong Medical University, 10Center for Diagnosis
1
Department of Hepatology, Lanzhou University Second Hospital,
2
Department of Hepatology, Lanzhou University Second Hospital Background: Background: Since the last decades of the twentieth
Background: Pan-genotypic direct-acting antivirals (DAAs) have century to the present day, there has been an increase in the incidence
transformed hepatitis C virus (HCV) management by simplifying of viral hepatitis. The global coverage of territories and the high
treatment and offering cure rates above 95%. However, studies on epidemic potential of this group of diseases maintain their social and
coblopasvir, a novel NS5A inhibitor, remain limited in China. This study economic significance. The WHO «Global Hepatitis Report» (2017)
aimed to evaluate the efficacy and safety of coblopasvir in combination noted that approximately 325 million people worldwide suffer from
with sofosbuvir (SOF) for the treatment of chronic HCV infection in viral liver diseases, and mortality from them, unlike HIV infection,
China. tuberculosis and malaria, continues to rise. The leading role in the
Method: This retrospective, real-world study included treatment-naive occurrence of these changes is played by failures and dysfunctions of
patients with chronic HCV infection who received coblopasvir (60 mg) cytokine regulation of immunobiological processes. The chronization
and SOF (400 mg) for 12 weeks at a tertiary hospital in Northwest China. of any inflammatory process is based on the relationship between
Baseline characteristics were recorded. Cirrhosis was defined as liver periodontal conditions with proinflammatory properties and anti-
stiffness measurement (LSM) ≥14.6 kPa, assessed by Fibroscan, inflammatory activity.
or as indicated in clinical records. Diagnoses of fatty liver disease The aim of the study was to examine the levels of proinflammatory
and hepatocellular carcinoma (HCC) were based on radiographic γ-INF and anti-inflammatory IL-4 in oral fluid (OF) in patients with HCV
or medical records. Diabetes mellitus was diagnosed by a serum before and after complex treatment.
fasting glucose ≥7.0 mmol/L or medical records. Estimated glomerular Method: Мethods: Cytokines of the OF were tested in 45 patients
filtration rate (eGFR) was calculated with MDRD formula. The primary with HCV before and after complex treatment. The biological material
endpoint was sustained virologic response (SVR), defined as RNA <15 to be tested was unstimulated mixed saliva – OF, obtained without
IU/mL. Secondary endpoints included rapid virologic response (RVR, stimulation and collected with a sterile syringe into sterile Eppendorf
RNA <50 IU/mL) and changes in alanine aminotransferase (ALT), tubes. Samples were frozen and stored at –20 °C. Then the samples
aspartate aminotransferase (AST), total bilirubin (TBIL), LSM and were thawed at room temperature, centrifuged at 5000 rpm in the cold.
eGFR before and after treatment. The measurements were presented Mucin was precipitated using 6 units of Lydase per 1.0 ml of OF by our
with median and inter-quantile range (IQR). Non-parament tests were patented method (Patent RA No. 3295 A dated at May 16, 2019). The
used to determine statistical significance. concentrations of cytokines γ-INF and IL-4 were determined by the
Result: A total of 292 patients (median age 58 years; range 19–82; method of solid-phase enzyme-linked immunosorbent assay (ELISA)
50.7% female) were included from February 2023 to June 2024. HCV using the Vector-Best test systems and were measured using a Statfax
genotypes included 1b (32.9%), 2a (54.1%), 3a/3b (3.4%), 6a (1.4%) 303 Plus photometer.
and other (8.2%). Among the patients, 64 and 25 had compensated Result: Results: In patients with HCV, before the complex treatment,
and decompensated cirrhosis, respectively. Comorbidities the content of proinflammatory γ-INF in OF was 2.46±6.52, while after
included fatty liver in 27 (9.2%), HCC in 12 (4.1%), and diabetes the complex treatment it decreased to 1.58±6.89; OR: 0.89±1.41;
in 45 (15.4%) patients. SVR rate at 12-week follow-up after end of CI: [-1.93; 3.7], however, the difference in data was statistically
therapy was 100.0% (52/52), including patients with compensated insignificant (p>0.121). The content of anti-inflammatory IL-4 had the
or decompensated cirrhosis (17/17), those with mild or moderate following picture: 0.2±0.79 vs. 14.36±28.48; OR: -14.16±4.25; CI:
renal injuries (9/9), and those aged ≥70 years (3/3). After 4 weeks of [-22.72; -5.61], i.e. there was a 72-fold increase in the level with a high
treatment, the RVR rate was 97.8% (225/230), increasing to 100.0% degree of reliability (p<0.004).
(232/232) at 12 weeks. ALT and AST levels decreased significantly, Conclusion: Conclusion: Thus, the results will be important for
with median (IQR) ALT dropping from 49 (25~89) to 19 (12~27) choosing the tactics of complex treatment of patients with HCV. As
U/L and AST from 51 (32~84) to 28 (22~34) U/L (p <0.05). Median further steps, it is recommended to take biopsies of the oral mucosa of
TBIL decreased from 17.0 to 15.6 μmol/L and LSM from 9.3 to 8.4 those participating in this study for immunohistochemical examination
kPa after 12-week therapy (p <0.05). No significant changes in median (CD 20, CD 3 markers), which will allow a more detailed study of the
eGFR were observed (105 vs 104 ml/min/1.73m2) (p >0.05). No drug- state of local immunity of the oral cavity in patients with HCV.
related adverse events were reported.
Conclusion: The 12-week regimen of coblopasvir plus sofosbuvir OP0028
demonstrated high efficacy and safety in Chinese patients with chronic
“Hepatitis Free Mongolia, Phase 2” - A provincial-level HCV
HCV infection, including those with advanced age, compensated or
Elimination Model in Rural Mongolia.
decompensated cirrhosis, and mild to moderate renal injury.
Meredith Potts1,2, Mandakhnaran Davaadorj1
Table and Figure:Figure 1.Table1 Baseline characteristics and
virological response after DAAs treatment of coblopasvir and
1
FIRE - Flagstaff International Relief Effort, 2ROTARY INTERNATIONAL
sofosbuvir among Chinese patients with chronic HCV infection Background: Mongolia has the highest rate of liver cancer and among
Figure 2.Figure 1 Changes in ALT, AST, LSM and eGFR before and the highest rates of hepatitis B (HBV), C (HCV), and D globally. Over
after DAAs treatment with coblopasvir and sofosbuvir among Chinese 95% of liver cancer cases are associated with HBV or HCV. In 2017,
patients with chronic HCV infection the Government of Mongolia launched the Healthy Liver Program
(HLP) to combat viral hepatitis. By 2018, 40% of individuals over 15
had been screened for HBV and HCV, which increased to 51% by
OP0027
April 2022. This collaborative program aimed to eliminate HCV across
Study of the Level of Proinflammatory γ-INF and Anti-inflammatory Sukhbaatar province in rural Mongolia while developing a scalable
IL-4 in the Oral Fluid of HCV-Infected Patients Before and After model to achieve the World Health Organization’s (WHO) elimination
Complex Treatment targets of 90% population testing and 80% cure rates for those testing
Vahe Yurii Azatyan1, Lazar Karleni Yessayan1, Hasmik Levoni positive.
Ghazinyan2, Melaniya Vahagi Shmavonyan3, Alvard Husiki Method: New strategies implemented in Phase 2 to facilitate HCV
Hovhannisyan3, Violeta Alberti Sargsyan4, Sona Roberti Sargsyan4, elimination include leveraging Mongolia’s extensive social service
Gayane Gurgeni Melik-Andreasyan 5, Marine Grigori Hayrapetyan6, network, establishing a province-wide patient registry, and providing
Armen Abgari Muradyan7 financial support for those unable to afford treatment. Activities
1
Yerevan State Medical University, Department of Therapeutic included:
Stomatology, 2National center of infectious diseases Yerevan, Utilizing Mongolia’s national registration system, which assigns every
Armenia, 3Yerevan State Medical University, Department of Infection citizen a unique numerical identifier linked to a local social worker and
Diseases, 4«Violeta» Medical Center Yerevan, Armenia, 5National healthcare clinic. Local social workers and healthcare workers were
Center of Disease Control and Prevention, Ministry o, 6Yerevan State trained as Hepatitis Coordinators to ensure every community member
Medical University (YSMU), Department of Public Health, 7Yerevan was screened and treated if HCV positive.
State Medical University (YSMU), Rector of YSMU Creating a patient registry encompassing 44,267 individuals across
the province, enabling Hepatitis Coordinators and project leaders to adverse events related to SOF/VEL were ≤grade 2. Of 27 infants tested
find the missing people. for HCV RNA, all were undetectable at 2 months and/or 6 months of
Financial assistance for individuals unable to afford treatment, ensuring age. Infant retention was 29/32 (91%), 14/18 (78%), and 5/12 (42%) at
equitable access to care. the 2-month, 6-month and 12-month visits.
Result: 36,463 individuals were tested for hepatitis B and C from Conclusion: The interim data from the STORC study provides
the target population of 44,267 individuals aged 15 and older in preliminary reassurance regarding the safety and efficacy of SOF/VEL
Sukhbaatar province. Of these, 7,044 were screened through this administration after 20 weeks’ gestation. Recruitment for the STORC
project, addressing critical gaps from earlier initiatives. Additionally, study is currently ongoing.
5,190 individuals were confirmed as “unavailable” or relocated out of Table and Figure:Figure 1.HCV viral response to sofosbuvir/velpatasvir
the province. This project screened 93.3% of the available population during pregnancy for all participants who have completed at least 4
for hepatitis B and C. Among those testing positive for anti-HCV, 76% weeks of treatment
underwent confirmatory viral load testing. Of those requiring treatment,
41.5% have been cured, and 34.5% have initiated treatment. High
OP0030
adherence rates suggest that the majority will complete their regimen.
It is projected that 80% of those needing treatment will be cured by Glecaprevir/Pibrentasvir in HIV/HCV-coinfected patients treated
Spring 2025, meeting the WHO elimination targets. with bictegravir
Conclusion: Hepatitis Free Mongolia, Phase 2, has demonstrated Aleksandra Berkan-Kawinska1, Anna Piekarska1, Hanna Berak2,
a scalable model for provincial-level HCV elimination. Key factors Wlodzimierz Mazur3, Aleksander Garlicki4, Magdalena Tudrujek-
contributing to its success included the establishment of a detailed Zdunek5, Beata Lorenc6, Dorota Dybowska7, Lukasz Socha8, Anna
patient registry, effective collaboration with local governments and Parfieniuk-Kowerda9, Robert Flisiak9
healthcare systems, and equitable access to treatment facilitated 1
Medical University of Lodz, 2Warsaw Medical University, 3Medical
through financial assistance. The project also underscored integrating University of Silesia, 4Collegium Medicum, Jagiellonian University,
social support systems to ensure comprehensive care delivery. This
5
Medical University of Lublin, 6Pomeranian Center of Infectious
model offers valuable insights and a replicable framework to achieve Diseases, 7Nicolaus Copernicus University, Bydgoszcz, 8Pomeranian
national and global hepatitis elimination goals. Medical University, 9Medical University of Białystok
Table and Figure:Figure 1. Background: Pangenotypic direct-acting antivirals (DAAs) are widely
Figure 2. approved for the treatment of chronic hepatitis C (CHC). However,
choice of DAAs in people living with HIV (PLWH) is often limited due
OP0029 to possible interactions with antiretroviral medications. One of the
most commonly used highly active antiretroviral therapy (HAART) is
Safety, Tolerability, and Outcomes of Sofosbuvir/Velpatasvir in bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF). It has
Treatment of Chronic Hepatitis C Virus during Pregnancy: interim been proven that coadministration of B/FTC/TAF and sofosbuvir/
results from the STORC study velpatasvir (SOF/VEL) is unlikely to induce clinically significant
Stacey Scherbakovsky1, Catherine Chappell2, Jasmin Charles3, interactions, however, coadministration of B/FTC/TAF with gelcaprevir/
Marcela Smid3, Kara Rood4, John Cafardi5, Tatyana Kushner6, pibrentasvir (GLE/PIB) has not been studied. The aim of this study was
Mia Biondi7, Jordan Feld7, Mark Yuddin8, Genevieve Eastabrook9, to assess the real-life effectiveness and safety of GLE/PIB in HIV/HCV-
Cathleen Letterio1, Kyung Min Kwon1, Bruce Kreter1, Sharon Hillier2 positive patients treated with B/FTC/TAF.
1
Gilead Sciences, 2University of Pittsburgh, 3University of Utah, 4Ohio Method: This was an observational, retrospective study based on
State University, 5The Christ Hospital, 6Weill Cornell, 7University Health the EpiTer-2 database, which included patients with CHC treated in
Network, 8University of Toronto, 9London Health Science Centre years 2019-2023 in Poland with the use of DAA therapies registered in
Background: Hepatitis C virus (HCV) prevalence is increasing among European Union. HIV/HCV-coinfected patients who received second
pregnant women, yet postpartum treatment rates are less than 10%. generation DAA-based therapies during B/FTC/TAF treatment were
Use of direct acting antivirals during pregnancy could cure HCV included.
infection during a time of high healthcare engagement, reduce HCV- Result: A total of 139 individuals met the inclusion criteria. Of these,
associated maternal morbidity and prevent perinatal transmission. 38 were treated with GLE/PIB and 101 were treated with SOF/
However, limited safety and efficacy data exist for this population. VEL ± ribavirin (RBV). No significant differences in baseline patient
The STORC study is an international, multi-center study evaluating the characteristics were observed. SVR12 rates reached 78.9% and
safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) in pregnant 80.2% for GLE/PIB and SOF/VEL, respectively, in ITT analysis (p >
people. 0.05), and 100% and 98.8%, respectively, in modified intent-to-treat
Method: In this phase 4, open-label, single-arm study, pregnant (mITT) analysis (p > 0.05) (Figure 1). Overall, adverse events occurred
persons with HCV infection were enrolled between 20+0- and in 6.5% of patients (9/139 patients), accounting for 3/38 (7.9%) in
30+0-weeks’ gestation and treated with a 12-week course of SOF/VEL. patients treated with GLE/PIB and 6/101 (5.0%) in patients treated with
HCV RNA testing was performed at screening, enrollment, 4, 8 and 12 SOF/VEL (p = 0.467) (Table 1). The risk of death during treatment and
weeks after SOF/VEL initiation, at delivery and 12 weeks after SOF/VEL follow-up (2.6% vs. 0.0%, p = 0.273) or liver decompensation (0.0%
completion (SVR12). The primary outcomes were gestational age at vs. 0.99%, p = 0.727) was comparable between groups (GLE/PIB and
delivery and SVR12. Infants were followed for one year. SOF/VEL, respectively).
Result: From July 2022 to May 2024, 51 pregnant people with HCV Conclusion: To our knowledge, this is one of the first studies to assess
were screened and 41 were enrolled. The enrolled participants had a the real-life effectiveness and safety of GLE/PIB in HIV/HCV-positive
median age of 31 (range 18, 40). 33 (80%) identified as White, 8 (15%) patients treated with bictegravir. The study showed that real-life results
identified as other races, including Black, Native American, Asian of therapy with GLE/PIB or SOF/VEL did not differ significantly in
and multiracial and 6 (11.5%) identified as Hispanic. One participant HIV/HCV-coinfected patients treated with B/FTC/TAF. Both regimens
discontinued treatment after one dose due to vomiting. Participants allowed encouraging SVR12 rates and treatment safety, as well as
enrolled with median HCV RNA of 5.81 (range 3.23, 7.18) log copies/ tolerability, were also comparable between the study groups.
mL. After initiation of SOF/VEL, 28/36 (78%) at 4 weeks, 28/33 (85%) at Table and Figure:Figure 1.Figure 1
8 weeks and 27/28 (96%) at 12 weeks of treatment had undetectable Figure 2.Table 1
HCV RNA (Figure). All participants with HCV RNA obtained at delivery
(n=25) and at the SVR12 (n=26) visit were undetectable. The OP0031
maternal retention rate at the SVR12 visit was 27/31 (87%). Of the 32
participants who have delivered, median gestational age was 38+2
weeks (range 33+5, 41+1) and 5 (16%) had preterm delivery < 37
weeks. 19 (53%) participants completed treatment prior to delivery. All
Monotherapy with the Capsid Assembly Modulator ALG-000184 Relationship between Metabolic dysfunction-Asscociated
Results in High Viral Suppression Rates in Untreated HBeAg+ Steatotic Liver Disease and Bone Mineral Density in Post-
Subjects with Chronic Hepatitis B Virus Infection menopausal Women in Primary Healthcare Center
Man Fung Yuen1, Kosh Agarwal2, Alina Lucov3, Alexei Haceatrean3, Minseong Kim1
Min Wu4, Kha Le4, Thanh Van4, Jen Rito4, Lawrence Blatt4, Sushmita 1
Millenium Seoul Internal Medicine Clinic and Health Care Center
Chanda4, Tse I Lin4, Hardean Achneck4, Ed Gane5 Background: Metabolic dysfunction-asscociated steatotic liver
1
Queen Mary Hospital, The University of Hong Kong, 2King‘s College disease (MASLD) and bone mineral density (BMD) are significant
Hospital, Institute of Liver Studies, United Kingdom, 3ARENSIA factors in metabolic disorders and fracture risk among premenopausal
Exploratory Medicine, Republican Clinical Hospital and Nicolae women. However, their relationship remains poorly understood in
Testemitanu State University of Medicine and Pharmacy, Moldova,
this population. This study’s aim is to investigate bone metabolic
4
Aligos Therapeutics, Inc., 5Faculty of Medicine, University of
characterics with MASLD.
Auckland, New Zealand
Method: In this single-center, retrospective study with BMD, liver
Background: ALG-000184 is a prodrug of ALG-001075, a highly function test and abdominal ultrasound involving 66 screening
potent capsid assembly modulator-empty (CAM-E) that has been participants. Normal BMD and osteopenia is 22 cases, and osteoporosis
shown in vitro to induce the formation of empty capsids, inhibit hepatitis is 44 cases. 20 individuals were diagnosed with MASLD, while 30
B virus (HBV) replication, and prevent the establishment/replenishment had normal liver status. Within the MASLD group, approximately 10
of cccDNA. participants exhibited increased breast density, compared to 20 out of
Method: ALG-000184-201 is a multi-part, multi-center, randomized 30 individuals with normal liver status showing the same.
clinical trial evaluating the safety, pharmacokinetics, and antiviral Result: Our analysis revealed a notable association between MASLD
activity of ALG-000184 in healthy volunteers and subjects with and elevated breast density in premenopausal women. The observed
untreated chronic HBV infection (NCT04536337). Here, we report odds ratio (OR) indicated a significant link between MASLD and
safety and antiviral activity data in untreated HBeAg+ subjects who increased breast density (p < 0.05). Subgroup analyses consistently
received 300 mg ALG-000184 monotherapy for ≤ 92 weeks. supported this observation.
Result: A total of 10 untreated HBeAg+ subjects (9 Asian,1 non-Asian) Conclusion: Our study highlights a significant association between
with chronic HBV infection received 300 mg ALG-000184 monotherapy MASLD and increased breast density among premenopausal women,
for up to 92 weeks. Baseline disease characteristics were typical of the as observed in a cross-sectional analysis. These findings suggest
HBeAg+ patient population, e.g., younger age, and higher baseline potential interplay between metabolic disorders and breast health in
levels of viral markers. The HBV genotypes were B (5 Asian subjects), this demographic. Further prospective investigations are needed to
C (4 Asian subjects), and D (1 non-Asian subject). The mean (SEM) elucidate underlying mechanisms and clinical implications.
ALT level was 60.7 (11.7) U/L. Mean (SEM) levels of HBV DNA were
8.0 (0.2) log10 IU/mL; HBV RNA 5.3 (0.4) log10 copies/mL; HBsAg 4.3
(0.1) log10 IU/mL; HBeAg 2.3 (0.2) log10 PEI U/mL; and HBcrAg 8.3 OP0033
(0.2) log10 U/mL. The real life use of bulevirtide for treatment of chronic HDV
By Week 92, the maximum mean reduction from baseline in HBV DNA infection: an interim analysis in the PITER cohort
was 7.3 log10 IU/mL; HBV RNA 5.5 log10 copies/mL; HBsAg 1.2 log10 Loreta Kondili1, Maria Giovanna Quaranta1, PITER Collaborating
IU/mL; HBeAg 1.7 log10 PEI U/mL; and HBcrAg 2.6 log10 U/mL. At Investigators
Weeks 48, 72, and 84, 6/10 (60%), 8/9 (89%), and 7/7 (100%) HBeAg+ 1
National Center for Global Health, Istituto Superiore di Sanità, Rome
subjects achieved sustained HBV DNA < 10 IU/mL (LLOQ, Figure 1B). Italy
All subjects achieved sustained HBV RNA < 10 copies/mL (LLOQ) by Background: Chronic infection by the Hepatitis Delta virus (HDV)
Week 44. Multi-log10 declines were observed in HBV antigens (Figure causes aggressive and difficult-to-treat Hepatitis in Hepatitis B antigen
2). Significant HBeAg declines and increases in anti-HBe antibody (HBsAg)-positive patients.
levels showed a sustained positive trend towards HBeAg loss. We aimed to update the status of patients with chronic HDV infection
No viral breakthrough, as assessed by HBV DNA levels, was observed enrolled in the PITER HBV/HDV cohort after one year from bulevirtide
in any subject for up to 92 weeks of monotherapy (Figure 1A). approval.
300 mg ALG-000184 monotherapy was well-tolerated with no serious Method: This is an interim analysis of consecutive anti-HDV-positive
adverse events (SAE) reported and no treatment emergent AE (TEAE) patients enrolled in the PITER cohort. The chi-square test was used
leading to discontinuation. In three subjects, asymptomatic ALT to analyze differences in proportions between treated and untreated
elevations were reported as grade 3 TEAEs. All these events occurred patients. Following the data validation, multivariable analysis will be
along with a significant decline in HBV DNA and resolved with performed.
continued ALG-000184 dosing. No synthetic or excretory dysfunctions Result: Of 640 anti-HDV positive patients, 358 (56%) tested HDV-RNA
of the liver were observed. positive, of whom 181 (51%) were on bulevirtide therapy. Of the HDV-
Conclusion: 300 mg ALG-000184 monotherapy led to rapid, profound, RNA positive treated patients, 19 (10%) tested HDV-RNA negative at
and sustained HBV DNA and HBV RNA viral suppression in untreated enrolment, of whom 16 (84%) had liver cirrhosis, and 11 (58%) had
HBeAg+ subjects. Viral suppression exceeds those previously reported altered transaminase levels. Cirrhosis was reported in 82% and 74%
with nucleos(t)ide analogs, indicating that ALG-000184 monotherapy (p=0.057) of treated and untreated patients, respectively. Child A and
may be more effective in achieving and maintaining suppression in Child B cirrhosis were reported in 93% and 87% of treated patients and
patients with chronic HBV infection. These data support continuing 76% and 22% (p=0.02) of untreated patients, respectively. HCC was
dosing in this cohort for up to 96 weeks and further evaluation in a reported in 8% and 16% of treated and untreated patients, respectively
Phase 2 clinical trial. (p=0.03). Ongoing NUC therapy was reported in 91% of treated and
Table and Figure:Figure 1.Figure 1: Individual HBV DNA Levels Over 76% of untreated patients (p=0.001). No significant differences were
Time in HBeAg+ Subjects Following 300 mg ALG-000184 Monotherapy observed in the age distribution, country of birth, gender, transaminase
for up to 92 Weeks and gamma-GT levels, HBV-DNA positivity, previous Interferon use,
Figure 2.Figure 2: Mean Declines in HBsAg, HBeAg and HBcrAg and years of NUC therapy (p > 0.05). During the first year of follow-up,
Levels From Baseline in HBeAg+ Subjects Following 300 mg ALG- 1.1% and 9% (p=0.002) of patients died in the treated and untreated
000184 Monotherapy group, respectively. Both groups had similar liver decompensation
(0.7% and 0.8%) and HCC incidence (0.6%).
OP0032 Conclusion: During the first year of bulevirtide therapy, patients with
more severe liver disease were prioritized for treatment. About 50%
of patients with an active HDV infection, of whom 25% have cirrhosis,
still need to be treated. Negative HDV-RNA should be confirmed with
current, more sensitive tests in anti-HDV-positive patients with cirrhosis Background: Low-level viremia (LLV, HBV DNA ≥20 IU/mL but <2000
and altered transaminase levels. IU/mL) persists in chronic hepatitis B (CHB) patients despite nucleos(t)
ide analog (NAs) therapy, increasing risks for hepatocellular carcinoma
OP0034 (HCC) and liver fibrosis. This study aimed to assess whether adjusting
NAs regimens reduces HCC incidence and fibrosis progression in
Discontinuation of NUC Therapy In Non-Cirrhotic Chronic CHB patients with LLV.
Hepatitis B Patients Method: This retrospective analysis included 307 CHB patients with
Shrey Bhatt1, Ujjwal Sonika1, Siddharth Srivastava1, Deep Patel1, LLV following initial NAs therapy, who underwent treatment adjustments
Ajay Kumar1, Ashok Dalal1, Sanjeev Sachdeva1, Barjesh Chander between August 2007 and April 2017. Patients were classified into two
Sharma1 groups: persistent LLV (HBV DNA ≥20 IU/mL but <2000 IU/mL) and
1
Govind Ballabh Pant Institute of Postgraduate Medical Education complete virological response (CVR; HBV DNA <20 IU/mL) based
and Research (GIPMER) on viral levels 48 weeks post-adjustment. Outcomes, including HCC
Background: Nucleos(t)ide analogs (NUC) are recommended for incidence and liver fibrosis progression, were monitored over 96
chronic hepatitis B patients. It decreases progression of liver disease, months.
complications and improves quality of life. Indefinite NUC therapy Result: Of the 307 patients, 53 (17.3%) had persistent LLV, and 254
was recommended, associated with side effects, non-adherence, (82.7%) achieved CVR. The persistent LLV group exhibited significantly
cost and patient’s willingness to stop therapy. Multiple bodies have higher PLT, ALT, AST, serum qHBsAg, FIB-4 levels, and HBeAg positivity
given recommendations to discontinue NUC therapy in chronic after 48 weeks (all p<0.05). HCC incidence was higher in persistent
hepatitis B patients. No single consensus to discontinue NUC therapy LLV group (30.2%) compared to CVR group (13.4%, p<0.001).
in such patients till date. Current study observed clinical outcomes of Logistic regression analysis indicated that persistent LLV was a risk
discontinuing NUC therapy. factor for liver fibrosis progression while Cox regression identified age
Method: Retrospective data of 29 patients of chronic hepatitis B patients and persistent LLV as independent risk factors for HCC occurrence.
without cirrhosis treated at a tertiary care hospital were analysed in Conclusion: Persistent LLV is a significant risk factor for HCC and
whom NUC was discontinued fulfilling APASL 2015 recommendations liver fibrosis progression in CHB patients even after NAs regimen
for NUC discontinuation. LFT and hepatitis B profile at 3 months after adjustment. This highlights the need for enhanced long-term monitoring
discontinuation of NUC therapy were retrieved. Patients with relapse of and management of LLV patients and the exploration of more effective
hepatitis B infection having significant HBV DNA load and/or abnormal treatment strategies.
LFT were restarted on NUC therapy. All the patients were followed up Table and Figure:Figure 1.Kaplan-Meier curve of cumulative incidence
at 12 montss and 24 months of first discontinuation of NUC therapy of HCC between persistent LLV and CVR groups
with HBV DNA load to look for relapse.
Result: Total 29 patients (18 males), with median age of 24 years OP0036
were included. 15 patients were taking Tenofovir and 14 patients
30% of Inactive HBsAg Carriers Achieved Clinical Cure at 48
were taking Entecavir from the beginning of the therapy with median
Weeks with Pegylated Interferon Alpha-2b Therapy: A Multicenter
duration of treatment of 54 months at the discontinuation. 15 patients
Real-World Study (STARHB Project in China)- 2.5 years Data
were HBeAg reactive and 14 patients were HBeAg non-reactive.
Update
At first discontinuation of NUC therapy, median S. AST and S. ALT
were 25 U/L and 27 U/L with median duration of negative HbeAg Shan Ren1, Jing Zhao1, Su Jun Zheng2, Bing Liang Lin3, Yong Fang
and negative HBV DNA load of 25 months and 35 months. At 3 months Jiang4, Qing Fa Ruan5, Yan Huang6, Yi Lan Zeng7, Jia Wei Geng8,
of discontinuation, 14 patients were restarted on NUC therapy (7 on Hai Fang Cao9, Wen Hua Zhang10, Ying Guo11, Xiao Rong Mao12, Zhi
Entecavir, 7 on Tenofovir) with median S. AST, S. ALT and HBV DNA Liang Gao3, Tian Yuan Shi13, Yue Yong Zhu14, Zu Jiang Yu15, Xiao
load of 34.5 U/L, 33 U/L and 97,50,000 IU/ml, respectively. Of these Ping Wu16, Qing Mao17, Xiu Lan Xue18, Ying Li He19, Jia Shang20,
14 patients, 10 patients were HBeAg reactive while 4 patients were Shuang Suo Dang21, Hai Dong Zhao22, Rong Shan Fan23, Jiang Ling
HBeAg non-reactive at the beginning of NUC therapy. 15 patients did Yang24, Jian Qi Lian25, Hai Bing Gao26, Xin Yue Chen2
not require restart of NUC therapy at 3 months with median S. AST
1
Beijing You‘an Hospital, Capital Medical University, 2Beijing You‘an
and S. ALT of 25 U/L and 26 U/L with negative HBV DNA load. Patients Hospital, Capital Medical University, 3The Third Affiliated Hospital
with restart of NUC therapy, 5 patients had detectable HBV DNA of Sun Yat-sen University, 4The Second Xiangya Hospital of Central
load at 12 months. Patients without restart of NUC therapy, 1 patient South University, 5Xiamen Hospital of Traditional Chinese Medicine,
had detectable HBV load at 12 months. 24 patients had follow-up
6
Xiangya Hospital Central South University, 7Public Health Clinical
Center of Chengdu, 8The First People‘s Hospital of Yunnan Province,
data post 24 months of the first discontinuation of NUC therapy. All the 9
The 4th People‘s Hospital of Qinghai Province, 10Gansu Wuwei
patients had negative HBV DNA load, without HBV flare. 5 patients are
Tumour Hospital, 11The Third People‘s Hospital of Taiyuan, 12The First
on regular follow-ups without HBV flare.
Hospital of Lanzhou University, 13The second hospital of longyan,
Conclusion: Discontinuation of NUC therapy can be attempted in 1
4the First Affiliated Hospital of Fujian Medical University, 15The First
non-cirrhotic chronic hepatitis B patients who achieved sustained Affiliated Hospital of Zhengzhou University, 16The First Affiliated
on-therapy virologial remission and seroconversion. These patients Hospital of Nanchang University, 17The southwest hospital of AMU,
should remain under strict clinical and laboratorial follow-up protocols 1
8the First Affiliated Hospital of Xiamen University, 19The First Affiliated
to detect and manage relapses in timely manner. Patient motivation for Hospital of Xi‘an Jiaotong University, 20People‘s Hospital of Henan
therapy discontinuation and regular follow-up remains crucial. province, 21The Second Affiliated Hospital of Xi‘an Jiaotong University,
2
2Xiamen Changgeng Hospital Co., Ltd., 23Shenzhen Hospital of
OP0035 Integrated Traditional Chinese and Western Medicine, 24Ningbo
Beilun District Traditional Chinese Medicine Hospital, 25The Second
Effect of adjusting nucleos(t)ide analog antiviral treatment on the Affiliated Hospital of Air Force Medical University, 26Mengchao
outcome of patients with low-level viremia associated with HBV Hepatobiliary Hospital of Fujian Medical University
Xuyang Li2, Wucai Yang1, Mengwen He2, Dong JI1, Jing Chen3,
Background: This study aimed to investigate the efficacy and safety
Yudong Wang4, George Lau4,5
of achieving functional cure (HBsAg loss) using Pegylated Interferon
1
Senior Department of Hepatology, the Fifth Medical Center of alpha-2b (PEG IFNα-2b) treatment in inactive HBsAg carriers (IHC).
Chinese PLA General Hospital, Beijing 100039, China, 2Peking
Method: The STARHB Project (The STUDY ON TREATMENT FOR
University 302 Clinical Medical School, Beijing 100191, China, 3JC
INACTIVE CARRIERS OF HEPATITIS B) is a multicenter real-world
School of Public Health and Primary Care, Chinese University of Hong
study in China focused on the functional cure of IHC, aiming to
Kong, Hong Kong SAR, China, 4Humanity and Health Clinical Trial
onboard approximately 25,000 patients (ChiCTR2200061541). Based
Center, Humanity and Health Medical Group, Hong Kong SAR, China,
5
Zhongshan Hospital, Fudan University, Shanghai, China on patient preferences, participants were assigned to a control group
(without antiviral treatment) or treatment groups (NAs group and PEG although trends are leading towards worse prognosis. Hence,
IFNα-2b ± NAs group). The basic treatment duration was 48 weeks, physicians must take into consideration the diabetes status of HCC
extendable to 96 weeks as needed patients on immunotherapy due to its impact on their clinical outcomes
Result: As of Nov. 2024, 15,070 individuals were screened, and and negative prognostic effect of metformin use.
10,894 eligible IHC patients were included in the mITT population Table and Figure:Figure 1.Forest Plot 1. The overall survival of
baseline analysis. This cohort was 64.9% male with a mean age of 43 metformin vs non-metformin group of diabetic patients with advanced
years; 6.3% were under 30 years old, and 41.5% had fatty liver. The hepatocellular carcinoma on immunotherapy
mean HBsAg level was 223 IU/ml, with 81.8% below 500 IU/ml. The
mean HBV DNA level was 220 IU/ml, with 58.5% having undetectable
OP0038
HBV DNA at baseline. The mean ALT was 22 U/L. Liver biopsies were
performed on 60 patients at baseline, with 33.3% showing significant CHEK1 suppresses hepatocellular carcinoma progression by
liver necroinflammation and/or fibrosis (≥ G2 and/or ≥ S2). At present, modulating reprogramming of tumor-associated macrophages
729 patients have completed the 48-week follow-up. In the control Yanqiu Li1, Yao Liu1, Xianbo Wang1
group (n=11), 4 achieved virological response (VR), with 1 achieved 1
Center for Integrative Medicine, Beijing Ditan Hospital, Capital
HBsAg loss. In the NAs group, the VR rate at 48 weeks was 100% Medical University, Beijing, China.
(17/17), with 1 achieved HBsAg loss. Among those treated with PEG Background: Checkpoint kinase 1 (CHEK1) is a cell cycle checkpoint
IFNα-2b ± NAs, the VR rate at 48 weeks was 91.01% (638/701), with kinase that plays a crucial role in repairing damaged DNA and
an HBsAg loss rate of 30% (210/701). ROC analysis indicated that maintaining genomic stability. However, the mechanisms of CHEK1 in
baseline HBsAg levels, 12-week and 24-week HBsAg levels, and 12- hepatocellular carcinoma (HCC) progression and tumor-associated
week AST levels could predict HBsAg loss at 48 weeks. macrophages reprogramming remain unclear. This study aimed to
Conclusion: PEG IFNα-2b therapy can effectively achieve functional explore the potential role and mechanism of CHEK1 on HCC through
cure in IHC patients, with a 48-week HBsAg loss rate of 30%. Lower the in vivo and in vitro experiments.
baseline, 12-week, and 24-week HBsAg levels, along with higher 12- Method: Utilizing the Tumor Immune Estimation Resource (TIMER)
week AST levels, are predictors of functional cure at 48 weeks. Thus, to determine the expression levels of CHEK1 in tumor samples and
the IHC population is a favorable group for pursuing clinical cure for evaluated its prognostic significance in HCC using the Gene Expression
hepatitis B Profiling Interactive Analysis (GEPIA) database. Establishing a stable
Table and Figure:Figure 1.Table1 :Patient demographics and baseline CHEK1-knockdown HuH 7 cells and macrophages cell lines using
characteristics RNA interference to investigate the impact of CHEK1 on polarization
Figure 2.Fig1.HBsAg loss rate among patients with treatment of PEG and migration of macrophage, proliferation of HuH 7 cells, and
IFNα±NAs at week48. angiogenesis of human umbilical vein endothelial cells (HUVECs). By
injecting a plasmid carrying the Akt/Myc gene via tail vein, an HCC
OP0037 model in C57BL/6J mice was established. The mice were treated with
the Prexasertib, a CHEK1 inhibitor, PD-L1 or a combination of both to
THE IMPACT OF METFORMIN ON THE OVERALL SURVIVAL
observe the therapeutic efficacy of Prexasertib.
OF DIABETIC PATIENTS WITH ADVANCED HEPATOCELLULAR
Result: CHEK1 was significantly upregulated in HCC, and its
CARCINOMA ON IMMUNOTHERAPY: A META- ANALYSIS
expression level was positively correlated with tumor grade and
Regina Dimaculangan1, Jared Cordero1, Faith Co1, Ian Cua1 negatively related to survival probability. In HuH7 cells, Prexasertib
1
St. Luke‘s Medical Center - Global City showed a dose-dependent effect on CHEK1 expression and cell
Background: Non-alcoholic steatohepatitis (NASH) is a common proliferation. Prexasertib-treated and CHEK1-knockdown HuH7 cells
known risk factor for developing hepatocellular carcinoma (HCC). inhibited macrophage migration, while Prexasertib-treated and CHEK1-
Many patients with NASH are given metformin, a widely prescribed knockdown macrophages suppressed HuH7 cells proliferation.
medication for type 2 diabetes and obesity. Its primary mode of action Furthermore, specific knockdown of CHEK1 in J774A.1 using shRNA
involves the activation of AMP-activated protein kinase (AMPK), a resulted in enhanced M1 polarization (increased iNOS expression
central regulator of cellular energy homeostasis. Beyond its anti- and CD86+ cell proportion) and inhibited M2 polarization (decreased
hyperglycemic effects, it also exhibits pleiotropic properties that extend Arg-1 expression and CD206+ cell proportion) compared to control
to modulating various cellular processes, including inflammation, cells. Additionally, different concentrations of Prexasertib and CHEK1
metabolism, and immune response. In this similar mechanism, growing knockdown HuH7 cell culture supernatant inhibited the angiogenesis
evidence indicates that metformin also has anti-cancer properties. It ability of HUVECs, and Western Blot also suggested that Prexasertib
has shown significant synergistic effects in combination with standard and CHEK1 knockdown reduced VEGFA expression in HuH7 cells and
chemotherapy and immune check- point inhibitors (ICI). However, thus inhibited angiogenesis. In vivo experiments also demonstrated
its effect on advanced HCC treated with ICI (e.g. atezolizumab + that Prexasertib decreased tumor number and burden, inhibited M2
bevacizumab, pembrolizumab, durvalumab) is not well understood. polarization and reduced PD-L1 and VEGFA expression.
Method: This meta-analysis aims to determine the effect of metformin Conclusion: Overexpression of CHEK1 is closely associated
in the overall survival of diabetic patients with advanced HCC treated with poor prognosis and immune infiltration in HCC. Knockdown
with ICIs. Major electronic databases and grey literature sources of CHEK1 in HuH7 cells and macrophages or treatment with the
were searched up to January 2023 for studies assessing the effect of Prexasertib suppresses HCC proliferation and angiogenesis as well as
metformin in the survival of diabetic HCC patients on immunotherapy. macrophage migration and polarization. Therefore, CHEK1 may serve
Result: The hazard ratios for the overall survival of metformin as a potential prognostic biomarker and therapeutic target for HCC.
(experimental) vs non-metformin (control) groups were compared Table and Figure:Figure 1.Expression and mechanism of CHEK1 in
from the studies done by Kang 2022, Lin 2022 and Ramini 2023. hepatocellular carcinoma cells and tumor-associated macrophages
Resulting I2 of 0% (p value = 0.54) implies that heterogeneity does Figure 2.Therapeutic effects and mechanisms of CHEK1 inhibitors in
not exist. Resulting pooled hazard ratio of 1.08, with a narrow 95% mice with hepatocellular carcinoma
confidence interval 0.85 to 1.38, is not significant (Z = 0.65, p = 0.51),
implying no significant difference between the two groups. The forest OP0039
plot also shows that the diamond market intersects the 1 axis or the
line of no effect, suggesting that the hazard ratio is not significant. Revisiting AASLD Guidelines: A Real-world Analysis of
However, eyeballing the said forest plot, all 3 studies tend toward the Postoperative Adjuvant Therapy in Hepatocellular Carcinoma
non-metformin or control group which signifies a worse prognosis with Patients
metformin on HCC patients on ICIs. Yue Huang1, Siyi Lei1, Hong Peng1, Xinhua Luo1
Conclusion: The use of metformin has no significant difference in the 1
Department of Infectious Diseases,Guizhou Provincial People’s
overall survival in diabetic HCC patients receiving immunotherapy, Hospital
Background: According to the guidelines of the American Association stroma). Blood vessels were classified based on the presence of VETC
for the Study of Liver Diseases (AASLD), postoperative adjuvant (Vessels that encapsulate tumor clusters)
therapy (PAT) is recommended for high-risk hepatocellular carcinoma Result: The T+AI group showed a significant increase in treatment-
(HCC) patients to reduce the postoperative recurrence risk. However, related immune cell counts compared to the T group.CD8+ TILs
additional real-world data are required to validate these risk factors. were identified as a prognostic factor for neoadjuvant treatment
Method: A retrospective analysis was conducted on 138 patients in overall survival(OS)( P=0.008) and disease free survival(DFS)
diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC (P=0.01). Pathological analysis revealed lower CAIX and VETC
who had undergone curative resection. Kaplan-Meier survival curve positivity in the T+AI group(P=0.01 and P=0.03), with significant
was used to analyze recurrence-free survival time (RFS) and judge differences in immune cell infiltration and vascular classfications.
whether PAT benefits. A recurrence prediction model was developed Additionally, VETC and CAIX positivity was associated with higher
using Cox regression analysis, stratified by PAT. tumor residual rates and lower CD8+ TIL levels(P=0.01 and P=0.02),
Result: PAT improved RFS not only in the high-risk group but also might indicating its detrimental impact on treatment efficacy.
in the low-risk group (P < 0.05), which is grouped by the AASLD Conclusion: The combination of TACE with immunotherapy and
guidelines recommended. Consequently, we developed a new model anti-angiogenic agents enhances therapeutic outcomes in HCC by
(SAMP) for predicting early recurrence, incorporating maximum tumor promoting immune infiltration.The reduced of hypoxic conditions and
diameter (MDT), alpha-fetoprotein (AFP) levels, poorly differentiation changed of vascular classfications might be the reason that behind
and sarcopenia. The area under the ROC curve (AUC) for SAMP the immune infiltration promotion.
showed the highest accuracy compared with other prediction models Table and Figure:Figure 1.The evaluation of immune cell
(6 months 0.72[0.62-0.82], 12 months 0.72[0.63-0.81] and 2 years
0.68[0.59-0.77]).According to the SAMP, PAT significantly enhanced OP0042
RFS in the middle-high risk groups (P < 0.05), but did not affect RFS in
low-risk group (P = 0.88). Classifications and Outcomes of Local Tumor Progression of
Conclusion: High-risk factors recommended by the AASLD Hepatocellular Carcinoma after Thermal Ablation: A Longitudinal
guidelines are insufficiently effective in distinguishing all patients Multicenter Study
who would benefit from PAT. Conversely, the new prediction model Fangying Fan1, Miao Cui2, Yongyue Wei2, Jie Yu1
SAMP demonstrates a robust capability in identifying the risk of 1
Chinese PLA General Hospital, Beijing, China, 2Peking University
postoperative recurrence and effectively discerning patients who do Center for Public Health and Epidemic Preparedness & Response
not require PAT. Background: The prognostic indications of local tumor progression
Table and Figure:Figure 1.he K-M survival curve of the risk group (LTP) after thermal ablation for hepatocellular carcinoma (HCC)
recommended by AASLD guidelines in analysis of the 2-year RFS remained controversial. We aimed to identify and validate LTP
Figure 2.SAMP score scatter plot combined with clinical data heat map classification and to discriminate the at-risk LTP category and its
of SAMP risk groups. impact on survival.   
Method: HCC patients within Barcelona Clinic Liver Cancer (BCLC)
OP0041 stage 0 to B underwent thermal ablation at five Chinese medical
centers from 2006 to 2020 were incorporated. Data including the
Pathological Study of the Tumor Microenvironment After
size, position, occurrence time, critical location and vascular invasion
Neoadjuvant Therapy in Hepatocellular Carcinoma: Why Does
of LTP, were collected and analyzed for risk classification. Different
TACE Combined with Anti-Angiogenics and Immunotherapy
LTP phenotypes were characterized by an unsupervised hierarchical
Outperform TACE Alone?
cluster analysis and its relative risks (RRs) for all-cause mortality,
Xintao He1,2, Tianyi Dai1,2, Aihua Yang1,2, Jianan Shen1,2, Jun Chen1,2 cancer-specific mortality and stage-progression mortality were
1
Department of Pathology, Nanjing Drum Tower Hospital Clinical assessed by multitype recurrent event model after adjusting for clinical
College of Nanjing University of Chinese Medicine, Nanjing, China, covariables in discovery set. An easy-accessible decision algorithm
2
Department of Biobank, Nanjing Drum Tower Hospital Clinical was designed for LTP classification in clinical settings, thus a separated
College of Nanjing University of Chinese Medicine, Nanjing, China validation set was stratified by the algorithm and was assessed the
Background: Hepatocellular carcinoma (HCC) is the leading form RRs of each phenotype.
of primary liver cancer. The insidious onset of HCC often results in Result: A total of 2,616 HCC patients with 6,919 tumors were included
late-stage diagnosis, limiting treatment options. Transcatheter arterial in the study, among whom 370 patients developed 504 LTP lesions. LTP
chemoembolization (TACE) is commonly used for unresectable lesions were stratified into 3 categories of LTP-Ⅰ, LTP-Ⅱ and LTP-Ⅲ, with
tumors, yet its effectiveness diminishes with repeated use, leading markedly distinguished features and prognostic risks. Compared to
to high recurrence rates. TACE combined with anti-angiogenic and non-LTP patients, LTP-Ⅰ (45.6% of LTPs) was characterized by relative
immunotherapy has shown significant progress in neoadjuvant safe location and small-size lesions with the RR of all-cause mortality
treatment, although the underlying mechanisms remain unclear. This being 0.92 (0.71, 1.19), and LTP-Ⅱ (48.2% of LTPs) was characterized
study aims to explore the reasons for the enhanced efficacy of TACE by vascular critical location, short occurrence time and larger lesion
when combined with anti-angiogenic and immunotherapy from a size with the RR of all-cause mortality being 1.41 (1.17, 1.68). LTP-
pathological perspective in the context of hepatocellular carcinoma. Ⅲ (6.2% of LTPs), which was featured by vascular thrombosis and
Method: A retrospective analysis was conducted on 49 HCC patients obvious tumor progression with significantly poor prognosis, and
treated with TACE before surgical resection at Nanjing Drum Tower the RRs for all-cause mortality were being 3.18 (2.10, 4.82). RRs for
Hospital from January 2019 to December 2022. Patients were divided cancer-specific mortality and stage-progression mortality were also
into two groups: TACE alone (T) and TACE with anti-angiogenic and risk-sharped for LTP-Ⅰ, LTP-Ⅱ and LTP-Ⅲ (p<0.001), respectively.
immunotherapy (T+AI). Clinical data, including overall survival (OS) Decision tree algorithm including 5 factors classified LTPs in the
and disease-free survival (DFS), were collected. All pathological appropriate subtype with 92.0% accuracy in the discovery set and
tumor tissue paraffin sections underwent immunohistochemical 90.0% accuracy in the validation set.
examination, including markers such as CD4, CD8, CD20, CD66b, Conclusion: The characteristics-driven LTP risk category, accurately
Foxp3, PD1, CAIX, and CD34. Immune cells were recorded based on discerned the high-risk LTP lesions from multicenter data, provided
four indicators: 1. invasion margin (manual counting of infiltrating cells reliable prognostic estimates of LTP patient prognosis lesions and
in high-power fields selected from the tumor periphery), 2. center of may help improving the treatment decision-making. Identification
tumor (manual counting of infiltrating cells in high-power fields within of LTP phenotypes might be useful in patients’ treatment decision
the tumor), 3. tumor-infiltrating lymphocytes percentage (TILs, the when after thermal ablation.
percentage of positive lymphocytes in the central area of the tumor), Table and Figure:Figure 1.Local tumor progression risk grading with
and 4. non-tumorous tissue infiltrating lymphocytes percentage (NILs, phenotypic attributes
the percentage of positive lymphocytes in the central area of the
 OP0043 Background: With the implementation of the new nomenclature on
LIPID PROFILE AND LIVER STEATOSIS IN PATIENTS WITH steatotic liver disease (SLD), three main subgroups consisting of
ARTERIAL HYPERTENSION . metabolic dysfunction-associated liver disease (MASLD), MASLD with
increased alcohol intake (MetALD), and alcohol-related liver disease
Aliya Konysbekova1, Mahabbat Bekbosynova , Gulzhan
(ALD) have been defined. However, the risk of SLD for all-cause
Myrzakhmetova, Seitkasym Sh K, Kaliaskarova K.
mortality and adverse outcomes as well as the different risks between
1
UMC, Heart Center MASLD, MetALD, and ALD needs further clarification.
Background: Background Abnormal accumulation of liver lipids Method: In this cross-sectional population-based Gutenberg Health
is a hallmark of steatosis, a conditional part of the spectrum of non- Study, data of 13,599 participants enrolled between 2007 and 2012
alcoholic fatty liver disease. Significant changes in lipid metabolism with 5-year follow-up data were analysed. The fatty liver index (FLI)
are observed in non-alcoholic fatty liver disease. A marked increase with a score of ≥60 was used to define SLD. The subgroups of SLD
in free cholesterol levels occurs as steatosis progresses to non- (MASLD, MetALD, and ALD) were defined according to the new
alcoholic steatohepatitis, and total plasma cholesterol correlates with nomenclature. The fibrosis score 4 (FIB-4) was calculated to determine
the presence of liver inflammation (Wouters K et al, 2008). patients at risk of fibrosis (≥1.3). All-cause mortality (10-year follow-up)
Method: In order to determine the relationship between blood lipid and several adverse outcomes (i.e. hepatic decompensation, major
levels and the development of liver statohepatitis, a survey of 350 adverse cardiac events [MACE], extrahepatic cancer) were analysed
patients was conducted. 56% of the group were men, and 44% were and compared across the subgroups of SLD. Cox regression models
women. The average age of patients was 53.6±8.8 years. The results were used to estimate adjusted hazard ratios (HR) and their 95%
of the Fibroscan CAP steatosis were coded as follows: 0 - no, 1 - S1, confidence intervals (CIs).
2 - S2, 3 - S3. Statistical analysis of the data was performed using the R Result: The overall prevalence of SLD was 37.3% (n=5,074), whereas
program. As part of the analysis of patient data, a statistically significant the prevalence of MASLD, MetALD, and ALD were 30.5% (n=4,154),
moderate positive correlation (p<0.001) was revealed between the 5.3% (n=717) and 1.5% (n=202), respectively. Almost half of the
steatosis index and patient obesity (Pearson’s cor 0.466, df = 298, population were women (48.9%, n=6,644), and the mean age was 54.3
p-value < 2.2e-16) and BMI (Pearson’s cor 0.463, df = 298, p-value < (±11) years. An elevated FIB-4 ≥1.3 was present in 20.2% (n=1,021)
2.2e-16). A statistically significant negative weak correlation (p<0.001) with SLD. The cumulative incidence of all-cause mortality was higher
was also found between the steatosis index and HDL (Pearson’s cor in SLD and its subgroups MASLD, MetALD, and ALD compared to
-0.204, df = 297, p-value = 0.0003085). In addition, a statistically no SLD (p<0.0001) (Figure 1). An elevated FIB-4 (≥1.3) increased
significant positive weak correlation (p<0.001) was found between the the cumulative incidence of all-cause mortality across all investigated
steatosis index and LDL (Pearson’s cor 0.133, df = 297, p-value = SLD subgroups compared to a FIB-4 <1.3 (p<0.0001) (Figure 2).
0.02175). A regression analysis was performed, where the dependent After adjustment for age, sex, socioeconomic status, education, and
variable was the results of Fibroscan+CAP, and the independent smoking, MASLD (HR 1.4, 95% CI 1.2-1.7) and MetALD (HR 1.3, 95%
variables were total cholesterol, HDL, LDL, age, gender, presence or CI 1.0-1.7) but not ALD (HR 1.2 95% CI 0.8-1.9) showed a higher risk
absence of diabetes, absence and degree of hypertension. for all-cause mortality. A higher risk for adverse outcomes was seen
Result: HDL has a statistically significant negative effect on the results in MASLD (hepatic decompensation: HR 1.2 95% CI 1.0-1.4; MACE:
of the CAP -Fibroscan (p < .001). That is, the higher the HDL, the lower HR 1.4, 95% CI 1.2-1.6; extrahepatic cancer: HR 1.2, 95% CI 1.0-1.4),
the steatosis fibroscan value, that is, steatosis is absent or at a low whereas no differences were seen with MetALD and ALD.
stage. Steatosis is also affected by the patient’s gender (p < 0.05). Conclusion: The prevalence of SLD and especially MASLD is high
Gender was coded as follows: 1 - women, 2 - men. That is, in men, in the general population. Patients with SLD and any of its three main
steatosis develops less, and in women, steatosis develops more often. subgroups show higher all-cause mortality, whereas the risk for adverse
Steatosis is also affected by the presence or absence of hypertension outcomes is particularly increased in those with MASLD. These results
and its stage (p < .005). Hypertension is coded in the database highlight the importance of screening for SLD and related metabolic
as follows: 0 - absent, 1 - 1st degree hypertension, 2 - 2nd degree risk factors using non-invasive Tests to improve outcomes.
hypertension, 3 - 3rd degree hypertension. The higher the degree of Table and Figure:Figure 1.Higher all-cause mortality in SLD subgroups
hypertension, the more often the patient develops liver steatosis. (MASLD, MetALD and ALD) compared to no SLD
Conclusion: Elevated LDL levels are associated with the severity of Figure 2.Stratification by FIB-4 ≥1.3 revealed a higher risk of all-cause
steatosis in patients with arterial hypertension mortality across all investigated SLD subgroups compared to FIB-4
<1.3
OP0044
Risk of all-cause mortality and adverse outcomes from steatotic OP0045
liver disease and its subgroups in the general population Safety of statins in Asian cohort with biopsy proven MASLD
Maurice Michel1,2, Angelo Armandi1,3, Alexander Gieswinkel4, Wei Lun Liou1, Yi Ying Pei1, Kevin KimJun Teh1, Mark ChangChuen
Alexander Schuster5, Thomas Münzel4,6, Stavros Konstantinides7, Cheah1, Wei Qiang Leow2, Tony KiatHon Lim2, George BoonBee
Matthias Michal8, Beate Straub9, Irene Schmidtmann10, Oliver Goh1
Tuescher8, Philipp Wild4, Karl Lackner11, Peter Galle2, Joern 1
Department of Gastroenterology and Hepatology, Singapore General
Schattenberg1,2 Hospital, 2Department of Pathology, Singapore General Hospital
1
Department of Internal Medicine II, University Medical Center Background: Individuals with metabolic dysfunction associated
Saarland, 2Department of Medicine I, University Medical Center steatotic liver disease (MASLD) may be more susceptible to develop
Mainz, 3Division of Gastroenterology and Hepatology, Department
drug induced liver injury (DILI). Statins is recommended for treatment
of Medical Sciences, University of Turin, 4Preventive Cardiology and
of hyperlipidemia; however, it is often under-prescribed in patients with
Preventive Medicine, Department of Cardiology, University Medical
MASLD due to fear of higher risk of hepatotoxicity. To date, there have
Center Mainz, 5Department of Ophthalmology, University Medical
been no studies that specifically examine the safety of statins in Asian
Center of the Johannes Gutenberg University Mainz, 6Center for
Cardiology - Cardiology I, University Medical Center of the Johannes with MASLD. We evaluate the safety of statins in a cohort of Asian
Gutenberg University Mainz, 7Center for Thrombosis and Hemostasis, patients with biopsy proven MASLD.
University Medical Center Mainz, 8Department of Psychiatry and Method: The study cohort comprised patients with biopsy proven
Psychotherapy, University Medical Center of the Johannes Gutenberg MASLD seen in our department from 2009 to 2022. Clinical data were
University Mainz, 9Institute of Pathology, University Medical Center prospectively collected. We studied and compared the demography
of the Johannes Gutenberg University Mainz, 10Institute of Medical and characteristics of patients with or without statins. We compared
Biostatistics, Epidemiology and Informatics, University Medical Center their liver enzymes at baseline and at latest follow-up visit to assess the
of the Johannes Gutenberg University Mainz, 11Institute for Clinical safety of statins regarding liver function.
Chemistry and Laboratory Medicine, University Medical Center Mainz Result: There were 215 patients with biopsy proven MASLD, 115
(53.5%) were female. The median age of all patients was 59.9 years. decreased. These changes likely reflect lifestyle shifts, including
136 patients received statins during the follow up. There were higher increased alcohol consumption and decreased physical activity.
proportion of patients with diabetes mellitus (58.8% vs 40.5%) and Public health interventions addressing these factors are needed to
hyperlipidemia (100% vs 29.1%) in the statins’ cohort. NAFLD activity prevent rising liver disease morbidity and mortality.
scores and fibrosis stage were similar between the two cohorts. Table and Figure:Figure 1.Comparison of Age-Adjusted Clinically
Baseline ALT was higher in the non-statins’ cohort (73 vs 51, p=0.03). Significant Fibrosis Prevalence Among U.S. Population aged 18 Years
Simvastatin and Atorvastatin were the most used statins (89.9%). The or Older and Across Demographic Subgroups in Pre-Pandemic (2017–
median duration of statins use was 53 months. At the latest follow up, 2020) and Pandemic (2021–2023) NHANES Cycles.
ALT was significantly lower in both statins (48 vs 61, p<0.01), and non- Figure 2.Predictors of Clinically Significant Fibrosis: Univariate and
statins cohort (41.5 vs 73, p<0.01). There was no significant difference Multivariate Logistic Regression Analysis.
in the liver enzymes between the cohorts at follow up. Statins cohort
also achieved significant improvement in BMI (27.9kg/m2 vs 27.1 kg/
OP0047
m2, p=0.03) and liver stiffness (11.4kPa vs 9.6kPa, p=0.02).
Conclusion: In this cohort of Asian patients with biopsy proven Comparison Of Renal Impairment And Liver Fibrosis Between
MASLD, the use of statins was safe and not associated with worsening Diabetic And Non Diabetic Non-Alcoholic Fatty Liver Disease
liver enzymes or liver fibrosis. Statins therapy should be encouraged in Patients
this cohort to treat hyperlipidemia and reduce cardiovascular events. Kishore S1, Manish Kumar1, Sarita Jilowa1
Table and Figure:Figure 1.Table 1: Baseline demographics of biopsy 1
Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram
proven MASLD patients on statins versus no-statins Manohar Lohia Hospital
Figure 2.Table 2. Liver profile of statins vs non-statins group at follow Background: Non-alcoholic fatty liver disease (NAFLD) encompasses
up. a spectrum of conditions, including simple steatosis, steatohepatitis,
fibrosis, cirrhosis, and potentially hepatocellular carcinoma. NAFLD is
OP0046 recognized as an independent risk factor for chronic kidney disease
(CKD), with both conditions sharing interlinked pathogenesis. There
Changing Landscape of Steatotic Liver Diseases and Liver
is limited understanding of the prevalence of renal impairment and
Fibrosis in the United States During the COVID-19 Pandemic
hepatic fibrosis in diabetic and non-diabetic individuals with NAFLD in
Abdelrahman Attia1, Mohammad Rezaee2, YeeHui Yeo1, Minsun India. This study aims to compare renal impairment and liver fibrosis
Kwak1, Hyunseok Kim1, Mazen Noureddin3, JUDONG YANG1 in diabetic and non-diabetic NAFLD patients attending a tertiary care
1
Cedars Sinai Medical Center, 2Middle East Liver Diseases Center, hospital in Delhi.
3
Methodist Hospital Method: This observational cross-sectional comparative study was
Background: Steatotic liver diseases (SLDs), including metabolic conducted at ABVIMS and Dr. RML Hospital from April 1, 2023, to June
dysfunction-associated steatotic liver disease (MASLD), metabolic 30, 2024. A total of 88 patients with NAFLD patients were included,
dysfunction and alcohol-related liver disease (MetALD), and alcohol- with 44 diabetic and 44 non-diabetic patients, all aged over 18 years.
related liver disease (ALD), are major liver diseases. Our study Patients with serology positive for Hepatitis B and C viruses were
examined changes in the prevalence of SLDs and clinically significant excluded from the study. Demographic characteristics, medical history,
fibrosis (CSF) in U.S. adults before (2017–2020) and during (2021– and physical examinations were recorded. Laboratory investigations
2023) the COVID-19 pandemic. assessed liver and kidney functions and insulin resistance. Renal
Method: We conducted a serial cross-sectional analysis using the impairment was evaluated using the estimated glomerular filtration rate
National Health and Nutrition Examination Survey (NHANES) data (eGFR) 2021 CKD-EPI equation and the spot urine albumin-creatinine
from 2017–2020 (n=8,965) and 2021–2023 (n=6,337). Participants ratio. eGFR less than 80 ml/min/1.73sq.m. and Urine ACR more than
aged 18 years or older who completed demographic, socioeconomic, 30mg/g was considered abnormal. Liver fibrosis was assessed using
clinical, and liver health assessments with vibration-controlled 2D-Shear wave elastography.
transient elastography were included. Age-adjusted prevalence of Result: Diabetic NAFLD patients were significantly older (mean age
SLDs (controlled attenuation parameter (CAP) score >285 dB/m), CAP 50.86 years) compared to non-diabetic patients (mean age 39.09 years)
scores, and CSF (liver stiffness measurement (LSM) greater than 8.6 (p=0.001). Obesity was prevalent in both groups. In the non-diabetic
kPa) were compared across pre-pandemic and pandemic cycles. group, 34.09% were insulin sensitive (HOMA-IR <1.64), while 65.91%
Physical activity, alcohol consumption, and body composition data were insulin resistant (HOMA-IR ≥1.64). Diabetic patients exhibited
were evaluated for lifestyle changes contributing to SLD trends. higher levels of renal impairment, with elevated urea (p=0.003), serum
Result: Between pre-pandemic and pandemic periods, age-adjusted creatinine (p=0.004), and lower eGFR (p<0.001). Renal impairment
ALD prevalence increased from 0.94% to 2.27% (P=0.003) and MetALD was present in 68.18% of diabetic patients compared to 20.45% of
from 2.60% to 4.42% (P=0.003), while MASLD declined from 30.13% to non-diabetic patients (p<0.001). Liver-related parameters showed
25.46% (P=0.003). Vigorous physical activity dropped from 212.51 to higher AST (p=0.001) and ALT levels (p=0.027) in diabetic patients.
84.99 min/week (P<0.001) and moderate activity from 195.06 to 76.52 Hepatic stiffness was significantly higher in diabetic patients (mean
min/week (P<0.001). Moderate/excessive alcohol use rose from 6.3% 7.9 ± 2.09 kPa) compared to non-diabetic patients (mean 7.07 ± 4.14
to 9.6% (P<0.001), with nondrinkers/light drinkers falling from 93.7% to kPa, p<0.001). Subgroup analysis of pre-diabetic and non-diabetic
90.4% (P<0.001). Appetite changes increased (P<0.001), with more subjects revealed no significant differences in renal impairment or
individuals experiencing poor appetite or overeating. No differences hepatic fibrosis.
were found in BMI, weight, waist circumference, cholesterol, fasting Conclusion: Our study indicates that renal impairment and liver
glucose, HbA1c, or blood pressure. CAP scores were stable (260.56 fibrosis are more prevalent in diabetic NAFLD patients compared to
vs. 261.17 dB/m, P=0.804). CSF prevalence increased from 8.3% to non-diabetic NAFLD patients. Notably, 20.45% of non-diabetic NAFLD
10.5% (P=0.028), as shown in Figure 1, and LSM rose from 5.82 to patients also exhibited renal impairment. Early detection through renal
6.10 kPa (P=0.149), notably among low-income individuals (5.80 to function tests and 2D Shear Wave Elastography at the initial stages
6.82 kPa, P=0.04). Multivariable analysis showed the pandemic period of the disease, provides a valuable opportunity to prevent disease
was linked to higher CSF odds (aOR: 1.47; 95% CI: 1.00–2.17), and complications.
moderate/excessive alcohol intake increased CSF odds (aOR: 2.13; Table and Figure:Figure 1.Box plot showing urine albumin creatinine
95% CI: 1.15–3.95), as illustrated in Figure 2. Subgroup analysis ratio (ACR) among the diabetic and non diabetic NAFLD groups.
revealed significant SLD changes among males (P=0.002), non- Figure 2.Bar chart showing grade of liver fibrosis assessed by 2D-
Hispanic Whites (P=0.003), and age groups 18–34 (P=0.033) and elastography in both groups.
35–49 (P=0.023).
Conclusion: During the COVID-19 pandemic, the prevalence of
OP0048
ALD, MetALD, and CSF increased among U.S. adults, while MASLD
The role of the small intestine bacterial overgrowth in patients clinical supporting tools may facilitate effective management. We
with metabolic dysfunction–associated fatty liver disease sought to leverage a machine learning (ML) method to develop,
Ilona Minosayn1, Olga Tarasova1, Harshada Pednekar1, Mangesh explain, and validate a predictive model for short-term mortality in ICU
Shelar1, Farjana Najneen1, Mohd Amir1 patients with ACLF.
1
Peoples‘ Friendship University of Russia named after Patrice Method: Utilizing the MIMIC-IV database, a large ICU cohort with
Lumumba detailed clinical information, we identified patients with NACSELD
criteria-defined ACLF and determined the predictors of 30-day
Background: Metabolic dysfunction-associated fatty liver disease
mortality. Along with five-fold cross-validation and resampling
(MAFLD) is a prevalent metabolic disorder characterized by the
methods, ML models were developed, and the best-performing model
accumulation of hepatic fat in the absence of excessive alcohol
was selected. The Shapley value was calculated to explain the model.
consumption. This condition can progress to metabolic dysfunction-
Internal and external validations were performed.
associated steatohepatitis (MASH), potentially culminating in cirrhosis
Result: Of 5994 with cirrhosis admitted to ICU, 1511 were found to
or hepatocellular carcinoma. The principal risk factors for MAFLD
have ACLF. The CatBoost ACLF (CBA) model was found to have the
encompass obesity, insulin resistance, and metabolic syndrome.
greatest accuracy, with an area under curve (AUC) of 0.87. The AUC
Furthermore, small intestine bacterial overgrowth (SIBO) is posited
for grade one ACLF was 0.84 while it was 0.86 for the subgroup with
to play a significant role in the onset and progression of MAFLD,
grade two & three ACLF. These models showed robust calibration. The
although conflicting data regarding this association persist. Transient
top twelve predictors were selected and presented similar predictive
elastography (TE) utilizing a controlled attenuation parameter (CAP)
performance. The comparison between the CBA model’s predicted
has been sanctioned for evaluating the advancement of liver disease
result and actual mortality exhibited a remarkable consistency (Figure
in the context of MAFLD.
1). Categorization of patients based on the mortality probability yielded
Aim: to interpret the role of SIBO in MAFLD and its potential impact on
three distinct mortality probability curves (Figure 2). The 30-day mortality
disease progression.
probabilities of the high, medium, and low risk groups were 96.7%,
Method: The study comprised 74 participants, with a mean age of 46
71.9%, and 14.9%, respectively. The simplified CBA model (AUC:
years (range: 23-69). Among these, 26 (35%) were men and 48 (65%)
0.87, 95%CI:0.83-0.90) outperformed contemporary scoring systems
were women. All participants underwent laboratory examinations, and
including CLIF-C ACLF (AUC:0.77, 95%CI:0.74-0.79) and MELD 3.0
other liver diseases were systematically excluded. Transabdominal
(AUC:0.76, 95%CI:0.73-0.79) with significance and was validated
ultrasound employing TE with CAP (Echosens, France) and a hydrogen
using an internal validation cohort and an independent external cohort
breath test for SIBO using a portable hydrogen analyzer (Gastro+™
with the same diagnosis criteria and eligibility. A simple-to-use online
Gastrolyzer by Bedfont Scientific Ltd) were conducted.
tool was created to assist physicians and researchers worldwide in
Result: Out of the 74 subjects, 34 (45%) were diagnosed with SIBO,
utilizing our predictive models for ACLF patient mortality risk.
while steatosis was identified in 40 (54%) through the application of
Conclusion: The well-validated and calibrated CBA model predicted
CAP. Within the cohort of SIBO-positive individuals, steatosis was
30-day mortality with high accuracy and outperformed existing
detected in 16 (47%). Conversely, among the 40 SIBO-negative
predictive models. The interpretation of the model provided the
individuals, 24 (60%) exhibited steatosis (p=0.086). Notably, there
nuanced impact of predictors on mortality. The online tool could assist
was no observed increase in the degree of steatosis within the SIBO-
healthcare providers with clinical decision-making.
positive group.
Table and Figure:Figure 1.Figure 1. Comparison of Predicted Mortality
Conclusion: The investigation did not reveal any significant correlation
Rates with Actual Survival Status. The green line represents the
between SIBO and MAFLD.
predicted probability of death, and the patient status bar represents
the patient’s 30-day true survival status. The comparison highlights the
OP0049 accuracy of the models in predicting mortality outcomes.
Development and Validation of a Predictive Machine Learning Figure 2.Figure 2. Mortality Probability of Patients with Acute-on-Chronic
Model for Short-Term Mortality in ICU Patients with Acute-on- Liver Failure at Day 30 Categorized by the Prediction of the CBA Model.
Chronic Liver Failure The red line represents high risk ACLF patients, while green and blue
Yee Hui Yeo1, Mengyi Zhang2, Martin S. Schulz3, Jian Zu2, Yingli He4, represent low risk and medium risk patients, respectively. The P-value
Yi Liu5, Juan Li4, Taotao Yan4, Yuan Wang5, Hirsh Trivedi1, Xiaodan is calculated using logarithmic rank test to determine the differences
Sun2, Zhujun Cao6, Chun Ying Wu7,8,9, Jonel Trebicka3,10,11, Fanpu in mortality probability among subgroups of different severity levels.
Ji5,12,13
1
Karsh Division of Gastroenterology and Hepatology, Department OP0050
of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA, DPMAS therapy in acute-on-chronic liver failure patients: a
2
School of Mathematics and Statistics, Xi’an Jiaotong University, prospective, multicenter and cluster-controlled study ((PADSTONE
Xi’an, China, 3Department of Internal Medicine B, University of Study)
Münster, Münster, Germany, 4Department of Infectious Diseases,
Beiling Li1, PADSTONE Study Group, Jinjun Chen1
The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China,
5
Department of Infectious Diseases, The Second Affiliated Hospital
1
Nanfang Hospital Southern Medical University
of Xi’an Jiaotong University, Xi’an, China, 6Department of Infectious Background: Liver failure is a life-threaten syndrome and cause high
Diseases, Ruijin Hospital, Shanghai Jiao Tong University School short-term mortality. Double plasma molecular adsorption system
of Medicine, Shanghai, China, 7Institute of Biomedical Informatics, (DPMAS) is one of the available artificial liver support systems which
National Yang Ming Chiao Tung University, Taipei, Taiwan, China, its efficiency for chronic liver disease (CLD) patients with liver failure
8
Division of Translational Research, Taipei Veterans General Hospital, remains controversial.
Taipei, Taiwan, China, 9College of Public Health, China Medical Method: A prospective, multicenter and cluster-controlled study was
University, Taichung, Taiwan, China, 10European Foundation for conducted (NCT05129904) and 57 tertiary hospitals were recruited
Study of Chronic Liver Failure, Barcelona, Spain, 11Department of and allocated to the DPMAS treatment clusters (n=28) and standard
Gastroenterology and Hepatology, Odense University Hospital, medical treatment (SMT) clusters (n=29). Outcomes included disease
Odense, Denmark, 12Key Laboratory of Environment and Genes
progression, survival, death and liver transplantation and safety of
Related to Diseases (Xi‘an Jiaotong University), Ministry of Education
DPMAS therapy. Twelve-months is required for each participant to
of China, Xi‘an, China, 13Key Laboratory of Surgical Critical Care and
complete post-discharge follow-up.
Life Support (Xi‘an Jiaotong University), Ministry of Education, Xi‘an,
Result: In total, 648 liver failure patients were enrolled in DPMAS
China
group and 615 patients in SMT group. MELD score was comparable
Background: Prediction of short-term mortality in patients with acute on between these two groups (24±5 vs. 24±6, p=0.984). For the DPMAS
chronic liver failure (ACLF) defined by the North American Consortium group, 31.9% patients had 2 DPMAS treatment sessions and 77.1% of
for the Study of End-Stage Liver Disease (NACSELD) criteria with the initial DPMAS treatment was with subsequent plasma exchange.
Unfractionated heparin was the most common anticoagulants used critical and life-threatening complication in patients with acute-on-
in DPMAS treatment. The total bilirubin, ALT and CRP levels were chronic liver failure (ACLF), characterized by a high rate of short-
all significantly improved after the initial DPAMS therapy. The 28- term mortality. Cytokines play a pivotal role in the pathogenesis of
day transplant-free mortality was much lower in DPAMS group than IPA and have been implicated as potential diagnostic biomarkers.
SMT group (15.7% vs. 20.0%, p=0.048). Allergy (3.7%) and dialyzer The objective of this study is to conduct a comprehensive evaluation
coagulation (3.2%) as well as the arterial hypotension (2.9%) were the of the diagnostic efficacy of cytokines in the context of IPA among
common adverse events during DPMAS treatment. ACLF patients.
Conclusion: DPMAS treatment for CLD patients with liver failure Method: In this single-center, proof-of-concept and prospective study,
can significantly improve the liver function markers and the 28-day we enrolled 216 ACLF patients. Plasma samples and corresponding
mortality. DPMAS therapy was associated with few adverse events and clinical data were collected throughout their hospitalization. Based on
its safety is confirmed. established diagnostic criteria for IPA, 16 patients were designated
as the IPA group. For comparative analysis, 32 patients with bacterial
pneumonia without IPA (BP group) and 32 patients without any infectious
OP0051
complications (non-infection group) were matched as controls based
Organ Failure-Based Clinical Classification at Onset of Acute-on- on gender, age and the severity of liver decompensation. Plasma levels
Chronic Liver Failure: A Prospective Multicenter Cohort Study of a panel of cytokines, including including interleukin (IL)-33, IL-17A,
Yu Wu1, Man Man Xu1, Ling Wen Wang1, Bin Huai Zou1, Yu Chen1 IL-23, IL-31, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, interferon
1
Fourth Department of Liver Disease, Beijing You‘an Hospital Affiliated (IFN)-γ, tumor necrosis factor (TNF)-α and soluble IL-2 receptor
to Capital Medical University (sIL-2r), were quantified at the time of IPA diagnosis. The diagnostic
Background: The heterogeneity in ACLF definitions proposed by performance of these cytokines for IPA was evaluated using receiver
different expert associations worldwide has led to variations in clinical operating characteristic (ROC) curve analysis.
phenotypes and prognosis. This study proposes a new approach for a Result: No significant difference was observed for patients
unified definition based on the type of organ failure within the first week baseline characteristics among IPA, BP and non-infection groups.
of disease onset. Among the three groups, significant differences were observed in IL-
Method: This prospective cohort study collected clinical data from 33 levels (163.07 [IQR 108.30; 211.22] vs 12.82 [IQR 0.00; 50.55] vs
hospitalized ACLF patients presenting with liver failure (total bilirubin 0.00 [IQR 0.00; 52.51] pg/ml, p = 0.033), IL-6 levels (33.82 [IQR 5.87;
≥5 mg/dL, INR ≥1.5) across four liver centers in China. Patients with 50.04] vs 12.09 [IQR 5.56; 21.32] vs 7.67 [IQR 2.58; 11.47] pg/ml, p
persistent liver failure within the first week of onset were classified = 0.004), IL-4 levels (0.16 [IQR 0.11; 0.27] vs 0.11 [IQR 0.10; 4.92] vs
as Type I ACLF, while those with concurrent extrahepatic organ 0.11 [IQR 0.10; 0.12] pg/ml, p = 0.025) and IL-23 levels (10.14 [IQR
failure were categorized as Type II ACLF. We compared the clinical 9.03; 11.09] vs 10.95 [IQR 10.05; 12.87] vs 11.28 [IQR 9.67; 12.46] pg/
characteristics and prognosis of Type I and Type II ACLF patients, as ml, p = 0.033), in which only plasma IL-33 level (163.07 [IQR 108.30;
well as the inclusivity of these classifications within existing mainstream 211.22] vs 12.82 [IQR 0.00; 50.55] pg/ml, p < 0.001) was significantly
ACLF definitions. higher in the IPA group, when compared with BP group. ROC curve
Result: A total of 864 patients were included in the analysis population. analysis and determination of cut-off values revealed that IL-33 (AUC
Type I ACLF occurred in 86.9% of cases, primarily in patients with = 0.871, cut-off = 66.97 pg/ml, p < 0.001) effectively discriminated
non-cirrhotic chronic liver disease (34.3%) or compensated cirrhosis between IPA and pulmonary bacterial infections, with a sensitivity of
(48.6%), while Type II ACLF, observed in 13.1% of cases, predominantly 93.80% and a specificity of 84.40%. Furthermore, IL-33 levels were
developed in patients with cirrhosis (73%) (P < 0.001). Mortality rates significantly higher at the time of IPA infection compared to 5-7 days
at 28 and 90 days were significantly higher in Type II ACLF patients before infection (154.86 vs 2.01 pg/ml, p = 0.003) and 5-7 days after
(43.2% and 52.3%) compared to those with Type I ACLF (15.8% and antifungal treatment (154.86 vs 28.01 pg/ml, p = 0.042).
24.9%) (P < 0.001). Patients with Type I ACLF met the APASL criteria Conclusion: Plasma IL-33 levels demonstrate robust diagnostic
more frequently (82.9%), whereas those with Type II ACLF more often potential for IPA in ACLF patients, particularly in distinguishing
met the EASL criteria (69.4%). For predicting the 90-day prognosis aspergillus from bacterial infections.
in Type I ACLF, the COSSH-ACLF II score achieved the highest
AUROC at 0.788 (95% CI: 0.749-0.828). In Type II ACLF, the CLIF-C OP0053
OF score provided the highest AUROC for predicting 90-day mortality,
Dynamic Risk Assessment of Hepatic Encephalopathy: A Novel
at 0.902 (95% CI: 0.840-0.964), outperforming the MELD, MELD-Na,
Network Approach
and COSSH-ACLF II scores (P < 0.05) and showing no significant
difference when compared to the CLIF-C ACLF score (0.872 [95% CI: Zixing Wang1, Suzhen Jiang1, Feng Liu1, Xiaoxiao Wang1
0.791-0.953], P = 0.426).
1
Peking University People‘s Hospital, Peking University Hepatology
Conclusion: This new clinical classification approach takes into Institute
account the characteristics defined by both Eastern and Western Background: Hepatic encephalopathy (HE) is a prevalent and
ACLF, and is expected to improve the comparability and interpretability serious complication in patients with liver cirrhosis. Early detection
of data in global studies, enhancing global understanding and and screening are crucial for improving patient prognosis; however,
management of ACLF. no single diagnostic test offers sufficient accuracy. To address this
Table and Figure:Figure 1.Graphic Abstract challenge, we developed an innovative tool designed for dynamic
risk assessment of HE, optimizing the timing and effectiveness of
screening efforts.
OP0052
Method: We retrieved 980 blood test items for 3487 cirrhosis patients
Plasma Interleukin-33 as a Novel Diagnostic Marker for Invasive from our laboratory information system, focusing on biomarkers that
Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure: A could signal the risk of HE. Candidate tests were selected based
Prospective Study on rigorous criteria: clinical utility (with an average of three tests per
Lanyue Huang1, Wei Liu1, Yunhui Liu1, Liang Chen1, Meng Zang1, patient), expert consensus (approval from two senior hepatologists),
Yuxin Niu1, Yuzhao Feng1, Qiuyu Cheng1, Tingting Liu1, Mi Song1, Qin predictive relevance (evaluated using random forest variable
Ning1, Tao Chen1 importance ranking), clarity of risk direction (≥20% risk associated with
1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical test result elevation or reduction), and information independence. Nine
College and State Key Laboratory for Diagnosis and Treatment of selected biomarkers were integrated with 3 demographic factors, 4
Severe Zoonostic Infectious Disease, Huazhong University of Science comorbidities, and 8 cirrhosis-related complications (including HE)
and Technology, Wuhan, 430030, Hubei Province, China into a Bayesian network model. The model was constructed based on
Background: Invasive pulmonary aspergillosis (IPA) represents a expert-curated associations and was trained and validated using two
cohorts (sample sizes: 2789 and 698, respectively; Figure 1A).
Result: The network provides a comprehensive visualization of free survival rate of HBV-ACLF patients. Compared with patients
independent risk pathways, including the progression of cirrhosis- meeting the COSSH and EASL-ACLF standards, G-CSF treatment
related complications (Figure 1B). It dynamically updates risk is more suitable for patients meeting the APASL-ACLF standards
assessments as new laboratory results become available. The model or patients with early and middle stage of liver failure meeting the
demonstrated robust predictive power for HE onset, with area under Chinese Guidelines for the Diagnosis and Treatment of Liver Failure
the curve (AUC) values of 0.926 versus 0.670 at baseline (network (2018 edition).
vs. Model for End-Stage Liver Disease score) and an improved 0.962 Table and Figure:Figure 1.Table 1. Demographical and clinical
versus 0.707 following most updated test results. Given its high characteristic of patients in G-CSF and SMT group(afer PSM).
predictive accuracy, the network also serves as an effective tool for Figure 2.Figure 1. G-CSF can effectively improve the 90-day transplant-
determining the optimal timing for HE screening (Figure 1C). free survival rate of HBV-ACLF patients. Compared with patients
Conclusion: The proposed network is user-friendly and represents meeting the COSSH and EASL-ACLF standards, G-CSF treatment
a significant advancement in the management of cirrhosis patients. is more suitable for patients meeting the APASL-ACLF standards
By enhancing clinical decision-making, it has the potential to improve or patients with early and middle stage of liver failure meeting the
patient outcomes through timely identification and intervention for HE. Chinese Guidelines for the Diagnosis and Treatment of Liver Failure
Table and Figure:Figure 1.Figure 1 (2018 edition).

OP0054 OP0055
Efficacy of Granulocyte Colony-stimulating Factor in hepatitis Assessing Liver Fibrosis Regression Using Simple Blood Tests
B virus-associated acute-on-chronic liver failure patients: A in Hepatitis C Virus (HCV) Patients Treated with Direct-Acting
multicenter study Antiviral Agents
Jing Yuan1,2, Jing Chen1,2, Haibin Su1,2, Yu Chen 3, Tao Han4, Tao Hamza Benazzouz1, Maryeme Kadiri1, Fatimazahra Chabib1, Nawal
Chen5, Xiaoyan Liu1,2, Qi Wang6, Pengbin Gao 7, Jinjun Chen 8, Lagdali1, Mohamed Borahma1, Fatimazahra Ajana1
Jingjing Tong1,2, Chen Li1,2, Jinhua Hu1,2 1
Hepatogastroenterology Departement, Medecine C, Ibn Sina Rabat
1
The Fifth Medical Center of Chinese PLA General Hospital, Beijing, Background: The advent of novel direct-acting antivirals (DAAs) has
China, 2Chinese PLA General Hospital, Beijing, China, 3Liver Disease transformed the management of chronic hepatitis C. These agents
Center, You‘an Hospital, Capital Medical University, 4Department have significantly increased sustained virological response (SVR) rates
of Gastroenterology and Hepatology, Tianjin Union Medical in patients with chronic hepatitis C (CHC). In this study, we evaluated
Center, Nankai University, 5Department and Institute of Infectious
changes in fibrosis using the FIB-4 and APRI scores following DAA
Disease,Tongj Hospital,Tongji Medical College,Huazhong University
treatment for CHC.
of Science and Technology Wuhan, China, 6Center of Liver Diseases,
Method: This was retrospective, descriptive, and analytical study
Beijing Ditan Hospital, Capital Medical University Beijing, China,
conducted in a gastroenterology department over 8 years including
7
Third Department of infectious Diseases, Fifth Hospital,Shijiazhuang
Shijiazhuang, China, 8Liver Disease Center, Nanfang Hospital, 165 patients diagnosed with chronic hepatitis C. The data normality
Southern Medical University Guangdong, China test for this study was conducted using the Shapiro-Wilk test. The FIB-
4 and APRI values before and after treatment were compared using
Background: Granulocyte Colony-stimulating Factor (G-CSF) have the Wilcoxon test.
been used for treating acute-on-chronic liver failure (ACLF), but this Result: 165 patients were enrolled in this study. Median age at
strategy remains controversial. The aim of this study was to assess the diagnosis was 60[52;70] years; sex ratio M/W was 0.8. 12(8%) had
impact of G-CSF on survival in patients with liver failure and to select alcohol use disorder, 5(3%) had use of cannabinoid substances.5(3%)
the appropriate treatment population. had history of drug injection.8(5.3%) had high-risk sexual practices.
Method: This multicenter, nonrandomized, open-label prospective Concerning laboratory results, 51(37%) patients had cytolysis,
study was conducted at 7 medical facilities in China. Patients meeting 12(11.4%) had cholestasis,and 6(8.7%) presented with sign of
the APASL-ACLF criteria were screened and assigned to the G-CSF hepatocellular insufficiency.
group (300mg/d G-CSF for the first 6 days and every other day On ultrasound, 27(23.5%) patients showed signs of chronic liver
thereafter until day 18) or the standard drug therapy group (SMT disease, 21(18.3%) exhibited signs of portal hypertension. A total
group) based on their willingness. All participants were followed up of 56(33.9%) patients underwent upper endoscopy, 28 (50%) had
for at least 90 days. The primary endpoint was 90-day transplant-free esophageal varices, 13(24.5%) had hypertensive gastropathy.
survival, analyzed by per-protocol. Survival rates were calculated. For fibrosis assessment, 64(38.7%) patients underwent liver biopsy,
Kaplan–Meier curves were delineated and compared using the log- 62(37.57%) underwent a Vibration Controlled Transient Elastography
rank test. Differences in patient background were corrected using (VCTE), and 7(7.22%) a FibroTest. A total of 124(75.15%) presented
propensity score matching (PSM), and the appropriate treatment with fibrosis, with 32(25.4%) at stage F4, 24(19%) at F3, 31(24.6%) at
population was selected by subgroup analysis. F2, and 37(29.4%) at F1. The median Fib-4 and APRI score at baseline
Result: The 284 participants were allocated to either the G-CSF were 3.13[1.48; 4.34] and 1.36 [0.91;2.16], respectively.
group (n=119) or the SMT group (n=165). A per-protocol set of 252 150(90%) patients were treated with Sofosbuvir and Daclatasvir for
samples were analyzed. The G-CSF group exhibited a significantly 94(69.7%) cases. SVR was achieved for 97(81.5%) patients.
higher 90-day transplant-free survival compared with the SMT group 112(67.87%) patients were available for analysis at 48 weeks; FIB-4
(78.8% vs. 68%, P<0.05). After PSM, 86 cases were selected in each index showed significant decreases compared to those at baseline
group. The transplant-free survival at day 90 in the G-CSF group (3.13[1.48; 4.34] vs 1.36[0.91;2.16], p<0.001). APRI score showed
was still significantly higher than the SMT group (80.2% vs. 66.3%, significant decreases compared to those at baseline (1.008[0.441;1.93]
P=0.024). Multivariate analysis showed that G-CSF therapy was an vs 0.358[0.249;0.514], p<0.001). Furthermore, patients with stage F3
independent protective factor for 90-day prognosis in HBV-ACLF or F4 experienced a reduction in their FIB-4 and APRI scores, from
patients. As for subgroup analysis, in the subgroup of patients defined 4.044 [3.39;5.61] to 1.65 [1.19;2.8] and from 1.525 [1.03;2.28] to
by Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF 0.582 [0.303;0.654], respectively. In this group, it was observed that
criteria, or European Foundation for the Study of Chronic Liver Failure 22(43.1%) patients had a FIB-4 score below 1.45, and 30(58.8%)
(EASL) ACLF criteria, G-CSF did not improve 90-day transplant-free patients had an APRI score below 0.5 after treatment.
survival (72.3% vs. 61.9%, 43.8% vs. 43.3%, P=0.109, 0.606), but in Conclusion: Hepatitis C virus infection can lead to liver-related events,
the subgroup who met the Chinese Guidelines for the Diagnosis and The achievement SVR can stop or reverse the damage of liver. In our
Treatment of Liver Failure (2018 edition), especially in the early and study, patients with SVR after antiviral therapy showed significant
intermediate stage, G-CSF improved 90-day transplant-free survival regression of validated fibrosis scores FIB-4 and APRI.
compared with SMT group obviously (82.3% vs. 65.7%, P=0.017).
Conclusion: G-CSF can effectively improve the 90-day transplant-
 OP0056 Method: This retrospective, multicenter clinical study included
The study of the risk of long-term adverse events in patients with patients diagnosed with CHC related DCC between January 2018 and
hepatitis C after treatment with Direct-acting antivirals June 2023. The study was conducted at Guangzhou Eighth People’s
Hospital, Guangzhou Medical University and other 8 territory hospitals
Nuo Si1, Jing Liang2, Gang Liu2, Hongmin Lv2, Fei Tang2, Fenghui Li2,
in Guangdong (detail lists were shown in Table 1). Patients were
Baibo Xu2
treated with DAA + ribavirin (RBV) for 12 weeks, for those intolerant
1
Tianjin Third Central Hospital branch, 2Tianjin Third Central Hospital to RBV, a 24-week regimen of DAA was administered, as per clinical
Background: The study examines the outcomes of patients with guidelines. SOF based regimen was the major regimen. The study
hepatitis C who have received direct-acting antiviral treatment, evaluated virological parameters before treatment, 12 weeks post-
focusing on the recurrence of HCV, the occurrence and recurrence treatment (SVR12) and 1 year following SVR 12, and the rate of hepatic
of hepatocellular carcinoma, and the progression to cirrhosis or recompensation, et al.
decompensated cirrhosis, analyzing the risk factors associated with Result: A total of 136 patients with CHC related DCC who had completed
these conditions. DAA therapy were included, with a median follow-up duration of 12
Method: A retrospective statistical analysis was conducted on the months. Baseline Characteristics were shown in Table 1. Among them,
clinical data of patients with hepatitis C who received direct-acting 70 patients (51.4%) received combination therapy with RBV. SOF/VEL
antiviral treatment at the outpatient and inpatient departments of was used in 125 patients (91.9%), 67 of whom received RBV; SOF/
the Gastroenterology Department of the Third Central Hospital of LDV was used in 10 patients (7.3%), with 3 receiving RBV. All patients
Tianjin from April 2018 to August 2020. The follow-up was concluded completed treatment, the overall SVR12 rate was 93.3% (127/136).
on June 30, 2024, with an average follow-up time of 4.3 years. The SVR12 was achieved in 94.9% (94/99) of CP class B patients and
study observed the sustained virological response rate and followed 89.2% (33/37) of CP class C patients, respectively. By genotype (GT),
up on the incidence of new hepatocellular carcinoma, recurrence of the SVR12 rates were as follows: GT1, 100% (30/30); GT 2, 100% (8/8);
hepatocellular carcinoma, progression to cirrhosis, or decompensation GT 3, 87.5% (35/40); GT 6, 90% (18/20); unknown GT, 94.7% (36/38).
of cirrhosis. Adverse events (AEs) such as anemia, fatigue occurred in 19 patients
Result: Among the 203 patients, the SVR rates of 1 year, 2 years, 3 (13.9%) during treatment, no treatment discontinuation due to AEs. At
years and the end of follow-up were 98.9% in the cirrhosis group, and SVR 12 (n=136) and at 1 year following SVR 12 (n=91), compared to
the SVR rates of 1 year, 2 years, 3 years and the end of follow-up were baseline, significant improvements were observed in the FIB-4 index,
99.1%, 99.1%, 99.1% and 100% in the non-cirrhosis group, respectively. MELD score, and CP score, along with reductions in total bilirubin
During long-term follow-up, a total of 33 patients developed liver- (TB) ,aspartate aminotransferase (AST), and alanine aminotransferase
related adverse events, including 4 patients with HCV recurrence, 9 (ALT) levels (all P < 0.05). The mean levels of hemoglobin and albumin
patients with hepatocellular carcinoma, 6 patients with liver cancer increased significantly, P < 0.05. MELD score improved by ≥3 points
recurrence, 8 patients with cirrhosis progressed from compensatory in 49 patients (53.8%) and worsened by ≥3 points in 9 patients (9.8%).
to decompensated, and 6 patients with non-cirrhosis progressed to A total of 64 patients (70.3%) achieved recompensation, including 52
cirrhosis. Survival analysis showed that the incidence of liver adverse (57.1%) classified as CP class A or 27 (29.6%) with MELD improved
events was significantly higher in the cirrhotic group than in the non- to a score of <10 (Figure 1). Three patients followed up at 1 year after
cirrhotic group. Univariate analysis showed that sex, cirrhosis, FIB-4, post-treatment experienced virological relapse.
platelet, albumin and total bilirubin were associated with liver adverse Conclusion: Antiviral therapy in patients with CHC related DCC
events. Multivariate analysis showed that males (P=0.008,HR 3.197, achieved high SVR12 rate, along with significant improvements in liver
95%CI 1.359-7.519) and cirrhosis (P=0.046,HR 2.844, 95%CI 1.019- biochemical parameters, fibrosis markers, MELD scores, and Child-
7.939) were associated with liver-related adverse events. Pugh scores, demonstrating good safety. The treatment markedly
Conclusion: The treatment of hepatitis C with direct-acting antiviral enhanced clinical outcomes in both short-term and 1 year following
drugs can achieve a high rate of sustained virological response (SVR); SVR 12, with a high recompensation rate.
however, even after achieving SVR, patients may still experience HCV Table and Figure:Figure 1.Table 1: Baseline Characteristics of Patients
recurrence, new onset hepatocellular carcinoma (HCC), or recurrence Figure 2.Figure1:Changes in CP class and MELD categories (MELD
of HCC, as well as progression to cirrhosis or decompensated <10, MELD 10–15, MELD 16–20, and MELD ≥ 21 after treatment with
cirrhosis. Therefore, patients infected with HCV who have achieved DAAs at 1 year following SVR12
SVR still require close monitoring, especially male patients and those
with cirrhosis who should be vigilant.
OP0058
Table and Figure:Figure 1.Survival Analysis of Hepatic Adverse Events
in Patients with Cirrhosis Compared to Those without Cirrhosi Clinical Characteristics of Patients with Chronic Hepatitis C and
Figure 2.Univariate and Multivariate Logistic Regression Analysis of the Genotype 3 Infection in Northwest China: a Multicenter Cross-
Risk of Hepatic Adverse Events in Patients sectional Study
Yishan Liu1, Yujia Jing 2, Jingyi Xie1, Manling Bai3, Zhangqian Chen
4
, Qiang Xu5, Hong Du6, Yuxiu Ma7, Liting Zhang8, Yu Li9, Yunyu
OP0057
Zhao1, Shanshan Zhu2, Xiaoqin Gao8, Wei Zhang4,10, Xinggang
Efficacy and Prognosis of Direct-Acting Antiviral Therapy in Bai3,10, Guoying Yu7, Hongli Wang11, Jianqi Lian6, Xiaozhong Wang5,
Chronic Hepatitis C–Related Decompensated Cirrhosis Yongping Zhang12, Jiuping Wang4, Fanpu Ji1,13, Jianjun Fu2, Ning
Jianping Li1, Songlian Liu1, Qikai Ning1, Hui Li2, Jinfeng Liu3, Jinyan Gao1
Jiang4, Haifei Su5, Qin Yan6, Xi He7, Bozhi Chen8, Xujing Liang9, 1
The Second Affiliated Hospital of Xi‘an, Xian Jiaotong University,
Jinlian Lin3, Honglian Bai3, Fang Wang4, Xiaoxing Mai3, Changxiang Xi’an, China, 2Xi‘an Central Hospital, Xi’an, China, 3Wuwei People‘s
Lai4, Meisan Liu2, Yujuan Guan1 Hospital, Wuwei, China, 4Xijing Hospital of Air Force Medical
1
Guangzhou Eighth People’s Hospital , Guangzhou Medical University, Xi‘an, China, 5Hospital of Traditional Chinese Medicine
University, 2Huadu District People’ Hospital of Guangzhou , 3The First Affiliated to Xinjiang Medical University, Urumqi, China, 6Tangdu
People‘s Hospital of Foshan, 4Shenzhen Third People’s Hospital, Hospital of Air Force Medical University, Xi‘an, China, 7the Fourth
5
Gaozhou People’s Hospital, 6Shenzhen Nanshan People’s Hospital, People‘s Hospital of Qinghai Province, Xining, China, 8First Hospital
7
The Affiliated Qingyuan Hospital ( Qingyuan People’s Hospital ), of Lanzhou University, Lanzhou, China, 9Shaanxi Provincial People‘s
Guangzhou Medical University , 8People‘s Hospital of Huazhou, 9The Hospital, Xi‘an, China, 10Department of Liver Disease, Daxing Hospital
First Affiliated Hospital of Jinan University of Xi‘an City, China, 11The Eighth hospital of Xi‘an City, Xi‘an, China,
Background: To evaluate the efficacy, clinical outcomes, and
1
2People‘s Hospital of Xinjiang Autonomous Region, Urumqi, China,
recompensation rate (Baveno VII criteria) of direct-acting antiviral (DAA)
1
3Shaanxi Provincial Clinical Medical Research Center of Infectious
Diseases, Xi‘an, China
therapy in the treatment of chronic hepatitis C–related decompensated
cirrhosis (CHC related DCC) in South China. Background: Hepatitis C virus (HCV) genotypes (GTs) have been
reported to associate with disease progression and sustained response (SVR) rate among patients with GT3b is lower than that
virological response (SVR) after receiving direct-acting antiviral agents observed in patients with GT3a infection, particularly among patients
(DAAs) treatment. Genotype 1 is the most prevalent genotype in Asia, with cirrhosis. However, the current treatment recommendations for
GT3 patients vary obviously regional distribution, with the highest patients with GT3 are based on clinical data generated in regions
prevalence in western China. Our study aimed to evaluate the clinical where GT3a predominates.
characteristics of patients with HCV genotype 3 (HCV GT3) infection Method: This multicenter, randomized, open-label study aims to
and the associated risk factors for disease progression in patients with evaluate the efficacy and safety of sofosbuvir (SOF)/velpatasvir (VEL)
chronic hepatitis C (CHC) in Northwest China. plus ribavirin (RBV) (Arm A) and SOF/VEL/voxilaprevir (VOX) (Arm B)
Method: A retrospective cohort study was conducted in patients with for 12 weeks in direct-acting antiviral agents (DAAs) treatment-naïve
CHC at 11 clinical centers in Northwest China. We compared the HCV patients with GT3b, compensated cirrhosis in China. The primary
baseline clinical characteristics of CHC patients infected with HCV GT3 endpoint was SVR at 12 weeks after the end of treatment (SVR12).
and other genotypes. We also performed univariate and multivariate Result: The study was conducted from 14 September 2022 to 12 April
Logistic regression analysis to explore the factors associated with 2024 at seven centers in China. Of the 64 patients screened, 61 were
cirrhosis in CHC patients with GT 3 infection. enrolled and received at least one dose of study drug. 30 (49%) and
Result: Totally, 1002 HCV infected individuals were included in the 31 (51%) received SOF/VEL plus RBV or SOF/VEL/VOX for 12 weeks,
study, including 427 patients with GT1, 242 with GT2, 299 with GT3 respectively. In 7 patients who didn’t complete the follow-up (Arm A,
(29.81%, GT3a 210, GT3b 87, and 2 unclassified subtypes), and 34 4 patients & Arm B, 3 patients), 1 patient withdrew consent and 6
with GT6 infection. The patients with GT3 infection (51.3±0.5 years) was patients lost follow-up. 54 has completed follow-up at 12 weeks after
younger than GT1 and GT2 patients (P<0.01), especially in cirrhosis the end of treatment (Arm A, 26 patients & Arm B, 28 patients). Of the
subgroup, the mean age of GT3 patients (52.09±0.51 years) was 61 patients enrolled, 47 (77%) were men, 37 (61%) were drug abusers,
lower than that of GT1 patients (59.41±0.85 years) and GT2 patients the mean age was 51.1±7.3 years. The median ALT was 95 (59, 124)
(58.07±1.12 years) (both P<0.01). In patients with GT3 infection, the U/L and the median HCV RNA was 6.5 (5.9, 6.9) log IU/mL. Baseline
proportion of males and cirrhosis were 77.9% and 47.8%, both higher characteristics were generally balanced across the treatment arms (all
than that of the GT1 and GT2 patients, respectively (all P < 0.01). p > 0.05). SVR12 was achieved by 49 patients, the total rates of SVR12
Compared with patients with other GTs infection, the GT3 patients have were 80% (49 0f 61) and 91% (49 of 54) in intention to treat (ITT) and
a higher serum level of ALT (90.1±4.21 IU/L), AST (79.02±3.08 IU/L), per protocol (PP) populations, respectively (Table 1). The SVR12 rates
TBIL (26.57±3.60 mg/dL), AFP (5.34 ng/ml), APRI (1.40) and FIB- were significantly lower in Arm A than those in Arm B in both ITT (70%
4 (3.13), but lower PLT (130×109/L) and serum ALB (40.61±0.41 g/L) & 90%, p = 0.046) and PP (81% & 100%, p = 0.021) populations.
(all P<0.01). There were no differences in age, sex, cirrhosis ratio, 5 patients who failed in achieving SVR12 were all in Arm A, among
comorbidities, HCV RNA load, PLT, ALT, AST, ALP, ALB, APRI and FIB- whom 3 experienced post-treatment virological relapse and 2 patients
4 between the patients GT3a and GT3b subtype. Multivariate Logistic had on-treatment virological failure. The genotype of these five patients
regression analysis showed that PLT≤150×109/L and ALB≤35 g/L was till GT3b while relapse. All the 61 patients included had baseline
were independent risk factors for cirrhosis. NS5A RASs A30K and L 31M, as well as 5 patients with virologic failure
Conclusion: Compared with other genotypes, HCV GT3 patients were at both baseline and relapse. In the NS5A and NS5B regions, several
mainly found in male patients in Northwest China, patients are younger new RASs emerged in these 5 patients, which haven’t been reported
and with, more severe inflammation and fibrosis stage in Northwest before (Table 2). 4 patients experienced adverse event (AE), none of
China. Low PLT count and hypoalbuminemia were independent risk which was assessed as related to study drugs.
factors for progression to cirrhosis in patients with CHC and GT 3 Conclusion: Compared to SOF/VEL plus RBV treatment, 12 weeks of
infection. SOF/VEL/VOX treatment achieved a significantly higher SVR12 rate in
Table and Figure:Figure 1.Baseline characteristics in different GTs HCV DAAs treatment-naïve HCV patients with GT3b, compensated cirrhosis
patients in Northwest China in China (NCT05467826).
Figure 2.Univariate and multivariate analyses for liver cirrhosis in GT3. Table and Figure:Figure 1.Treatment response to SOF/VEL plus RBV
and SOF/VEL/VOX.
Figure 2.Characteristics of patients with virologic failure treated by
OP0059
SOF/VEL plus RBV.
12-week treatment of sofosbuvir/velpatasvir plus ribavirin and
sofosbuvir/velpatasvir/voxilaprevir for HCV patients with GT3b
and compensated cirrhosis: a multicenter, randomized, open- OP0060
label study in China Safety and Efficacy of Direct-acting Antiviral Agents Therapy in
RUI HUANG1, FANPU JI2, YONGFANG JIANG3, SHENGHAO LI4, Patients with Liver Failure Complicated by HCV Infection
MINGHUA SU5, YUANBIN ZHONG6, HONGMEI ZU7, YANG DING8, Feilan Yang1, Lei Fu1
XIANGSHA KONG1, LAI WEI9, HUIYING RAO1 1
Xiangya Hospital, Central South University
1
Peking University Hepatology Institute, Peking University People’s Background: Direct-acting antiviral agents (DAAs) represent a
Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy breakthrough in hepatitis C treatment. However, the recommendation
for Liver Diseases, Beijing International Cooperation Base for Science of DAA therapy for patients with liver failure complicated by HCV
and Technology on NAFLD Diagnosis, 2Department of Infectious
infection remains controversial. This study aims to analyze the safety
Diseases, The Second Affiliated Hospital of Xi‘an Jiaotong University,
and efficacy of DAA therapy in such patients.
3
Department of Infectious Diseases, The Second Xiangya Hospital,
Method: A retrospective analysis was conducted on patients with
Central South University, 4Department of Hepatology, The 3rd People’s
liver failure complicated by HCV infection who were hospitalized at
Hospital of Kunming, 5Department of Infectious Diseases, the First
Affiliated Hospital of Guangxi Medical University, 6Department Xiangya Hospital of Central South University from January 1, 2017,
of Infectious Disease, The First Affiliated Hospital of Nanchang to April 30, 2024. Patients were categorized into treatment group and
University, 7Department of Hepatology, Fourth People‘s Hospital of control group based on whether they received DAA therapy. The study
Qinghai Province, 8Department of Infectious Diseases, Shengjing assessed the security and necessity of timely DAA therapy in these
Hospital of China Medical University, 9Hepatopancreatobiliary patients and compared the improvement rates in liver function and
Center, Ministry of Education Key Laboratory of Digital Intelligence MELD scores between the treatment and control groups.
Hepatology, Beijing Tsinghua Changgung Hospital, School of Clinical Result: 18 patients with liver failure complicated by HCV infection
Medicine, Tsinghua Medicine of Tsinghua University were included in the study, with 9 in the DAA treatment group and
9 in the control group. Baseline characteristics, including age (52.78
Background: Genotype (GT) 3b represents more than 50% of
vs. 59.00, p=0.448), ALT level (61.30 vs 183.80, p=0.354), AST level
patients with GT3 hepatitis C virus (HCV) infection in China, while
(159.32 vs. 377.23, p=0.075), PTA% (64.84 vs 65.38, p=0.975), HCV
GT3a predominates in most other countries. The sustained virological
RNA (6.37 vs 6.05 log10 IU/mL, p=0.639), MELD scores (17.54 vs.
18.85, p=0.469), and cirrhosis (55.6% vs 44.4%, p>0.05), showed no Background: Sodium/taurocholate co-transporting polypeptide
significant differences between the two groups. Following DAA therapy, (NTCP) belongs to the solute carrier (SLC) superfamily and is
all patients in the treatment group achieved SVR12, and TBIL, ALT, and expressed on the basolateral membranes of hepatocytes. In addition
AST values showed gradual improvement. The rate of improvement to mediating the uptake of taurocholic acid into hepatocytes, NTCP
was slightly higher in the treatment group than in the control group has been identified as the entry receptor for hepatitis B virus (HBV). In
(100% vs. 77.8%, P=0.471. Additionally, MELD scores demonstrated a this study, we aim to use the rapafucin 3D microarray to screen and
significant reduction in both the treatment and control groups. construct novel small-molecule inhibitor targeting NTCP, and evaluate
Conclusion: Timely administration of DAA therapy in patients with liver its efficacy in blocking HBV entry both in vitro and in vivo.
failure complicated by HCV infection is safe and effective in promoting Method: The rapamycin 3D microarray was used to screen for hits
recovery of liver function. targeting NTCP, and then the highly active compound JH-B10 was
Table and Figure:Figure 1.Table 1 Individual characteristics of patients synthesized through structure-activity relationship studies and
treated with DAA structural optimization. Subsequently, TCA-d4 uptake, qRT-PCR,
Figure 2.Figure 1 Dynamic changes in MELD score and HCV RNA level digital PCR, Northern blot, and immunofluorescence assays were
between treatment and control groups employed to systematically investigate the inhibitory effects of JH-B10
on taurocholic acid uptake and HBV infection in both HepG2-NTCP
OP0061 cell line and human primary hepatocytes. Simultaneously, RNA-
seq and metabolomics analysis were conducted to investigate the
Machine learning-based model used for predicting the risk of perturbation effects of JH-B10 on the host transcriptome and major
hepatocellular carcinoma in patients with chronic hepatitis B: A metabolic pathways, with the aim of evaluating its safety. Additionally,
retrospective study the potential binding modes and binding sites of JH-B10 and NTCP
Tong Wu1, Jianguo Yan2, Feixiang Xiong3, Xiaoli Liu1, Yang Zhou1, were analyzed using probe energy-based (SiteMap) as well as deep
Xiaomin Ji1, Peipei Meng1, Yuyong Jiang1, Yixin Hou1 learning-based (DeepSite) methods. Finally, the pharmacokinetic
1
Beijing Ditan hospital, Capital Medicine University, 2People’s parameters and in vivo antiviral activity of JH-B10 were assessed in
Liberation Army Fifth Medical Center, 3Beijing Ditan Hospital, Capital the liver-humanized mouse model.
Medical University Result: JH-B10 binds to the extracellular Cavity1 of NTCP through
Background: At present, predictive models that effectively stratify the hydrogen bonds and π-π stacking interactions, thereby exhibiting
risk levels for hepatocellular carcinoma (HCC) are insufficient. The aim inhibitory efficacy on HBV entry and taurocholic acid uptake with
of our study was to assess the 10-year cumulative risk of HCC among IC50 values of 63 nM and 1.8 nM, respectively. In HepG2-NTCP cells
patients suffering from chronic hepatitis B (CHB) by employing an and human primary hepatocytes, JH-B10 effectively blocks HBV
artificial neural network (ANN) infection with minimal perturbation to the host transcriptome and
Method: This research involved 1309 individuals as training group major metabolic pathways. During the infection period, intraperitoneal
from Beijing Ditan Hospital of Capital Medical University, whereas administration of 2mg/kg JH-B10 effectively maintains adequate drug
the validation group contained 408 individuals from the People’s concentrations in the mice, consequently reducing viral loads in serum
Liberation Army Fifth Medical Center. By performing a univariate and liver and inhibiting HBV infection in vivo.
analysis, we pinpointed factors that had an independent impact on the Conclusion: In the current work, we developed a novel and potent
development of HCC, which were subsequently employed to create NTCP small-molecule inhibitor JH-B10, which exhibited favorable
the ANN model. In order to evaluate the ANN model, we analyzed safety and anti-HBV entry activity both in vitro and in vivo, showing
its predictive accuracy, discriminative performance, and clinical promise for the treatment of HBV infection.
net benefit through measures including the area under the receiver Table and Figure:Figure 1.Graphic Summary
operating characteristic curve (AUC), concordance index (C-index),
and calibration curves. OP0063
Result: We incorporated nine distinct independent risk factors into
Estimation of Serum Antioxidant Activity with Liver Function tests
the ANN model’s development. Notably, in the training group, the
in patients with Hepatitis B
AUROC for the ANN model was reported as 0.929 (95% CI 0.910–
0.948), and the C-index was 0.917 (95% CI 0.907–0.927). These Saira Baloch1, Mohsin Shafi2
results were significantly superior to those of the mREACHE-B(0.700,
1
Assistant Professor, Bilawal Medical Collage, Liaquat University of
95% CI 0.639-0.761), mPAGE-B(0.800, 95% CI 0.757-0.844), HCC- Medical & Health Sciences, Jamshoro, Sindh, Pakistan, 2Assistant
RESCUE(0.787, 95% CI 0.732-0.837), CAMD(0.760, 95% CI 0.708- Professor (Institute of Health Management & Research Sciences,
0.812), REAL-B(0.767, 95% CI 0.719-0.816), and PAGE-B(0.760, Liaquat University of Medical & Health Sciences, Jamshoro, Sindh,
95% CI 0.712-0.808) models (p < 0.001). The ANN model proficiently Pakistan
categorized patients into low-risk and high-risk groups based on their Background: Abstract
10-year projections. The ANN model exhibited well clinical decision- Objective: This study aimed to assess the serum antioxidant activity
making performance, as indicated by decision curve analysis (DCA) and liver function in patients with Hepatitis B.
and calibration curves, in both the training and validation group. Method: Methods: A case-control study was used, involving fifty HBV
Conclusion: The model utilizing artificial neural networks demonstrates patients (30 males, 20 females), and fifty healthy, age- and gender-
strong performance in personalized predictions and could assist in matched control subjects. Data collection occurred between May and
assessing the likelihood of a 10-year risk of hepatocellular carcinoma August 2023. The antioxidant activity was evaluated using the DPPH
in patients suffering from chronic hepatitis B. method via ppm solution measured by UV-VIS spectrophotometer.
Table and Figure:Figure 1.Artificial neural network model page design Serum levels of alkaline phosphatase (ALP), alanine aminotransferase
accordin (ALT), and albumin were assessed by kit method on MICROLAB 300.
Figure 2.The ROC of 10-year HCC in training cohort and validation Result: Results: The results of the present study show that serum ALP
cohort levels in HBV male patients were significantly elevated compared to
controls. In contrast, serum ALP levels in HBV female patients were
found to be substantially higher than in the controls. Similarly, serum
OP0062
levels of ALT in HBV-infected male and female patients were increased
The novel and potent sodium/taurocholate co-transporting as compared to the control subjects. Antioxidant activity levels in male
polypeptide inhibitor JH-B10 blocks hepatitis B virus entry patients and female patients were shown to increase as compared to
Haibo Yu1, Juan Chen1 the controls (p<0.01).
1
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry Conclusion: Conclusion: Significant oxidative stress and impaired
of Education), Chongqing Medical University liver function were observed in male and female patients with HBV,
suggesting a link between viral infection, oxidative stress, and liver
dysfunction. virus co-infection were higher in CHB patients with ALT ≥ 40 U/L and
Keywords: Antioxidant Activity,Liver Function tests, Hepatitis B foreign nationalities. Further studies to determine the impact of HDV
co-infection on the disease progression in an HBV endemic area is
needed.
OP0064
Table and Figure:Figure 1.Fig 1. The anti-HDV positive rate according
A nationwide seroepidemiology study of hepatitis D virus infection to the geographical region in South Korea
in South Korea Figure 2.Fig 2. Predictive factors for positive anti-HDV in chronic
SungWon Lee1,2, JuYeon Cho3, JeongWon Jang4,2, JiWon Han4,2, hepatitis B patients
HeeYeon Kim1,2, JungHyun Kwon5,2, MyeongJun Song6,2, ChangWook
Kim7,2, SeulKi Han8, MoonYoung Kim8, InHee Kim9, YoungKul Jung10,
KwangIl Seo11, JeongEun Song12, JinDong Kim13
OP0065
1
Division of Hepatology, Department of Internal Medicine, College High Prevalence of Occult Hepatitis B Infection in Hepatitis C
of Medicine, Bucheon St. Mary‘s Hospital, The Catholic University of Virus-Infected Patients With Hepatocellular Carcinoma From
Korea, Bucheon, Republic of Korea, 2The Catholic University Liver Armenia
Research Center, College of Medicine, The Catholic University of Hasmik Test Ghazinyan1, Saro Khemichian2, Pascal Pineau3, Tatevik
Korea, Seoul, Republic of Korea, 3Department of Internal Medicine, Shahinyan4
Chosun University School of Medicine, Gwangju, Republic of Korea, 1
Yerevan MSC, 2Keck Medicine of USC , 3Institut Pasteur , 4LLC
4
Division of Hepatology, Department of Internal Medicine, College of Ecosense
Medicine, Seoul St. Mary‘s Hospital, The Catholic University of Korea,
Background: Co-infections of hepatitis B virus (HBV) and hepatitis C
Seoul, Republic of Korea, 5Division of Hepatology, Department of
Internal Medicine, College of Medicine, Incheon St. Mary‘s Hospital, virus (HCV) are frequent due to similar transmission routes. However,
The Catholic University of Korea, Incheon, Republic of Korea, the clinical implications of occult HBV infection (OBI) in HCV patients
6
Division of Hepatology, Department of Internal Medicine, College remain largely unexplored. OBI is defined as the presence of HBV
of Medicine, Daejeon St. Mary‘s Hospital, The Catholic University DNA in the liver or serum of patients who are HBsAg negative. This
of Korea, Daejeon, Republic of Korea, 7Division of Hepatology, study aims to determine the prevalence of OBI among chronic HCV
Department of Internal Medicine, College of Medicine, Uijeongbu patients and to assess its effects on liver disease progression, fibrosis,
St. Mary‘s Hospital, The Catholic University of Korea, Uijeongbu, and viral load dynamic
Republic of Korea, 8Department of Internal Medicine, Yonsei Method: This cross-sectional study involved 300 patients with confirmed
University Wonju College of Medicine, Wonju, Republic of Korea, chronic HCV infection, identified via polymerase chain reaction (PCR)
9
Department of Internal Medicine, Jeonbuk National University testing for HCV RNA. Blood samples were tested for HBsAg, hepatitis
Hospital, Jeonju, Republic of Korea, 10Department of Internal B core antibody (anti-HBc), and HBV DNA. OBI was defined by the
Medicine, Korea University Ansan Hospital, Korea University College absence of HBsAg coupled with detectable HBV DNA using sensitive
of Medicine, Ansan, Republic of Korea, 11Department of Internal PCR assays. Liver fibrosis was measured with transient elastography
Medicine, Kosin University College of Medicine, Busan, Republic (FibroScan), categorizing patients into fibrosis stages (F0-F4). Liver
of Korea, 12Department of Internal Medicine, School of Medicine, function was evaluated through tests for alanine aminotransferase
Daegu Catholic University, Daegu, Republic of Korea, 13Department (ALT) and aspartate aminotransferase (AST). Demographic factors,
of Internal Medicine, Jeju Halla General Hospital, Jeju, Republic of including age, gender, and alcohol use, were also analyzed. Statistical
Korea analyses utilized chi-square and t-tests to investigate the relationship
Background: Hepatitis D Virus (HDV) infection which requires the between OBI status and clinical parameters.
presence of hepatitis B virus leads to a more aggressive disease Result: OBI was identified in 15% (45 out of 300) of the HCV patients.
course in chronic hepatitis B (CHB) patients leading to an increased Those with OBI exhibited significantly elevated ALT and AST levels
healthcare burden. The estimated anti-HDV prevalence is reported compared to those without OBI (p<0.05), indicating more severe
to be 4.5% among all HBsAg-positive people, but data regarding liver damage. Additionally, patients with OBI had higher median liver
the prevalence rate of HDV in Korea is lacking. This study aimed to stiffness scores, signifying advanced fibrosis (p<0.01). Within the
elucidate the prevalence of HDV infection among chronic hepatitis B study, 35% of OBI-positive patients were classified in stages F3-F4,
patients residing in South Korea. compared to only 18% of OBI-negative patients. HCV RNA levels
Method: This prospective, multicenter cohort enrolled 2,009 were also significantly higher in the OBI group (p<0.01), suggesting
patients with CHB infection in twelve tertiary centers in South Korea. potential viral interactions that enhance HCV replication. No significant
Demographic, biochemical characteristics including liver disease differences were found in age, gender, or lifestyle factors between
status were reviewed. Competitive enzyme and chemiluminescence groups, though anti-HBc antibodies were more prevalent in the OBI-
immunoassays were used to detect anti-HDV antibodies at a central positive patients.
laboratory. Conclusion: The study highlights a notable prevalence of occult HBV
Result: The CHB patients had a mean age of 56.4 years and 62.6% of in HCV-infected patients, linked to poorer clinical outcomes, including
the patients were male. Forty-three patients (2.1%) had positive anti- higher liver enzyme levels, advanced fibrosis, and increased HCV RNA
HDV tests. Co-infection with HCV and HIV was noted in 30 patients levels. These findings indicate that OBI may exacerbate liver damage
(1.5%) and 2 patients (0.1%), respectively. The anti-HDV positive rates in chronic hepatitis C patients. Thus, screening for OBI in HCV patients
varied according to geographical region, and the seroprevalence is important for effective disease management, particularly in regions
ranged from 0 to 3.5%. (Fig.1) Among the foreign residents residing where both infections are common.
in Korea (6.2%, n=106), positive anti-HDV tests were significantly
higher compared to Korean nationals. (7.4% vs 1.9%, p=0.001)
OP0066
Positive anti-HDV test was noted in 2.7% and 1.7% of CHB patients
with and without liver cirrhosis, respectively. (p=0.164) Patients with Comparative Study of treatment of HBV ACLF Patients by tenofovir
and without hepatocellular carcinoma were positive for anti-HDV test without albumin infusion and tenofovir with albumin infusion
in 1.8% and 2.3%, respectively (p=0.539) The proportion of patients Sharker Mohammad Shahadat1, Lucky Siddiquei2, Salimur Rahman3
with liver cirrhosis and hepatocellular carcinoma was not significantly 1
Kurmitola General Hospital, 2DR. Amanat Khan Hospital, 3Anower
different according to the presence of anti-HDV. In multivariate Khan Modern Medical college Hospital
analysis, ALT≥40U/L, and foreign nationality were significant predictive Background: ACLF is an acute hepatic insult manifesting as jaundice,
factors for positive anti-HDV test. (Fig.2) complicated within 4 weeks by clinical ascites and/or encephalopathy
Conclusion: The national anti-HDV seroprevalence rate in South in a patient with previously diagnosed or undiagnosed chronic liver
Korea was lower than that of the global estimate. However, there was disease/cirrhosis, and is associated with a high 28-day mortality
a difference in the prevalence rate according to the geographical (ranging from 30% to 70).
region and in the foreign residents of Korea. The rates of hepatitis D
To compare treatment of   HBV ACLF patients by antiviral tenofovir OP0068
without albumin therapy and tenofovir with albumin infusion. Efficacy and Safety of Immune Checkpoint Inhibitor Rechallenge
Method: Total thirty HBV ACLF patients (age > 18 years with both in Unresectable Hepatocellular Carcinoma: A Retrospective,
sexes), were included in this study. Diagnosis of ACLF was confirmed Multicenter Cohort Study
by clinical condition, biochemical analysis, and virological data. The
JingKun Chen1, JiaLiang Wei2, ZhenDong Yang2, ShaoPing Liu3, Kang
cause of both chronic liver disease and acute insult in all patients were
Chen4, Chuang Qin5, Ze Su6, Lin Ye7, ShuQun Li7, JianYuan Meng8,
HBV. Patients were randomized into two groups, one group received
YingHui Wu9, CaiYi Dong1, JianHong Zhong1
tenofovir without albumin infusions and other group received tenofovir
with albumin infusion for 07 days and follows at least 03 months.
1
Hepatobiliary Surgery Department, Guangxi Medical University
Cancer Hospital, Nanning, China, 2Oncology Department, the
Result: After three months of therapy all patients had undetectable
First Affiliated Hospital of Guangxi Medical University, Nanning,
HBV DNA. At 90 days, total 24(80%) patients were survived. Out
China, 3Hepatobiliary Surgery Department, the People‘s Hospital of
of them 14(58.33%) in tenofovir with albumin infusion group and
Guigang, Guigang, China, 4Hepatobiliary Surgery Department, the
10(41.66%) in only tenofovir group. The difference was statistically
Second Affiliated Hospital of Guangxi Medical University, Nanning,
significant (p<0.05) between two groups. In 3rd follow up, Serum China, 5Hepatobiliary Surgery Department, The People‘s Hospital of
Bilirubin, MELD score and Child-Turcotte Pugh score also significantly Liuzhou, Liuzhou, China, 6Hepatobiliary Surgery Department, the First
(p<0.05) higher in only tenofovir without albumin group than tenofovir People‘s Hospital of Nanning, Nanning, China, 7Hepatobiliary Surgery
with albumin infusion group. Department, the Affiliated Hospital of Guilin Medical University,
Conclusion: In HBV-ACLF patients the use of nucleotide analogs Guilin, China, 8General Surgery Department,the Workers‘ Hospital
has clear survival benefit, which is significantly more with tenofovir of Wuzhou, Wuzhou, China, 9Oncology Department,The People‘s
with albumin infusion group. Serum bilirubin, CTP and MELD more Hospital of Wuzhou, Wuzhou, China
significantly improved with tenofovir with albumin infusion group.
Background: Immune checkpoint inhibitors (ICI) are one of the
Table and Figure:Figure 1.Treatment Outcome
standard treatment options for unresectable hepatocellular carcinoma
Figure 2.MELD Score
(HCC). However, primary or secondary resistance or severe immune-
related adverse events (irAEs) are prone to occur. This study explored
OP0067 the efficacy and safety of reinitiating ICI treatment after the occurrence
An ultrasound-based interpretable machine learning model for the of resistance or severe irAEs in patients with unresectable HCC who
classification of small hepatocellular carcinoma had previously received ICI treatment.
Method: The baseline and follow-up data of unresectable HCC
Fangying Fan1, Zhicheng Du2, Guojun Zhang2, Ping Liang3, Jie Yu3
patients who switched to another ICI treatment due to ICI resistance
1
Chinese PLA General Hospital, Beijing, China, 2Fujian Key Laboratory
or severe irAEs were retrospectively analyzed. The progression-free
of Precision Diagnosis and Treatment in Breast Cancer, Xiamen Key
survival (PFS), objective response rate (ORR), best overall response
Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen
Research Center of Clinical Medicine in Breast and Thyroid Cancers, (BOR), and irAEs of the two rounds of ICI treatment were analyzed.
Cancer Center and Department of Breast and Thyroid Surgery, Patients who received ICI treatment for the first time were defined as
Xiang‘an Hospital of Xiamen University, School of Medicine, Xiamen the ICI-1 cohort, and patients who underwent ICI rechallenge were
University, No. 2000, Xiang‘an East Road, Xiang‘an District, Xiamen, defined as the ICI-2 cohort.
China., 3Chinese PLA General Hospital, Beijing Result: From March 2019 to May 2024, there were a total of 3,611
unresectable HCC patients who received ICI treatment in nine centers
Background: Our study aimed to develop a machine learning (ML)
from Guangxi province, China. Among them, 242 patients who switched
model utilizing grayscale US to distinguish ≤3cm small hepatocellular
to another ICI drug due to ICI resistance or the occurrence of severe
carcinoma (sHCC) from non-HCC lesions.
irAEs were finally included in the analysis. There were 222 males
Method: A total of 1052 patients with 1058 liver lesions ≤3cm from
(91.7%) and 20 females (8.3%). The median age (range) of the ICI-1
55 hospitals were collected and 756 liver lesions were randomly
cohort was 50 years old (27 - 74 years old), and that of the ICI-2 cohort
allocated into train and internal validation cohorts at a 8:2 ratio for
was 51 years old (28 - 75 years old). The median treatment durations
the development and evaluation of ML models based on multilayer
of the ICI-1 and ICI-2 cohorts were 4.0 (range 0.7 - 35) and 2.9 (range
perceptron (MLP) and extreme gradient boosting (XGBoost) methods
0.7 - 22.4) months, respectively. In the two cohorts, the treatment
(ModelU utilizing US imaging features; ModelUR adding US
modalities of ICIs included ICI monotherapy (ICI -1, n = 50 (20.7%);
radiomics features; ModelURC employing clinical features further).
ICI-2, n = 45 (18.6%)) and ICI combined with targeted drugs (ICI -1, n
The diagnostic performance of three models was assessed in external
= 192 (79.3%); ICI-2, n = 197 (81.4%)). Among the 242 patients, 94.6%
validation cohort (312 liver lesions from 14 hospitals). The diagnostic
(n = 229) switched ICI drugs due to disease progression. The median
efficacy of the optimal model was compared to that of radiologists in
PFS of the ICI-1 and ICI-2 cohorts were 6.0 (95%CI 5.0 - 7.0) and 4.5
external validation cohort. The SHapley Additive exPlanations (SHAP)
(95%CI 3.6 - 5.0) months, respectively. The ORRs of the ICI -1 and ICI-
method was employed to interpret the optimal ML model by ranking
2 cohorts were 33.9% and 17.8%, respectively, and the disease control
feature importance.  
rates (DCRs) were 67.8% and 49.2%, respectively. Among the 242
Result: ModelURC based XGBoost showed the best performance
patients, 23 patients had an objective response (complete response
(AUC = 0.934; 95% CI: 0.894-0.974) in the internal validation cohort. In
(CR) and partial response (PR)) in both BOR after using ICI-1 and
the external validation cohort, ModelURC also achieved optimal AUCs
ICI-2. Moreover, there were 7 patients whose BOR was progressive
(AUC= 0.899, 95% CI: 0.861-0.931). Upon conducting a subgroup
disease (PD) during ICI-1 treatment but became CR or PR when ICI-
analysis, no statistically significant differences were observed in the
2 treatment was reinitiated. There were 45 (18.6%) and 48 (19.3%)
diagnostic performance of the ModelURC neither between tumor
patients in the ICI-1 and ICI-2 cohorts, respectively, who experienced
sizes of ≤ 2.0 cm and 2.1-3.0 cm nor across different HCC risk
grade 3 or grade 4 irAEs. No immune therapy-related death events
stratifications. ModelURC exhibited superior ability compared to
were observed during the follow-up period.
all radiologists and ModelURC assistance significantly improved the
Conclusion: ICI rechallenge due to resistance or severe irAEs can still
diagnostic AUC for all radiologists (all P < 0.0001).
bring efficacy benefits to some patients with unresectable HCC, and
Conclusion: A diagnostic model for sHCC were developed and
no new safety signals were observed.
validated using ML and US features of large cohorts. This model
significantly improves the diagnostic performance of grayscale
ultrasound for sHCC compared to experts. OP0069
Table and Figure:Figure 1.Average performance comparison of The Impact and Mechanisms of Neurofibromin 1 (NF1) on the
ModelURC and radiologists in external validation. Progression of Intrahepatic Cholangiocarcinoma
Zhengfeng Xuan1, Tao Han1, Feng Cheng1
1
The First Affiliated Hospital with Nanjing Medical University years for anti-programmed death-ligand 1 (PD-L1) therapy (94 cases,
Background: Intrahepatic cholangiocarcinoma (ICC) is a rare biliary males: 84.0%). Older age (≥65 years; adjusted odds ratio [aOR], 1.85;
malignancy, accounting for approximately 10% to 15% of all primary p < 0.05) and prior radiation therapy (aOR, 1.41; p < 0.05) increased
liver cancers. Its pathogenesis remains poorly understood, and the risk of irAEs. Anti-PD-1 (aOR, 0.28; p < 0.05) or anti-PD-L1 (aOR,
the global incidence of ICC has been steadily increasing. Current 0.18; p < 0.05) was associated with lower irAE risk compared to anti-
knowledge of ICC pathogenesis primarily focuses on genetic mutations PD-(L)1 + anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
in well-characterized oncogenes and tumor suppressor genes, such combinations. In 832 patients receiving first-line therapy, irAEs were
as TP53 and KRAS. With the advent of next-generation sequencing linked to improved OS (29.0 [95% confidence interval, 25.0–34.2] vs.
technologies, mutations in ICC tumor samples have been identified, 22.4 [95% confidence interval, 19.6–26.9] months; adjusted hazard
facilitating investigations into their impact on ICC cellular functions. ratio [aHR], 0.79; 95% confidence interval, 0.63–0.98) with the median
Method: Next-generation sequencing (NGS) was performed on 110 follow up time of 26.4 (95% confidence interval, 23.8–29.0) months.
pairs of ICC tumor samples and their corresponding adjacent non- A nine-month landmark sensitivity analysis confirmed the association
tumor tissues to identify somatic mutations. Initially, mutations in NF1 between irAEs and prolonged OS (aHR, 0.70; p < 0.05), adjusting
were compared with tumor recurrence outcomes across the 110 for confounding factors including sex, age, locoregional therapy,
patients, and the expression levels of NF1 were analyzed in both Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative
mutated and non-mutated tumor tissues. The role and mechanisms Oncology Group performance status (ECOG PS), Child-Pugh score,
of NF1 mutations in ICC development and progression were further alpha-fetoprotein levels, and the ICI regimen.
elucidated through RNA interference and transgene expression Conclusion: Advanced age, prior radiotherapy, and dual ICI were
experiments conducted in ICC cell lines (HuCCT1 and RBE). identified as risk factors for irAEs. The occurrence of irAEs was
Result: In the present study, exome sequencing revealed that the associated with improved OS during frontline immunotherapy.
gene encoding neurofibromin 1 (NF1) was among the most frequently
mutated genes. Subsequently, it was demonstrated that NF1 promotes OP0071
the proliferation and migration of ICC both in vivo and in vitro, while
Efficacy and safety of pembrolizumab and lenvatinib in
mutated NF1 significantly suppresses these processes.
combination with GEMOX via different administration routes (HAIC
Furthermore, our findings indicate that NF1 interacts with YES1 and
vs intravenous) in advanced intrahepatic cholangiocarcinoma: a
enhances the association between YES1 and EGFR, which is essential
retrospective analysis of real-world evidence
for the activation of the ERK signaling pathway. In addition, we
Hongli Yu1, Caiyun Peng1, Shuai Wang1, Yinying Lu1, Jiamin Cheng1
demonstrated that NF1 mutations impair the phosphorylation of YES1,
weaken the association between YES1 and EGFR, and consequently
1
Comprehensive Liver Cancer Center, The Fifth Medical Center of
inhibit ERK phosphorylation activity. PLA General Hospital, Beijing, China.
Finally, overexpression of NF1 was shown to attenuate the tumor- Background: The combination of PD-1 inhibitors with TKIs and
suppressive effects of Dasatinib, a YES1 inhibitor, and Gefitinib, an GEMOX has shown potential in the treatment of advanced intrahepatic
EGFR inhibitor. cholangiocarcinoma (ICC). However, the impact of different
Conclusion: In conclusion, this study provides compelling evidence administration routes of GEMOX, specifically hepatic artery infusion
that neurofibromin 1 (NF1) plays a crucial role in promoting the chemotherapy (HAIC) and intravenous (IV) injection, on the efficacy
proliferation and migration of intrahepatic cholangiocarcinoma (ICC) and safety of this regimen remains unclear.
cells, both in vivo and in vitro. This finding highlights the potential of Method: It was a retrospective study enrolling patients with advanced
NF1 as a promising therapeutic target for ICC, offering new directions ICC who received pembrolizumab and lenvatinib combined with
for targeted treatment strategies. GEMOX via either HAIC or intravenous injection. Eligibility criteria
included pathologically confirmed ICC. Patients in the HAIC group
received the drugs through a hepatic artery catheter, while those in
OP0070
the intravenous group received the standard intravenous infusion. The
Impact of Immune-Related Adverse Events on Survival in the primary endpoint was overall survival (OS), and secondary endpoints
Immunotherapy of Advanced Hepatocellular Carcinoma included progression-free survival (PFS), objective response
Nan Zhang1, Dengmin Huang2, Jiongyuan Li1, Mingjian Piao3, rate (ORR), disease control rate (DCR), which were evaluated in
Chengjie Li3, Hanping Wang4, Yuanli Liu2, Haitao Zhao1 accordance with the mRECIST criteria. Log-rank tests were employed
1
Department of Liver Surgery, Peking Union Medical College Hospital, to compare the survival data. Adverse events (AEs) were recorded
Chinese Academy of Medical Sciences & Peking Union Medical according to the CTCAE v5.0.
College, Beijing, China., 2School of Health Policy and Management, Result: Seventy-one patients were included in the analysis, with 37
Chinese Academy of Medical Sciences & Peking Union Medical patients in the HAIC group and 34 patients in the IV group. There were
College, Beijing, China., 3 Department of Liver Surgery, Peking Union no significant differences in gender, age, tumor stage, and PS score
Medical College Hospital, Chinese Academy of Medical Sciences & between the two groups. The median follow-up time was 8.8 months.
Peking Union Medical College, Beijing, China., 4Division of Pulmonary The estimated median OS in the HAIC group was 27.9 (95%CI: 16.7-
and Critical Care Medicine, State Key Laboratory of Complex Severe 39.2) months, while in the IV group it was 12.4 (95%CI: 9.9-14.9)
and Rare Diseases, Peking Union Medical College Hospital, Chinese months (p=0.026). For PFS, the median PFS in the HAIC group was 7.1
Academy of Medical Sciences & Peking Union Medical College, (95%CI: 5.3-8.9) months and in the IV group was 8.5 (95%CI: 5.1-11.8)
Beijing, China. months (p=0.743). In the HAIC group, the ORR was 35.1%, and the
Background: Immune-related adverse events (irAEs) are a significant DCR was 81.1%. In the IV group, the ORR was 41.2%, and the DCR
challenge in the use of immune checkpoint inhibitors (ICIs) for treating was 76.5%. Regarding safety, the incidence of grade 3/4 AEs was
advanced hepatocellular carcinoma (aHCC). Understanding the risk 29.7% (11/37) in the HAIC group and 35.3% (12/34) in the IV group.
factors for irAEs and their impact on overall survival (OS) is crucial for Conclusion: In the treatment of advanced intrahepatic
optimizing first-line immunotherapy and improving patient outcomes. cholangiocarcinoma with the combination of pembrolizumab,
Method: A prospective cohort of patients with aHCC treated with ICIs lenvatinib, and GEMOX, the HAIC route for delivering GEMOX may
between January 2019 and June 2023 was analyzed (NCT03892577). offer a survival advantage.
The primary endpoint was OS. Multivariable Cox regression and Table and Figure:Figure 1.Table1. Outcomes
landmark analysis assessed the association between irAEs and OS,
while logistic regression identified risk factors for irAEs.
OP0072
Result: As of June 2024, irAEs occurred in 28.9% (310/1,073) of
cases. Median age varied across treatment groups: 56.5 years for
dual ICI (36 cases, males: 88.9%), 57.0 years for anti-programmed cell
death protein-1 (PD-1) therapy (943 cases, males: 87.3%), and 55.5
Retrospective Analysis of Efficacy Differences Between Lenvatinib disease (MASLD). In this prospective registry-based study, we sought
and Sorafenib in Patients with Mid-to-Late Stage Hepatocellular to evaluate the prevalence, predictors, and impact of these symptoms
Carcinoma Complicated by Diabetes on patient-reported outcomes (PROs) in patients with MASLD from
Jiaqi Liu1, Hongli Yu1, Wenjing Wang1, Jie Han1, Weihong Ma1, Türkiye, a country with one of the highest burdens of MASLD globally.
Zhipeng Liang1, Xinfeng Zhang1, Yinying Lu1 Method: A total of 1874 Turkish patients from the Global Liver Registry
1
The Fifth Medical Center of Chinese PLA General Hospital were included. The presence of pruritus and fatigue were determined
using the respective domains of Chronic Liver Disease Questionnaire-
Background: Lenvatinib and sorafenib have been listed as first-
NASH (CLDQ-NAFLD) and the Functional Assessment of Chronic
line treatment options in guidelines such as NCCN, China’s National
Illness Therapy-Fatigue (FACIT-F). The PROs were assessed using
Health Commission, and CSCO. However, there is a lack of research
the CLDQ-NASH, FACIT-F, and the Work Productivity and Activity
on their use in patients with diabetes. This study aims to explore the
Impairment: Specific Health Problem (WPAI:SHP) questionnaires.
effectiveness and prognosis of lenvatinib and sorafenib in treating
Result: The prevalence of pruritus and fatigue at baseline was 37%
patients with diabetes and mid-to-late stage hepatocellular carcinoma
and 33%, respectively. Both symptoms were significantly associated
(HCC).
with female sex, type 2 diabetes, depression, abdominal pain,
Method: We retrospectively included patients who received
and lack of regular exercise, as well as with each other (all cross-
sorafenib and lenvatinib as first-line systemic treatment for HCC.
sectional p-values <0.01). Patients with either of these symptoms had
The primary endpoint was overall survival (OS). We collected basic
significantly worse PROs in all domains of CLDQ-NAFLD, FACIT-F
patient information and pre-treatment blood routine and biochemical
and WPAI, with impairments up to 31% (all p<0.0001) (Figure).
indicators, and performed multifactorial COX regression analysis to
In follow-up (1 or 2 years), the symptoms persisted in 47−52% of
identify risk factors affecting prognosis. Subsequently, we used the
patients with baseline pruritus and 33−39% with baseline fatigue
Kaplan-Meier (K-M) curve to evaluate the prognosis of patients with
while 18-22% of those without pruritus and 5-6% without fatigue at
mid-to-late stage HCC treated with TKIs.
baseline developed de novo symptoms. At baseline, female sex,
Result: A total of 259 patients were included: 67 received lenvatinib
type 2 diabetes, depression, abdominal pain, and the lack of regular
treatment, and 192 received sorafenib treatment. There were no
exercise were independently associated with an increased risk of both
significant differences in baseline characteristics such as gender,
pruritus and fatigue in multivariate logistic regression models; fatigue
BMI, Child-Pugh score, and tumor diameter size between the two
was also linked to younger age (all p < 0.05). Notably, there was no
groups (P>0.05). As of the follow-up date, the median follow-up time
independent association between pruritus and fatigue with obesity
was 17.9 months (interquartile range, 8.3-27.6)(Table1). The median
or advanced fibrosis (p>0.05). Independent predictors of a higher
OS for sorafenib was 19.9 months (95% confidence interval [CI],
likelihood of resolution of pruritus included the absence of fatigue and
16.7-24.2), and for lenvatinib it was 16.3 months (95% CI, 11.7-25.4),
abdominal pain, odds ratios (OR) of 0.36 (95% CI: 0.22−0.59) and 0.60
with no statistically significant difference in OS (adjusted hazard ratio
(0.39−0.91), respectively (both p < 0.05). Independent predictors of
[aHR], 0.85; 95% CI, 0.61-1.18; P=0.34). Multifactorial COX regression
resolution of fatigue were the absence of pruritus and depression, OR
identified protective factors as diabetes (HR: 0.628, 95% CI: 0.408-
= 0.40 (95% CI: 0.26−0.62) and 0.50 (95% CI: 0.32−0.79), respectively
0.965, P=0.034), leukocyte count (HR: 0.71, 95% CI: 0.59-0.87,
(both p < 0.01). The same factors, when reversed, were independently
P=0.001), albumin (HR: 0.94, 95% CI: 0.89-0.98, P=0.006), and ALT
associated with an increased risk of developing de novo pruritus or
(HR: 0.996, 95% CI: 0.993-0.999, P=0.023), while risk factors included
fatigue, and the presence of type 2 diabetes was also associated with
liver cancer complications (HR: 1.746, 95% CI: 1.023-2.98, P=0.041),
a higher risk of de novo pruritus (OR = 1.66 (1.12-2.44), p = 0.01).
neutrophil count (HR: 1.55, 95% CI: 1.224-1.962, P<0.001), vascular
Conclusion: Pruritus and fatigue are common in patients with MASLD,
invasion (HR: 1.443, 95% CI: 1.005-2.073, P=0.047), and maximal
significantly impairing PROs and often persisting over time. Regular
tumor diameter (HR: 1.043, 95% CI: 1.000-1.087, P=0.049)(Table2).
assessment and management are essential to improve patients’ well-
Using the K-M curve to analyze the prognosis of patients with and
being and functioning.
without diabetes, the results showed that patients with diabetes treated
Table and Figure:Figure 1.
with lenvatinib as first-line therapy had a prognosis comparable to
those without diabetes (P=0.97), while those treated with sorafenib
and with diabetes had a trend towards better survival prognosis than OP0074
those without diabetes, although not statistically significant (P=0.052) Effectiveness of Lifestyle Change and Silymarin in Normalizing
(Figure1). and Reducing Liver Enzyme Levels in Patients with NAFLD and
Conclusion: For patients with mid-to-late stage HCC complicated by Metabolic Syndrome: focus on body weight loss
diabetes, sorafenib is more suitable as a first-line treatment compared Wattana Sukeepaisarnjaroen1, Roongruedee Chaiteerakij2,
to lenvatinib. Elvie Victonette B. Razon Gonzalez3, Rafiz Abdul Rani4, Maria
Table and Figure:Figure 1.Baseline characteristics of patients with liver Teresita R. Andal Gamutan5, Marie Michelle Simbol Cloa6, Leilanie
cancer and diabetes treated with different TKIs and Multivariate risk Salgado7, Ekawee Sripariwuth8, Madalinee Eternity Labio9, Sakkarin
regression analysis Chirapongsathorn10, Taned Chitapanarux11, Laura Colombo12,
Figure 2.K-M survival curve Nageswara Rao Yeluchuri12, Sanjay Hadigal12, Amit Ravindra
Birajdar12
OP0073 1
Khon Kaen University, 2Chulalongkorn University, 3West Visayas State
Pruritus and fatigue in patients with metabolic dysfunction University Medical Center, 4Universiti Teknologi MARA, 5De La Salle
associated steatotic liver disease (MASLD): Data from the Global Medical and Health Sciences Institute, 6Manial Doctors Hospital,
7
Cebu Doctor‘s University Hospital, 8Naresuan University , 9Makati
NASH/MASH Registry
Medical Center 2, 10Phramongkutklao Hospital, 11Chaiang Mai
Yusuf Yilmaz1,2,3, Caglayan Keklikkiran1,3, Andrei Racila1,4,5, Maria University, 12viatris
Stepanova1,4,5, Zobair Younossi1,4
Background: While lifestyle changes and weight loss are key
1
The Global NASH Council, Center for Outcomes Research in
components of standard care (SoC) for managing non-alcoholic fatty
Liver Diseases, Wahington DC, USA, 2Institute of Gastroenterology,
Marmara University, İstanbul, Türkiye, 3Department of liver disease (NAFLD), they are often difficult to achieve and maintain
Gastroenterology, School of Medicine, Recep Tayyip Erdoğan long-term, and patient compliance tends to be suboptimal. A recent
University, Rize, Türkiye , 4Beatty Liver and Obesity Research observational study (CT.gov ID: NCT05051527) investigated the use
Program, Inova Health System, Falls Church, VA, USA, 5Center for of medical-grade silymarin for NAFLD management in patients with
Outcomes Research in Liver Disease, Washington DC, USA metabolic syndrome (MetS).
Method: This study was conducted at 12 locations across Thailand,
Background: Despite being underappreciated, pruritus and fatigue
the Philippines, and Malaysia, involving adult NAFLD patients with at
are not uncommon in metabolic dysfunction-associated steatotic liver
least one elevated liver enzyme and confirmed MetS. Patients received
standard care for NAFLD (dietary and exercise advice) along with a statistically significant.
140 mg silymarin three times daily for 6 months. Patient assessments Table and Figure:Figure 1.Table 1. Differences between normal and
were carried out at the T1 visit (3 months) and the T2/End of Study patients with NAFLD under the age of 40
(EOS) visit (6 months). Proportion of patients with change in at least Figure 2.Table 2. Differences between normal and patients with NAFLD
one liver enzyme level was the endpoint. This subgroup analysis aged 41-60 years
reports the effectiveness of the treatment in patients who lost at >5%
of body weight compared to those who did not.
OP0076
Result: Out of the 360 NAFLD patients enrolled in the study, 56%
were male. The average age was 49.6 years (SD ±12.8), the average Real-World Evaluation of Therapy with Saroglitazar in MASLD-
weight was 78.7 kg (SD ±16.0), and the average BMI was 29.7 kg/m² Associated Compensated Advanced Chronic Liver Disease
(SD ±4.9). At baseline, the proportion of patients with abnormal AST, (cACLD) : An Open-Label, Single-Center Study
ALT, and GGT levels were 45% (161/360), 90% (324/360), and 47% Sujit Chaudhuri1, Agnibha Dutta1, Santosh Anand2
(170/360), respectively. 1
Manipal Hospitals, Broadway, Saltlake, Kolkata, India, 2Research
In patients who lost >5% of their body weight (n = 54), 72% had overall Scholar, Department of Pharmaceutical Sciences, Shri Venkateshwara
normalization of abnormal liver enzymes (AST normalized in 68%, ALT University, Gajraula, UP, India
in 64%, GGT in 55%). Additionally, 93% of patients showed a reduction Background: Metabolic dysfunction-associated steatotic liver disease
in elevated liver enzymes (AST reduced in 89%, ALT in 94%, GGT in (MASLD) can progress to advanced fibrosis and compensated
86%). Conversely, among the patients who did not achieve weight cirrhosis, with potential for decompensation if untreated. Saroglitazar
reduction (n = 255), 42% of the patients experienced normalization (Bilypsa®), a dual PPARαγ agonist, targets metabolic and inflammatory
of liver enzymes (AST normalized in 38%, ALT in 29%, GGT in 23%). pathways, showing promise in halting or reversing disease progression
Furthermore, 75% of patients showed a reduction in elevated liver in advanced MASLD stages. The Agile 4 Score, a reliable non-invasive
enzymes (AST reduced in 73%, ALT in 67%, and GGT in 68%). tool, complements other diagnostic methods in MASLD management.
Compared to patients who did not achieve weight reduction, patients This study aims to evaluate the impact of Saroglitazar in patients with
who lost >5% of their body weight experienced significantly higher advanced fibrosis and compensated cirrhosis.
normalization rates (OR (95% CI) = 3.66 [1.92, 6.97], P< 0.0001) Method: This study evaluated 86 MASLD associated compensated
and reduction rates (OR (95% CI) = 4.19 [1.46, 12.05], P= 0.0044) of advanced chronic liver disease (cACLD) patients diagnosed with
elevated liver enzymes. noninvasive Agile 4 Score ((≥ 0.251) or fibroscan imaging (LSM>14
Conclusion: It is well known that weight loss is one of the most kPa) or both and thorough clinical investigations. The patients were
important determinants for improvement during NAFLD management. treated with Saroglitazar (Bilypsa®) in the dose of 4mg daily and
Our study confirmed that achieving >5% weight loss leads to better monitored clinically, biochemical , imaging parameters and for
clinical outcomes compared to those who did not, highlighting the changes in liver stiffness (LSM), steatosis (controlled attenuation
critical role of lifestyle changes in managing this condition. Biochemical parameter, CAP) from baseline to follow-up visits every 6 months, up
improvements were also observed in patients without weight loss, to 144 weeks. During every follow up visits , patients were assessed
indicating that silymarin may support patients reach therapeutic goals. for any evidence of hepatic decompensations like jaundice, ascites,
encephalopathy or variceal bleeding . Statistical analysis was
OP0075 conducted using a paired sample t-test (95% CI, p<0.05 considered
significant). Safety was systematically monitored at each follow-up visit
Cardiovascular disease and age-related Non-alcoholic fatty liver
by documenting the frequency and severity of any adverse events.
disease in Mongolia
Result: At 24 weeks (n=74), 48 weeks (n=68), 96 weeks (n=53), and
Byambatsetseg Togtuunbayar1,2,3, Badamsuren Erdene-Ochir1, 144 weeks (n=41), liver stiffness (LSM) improved by 3.9 kPa (15.2%,
Amarsanaa Jazag4,1, Baatarkhuu Oidov5,1, Erdenebayar Gonchig, p=0.08), 9 kPa (35.4%, p<0.001), 13.2 kPa (51.9%, p<0.001), and
Dolgormaa Batsaikhan, Ganchimeg Gelenkhuu 13.7 kPa (53.9%, p<0.001), respectively. Steatosis, in terms of CAP
1
Happy Veritas Hospital Ulaanbaatar Mongolia, 2Department of improved by 22.2 dB/m (7.9%, p<0.05), 23.9 dB/m (8.5%, p<0.05),
Infectious Diseases, Mongolian National University of Medical 47.9 dB/m (17.1%, p<0.001), and 45.9 dB/m (16.3%, p<0.001).
Sciences, 3Mongolian Association for the Study of Liver Disease, Significant improvements were also observed in metabolic parameters
4
MASLD, Mongolian Association for the Study of Liver Diseases (triglycerides, LDL, total cholesterol) and liver enzymes (AST, ALT).
Ulaanbaatar Mongolia,, 5Mongolian National University of Medical Among the 41 patients followed for 144 weeks, no signs of hepatic
Sciences
decompensation were observed. Only minor adverse effects were
Background: In recent years, metabolic disorders and non-alcoholic reported in 2 patients, with one patient experiencing mild skin rashes
fatty liver disease caused by unhealthy lifestyles will increase. and another having loose motions, both resolving after a brief treatment
Therefore, we conducted a study determine whether the NAFLD is a pause.
risk factor for cardiovascular disease for the first time in our country. Conclusion: This study demonstrates that Saroglitazar (Bilypsa®)
Method: A random sample of 484 patients with hepatic and non- significantly improves liver stiffness and reduces steatosis in MASLD-
hepatic diseases was used to determine the degree of liver fibrosis associated cACLD, diagnosed via Agile 4 Score and FibroScan
and fatty liver using the Fibrotouch/transient elastography/ device, and imaging. Over 144 weeks, consistent improvements suggest that
the clinical cardiovascular disease was determined by questionnaire, Saroglitazar may halt or reverse disease progression. The treatment
categorized by age group. was well-tolerated, with no unexpected adverse events. Further
Result: Chest pain was found in 20% of normal patients up to 40 randomized controlled trials are needed to confirm these results.
years of age, in 32% of NAFLD patients, in 35% of normal patients with Table and Figure:Figure 1.Fig : Changes in Liver Stiffness Measurement
hypertension, in 58% of NAFLD patients with hypertension, in 30% of over treatment followup
normal patients with left-arm numbness, in 33% of NAFLD patients with Figure 2.Table: Baseline Population Demography (n=86)
left-arm numbness, in 56% of normal patients with arrhythmia, and in
51% of NAFLD patients patients with arrhythmia. Table 1
OP0077
In normal patients up to 41-60 years of age, chest pain was found in
28% of normal patients, in 30% of NAFLD patients, in 46% of normal ASSESSMENT OF FIBROSIS CHANGE RATES IN MASH DRUG-
patients with hypertension, in 62% of NAFLD patients with hypertension, TRIAL PLACEBO-ARM VIA PATHOLOGIST READINGS AND
in 39% of normal patients with left-arm numbness, in 37% of NAFLD qFIBROSIS VALUES
patients left-arm numbness, in 48% of normal patients with arrhythmia, Kutbuddin Akbary1, Dean Tai1, Galvin Gan1, Stephen A Harrison2, Julie
and in 58% of NAFLD patients with arrhythmia. Table 2 Dubourg3,4
Conclusion: Non-alcoholic fatty liver disease is a risk factor for 1
HistoIndex Pte Ltd, 2Pinnacle Clinical Research, 3Summit Clinical
cardiovascular disease. But the difference in the control group is not Research, 4Sagimet Biosciences
Background: Metabolic dysfunction-associated Steatohepatitis to qFibrosis scoring. The analysis of fibrotic structures, which
(MASH) drug trials face challenges in assessing treatment response incorporated a correction to account for the significant reduction in
due to substantial variability in the placebo group response rates, hepatic fat observed with EFX treatment, included a detailed zonal
observed both in pathologist readouts and qFibrosis continuous values analysis across the following defined hepatic zones: portal, peri-portal
(qFc). This significant variability hinders standardizing treatment effect (zone 1), peri-sinusoidal (zone 2), central, and peri-central (zone 3).
and sample size calculations in MASH clinical trials, and challenges Result: Steatosis-corrected qFibrosis stage revealed improvements
the interpretation of the “true” treatment effect. The placebo cohort in W24 fibrosis for 60% and 66% of subjects in the 28mg and 50mg
allows for describing the natural course of the disease. This study aims EFX groups respectively, versus 18% for placebo. Among subjects
to describe the placebo response rates in MASH drug trials, focusing with F2 or F3 fibrosis at BL, significant reductions in fibrotic area were
on pathologist readouts (NASH-CRN stage) versus qFc. noted primarily in the peri-portal (zone 1) and peri-sinusoidal (zone 2)
Method: Anonymized placebo responses from 5 MASH Phase 2b drug regions. This was most evident in F3 subjects who had significantly
trials are detailed, using NASH-CRN readouts and qFc values. Fibrosis less fibrosis in zones 1 and 2 after 24 weeks treatment with either
regression, progression, and no-change results are presented. NASH- 28mg or 50mg EFX, compared to placebo. The quantitative regression
CRN-based regression/progression was defined as a 1-stage change of fibrosis in these two zones was evident in subjects whether or not
in fibrosis at end-of-treatment (EOT) compared to baseline (BL). improvements in fibrosis had been seen by conventional pathologist
qFc, regression/progression was determined based on the change staging, highlighting the consistency and sensitivity of AI-enhanced
in qFc values at EOT compared to BL, using the standard error of imaging in detecting subtle but significant reductions in fibrosis for
mean (SEM). No-change in qFc is change of qFc values within SEM EFX-treated subjects.
at EOT compared to BL, and no-change in NASH-CRN stage in EOT Conclusion: Detailed zonal analysis provided by digital pathology
compared to BL, respectively. tools like qFibrosis offers valuable insights into specific patterns of
Result: Based on qFc values, average fibrosis regression rate from BL fibrosis reduction associated with EFX treatment of subjects with F2
to EOT in the placebo group was 38% (range: 19% - 49%), compared and F3 MASH.
to an average regression rate of 21% (range: 7% - 30%) based on Table and Figure:Figure 1.Figure 1A. Fibrosis Improvement ≥1-stage
NASH-CRN staging. Fibrosis progression rates based on NASH-CRN at Week 24
averaged 18% (range: 12%-29%), contrasting with qFc at 45% (range: Figure 2.Change in fibrosis from BL to Week 24 for different zones of
33%-76%). The percentage of patients with stable diseases was the liver
higher when assessed by the NASH-CRN staging approach (average
62%, range: 46%-81%), compared to qFc (average: 17%, range: 33%- OP0079
76%).
Conclusion: This study contributes to our understanding of the Association between triglyceride-glucose index and short-term
variance on placebo responses based on both pathologists’ staging mortality among patients with acute-on-chronic liver failure
and qF continuous values. The data underscores considerable Qiao Zhang1, Yamin Wang1, Juan Li1, Yushan Liu1, Xiaonan Wu1,
variability in placebo response across different studies, reflected in Xiaoli Zhang1, Yingli He1,2
pathologist staging and qFc values. The proportion of patients meeting 1
Hepatology Unit, Department of Infectious Diseases & Clinical
the definition of progression or regression was higher when assessed Research Center for Infectious Diseases, the First Affiliated Hospital
by qFc values . As a result, qFc decreased the proportion of patients of Xi’an Jiaotong University, Xi’an, Shaanxi, China., 2Shaanxi Clinical
considering with no change in fibrosis. Both NASH-CRN staging and Medical Research Center of Infectious Diseases & National Regional
qFibrosis-based continuous values are essential considerations in Infectious Diseases Center Co-constructed by National Health
understanding placebo responses in MASH drug trials. Commission of PRC and People‘s Government of Shaanxi Province,
Table and Figure:Figure 1.Figure 1: Biopsies from the placebo group of Xi’an, Shaanxi, China.
5 MASH Phase 2b trials showing rates of Progression [A], No-change Background: Acute-on-chronic liver failure (ACLF) is a life-threatening
[B], and Regression [C] of fibrosis as per the pathologist-based NASH- syndrome characterized by high short-term mortality, where metabolic
CRN staging and qFibrosis continuous values. disturbances, particularly in glucose and lipid metabolism, play a
critical role. This study aimed to evaluate the association between
the triglyceride-glucose (TyG) index and short-term mortality in ACLF
OP0078
patients, proposing it as a readily accessible prognostic biomarker.
AI and digital-based pathology corroborate reduction in fibrosis Method: A total of 136 ACLF and 101 non-ACLF patients were enrolled
observed by conventional pathology with efruxifermin treatment in the Registry Study for Optimal Management of Liver Failure in the
of patients with F2-F3 MASH in the HARMONY study Chinese Population (RESOLVE-C) between 2013 and 2024. TyG index
Mazen Noureddin1, Dean Tai2, Elaine Chng2, Yukti Choudhury2, values were calculated from fasting blood glucose and triglyceride
Cynthia Behling3, Pierre Bedossa4, Doreen Chan5, Mark Burch5, levels. Kaplan-Meier survival analysis, Cox regression, and restricted
Kimberly Barrett5, Reshma Shringarpure5, Erik Tillman5, Timothy cubic spline (RCS) analyses were used to evaluate the association
Rolph5, Kitty Yale5, Stephen A Harrison6 between TyG and short-term mortality. Dynamic changes in TyG levels
1
Houston Research Institute; Houston Methodist Hospital, Houston, were tracked from admission to 180 days in surviving patients.
TX, USA, 2HistoIndex, Singapore, 3Department of Pathology, Sharp Result: The TyG index was significantly lower in ACLF patients
Memorial Hospital, San Diego, CA, USA, 4Liverpat, Paris, France, compared to non-ACLF patients (8.38 ± 0.81 vs. 8.66 ± 0.94, p < 0.05,
5
Akero Therapeutics, San Francisco, CA, USA, 6Pinnacle Clinical Figure 1A)
Research, San Antonio, TX, USA The TyG index for the ACLF-1, ACLF-2, and ACLF-3
Background: Efruxifermin (EFX), a bivalent Fc-FGF21 fusion protein, groups was 8.72 (8.25, 9.03), 8.16 (7.78, 8.68), and 7.78 (7.21, 7.91),
demonstrated significant improvement in fibrosis by conventional respectively, showing a significant decreasing trend with increasing
pathology in the HARMONY trial (NCT04767529) for both 28mg and ACLF grade (p < 0.05, Figure 1B).
50mg groups. This was associated with significantly reduced hepatic At admission, the TyG index was significantly higher in
fat content reflected by significant improvement in key secondary surviving patients than in non-surviving patients for both 28-day (8.48
endpoints including resolution of MASH and the composite of ± 0.85 vs. 8.19 ± 0.71, p < 0.05, Figure 1C) and 90-day outcomes
fibrosis improvement and MASH resolution. This post-hoc analysis (8.55 ± 0.84 vs. 8.21 ± 0.75, p < 0.05, Figure 1D).
investigates the fibrosis changes across liver zones, utilizing Second The TyG index was negatively correlated with INR, as well
Harmonic Generation/Two-Photon Excitation Fluorescence (SHG/ as with the MELD-Na, CLIF-C ACLF, and COSSH-ACLF II scores (r =
TPEF) microscopy and HistoIndex’s proprietary qFibrosis scoring, and -0.557, -0.327, -0.308, and -0.341, respectively; all p < 0.001, Figure
concurrence with conventional pathologist consensus scoring. 1E-H).
Method: 108 paired, unstained biopsies available at baseline (BL) The multivariate Cox regression analyses showed higher
and week 24 (W24) were analyzed by SHG/TPEF imaging coupled TyG levels were independently associated with improved 28-day (HR:
0.657, 95% CI: 0.470–0.918, p = 0.014) and 90-day (HR: 0.641, 95% Department of Liver Diseases, Shanghai Public Health Clinical
1

CI: 0.484–0.850, p = 0.002) survival. Center, Fudan University, 2Department of Infectious Diseases,
RCS analysis revealed a non-linear association between TyG Huashan Hospital, Fudan University, 3Department of Infectious
levels with 28-day and 90-day mortality (p for non-linearity = 0.026 and Diseases, Shanghai Public Health Clinical Center, Fudan University
0.029, respectively). Background: Acute-on-chronic liver failure (ACLF) is a clinical
Dynamic monitoring revealed that TyG levels decreased syndrome characterized by acute hepatic decompensation,
during the acute phase within the first 14 days following admission and extrahepatic organ injury, and high short-term mortality in patients
subsequently increased during the recovery phase. with chronic liver diseases (CLD). Circulating cell-free mitochondrial
Conclusion: The TyG index is significantly associated with short- DNA (cf-mtDNA) has emerged as a novel biomarker with prognostic
term prognosis in ACLF patients, with higher levels linked to improved significance for various inflammatory and infectious diseases. This
survival outcomes. As a simple and cost-effective biomarker, the study aims to assess the predictive value of cf-mtDNA in the clinical
TyG index demonstrates potential for improving risk stratification and outcomes of hepatitis B virus-related ACLF (HBV-ACLF).
guiding individualized management strategies in patients with ACLF. Method: A total of 320 HBV-ACLF patients were included in
Table and Figure:Figure 1.Figure 1 Association between TyG and study population, with 192 patients in the derivation cohort and 128 in
disease severity in ACLF patients. (A) Comparison of TyG levels the validation cohort. Plasma cf-mtDNA levels were quantified using
between ACLF and Non-ACLF patients; (B) TyG levels across different qPCR.
ACLF grades (ACLF-1, ACLF-2, ACLF-3); (C) TyG levels in 28-day Result: Plasma cf-mtDNA levels in HBV-ACLF patients were
non-survivors vs. Survivors; (D) TyG levels in 90-day non-survivors significantly higher than in healthy controls and CLD patients (3.95
vs. survivors; (E–H) Correlation between TyG levels and INR, as well vs 2.82 vs 2.79 log10 copies/μL, p < 0.001). Plasma cf-mtDNA levels
as other prognostic scores. TyG, triglyceride-glucose; ACLF, acute- were positively correlated with several prognostic models for HBV-
on-chronic liver failure; INR, international normalized ratio; MELD-Na, ACLF, including the Model for End-stage Liver Disease (MELD) (r =
model for end-stage liver disease-sodium; CLIF-C ACLFs, Chronic 0.27, p < 0.001), the Chronic Liver Failure-Consortium ACLF (CLIF-C
Liver Failure-Consortium ACLF score; COSSH-ACLF IIs, Chinese ACLF) score (r = 0.36, p < 0.001), and the Chinese Group on the Study
Group on the Study of Severe Hepatitis B-ACLF II score. *p < 0.05, of Severe Hepatitis B-ACLF (COSSH-ACLF) score (r = 0.33, p < 0.001).
*** p < 0.001. Patients who died within 90 days had significantly higher plasma cf-
mtDNA levels than the survival group (4.18 vs 3.78 log10 copies/
OP0080 μL, p < 0.001). Sequential measurements of cf-mtDNA showed
a significant decrease in survivors (4.00 to 3.78 log10 copies/μL,
High incidence of liver-related events and hospitalizations in
p = 0.019), while non-survivors maintained persistently elevated levels
patients with viral- and alcohol-associated cirrhosis and grade 1
with minimal change (4.19 to 4.15 log10 copies/μL, p = 0.359). In the
ascites
training and validation cohorts, the AUROCs of plasma cf-mtDNA for
Haiyu Wang1, Jinlin Hou and Jinjun Chen predicting 90-day mortality in HBV-ACLF patients were 0.748 and
1
Nanfang Hospital, Southern Medical University 0.771, respectively. Combining cf-mtDNA with the COSSH-ACLF
Background: The natural course of cirrhotic patients with grade score enhanced the predictive accuracy for 90-day mortality, with an
1 ascites has not been well-studied. We aimed to study the risk AUROC of 0.914 in the derivation cohort and 0.930 in the validation
of liver-related outcomes in cirrhotic patients with grade 1 ascites in a cohort.
prospective cohort. Conclusion: Cf-mtDNA is a superior biomarker for predicting
Method: Cirrhotic patients due to chronic viral hepatitis and/or 90-day mortality in HBV-ACLF. Its association with multi-organ
alcohol-associated liver disease were enrolled from April 2019 to failure and disease severity highlights the potential utility in early risk
October 2022 and followed every 6 months until October 2023. assessment and treatment optimization.
All underwent imaging for ascites detection. Liver-related events Table and Figure:Figure 1.Figure 1 (A) Comparison of plasma cf-mtDNA
including decompensation, hepatocellular carcinoma, death and levels among HC, CLD, and HBV-ACLF patients. (B) Comparison of
hospitalizations were recorded. plasma cf-mtDNA levels between 90 day non-survivors and survivors
Result: A total of 2551 patients were screened, and 1843 were of HBV-ACLF in the derivation and validation cohorts.
included in this post hoc analysis. At baseline, 217 (11.8%) patients Figure 2.Figure 2 Kaplan-Meier curves of survival probability stratified
had grade 1 ascites, among whom 49 (22.6%) patients experienced by plasma cf-mtDNA levels in the derivation (A) and validation cohorts
liver-related events and had 122 hospitalizations at a median follow- (B). AUROC comparison of the prognostic accuracy between the
up of 35 months (IQR 23–47). Comparing with patients with no combined score and other established prognostic scores in predicting
ascites (n=1371), those with grade 1 ascites had significantly higher 90‐day mortality in the derivation (C) and validation cohorts (D).
incidence rate of liver-related events (p<0.0001, HR=4.79), all-
cause mortality (p<0.0001, HR=9.18) and hospitalization (p<0.0001, OP0082
HR=5.36); meanwhile, patients with grade 1 ascites and those with
grade 2/3 ascites (n=255) had comparable liver transplantation Optimization of timeframe criteria to define recompensation and
free survival (p=0.189, HR=1.53) and liver-related hospitalization stable recompensation in patients with HBV-related cirrhosis
(p=0.572, HR=1.11). Additionally, patients with grade 1 ascites had Zhiying He1, Xiaoning Wu1, Shuai Xia1, Jialing Zhou2, Zhongjie Hu3,
poorer outcomes than patients without ascites. The findings were Chunqing Zhang4, Yanqin Hao5, Wei Rao6, Yan Huang7, Jing Wang8,
confirmed in a retrospective cohort (n=285). Yongfeng YANG9, Xiaojuan Ou1, Bingqiong Wang10, Jidong JIA1, Hong
Conclusion: Compensated liver cirrhosis with grade 1 ascites had You1
poorer liver-related outcomes than without ascites, and comparable to 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
those with grade 2/3 ascites. University; Beijing Key Laboratory of Translational Medicine on
Table and Figure:Figure 1.Table 1. Characteristics of patients in the Liver Cirrhosis; State Key Lab of Digestive Health; National Clinical
prospective cohort stratified with presence and grade of ascites at Research Center of Digestive Diseases, Beijing, China., 2Beijing
inclusion. Friendship Hospital, Capital Medical University, 3Department of
Figure 2.Abstract figure Critical Care Medicine of Liver Disease, Beijing YouAn Hospital,
Capital Medical University, No. 8 YouAn Men Wai Street, Beijing,
1
00069, Fengtai, China, 4Department of Gastroenterology, Provincial
OP0081 Hospital Affiliated to Shandong First Medical University, 5Department
Circulating cell-free mitochondrial DNA as a prognostic biomarker of Infectious Diseases, The First Hospital of Shanxi Medical University,
in patients with HBV-related acute-on-chronic liver failure Taiyuan, China, 6 Division of Hepatology, Liver Disease Center, the
Affiliated Hospital of Qingdao University, Qingdao 266600, China,
Qiankun Hu1, Jiajia Han2, Chong Chen 3, Xueyun Zhang 2, Yuxian 7
Department of Liver and Infectious Diseases, Xiangya Hospital
Huang 1,2
Central South University, Changsha 410013, China, 8Depatment of 95.2% and PPV at 90.3%. Meanwhile, ICG-R15<4% could exclude
Gastroenterology, The Second Affiliated Hospital of Baotou Medical 41.9% (26/62) non-CSPH with sensitivity at 95.5% and NPV at 92.9%.
College, Baotou 014030, China, 9Liver Disease Department, the Performances of ICG-R15 for ruling-in or for ruling-out CSPH was also
Second Hospital of Nanjing, Affiliated to Medical School of South East validated with sensitivity analysis regarding to etiology control/removal,
University, Nanjing, Jiangsu, China, 10Beijing Friendship Hospital gender, age, overweight and liver functions in total set of patients.
Background: Timeframe of 12 months in concept of recompensation Conclusion: PDD estimated ICG-R15 ≥14% was able to correctly
by Baveno VII consensus had not been validated to ensure long-term identify CSPH and ICG-R15 <4% was able to safely exclude non-CSPH
stability of recompensation and need to be optimized. in cACLD patients. Multicenter validation studies were warranted.
Method: In this retrospective multi-center cohort study, treatment- Table and Figure:Figure 1.ROC curves. (A) ROC curves of ICG-R15
naïve HBV-related decompensated patients were enrolled at the and EHBF for CSPH diagnosis in training set. Level of significance:
onset of their first decompensation and followed up to 6 years for p =0.127 (Delong’s test). (B) ROC curves of ICG-R15 and EHBF for
every 6 months. Recompensation was defined as maintaining free of CSPH diagnosis in validation set. Level of significance: p =0.413
decompensation events for one (1-year criteria), two (2-year criteria), (Delong’s test). ROC, receiver operating characteristic curve; ICG-R15,
or three years (3-year criteria), along with liver function improvement indocyanine green 15-minute retention rate; EHBF, effective hepatic
to Child-Pugh A and/or MELD < 10 within the first 3 years of anti-HBV blood flow; CSPH, clinically significant portal hypertension; AUC, area
therapy. Stable recompensation was determined as maintenance of under the receiver operating characteristic curve; CI, confidence
free decompensation for another three years after recompensation. interval.
Result: In 243 treatment-naïve HBV-related decompensated patients,
79.0% (192/243), 60.5% (147/243) and 45.3% (110/243) of patients OP0084
achieved recompensation according to 1-year, 2-year and 3-year
A Novel Non-Invasive Diagnostic Model for High-Risk Varices in
criteria. During extended 3-year follow-up post-recompensation, the
Cirrhosis: A Multicenter Retrospective and Prospective Study
proportion of stable recompensation differed within those timeframe
criteria (1-year: 67.2% vs. 2-year: 76.9% vs. 3-year: 81.8%, P = 0.014), Wang Yanhu1, Junliang Fu2
but the difference between 2-year and 3-year criteria showed no
1
Chinese PLA General Hospital, 2the Fifth Medical Center, Chinese
statistical meaning (P = 0.538). Compared to recompensated patients PLA General Hospital
defined by 1-year criteria in multivariate analysis, the odds ratio for Background: The non-invasive diagnostic method recommended by
stable recompensation was 1.943 (P = 0.039) and 2.16 (P =0.037) in the Baveno VI and Baveno VII consensus for the diagnosis of high-risk
patients by 2-years and 3-0 years criteria. Furthermore, recompensated varicose veins (HRV) have limited endoscopy sparing rates or require
patients exhibited highest rate of further decompensation of 28.4% additional diagnostic device. This study aims to develop a novel
in 1-year criteria, compared to 16.9% and 14.2% in 2-year and diagnostic model to improve the diagnostic efficiency of HRV without
3-year criteria (P = 0.016). Specifically, further decompensation was requiring extra device.
dominated by further ascites (3-year rates: 24.4%, 14.1% and 13.5%, Method: A retrospective cohort and a prospective cohort were
P = 0.053). established, respectively. Data including endoscopy, abdominal
Conclusion: The timeframe criteria of at least 2 years free of ultrasound, liver stiffness measurements (LSM) by iLivTouch transient
decompensation was recommended for defining recompensation, elastography, and laboratory examination results were collected
as recompensated patients defined by a shorter 1-year criteria from cirrhotic patients aged 18-65 years. Univariate and multivariate
recommended by Baveno VII had lower proportion of stable logistic regression analyses were conducted to identify independent
recompensation and higher rate of further decompensation. predictors. The area under the receiver operating characteristic curve
(AUC) was calculated. A new diagnostic model was developed in the
OP0083 retrospective cohort as training cohort and validated in the prospective
cohort as validation cohort.
Indocyanine green clearance test via pulse dye densitometry for Result: As of June 19, 2024, the study included 3,405 patients with
portal hypertension diagnosis in compensated advanced chronic liver cirrhosis from 22 centers, comprising 2,862 patients in the training
liver disease patients cohort and 543 patients in the validation cohort. In the training cohort,
Miaoxia Liu1, Xiaofeng Zhang, Xiao Cheng, Qinjun He, Haiyu Wang, the Baveno VI (BV6) and Expanded Baveno VI (E-BV6) criteria spared
Beiling Li, Wenfan Luo, Junying Li, Hui Li, Zimo Lin, Jiankang Song, 17.68% and 29.00% of endoscopies, respectively. The HRV missing
Weibin Wang, Jing Huang, Yali Ji, Damei Zhou, Wanjun Xie, Qiaolan rates were 2.53% for BV6 and 7.59% for E-BV6. After adjusting the
Yang, Minghan Tu, Xiaoqin Luo, Xiaoyong Zhang, Huadong Yan, cutoff values for LSM and platelet count (PLT), we established a
Jinjun Chen Modified Baveno VI (M-BV6) criteria with an endoscopy sparing rate
1
Department of Hepatology Unit and Infectious Diseases, Nanfang of 22.68%, which is higher than BV6, with an equivalent HRV missing
Hospital, Southern Medical University rates of 2.53%. In the validation cohort, the endoscopy sparing rates
Background: Indocyanine green (ICG) clearance test calculated with for BV6 and M-BV6 were 26.34% and 32.04%, respectively, with HRV
repeated blood measurements is able to identify clinically significant missing rates of 1.83% for both.
portal hypertension (CSPH). We aimed to test the performance of Univariate and multivariate logistic regression analyses revealed that
pulse dye densitometry (PDD) estimated ICG 15-minute retention rate spleen area (SA) was an independent predictor for HRV diagnosis.
(ICG-R15) for CSPH diagnosis in compensated advanced chronic liver The AUCs for PLT, LSM, and SA for diagnosing HRV were 0.833,
disease (cACLD). 0.715, and 0.794, respectively. Then BV6-SA diagnostic model was
Method: cACLD patients received PDD estimated ICG-R15 and developed by incorporating SA into the BV6 criteria. Using this model,
hepatic venous pressure gradient (HVPG) measurement were the endoscopy sparing rates were 64.35% in the training cohort and
prospectively investigated. Performance of ICG-R15 for identification 74.68% in the validation cohort, with HRV missing rates of 4.26% and
of or excluding CSPH were established with monocentric set and 4.81%, respectively. The MBV6-SA model also significantly enhanced
validated with bicentric set of patients. endoscopy sparing rates compared with BV6.
Result: In the training set (n=96), ICG-R15 significantly correlated with Conclusion: This study is the first to validate the applicability of LSM
HVPG (r= 0.6514, P<0.001) with area under the receiver operating measured by iLivTouch in diagnosing HRV with the BV6 criteria, and
characteristic for CSPH diagnosis at 0.878 (0.808-0.947), and M-BV6 further improved the endoscopy sparing rates compared to
ICG-R15 ≥14% could identify 63.6% (28/44) CSPH with specificity at BV-6. Most importantly, the BV6-SA model and MBV6-SA model we
96.2% and positive prediction value (PPV) at 93.3%. ICG-R15<4% was established substantially increased the endoscopy sparing rates with
able to exclude 40.4% (21/52) non-CSPH with sensitivity at 95.5% and acceptable HRV missing rates. More data validation is now needed as
negative predictive value (NPV) at 91.3%. In validation set (n=106), further evidence to support the use of the new non-invasive diagnostic
ICG-R15 ≥ 14% could identify 63.6% (28/44) CSPH with specificity at model in clinical practice.
Table and Figure:Figure 1.Figure 1. The diagnose process of Baveno
VI criteria, Modified Baveno VI criteria, BV6-SA model and MBV6-SA OP0086
model Exploration of Strategies for Conducting Universal Hepatitis C
Figure 2.Table 1. Performance of different criteria in ruling out HRV in Virus (HCV) Screening among the General Population in China
training cohort and validation cohort
Qiran Zhang1, Yiqi Yu1, Quan Ming2, An Xiao3, Yan Wang4, Ruirui
You1, Wenhong Zhang1
OP0085 1
Department of Infectious Diseases, National MedicalCenter for
A multi-center, prospective, single-arm trial followed by an 12/48 Infectious Diseases, Huashan Hospital, 2The Third People‘s Hospital
week observational clinical trial to evaluate the safety and efficacy of Yichang, 3First People’s Hospital of Yunnan Province, Affiliated
of SOF/VEL treatment and prophylactic use of TAF in patients with Hospital of Kunming University of Science and Technology, 4The Six
GT1-6 HCV/HBV coinfection People‘s Hospital of Shenyang
Yifan Han1, Ning Lin1, Dazhi Zhang2, Zuxiong Hang3, Minghua Su4, Background: Remarkable efforts have been made in the management
Jiawei Geng5, Zhili Wen6, Xiaobo Lu7, Weize Zuo8, Hong You9, Yuemin of hepatitis C in China. The Centers for Disease Control and Prevention
Nan10, Liting Zhang11, Liaoyun Zhang12, Hongyu Chen1, Zhan Zeng1, (CDC) has already established effective and comprehensive
Yanyan Yu1, Xiaoyuan Xu1 procedures in hepatitis C virus (HCV) screening and linkage to
1
Peking university first hospital, 2the Second Affiliated Hospital of care regarding the high-risk populations. However, there remains a
Chongqing Medical University, 3Mengchao Hepatobiliary Hospital controversy over whether universal HCV screening should be carried
of Fujian Medical University, 4The First Affiliated Hospital of Guangxi out among the general population, and how can it be practical and
Medical University, 5The First People’s Hospital of Yunnan Province, linked to care well in community-based settings for such a large
6
The Second Affiliated Hospital of Nanchang University, 7The First sample. This study aims to investigate whether the universal screening
Affiliated Hospital of Xinjiang Medical University, 8The First Affiliated for HCV in general population in community-based settings is practical,
Hospital of Shihezi University, 9Beijing Friendship Hospital, 10Hebei and to find the strategies for the universal screening.
Medical University Third Hospital, 11The First Hospital of Lanzhou Method: The project was conducted along with the annual routine
University, 12The First Affiliated Hospital of Shanxi Medical University health examinations in citizens, and explored various models. All
Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) have participants were conducted rapid HCV antibody testing, whether by
similar transmission pathways, consequently leading to the widespread point-of-care testing (POCT) from fingertip blood, or using the residual
occurrence of patients with hepatitis B and C coinfection. HBV/HCV blood from other laboratory tests. In participants with positive results,
coinfection is more complex than single HBV or single HCV infection HCV RNA tests were conducted whether by “call-back”, or residual
and have the potential to exacerbate hepatic impairment. In this study, blood “reflex testing”. HCV genotype was conducted in all samples
we assessed the safety and efficacy of sofosbuvir/velpatasvir (SOF/ with positive HCV RNA results.
VEL) in HBV/HCV coinfected patients from thirteen centers in China, Result: A total of 21598 participants were screened in four provinces,
and evaluated prophylactic use of tenofovir alafenamide (TAF) for HBV and 20 of them had positive anti-HCV results (0.093%). Six of the
reactivation. 20 participants denied any risk factors, 2 of them had a history of
Method: This is a multicenter, prospective, single-arm, open-label 12- intravenous drug addiction, 1 of them have partner with HCV infection
week trial followed by a 12/48-week observational clinical trial. The history, 8 of them had history of blood transfusion before 1993 (the year
study included 105 adults with chronic HBV/HCV (GT1-6) coinfection. Chinese government started HCV screening in all blood banks), 3 have
These patients were enrolled in sixteen centers in China, from May 2021 already diagnosed with chronic HCV infection and initiated treatment.
to November 2024. Eighty-three non-cirrhotic patients were included in In the 11 participants with available sample (4 from reflex testing, 7
group 1 and twenty-two compensated cirrhosis patients in group 2. All from call-back and sample retake, 9 lost in call-back process), 6 was
patients will receive anti-HBV and HCV treatment after enrollment. The HCV RNA positive, of which the genotype was 1b in 3, 2a in 2, and 2b
specific treatment regimen is TAF alone for 4 weeks, then concurrent in 1.
TAF and SOF/VEL for 12 weeks. Non-cirrhotic patients continued TAF Conclusion: Universal screening in general population in non-
alone once daily for 12 weeks and compensated cirrhotic patients epidemic areas is inefficient and need optimization to concentrate
continued for 48 weeks. Group t-test or nonparametric test were used population at risk in the future. POCT anti-HCV screening and anti-HCV
for comparison between groups. Statistical significance was set at p reflex HCV RNA testing using the residual blood from routine health
< 0.05. tests may be applicable in large-scale screening in the community
Result: The study included 105 patients with HBV/HCV co-infection, settings.
with a median age of 51 years, and a median HCV RNA of 5.9 log10
IU/ml. At baseline, HCV RNA levels were 6.2 and 5.7 in the two groups, OP0087
with no statistical differences. At the end of SOF/VEL treatment, the
Pay-it-forward incentives for hepatitis virus testing in men who
cumulative sustained virological response was recorded at 97.6%,
have sex with men: a cluster randomized trial
with a complete 100% attainment observed in group 2. HCV RNA and
HBV DNA levels were dramatically decreased in all patients (p<0.001). Ye Zhang1, Weiming Tang2
ALT (p<0.001), AST (p<0.001), TBIL (p=0.006) levels were decreased
1
Nanjing Medical University, 2University of North Carolina at Chapel
and ALB (p<0.001) level was increased compared to pre-treatment in Hill
group 1 at the 12 weeks post-treatment. ALT (p<0.001), AST (p<0.001) Background: Pay-it-forward incentives involve having a person
levels were decreased, and ALB(p=0.002), PLT (np<0.001) levels receive a free test with community-generated messages and then
were increased compared to pre-treatment in group 2 at the 48 weeks asking if those who received a free test would like to donate money
posttreatment. LSM (p=0.003), APRI (p=0.007), and FIB-4 (p=0.004) to support others to receive free testing. Here we undertook a two-
were significantly decreased after treatment in group 2. Only one arm cluster-randomized trial to evaluate pay-it-forward incentives with
patient in group 1 with genotype 3 showed HBV reactivation. No drug- active community participation to promote hepatitis B virus (HBV) and
related adverse effects were observed in the study. hepatitis C virus (HCV) testing among men who have sex with men in
Conclusion: SOF/VEL greatly reduces HCV RNA levels and improves China.
liver function in patients with chronic HBV/HCV co-infection, with high Method: Men randomized to the pay-it-forward arm received free
safety. Patients with compensated cirrhosis also have significant HBV and HCV testing and were offered a chance to pay-it-forward by
improvement in indicators of cirrhosis after antiviral therapy. donating money to support the testing of another anonymous person.
Additionally, prophylactic use of TAF in patients with chronic HBV/HCV Each participant paid for their HCV and HBV test at 7.7 USD per test
coinfection prevents HBV reactivation to some extent. in the standard-of-care
Table and Figure:Figure 1.Figure-total arm. The primary outcome was the proportion of men who tested for
HBV and HCV.
Result: Between 28 March and 6 November 2021, 32 groups (10 men
per group) of men were randomized to the pay-it-forward (n = 160, 16 Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir
clusters) as a salvage therapy for chronic hepatitis C patients with failed
and standard-of-care (n = 162, 16 clusters) arms, respectively. HBV previous direct-acting antivirals treatment
and HCV rapid testing were higher in the pay-it-forward arm (59.4%) Yan Guo1, Songtao Zhao1, Yan Zhu1, Cheng Yang1, Jianping Li2, Lihua
than in the standard-of-care arm (25.3%) (proportion difference Zhang3, Changming Yang4, Huagang Xiong4, Dong Zhang5, Guangjun
35.2%, 95% confidence interval 24.1–46.3%). No adverse events were Tian5, Li Guo6, Bihua Gao6, Jie Xia1
reported. 1
Department of Infectious Diseases, Southwest Hospital, Third Military
Conclusion: The community-led pay-it-forward incentives improved Medical University (Army Medical University), Chongqing 400038,
HBV and HCV testing among men who have sex with men. 2
Department of Liver Diseases, GuangZhou Eighth People’s Hospital,
Table and Figure:Figure 1. Guangzhou Medical University, Guangzhou 510440, 3Department of
Figure 2. Infectious Diseases, Dongguan Ninth People‘s Hospital, Dongguan
523106 , 4Department of Liver Diseases, Guiyang Public Health
OP0088 Clinical Center, Guiyang 550004, 5Department of Liver Diseases,
Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015,
Peer-to-peer Education Improves Screening and Treatment among 6
Department of Infectious Diseases, Beihai People‘s Hospital of
Family Members of patients with HCV mono-infection or HIV/HCV Guangxi Zhuang Autonomous Region, Beihai 536000
co-infection
Background: To evaluate the effectiveness and safety of sofosbuvir/
Yang Luo1, Shifu Li1, Rusong Yang1, Kun Qi1 velpatasvir/voxilaprevir (SOF/VEL/VOX) as a salvage therapy for
1
Centers for Disease Control and Prevention of Yuxi chronic hepatitis C (CHC) patients in Western and Southern China who
Background: This study aims to explore the impact of peer-to-peer failed previous direct-acting antivirals (DAAs) treatment.
education on screening and treatment of spouses/sexual partners Method: Patients with hepatitis C who failed previous DAAs receiving
and offspring of patients with HCV mono-infection or HIVHCV co- SOF/VEL/VOX for salvage therapy from five hospitals in Chongqing,
infection in a tier 3 city with high HCV prevalence in China. Guangdong, Guizhou and Guangxi between Jan. 2022 and Dec. 2023
Method: (i) Family Members of HCV Mono-Infected Patients: Primary were recruited. All patients have received one or more courses of
healthcare workers and specialized nurses provide health education DAAs±RBV treatment in the past and experienced viral rebound during
to HCV-infected patients and assist with treatment linkage. Patients are follow-up. SOF/VEL/VOX ± RBV was used as a salvage treatment for
encouraged to act as peer supporters (undergoing or post-treatment) these patients. Clinical and laboratory data and adverse events (AEs)
to motivate their family members, including spouses, sexual partners, before and after treatment were collected.
and offspring, to undergo HCV antibody screening. Result: A total of 26 CHC patients receiving SOF/VEL/VOX salvage
(ii) Family Members of HIV/HCV Co-Infected Patients: Healthcare therapy were recruited. Baseline clinical characteristics of the patients
workers engage patient representatives (leaders in patient were shown in table 1. The mean age was 52.9 (±9.6) years, and 21
organizations) to facilitate HCV knowledge training during HIV social patients (80.8%) were males. 16 patients (61.5%) had drug injection
group activities, encouraging co-infected patients’ family members to history and 2 patients (7.7%) co-infected with HIV, 14 patients (53.8%)
undergo HCV antibody screening. had liver cirrhosis, 21 patients (80.8%) had a history DAAs treatment with
(iii) Follow-Up and Treatment Initiation: For individuals identified as SOF/VEL and 4 experienced multiple courses of DAAs treatment. The
HCV antibody-positive, follow-up is conducted by CDC and medical mean HCV RNA was 5.8 (±1.6) log10IU/ml at the baseline of salvage
staff in collaboration with peer supporters and patient representatives. therapy and the most common HCV genotype was GT 3 (61.5%) .
Patients are provided with professional education, free HCV RNA All patients completed 12 weeks of SOF/VEL/VOX±RBV treatment and
testing, and linkage to treatment with the SOF/VEL regimen for viremic achieved SVR at the end of treatment. Twenty-two patients completed
cases. 12 weeks of follow-up and all of them achieved SVR12, including those
Result: From June 2023 to November 2024, 3975 HCV infected with genotype 3 infection and liver cirrhosis (figure 1) . The ALT and
patients were identified in Yuxi City, Yunnan Province. 61.0% AST normalization rate were 94.1% and 93.8% respectively. Compared
(2425/3975) already initiated   treatment. Among those patients, we to baseline, the levels of ALT, AST, FIB-4 and APRI were significantly
encouraged 2125 peer supporters and 9 patient representatives. decreased after treatment (P<0.05, table 2). The aMAP score was
Through peer-to-peer education, an additional 3,125 family members also decreased after treatment, and the proportion of hepatocellular
of patients were motivated to receive HCV antibody screening including carcinoma (HCC) high-risk patients decreased from 52.6% to 33.3%,
48.4% spouses/sexual partners and 51.6% offsprings. Among those with more patients transferred to medium/low-risk (figure 2). Adverse
family members, 4.6% (144/3,125) were identified HCV antibody events were mild and well-tolerated, which including nausea and
positive.99.3% (143/144) of family patients further tested for HCV RNA diarrhea(7.7%), headache(3.8%) and lack of strength(3.8%). No
and 63.6% (91/143) were HCV viremic, including 94.5% (86/91) were serious adverse events or death events were reported.
HCV mono-infected and 5.5% (5/91) were HIV/HCV co-infected. At Conclusion: SOF/VEL/VOX was effective and well-tolerated for DAAs
the end ofNovember, 89% (81/91) of family patients initiated SOF/VEL experienced CHC patients in China, including difficult-to-treat cases
treatment, and untreated patients are still in education. Compared to such as those with GT 3 and cirrhosis.
before peer education (0% of patients’ family members were tested for Table and Figure:Figure 1.
antibodies), screening and treatment rates for this high risk population Figure 2.
were significantly higher, and treatment rates were significantly higher
in the family population (89%) than in the general population (61%). OP0090
Conclusion: By leveraging peer supporters and patient representatives
to provide peer-to-peer education for family members of individuals Evaluation of blood droplet volumes on the Cobas Plasma
with active HCV infection, we identified additional HCV cases within Separation Card for HCV RNA testing in resource-limited settings
family populations and facilitated their linkage to care. This approach Huma Qureshi1, Jesse Canchola2, Ghayas Hai3, Amtul Qudus4,
has the potential to accelerate HCV elimination in high-prevalence Benjamin La Brot2
regions. 1
Doctor‘s Plaza, Clifton, Karachi, Pakistan, 2Roche Molecular Systems,
Table and Figure:Figure 1.Flow chart of Peer-to-peer education among Pleasanton, California, USA, 3Doctor’s Laboratory, Clifton, Karachi,
family members of HCV infected patients Pakistan, 4Jinnah Postgraduate Medical Centre, Karachi, Pakistan
Figure 2. HCV care cascade of family members after peer-to-peer Background: Detection of viral RNA is essential for diagnosis of
education hepatitis C virus (HCV). Collection and preservation of plasma, the
preferred specimen type for HCV RNA testing, can present challenges
OP0089 in remote and resource-limited areas. The Cobas Plasma Separation
Card (PSC) is an alternative matrix to obtain dried plasma spots for
PCR analysis with no cold chain requirements, facilitating sample randomised 1:1 into 2 treatment arms. In Arm 1, participants received
collection in remote, underserved areas. The PSC is designed to bepirovirsen 300 mg QW (plus loading dose on Days 4 and 11) for 24
use capillary blood collected through a fingerstick and capillary tube weeks followed by up to 24 weeks of Peg-IFN 180 µg QW. At screening,
collection, but alternative sample collection options would broaden the participants were required to have ALT ≤2 times upper limit of normal
PSC utility. This study explored qualitative and quantitative HCV RNA (ULN) in both studies. Participants on-NA continued NAs throughout
detection with the PSC spotted with different venous blood volumes, in both studies. This post hoc analysis describes the relationship
compared with results from plasma. between maximum ALT fold increase relative to baseline and maximum
Method: This prospective non-interventional study enrolled HCV HBsAg decrease relative to baseline during the 24-week bepirovirsen
outpatient clinic (Karachi, Pakistan) patients >18 years of age, testing treatment period in Arm 1 of both studies.
positive for anti-HCV antibodies. Using a 24-gauge syringe, 5 mL whole Result: The analysis included N=68 B-Clear on-NA and N=55
blood was drawn by venipuncture from consenting patients; 3 mL was B-Together participants. Mean (standard deviation) baseline HBsAg
aliquoted into a plasma preparation tube for generating plasma. The was 3.29 (0.62) and 3.34 (0.56) log10 IU/mL in B-Clear and B-Together,
remainder was spotted directly from the needle onto three PSC each respectively. Most participants in the analysis had baseline ALT levels
using 6, 8, and 10 drops per spot in phase 1, or 8, 10, and 12 drops in ≤ULN (B-Clear: 91% [n=62/68]; B-Together: 93% [51/55]). Participants
phase 2. Air-dried PSCs were stored in polythene bags with desiccant with high maximum ALT fold increase had high maximum HBsAg
at room temperature for 10 to 15 days. PSC and plasma samples were decline in both studies during the bepirovirsen treatment period. In
processed in a local laboratory for measurement of HCV RNA viral B-Clear, all participants with a ≥10-fold increase in ALT (n=8) during
load (Cobas HCV, Roche) according to the manufacturer’s instructions. bepirovirsen treatment had a ≥3 log reduction in HBsAg, and most
Regulatory approval for PSC for use with Cobas HCV is pending. (88% [n=7/8]) experienced HBsAg loss. In B-Together, all participants
Result: A total of 294 patients were enrolled between April and with a ≥10-fold increase in ALT (n=7) during the bepirovirsen treatment
September 2024 of whom mean age was 45 years (range 18–88) and window had a ≥2.5 log reduction in HBsAg, and 71% (n=5/7) had
154 (52.4%) were male. Valid HCV RNA test results for all conditions HBsAg loss. However, HBsAg loss was also observed in participants
were available for 143 patients in phase 1 and 109 patients in phase with no or only limited ALT elevations.
2. The percentages of samples with detectable HCV RNA and overall Conclusion: HBsAg reductions during bepirovirsen treatment can be
percent agreement in plasma and PSC are shown in Table 1. HCV achieved with or without ALT elevations. The majority of participants
RNA detection rates were not significantly different from plasma, in both studies who experienced an ALT elevation of ≥10-fold from
and overall percentage agreement was over 88%, for any PSC spot baseline experienced HBsAg loss.
number (Fisher Exact test P > 0.1). The mean difference in log viral Funding: GSK (209668/209348)
load was highest for 6 spots in phase 1 (0.81 log IU/mL lower in PSC;
Table 2). Differences were variable for 8 or 10 spots in phase 1 or 2.
OP0092
For 12 spots, the viral load was slightly higher (0.28 log IU/mL) than in
plasma in phase 2. Evaluating Persistence in Patients with Chronic Hepatitis B (CHB)
Conclusion: Direct spotting of venous blood from a syringe onto PSC Infection Treated with Long-term Nucleos(t)ide Analogues (NAs)
is a viable alternative to pipetting from PPT and may reduce logistical in Japan
challenges with sample collection while maintaining high diagnostic Shinya Kawamatsu1, Kiran Rai2, Vera Gielen3, Amisha Patel2, Olivia
accuracy, especially with larger blood volumes. This approach may Massey2, Seth Anderson4, Yutaka Handa1, Ethan Yichen Lee1, Jun
be particularly beneficial in resource-limited settings and in patient Inoue5, Poppy Payne2, Isabel Jimenez2, Kejsi Begaj4, Afisi Ismaila4
populations for whom capillary blood draw is challenging (eg, those 1
GSK, Tokyo, Japan, 2Adelphi Real World, Bollington, United
with heavily calloused hands). Kingdom, 3GSK, London, United Kingdom, 4GSK, Pennsylvania, USA,
Table and Figure:Figure 1.Table 1. Detectability of HCV RNA in PSC
5
Division of Gastroenterology, Tohoku University Graduate School of
vs. Plasma Medicine, Sendai, Japan
Figure 2.Table 2. Bland-Altmann Bias vs. Plasma Background: The WHO estimated 254 million people living with CHB
infection globally in 2022. NAs are the current standard of care for CHB
OP0091 infection, with most patients requiring long-term treatment to inhibit
viral replication. Whilst NA treatment does not eradicate the virus and
Characterisation of the Relationship Between HBsAg Loss and
rarely (≤5%) achieves functional cure, treatment persistence can delay
ALT Elevation During Bepirovirsen Treatment in Patients With
disease progression and improve clinical presentation. We aimed to
Chronic Hepatitis B
describe persistence to second-generation NAs among Japanese
LinMing Shen1, Rob Elston2, Lauren Maynard2, Dickens Theodore3, adult patients with CHB infection.
Melanie Paff4, Divya Lakshminarayanan4, Maxwell Hu5, Leigh Felton2 Method: Population-based retrospective study using the Japanese
1
GSK, Waltham, MA, USA, 2GSK, Stevenage, Hertfordshire, UK, 3GSK, Medical Data Center Claims Database to identify patients (≥18 years)
Durham, NC, USA, 4GSK, Collegeville, PA, USA, 5GSK, Shanghai, diagnosed with CHB infection and indexed on initiation of a single-
China agent second-generation NA (entecavir, TAF or TDF) between January
Background: In the Phase 2b studies B-Clear and B-Together, 2007–August 2023. Participants had continuous medical/pharmacy
treatment with the novel antisense oligonucleotide bepirovirsen, either enrolment ≥12 months prior to and ≥4 months after index. Patients
alone, with background nucleos(t)ide analogue (NA) therapy, or in a with HIV, HCV or HDV, or ≥1 first- or second-generation NA during
sequential regimen with pegylated interferon-α-2a (Peg-IFN), induced the baseline period were excluded. NA treatment discontinuation and
hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) restart were assessed. Cox regression modelling was used to assess
DNA loss. In both studies, some participants experienced transient factors associated with NA treatment discontinuation. Descriptive data
alanine aminotransferase (ALT) increases in association with HBsAg were stratified by age.
reductions. These findings suggest that ALT increases may reflect a Result: Of the 2,473 eligible patients, 1,623 (66%) were male (Table).
therapeutic response to bepirovirsen, instead of representing disease The mean (SD) for age was 49.9 (10.4) years, and for CCI score was
activity or drug-induced liver injury in patients with chronic HBV 1.1 (2.0). Median (95% CI) survival time for time on treatment was
infection. This post hoc analysis aimed to characterise the relationship 40.1 (37.9, 42.4) months. Entecavir and TAF were the commonly
between maximum ALT increase and maximum HBsAg decline used indexed NAs. Treatment discontinuation was observed in 20.3%
during bepirovirsen treatment in On-NA participants in B-Clear and (n=501) of the patients; median (Q1, Q3) time to discontinuation was
B-Together. 12.2 (3.9, 29.5) months. Patients aged 18–34 years had the highest
Method: In B-Clear, participants on- and not-on-NA were randomised proportion of discontinuation (n=53; 31.2%) compared with patients
(3:3:3:1) into 4 treatment arms. In Arm 1, participants received aged ≥35 years. Median (Q1, Q3) time to discontinuation was shortest
bepirovirsen 300 mg once weekly (QW) (plus loading dose on Days for patients aged ≥65 years (4.4 [1.2, 13.8] months). Of those who
4 and 11) for 24 weeks. In B-Together, participants on-NA were discontinued, 50.7% of the patients (n=254) restarted NAs, and 14.6%
(n=73) restarted NAs multiple times. Median (Q1, Q3) time to restarting Nicolae Testemitanu State University of Medicine and Pharmacy,
NA from first discontinuation was 5.4 (3.4, 11.7) months. Proportion of Moldova, 4Aligos Therapeutics, Inc., 5Department of Medicine, School
patients restarting NA treatment was highest in the 35–49 years age of Clinical Medicine, The University of Hong Kong, China
group (59.3%); 18–34 years (n=25; 47.2%) took the longest (8; 3.5, Background: ALG-000184 is a prodrug of ALG-001075, a highly
21.6 months) to restart NA treatment. Age group 35–64 years, index potent capsid assembly modulator-empty (CAM-E) that has been
treatment of TAF and HCC diagnosis at baseline were significantly shown in vitro to induce the formation of empty capsids, inhibit hepatitis
(p<0.01) associated with a reduced probability of NA treatment B virus (HBV) replication, and prevent the establishment/replenishment
discontinuation. of cccDNA.
Conclusion: This study provides valuable insights into the NA Method: ALG-000184-201 is a multi-part, multi-center, randomized
treatment pattern in patients with CHB infection in Japan across clinical trial evaluating the safety, pharmacokinetics, and antiviral
age groups. Considering factors such as age, comorbidities, and activity of ALG-000184 in healthy volunteers and subjects with
preventive NA administration for HBV reactivation can enhance the untreated chronic HBV infection (NCT04536337). Here, we report
clinical management of the disease. The results emphasize the need safety and antiviral activity data in untreated HBeAg(-) subjects who
for alternative CHB therapies with shorter and finite treatment durations received 300 mg ALG-000184 monotherapy for ≤ 84 weeks.
to improve patient persistence and outcomes. Result: A total of 11 untreated HBeAg(-) subjects (3 Asian and 8
Funding: GSK Study 217942 non-Asians) with chronic HBV infection received 300 mg ALG-000184
Table and Figure:Figure 1.Table: Baseline demographics and clinical monotherapy for up to 84 weeks. Baseline disease characteristics
characteristics of patients treated with second-generation NA were typical of the HBeAg(-) patient population, e.g., older age and
lower baseline levels of viral markers. HBV genotypes were B (n=2), C
OP0093 (n=1), A (n=1) and D (n=7). The mean (SEM) levels of HBV DNA were
4.3 (0.2) log10 IU/mL; HBV RNA 2.0 (0.3) log10 copies/mL; HBsAg 3.5
Clinical aspects of Hepatitis Delta - a retrospective analysis of
(0.2) log10 IU/mL; and HBcrAg 3.2 (0.3) log10 U/mL.
patients’ data from 2004 to 2024
By Week 84, the maximum mean reduction from baseline in HBV
Gulnara Aghayeva1,2 DNA was 4.3 log10 IU/mL and in RNA was 1.0 log10 copies/mL. All
1
Liver Disease Center Referance clinic, 2Sechenov Medical University HBeAg(-) subjects achieved sustained HBV DNA suppression by
Background: The hepatitis delta virus (HDV) is the most severe form Week 24. At Week 48, 11/11 (100%) subjects achieved sustained HBV
of viral hepatitis. Hepatitis Delta eventually leads to the development DNA < 10 IU/mL (LLOQ) and 10/11 (91%) subjects achieved HBV DNA
of serious complications, primarily liver cirrhosis and hepatocellular < 4.29 IU/mL (LLOD, Figure B). All subjects achieved sustained HBV
carcinoma. RNA < 10 copies/mL (LLOQ) by Week 8. While no apparent HBsAg
Method: We collected data from 1595 outpatient patients with chronic decrease was observed, HBcrAg had a maximum mean reduction of
hepatitis B who were evaluated in the Liver Diseases Department in 0.7 log10 U/mL from baseline. Importantly, no viral breakthrough, as
Baku, Azerbaijan between January 2004 and January 2024. Since the assessed by HBV DNA levels, was observed in any subject (Figure A).
initiation of Supersonic Aixplorer SWE and Fibroscan the degree of 300 mg ALG-000184 monotherapy was well tolerated with no serious
fibrosis has been determined and recorded in all patients. We had 84 adverse events and no treatment emergent adverse events leading
patients on Peg-IFN-alfa (Pegasys 180, 135, 90 kg/) weekly s/c and 7 to discontinuation reported. One non-Asian subject experienced a
on the treatment with Peg-IFN-alfa+BLV. Grade 3 TEAE of ALT elevation without changes in liver bilirubin, INR
Result: According to the data received for 20 years, we identified the or albumin. Another subject with abnormal cholesterol (Grade 1) and
prevalence of hepatitis D to be 13,4 % of HBsAg-positive patients. The triglycerides (Grade 2) at baseline experienced a Grade 3 TEAE of
data on the percentage of cirrhotic patients in different age groups cholesterol and triglycerides increase. All Grade 3 TEAEs resolved
showed that in the group of patients over 60 years old, 80% had with continued ALG-000184 dosing.
cirrhosis, while more importantly, cirrhosis was observed in 46% in the Safety and antiviral effects were similar between HBeAg(-) Asian and
group from 20-39 years, representing the most young and active group non-Asian subjects.
and 50% in the group 40-60 years old. Conclusion: 300 mg ALG-000184 monotherapy led to rapid,
91 patients received treatment (43%). 22 (24%) obtained sustained profound and sustained HBV DNA and RNA viral suppression in
virologic response, 22 (24%) relapsed and 47 (52%) have not untreated HBeAg(-) subjects. Viral suppression exceeds what has
completed treatment due to high cost and incompliance. During 2004- been reported previously with nucleos(t)ide analogs, indicating that
2024 53 (25%) died, 11 (5%) developed HCC and 7 (3%) underwent ALG-000184 monotherapy may be more effective in achieving and
liver transplantation. maintaining suppression in patients with chronic HBV infection. These
Conclusion: Dual HBV/HDV infection is one of the most rapidly data support continuing dosing in this cohort for up to 96 weeks and
progressive causes of advanced liver disease that can end up with further evaluation in a Phase 2 clinical trial.
dangerous complications such as cirrhosis and HCC. The prevalence Table and Figure:Figure 1.A. Individual HBV DNA Levels Over Time in
of HDV infection is 13,4 % in HBsAg-positive individuals. The results of HBeAg(-) Subjects Following 300 mg ALG-000184 Monotherapy for
our study suggest that co-infection with hepatitis B and D viruses could up to 84 Weeks
represent an important cause of liver disease in certain populations. It Figure 2.B. Individual Time to HBV DNA < LLOQ in HBeAg(-) Subjects
is necessary to improve the diagnostics of hepatitis delta and make Following 300 mg ALG-000184 Monotherapy for up to 84 Weeks
treatment more accessible to most patients. To prevent the spread of
hepatitis Delta, it is necessary to strengthen the work on vaccinating OP0095
the population against hepatitis B.
Predictors of alanine aminotransferase (ALT) flares in patients
initiating treatment for chronic hepatitis B virus (HBV) infection: A
OP0094 Hong Kong-based electronic health record (EHR) database study
Monotherapy with the Capsid Assembly Modulator ALG-000184 Myriam Drysdale1, Wallis Lau2,3, Iain A Gillespie4, Luis Antunes5,
Results in Rapid Viral Load Reduction and High Viral Suppression Sophia Rodopoulou6, Sohee Park7, Xiaohui Sun8, Loey Mak9,10,
Rates in Untreated HBeAg(-) Subjects with Chronic Hepatitis B Dickens Theodore11, Ian CK Wong12
Virus Infection 1
GSK, London, UK, 2Research Department of Practice and Policy,
Ed Gane1, Kosh Agarwal2, Alina Jucov3, Alexei Haceatrean3, Min Wu4, UCL School of Pharmacy, London, UK, 3Department of Pharmacology
Kha Le4, Thanh Van4, Jen Rito4, Lawrence Blatt4, Sushmita Chanda4, and Pharmacy, University of Hong Kong, Hong Kong, China, 4GSK,
Tse I Lin4, Hardean Achneck4, Man Fung Yuen5 Stevenage, UK, 5IQVIA, Lisbon, Portugal, 6IQVIA, Athens, Greece,
1
Faculty of Medicine, University of Auckland, New Zealand, 2King‘s
7
Aston Pharmacy School, Aston University, Birmingham, UK, 8IQVIA¸
College Hospital, Institute of Liver Studies, United Kingdom , London, UK, 9HKU, Hong Kong, China, 10State Key Laboratory of
3
ARENSIA Exploratory Medicine, Republican Clinical Hospital and Liver Research, The University of Hong Kong, Hong Kong, China,
1GSK, Durham, NC, USA, 12University of Hong Kong, Hong Kong,
1
HBV infection; 4.5% of the Hong Kong population were estimated to
China be infected with HBV in 2020. Loss of HBsAg, often considered as
Background: ALT flares commonly observed in patients with chronic a proxy for functional cure of CHB infection, improves survival and
hepatitis B (CHB) can be spontaneous, or a result of treatment initiation/ sustains disease remission, but it occurs infrequently (≤5%) with
discontinuation, likely caused by a stimulation of the immune system current therapies (interferon [IFN] and nucleos(t)ide analogues [NA]).
against infected hepatocytes. We aimed to describe the association We assessed the impact of HBsAg loss on long-term clinical outcomes
between selected characteristics of Asian adults living with CHB and (compensated cirrhosis [CC], decompensated liver disease [DLD],
the occurrence of first ALT flare after treatment initiation, as well as HCC, and all-cause mortality [ACM]) in patients with CHB infection in
describe characteristics of first on-/post- treatment flare. an Asian population.
Method: A retrospective cohort study was conducted using EHR Method: A retrospective observational cohort study was conducted
data from the Hong Kong CDARS database in patients initiating using electronic health record data from the Hong Kong Clinical
treatment (IFN or NA therapy) between 2005–2019. The association Data Analysis and Reporting System database. The study included
between patient demographic, clinical, biochemical and treatment treated and untreated adults with CHB infection (≥1 diagnostic code
characteristics and onset of first on-treatment ALT flare (defined as for CHB infection or two positive HBsAg test results ≥6 months apart)
>5x ALT ULN and >2x ALT baseline or nadir) was investigated using between January 2005–December 2019. HBsAg loss was defined
multivariable time-dependent Cox proportional hazards regression as ≥2 consecutive negative laboratory HBsAg results ≥6 months
modelling. Kaplan–Meier curves were used to assess time to initial apart. Marginal Structural Modelling was employed to describe the
flare. association between HBsAg loss on study outcomes in the presence of
Result: A total of 10,145 patients, mainly men (60%; mean [SD] age hypothesised time-dependent (anti-HBV treatment) and other potential
55 [13] years) were included after initiating treatment (>95% NA sources of confounding.
monotherapy). Almost 63% of the patients (n=6,383) had ALT level Result: Of the 71,077 patients included, 1,639 patients experienced
above normal at baseline. Few participants (n=794; 7.8%) experienced HBsAg loss (exposed population) during follow-up and 69,438 did
≥1 on-treatment flare during follow-up (82.4% [n=654] had a single not (comparator population, Table 1). NA monotherapy (92%) was
flare). Of those who discontinued treatment (n=1,806; 17.8%), 6.0% the most common treatment at study entry. Mean age of both the
(n=109) experienced ≥1 post-treatment flare during follow-up (95.4% exposed and comparator population was 53 years. The proportion of
had a single flare). On- and post-treatment flare rates were 28.9 and male patients was higher in the exposed vs comparator population
45.0 events per 1000 person-years, respectively. Contrary to NA (68% vs 58%). With HBsAg loss, a lower risk was observed for DLD
treatment, rates of on-treatment flares with IFN were higher than post- (odds ratio [OR] 0.26; 95% CI, 0.08–0.83), HCC (OR 0.34; 95% CI,
treatment (Figure). Median (95% CI) time to on-/post-treatment first 0.19–0.61), and ACM (OR 0.74; 95% CI, 0.57–0.97), and a trend to
flare was 337 (284–384) days and 284 (207–348) days, respectively; lower risk was observed for CC (OR 0.59; 95% CI, 0.30–1.14) when
median duration was 45 days and 98 days, respectively (Table). using an ‘intention-to-treat’ approach. Each additional month of HBsAg
Median starting value of first on-/post-treatment flare was 288 IU/L loss exposure was associated with a decrease in the odds of HCC
and 319 IU/L respectively; median peak value was 353 IU/L and 344 and ACM; a trend towards a decrease in the odds of CC and DLD was
IU/L, respectively. On-treatment flares were independently associated observed.
with male sex and increasing age, a history of ALT flares, increased Conclusion: In line with the literature, HBsAg loss in this study was
ALT levels at baseline, history of liver disease, evidence of hepatoxic associated with a lower risk of long-term clinical outcomes (DLD, HCC,
medication and type 2 diabetes. Conversely, HBeAg negativity ACM), and possibly with a reduced risk of CC. This retrospective study
decreased the risk as did increasing HBV DNA levels. Compared with provides valuable insights into the relationship between HBsAg loss
NAs, initiating treatment with IFN increased the incidence of flares and clinical outcomes in patients with CHB infection over several years
threefold. However, IFN is seldom used to treat patients with CHB in in a real-world setting in Hong Kong. Funding: GSK Study 209779
Hong Kong reflecting the lower number of events. Table and Figure:Figure 1.Table 1. Baseline characteristics at study
Conclusion: A better understanding of the causes and consequences entry index date
of on-/post-treatment ALT flares is essential for proactive management
in patients living with CHB. A set of predictors including host and viral OP0097
factors as well as anti-HBV medications were identified to play a role in
Investigation of the ceRNA mechanism by which Qizhu Anticancer
the increased risk of ALT flares.
Prescription enhances the expression of senescence-related
Funding: GSK Study 212764
genes in hepatocellular cancer cells
Table and Figure:Figure 1.Incidence of ALT flares in patients with CHB
RUI HU1,2, Jing Li1,2, Mengqing Ma1,2, Jialing Sun2, Xin Zhong2, Jinyu
(number of events per person-years)
Yi1,2, Qi Huang1,2, Minling Lv1,2, Xiaozhou Zhou2,1
Figure 2.Time-dependent Cox proportional hazards model of
association between baseline variables and onset of first on-treatment
1
MACAU UNIVERSITY OF SCIENCE AND TECHNOLOGY, 2Shenzhen
ALT flare: multivariable analysis Traditional Chinese Medicine Hospital
Background: Hepatocellular carcinoma (HCC) is the sixth most
common malignancy and the third leading cause of cancer-related
OP0096
deaths worldwide. Qizhu anticancer prescription (QZACP), a traditional
Impact of Hepatitis B Surface Antigen (HBsAg) Loss on Long- Chinese medicine, has shown efficacy in improving quality of life and
term Clinical Outcomes in Hong Kong SAR of China Patients with extending survival in HCC patients, but its precise mechanisms remain
Chronic Hepatitis B Virus (HBV) Infection: A Retrospective Cohort unclear.
Study Method: UHPLC-Q-Orbitrap was used for QZACP quality control.
Iain A Gillespie1, Myriam Drysdale2, Luis Antunes3, Catarina A primary liver cancer model was established in C57BL/6 mice with
Camarinha3, Adrienne YL Chan4, Wallis Lau5,6, Christopher Lee7, Loey diethylnitrosamine. RNA sequencing provided senescence-associated
Mak4, Xiaohui Sun7, Dickens Theodore8, Ian CK Wong9 gene expression data in the control, model, and QZACP groups.
1
GSK, Stevenage, UK, 2GSK, London, UK, 3IQVIA, Lisbon, Portugal, Bioinformatics analyzed LIHC cohort data from TCGA to identify
4
HKU, Hong Kong, China, 5Research Department of Practice and ARGs linked to prognosis. The IOBR algorithm characterized tumor
Policy, UCL School of Pharmacy, London, UK, 6Department of microenvironment and immunological features. Data from Mirecords,
Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, TarBase, miRTarBase, and starBase databases were used to construct
China, 7IQVIA, London, UK, 8GSK, Durham, NC, USA, 9University of the lncRNA-miRNA-mRNA regulatory network.
Hong Kong, Hong Kong, China Result: QZACP upregulated 135 ARGs with reduced expression
Background: In 2022, chronic HBV infection caused 1.1 million and downregulated 48 ARGs with increased expression in the model
deaths worldwide, primarily due to severe liver complications. The group. KEGG analysis showed enrichment in Circadian rhythm,
Western Pacific region has a disproportionately high prevalence of Biosynthesis of amino acids, and Cysteine and methionine metabolism
pathways. TCGA and Human Protein Atlas data indicated that EPHX2, of Pharmacology; Zhongshan school of Medicine; Sun Yat-sen
CPS1, SLC22A7, GNMT, SLC25A25, SELENBP1, FBN2, and CXCL14 University, 3Guangzhou Virotech Pharmaceutical Co., Ltd.
were transcriptionally downregulated in HCC, while CRY2 and Background: Oncolytic viruses (OVs) selectively replicate within tumor
TESC were upregulated. Protein-level expression of EPHX2, CPS1, cells and induce immune cell recruitment to the tumor microenvironment,
SLC22A7, GNMT, SLC25A25, SELENBP1, and CRY2 was reduced transforming “cold” tumors into “hot” tumors. This process enhances
in HCC. These genes are associated with survival prognosis and the efficacy of immunomodulatory agents such as immune checkpoint
tumor microenvironment features, serving as key QZACP targets. A inhibitors (ICIs). In this study, we evaluated the safety, tolerability, and
ceRNA network was constructed with 11 ARGs, 430 miRNAs, and 105 preliminary efficacy of oncolytic virus M1-c6v1 (OVM) in combination
lncRNAs. Within this network, differentially expressed lncRNAs (FGD5- with the PD-1 antibody camrelizumab and the anti-angiogenic agent
AS1, SNHG16, GAS5, MZF1-AS1, MCM3AP-AS1) and miRNAs (hsa- apatinib in patients with advanced hepatocellular carcinoma (HCC).
miR-17-5p, hsa-miR-107, hsa-let-7c-5p, hsa-miR-370-5p, hsa-miR- Method: This was a single-arm, phase 2, open-label clinical trial
424-5p, hsa-miR-143-3p) may regulate HCC onset and progression. (NCT04665362) that enrolled patients aged ≥18 years with locally
Conclusion: Comprehensive analyses employing RNA sequencing advanced, metastatic, or unresectable HCC, with Child-Pugh class A
and integrative database investigations have unveiled the molecular liver function, who had not previously received systemic therapy for
mechanisms by which QZACP modulates the tumor microenvironment liver cancer. Patients received OVM (1×10⁹ CCID50) by intravenous
and improves HCC prognosis through multiple pathways and targets. infusion every 28 days for 5 consecutive days. Camrelizumab (200
These findings underscore its potential as a promising therapeutic mg) was administered intravenously every 2 weeks, and apatinib
strategy for clinical application in HCC management. (0.75 g) was taken orally daily. Treatment continued for 1 year or until
Table and Figure:Figure 1.Graphical abstract disease progression, intolerability, death, withdrawal, or loss to follow-
Figure 2.mRNA–miRNA–lncRNA Network of ARGs Modulated by up, whichever occurred first. The primary objective was to evaluate
QZACP the safety and tolerability of the combination therapy. The secondary
objective was to assess the preliminary efficacy of this regimen in
OP0098 patients with advanced/metastatic HCC.
Result: As of January 2023, 13 patients were enrolled. All patients
Effectiveness and Safety of Hepatic Arterial Infusion Chemotherapy
were classified as Barcelona grade C, 92.3% had a history of HBV
for Systemic Chemotherapy Refractory Pancreatic Cancer with
infection, and 76.9% had intrahepatic tumors larger than 10 cm. In
Liver Metastases
the safety population (13 patients), 94% of adverse events (AEs) were
Yaqin Wang1, Yuewei Zhang1
grade 1 or 2, with the most common AEs being influenza-like symptoms
1
Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua and transient, asymptomatic reductions in blood cell counts. In the
University efficacy analysis population (10 patients), the combination therapy
Background: This study aimed to assess the efficacy and safety of successfully reduced tumor size in the majority of patients (90%),
hepatic arterial infusion chemotherapy (HAIC) in managing pancreatic as per mRECIST criteria. The overall response rate (ORR) was 60%
cancer liver metastases following the failure of first-line chemotherapy. (6/10), with 1 patient achieving complete remission (CR) and 5 patients
Method: A retrospective analysis was conducted on patients treated achieving partial remission (PR). The median progression-free survival
with hepatic arterial infusion of oxaliplatin combined with 5-fluorouracil (mPFS) was 14.3 months. No viral shedding was detected in urine,
from November 2021 to February 2023. The study included patients feces, or nasal swabs during treatment.
with pancreatic cancer liver metastases that had progressed after Conclusion: This study demonstrates that the combination of oncolytic
initial chemotherapy. Alongside HAIC treatment, 23 patients received virus M1-c6v1 with apatinib and camrelizumab has promising efficacy
second-line chemotherapy drugs such as gemcitabine or capecitabine, and manageable safety in patients with advanced HCC. The regimen
and 9 patients underwent concurrent targeted therapies. Efficacy was may represent a novel therapeutic option for these patients. The trial is
assessed according to RECIST 1.1 criteria, with overall survival (OS) ongoing, and further results will be reported in due course.
and progression-free survival (PFS) determined using the Kaplan-Meier Table and Figure:Figure 1.Treatment flowchart
method. Differences between patient groups were analyzed using the Figure 2.Tumor relief status
log-rank test. Adverse events during treatment were evaluated using
the Common Terminology Criteria for Adverse Events (CTCAE) version
OP0100
5.0.
Result: By July 2023, with a median follow-up of 8.0 months, 20 out The Role of Non-Invasive Scores and Treatment Modalities in
of 23 patients had died, 3 were alive, and none were lost to follow- Hepatocellular Carcinoma: A Single-Center Experience
up. According to RECIST 1.1 criteria, the objective response rate Ahmet Burak Fedai1, Dilara Turan Gökçe2, Derya Ari1, Meral Akdoğan
(ORR) was 39.2%, and the disease control rate (DCR) was 69.6%. The Kayhan1
median intrahepatic progression-free survival (mPFS) was 4.6 months, 1
Ankara Bilkent City Hospital, Department of Gastroenterology,
and the median overall survival (mOS) was 8.0 months. Patients who 2
Sincan Training and Research Hospital, Department of
received targeted therapy during HAIC showed more significant Gastroenterology
survival benefits compared to those who did not, with intrahepatic Background: The aim of this study is to evaluate the demographic
mPFS of 5.2 months versus 4.1 months (P=0.025) and mOS of 9.4 characteristics and survival outcomes of patients followed up with
months versus 7.8 months (P=0.194). Patients with highly vascularized a diagnosis of hepatocellular carcinoma (HCC) based on different
liver metastases benefited more in terms of survival compared to treatment modalities. Specifically, differences in survival durations
those with less vascularized tumors. Adverse reactions to HAIC were among chemoembolization, radioembolization, and ablation treatments
generally manageable, with no treatment-related fatalities. were examined.
Conclusion: HAIC-based comprehensive treatment is a safe and Method: The clinical data of 250 HCC patients followed for 4 years
effective strategy for managing first-line chemotherapy refractory at Ankara Bilkent City Hospital were analyzed. These data included
pancreatic cancer liver metastases. age, gender, liver function scores (ALBI and Child-Pugh), BCLC stage,
etiology, treatment modalities, follow-up durations, and mortality status.
OP0099 Result: The mean age of the patient group was 62.64 years (minimum:
21 years, maximum: 86 years). The majority of patients were male, with
Oncolytic virus M1-c6v1 combined with camrelizumab and
a male-to-female ratio of 4.5:1 (189 males and 42 females). Regarding
apatinib in patients with advanced hepatocellular carcinoma: A
etiology, chronic liver disease due to HBV was the most common
phase 2 open-label trial evaluating safety, and efficacy
cause (55.4%), followed by non-alcoholic fatty liver disease (22.51%).
Chan Xie1, Liang Peng1, Xingrong Zheng1, Wenbo Zhu 2, Songmin The median follow-up duration was 25.64 months (minimum: 6 months,
He3 maximum: 134 months). During follow-up, 39.83% of patients passed
1
Third Affiliated Hospital of Sun Yat-sen University, 2Department
away. The most common BCLC stages at presentation were BCLC A and older. MWA could be an alternative for the oldest
(34.8%) and BCLC B (22.4%). old or the ill patients who cannot afford LLR, while LLR is still the first
Supportive therapy was administered to 33 patients (14.41%), surgical option of treatments for early-stage 3–5 cm hepatocellular
resection to 21 patients (9.17%), and liver transplantation to 14 patients carcinoma in capable elderly’s.
(6.11%). Among local therapies, ablation was the most frequently Table and Figure:Figure 1.Figure 1. Study flow chart.
applied method, performed on 54 patients (23.58%), followed by Figure 2.Figure 4. Kaplan–Meier survival curves for the three age
radioembolization (20.52%, 47 patients) and chemoembolization cohorts (after PSM). Kaplan–Meier survival curves for (A) OS for the
(17.90%, 41 patients). Systemic therapies included Sorafenib (7 60–64 year old cohort; (B) OS for the 65–72 year old cohort; (C) OS
patients) and other agents such as Atezolizumab + Bevacizumab (2 for the ≥ 73 year old cohort; (D) DFS for the 60–64 year old cohort; (E)
patients), Durvalumab + Tremelimumab (1 patient), and Lenvatinib (1 DFS for the 65–72 year old cohort; (F) DFS for the ≥ 73 year old cohort.
patient).
Local ablative therapies, including microwave and radiofrequency
OP0102
ablation, demonstrated a significantly longer mean survival duration of
42.2 months compared to other treatments (p=0.013). No statistically Efficacy and safety of tremelimumab plus durvalumab in
significant difference was found between chemoembolization and participants from mainland China with unresectable hepatocellular
radioembolization in terms of survival (p=0.178), with mean follow-up carcinoma: extension cohort of the randomized, open-label,
durations of 22.14 months and 18.45 months, respectively. multicenter, global, Phase 3 HIMALAYA study
Significant relationships were identified between mortality and several Shukui Qin1, Wei Wang2, Mingjun Zhang3, Helong Zhang4, Cheng
factors, including Child-Pugh score (p=0.000), portal vein thrombosis Yi5, Zhenggang Ren6, Yongqiang Li7, Hong Zhao8, Xiaoming Chen9,
(p=0.005), increasing BCLC stage (p=0.000), and ALBI score Yabing Guo10, Peiguo Cao11, Yuxian Bai12, Haitao Li13, Hongtao Hu14,
(p=0.001). Based on ALBI scores, patients were distributed as follows: Jieer Ying15, Ling Zhu16, Xiao Qu17, Ziye Luo17, Sajid Ali18, Ghassan K.
ALBI 1 (53.91%), ALBI 2 (32.61%), and ALBI 3 (13.48%). Patients with Abou-Alfa19,20,21
lower ALBI scores were more frequently treated with local ablative 1
Cancer Center of Nanjing, Jinling Hospital, 2Department of
therapies. Among those receiving supportive therapy, 87% were in the Gastroenterology and Urology II, Hunan Cancer Hospital,
ALBI stage 3 group.
3
Department of Oncology, Second Affiliated Hospital of Anhui Medical
Conclusion: In conclusion, ablation therapy was found to be associated University, 4Department of Oncology, Tang Du Hospital, The Fourth
with longer survival durations compared to chemoembolizationin Military Medical University, 5Department of Medical Oncology, Cancer
the study. The ALBI stage, whose use in HCC is increasing, was as Center, West China Hospital, Sichuan University, 6Department of
guiding as BCLC and Child-Pugh in treatment selection for our patient Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital,
population. Fudan University, 7Department of Digestive Oncology, Guangxi
Medical University Cancer Hospital, 8Department of Hepatobiliary
Surgery, National Cancer Center/National Clinical Research Center
OP0101 for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences
A multicenter case–controlled study on laparoscopic hepatectomy and Peking Union Medical College, 9Department of Interventional
versus microwave ablation as first-line therapy for 3–5 cm Therapy, Guangdong General Hospital, Guangdong Academy of
hepatocellular carcinoma in patients aged 60 and older Medical Sciences, 10State Key Laboratory of Organ Failure Research,
Guangdong Provincial Key Laboratory of Viral Hepatitis Research,
Zhen Wang1, Jie Yu1, Ping Liang1
Department of Infectious Diseases, Nanfang Hospital, Southern
1
Department of Interventional Ultrasound, Fifth Medical Center of Medical University, 11Department of Oncology, Third Xiangya
Chinese PLA General Hospital, China, Hospital, Central South University, 12Department of Gastrointestinal
Background: There is currently a lack of convincing evidence for Oncology, Harbin Medical University Cancer Hospital, 13Department
microwave ablation (MWA) and laparoscopic liver resection (LLR) of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital
for patients ≥ 60 years old with 3–5 cm hepatocellular carcinoma. of Fujian Medical University, 14Department of Minimal-Invasive
Method: Patients were divided into three cohorts based on restricted Intervention, The Affiliated Cancer Hospital of Zhengzhou University,
cubic spline analysis: 60–64, 65–72, Henan Cancer Hospital, 15Department of Abdominal Oncology,
and ≥ 73 years. Propensity score matching (PSM) was performed to Zhejiang Cancer Hospital, 16Department of Hepatobiliary Surgery,
balance the baseline variables in a 1:1 ratio. Overall The Central Hospital of Wuhan, Tongji Medical College, Huazhong
survival (OS) and disease-free survival (DFS) were assessed, followed University of Science and Technology, 17China R&D, AstraZeneca,
by a comparison of complications, hospitalization,
1
8Global Medicines Development, AstraZeneca, 19Department of
and cost. Medicine, Memorial Sloan Kettering Cancer Center, 20Weill Medical
Result: Among 672 patients, the median age was 66 (IQR 62–71) College, Cornell University, 21Trinity College Dublin, Dublin, Ireland
years. After PSM, two groups of 210 patients each were Background: In the Phase 3 HIMALAYA study (NCT03298451) in
selected. During the 36.0 (20.4–52.4) month follow-up period, the participants with unresectable hepatocellular carcinoma (uHCC),
1-year, 3-year, and 5-year OS rates in the MWA group were STRIDE (Single Tremelimumab Regular Interval Durvalumab)
97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR significantly improved overall survival (OS) versus sorafenib in the
0.98, P = 0.900). The corresponding DFS rates were primary analysis of the global cohort (OS hazard ratio [HR], 0.78;
78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P = 0.007). 96.02% confidence interval [CI], 0.65–0.93), with manageable safety.
The 60–64 age cohort involved 176 patients, with no a The OS benefit with STRIDE versus sorafenib persisted, with 5-year OS
significant difference in OS between the MWA and LLR groups (HR rates of 19.6% versus 9.4%. Here, we report the efficacy and safety
1.25, P = 0.370), MWA was associated with a higher results for STRIDE and durvalumab monotherapy versus sorafenib in
recurrence rate (HR 1.94, P = 0.004). A total of 146 patients were an extension cohort of HIMALAYA comprising participants enrolled in
matched in the 65–72 age cohort, with no significant mainland China.
differences in OS and DFS between the two groups (OS (HR 1.04, P = Method: Participants with uHCC and no previous systemic treatment
0.900), DFS (HR 1.56, P = 0.110)). In 76 patients aged from mainland China were randomized to STRIDE (tremelimumab 300
≥ 73 years after PSM, MWA provided better OS for patients (HR 0.27, mg for one dose plus durvalumab 1500 mg every 4 weeks [Q4W]),
P = 0.015), and there were no significant differences in durvalumab monotherapy (1500 mg Q4W), or sorafenib (400 mg twice
DFS between the two groups (HR 1.41, P = 0.380). Taken together, for daily). The primary objective was OS for STRIDE versus sorafenib. A
patients older than 65 years, the recurrence rate of key secondary objective was OS for durvalumab versus sorafenib.
MWA was comparable with LLR. Safety analysis indicated that LLR Other secondary objectives included progression-free survival (PFS)
was associated with more postoperative bleeding and objective response rate (ORR), per investigator assessment using
(P = 0.032) and hypoproteinemia (P = 0.024). Response Evaluation Criteria in Solid Tumors v1.1, and safety. Data
Conclusion: MWA was comparable to LLR in patients aged 65 years from the China cohort (data cut-off: Sep 26, 2024, 69% OS maturity
in the STRIDE and sorafenib arms) and the global cohort (primary Performance of ChatGPT4.0 in predicting advanced liver fibrosis
analysis; data cut-off: Aug 27, 2021, 71% OS maturity in the STRIDE in patients with metabolic dysfunction-associated steatotic liver
and sorafenib arms) are presented. diseases: a comparative analysis with conventional diagnostic
Result: In total, 180 participants from mainland China were randomized tools
to STRIDE (n=60), durvalumab monotherapy (n=64), or sorafenib Tongluk Teerasarntipan1, Prooksa Ananchuensook1, Kessarin
(n=56). In the China cohort, STRIDE demonstrated a clinically Thanapirom1, Piyawat Komolmit1, Sombat Treeprasertsuk1
meaningful improvement in OS versus sorafenib (HR, 0.76), consistent 1
Division of Gastroenterology, Department of Medicine, Faculty of
with the global cohort (Table 1). The OS trend with durvalumab Medicine, Chulalongkorn University, Bangkok, Thailand
versus sorafenib in the China cohort (HR, 0.81) was similar with the
Background: Accurate prediction of advanced liver fibrosis is
global cohort (Table 1). The PFS HR in the China cohort was 0.75 for
essential for managing patients with metabolic dysfunction-associated
STRIDE versus sorafenib, and 1.14 for durvalumab versus sorafenib.
steatotic liver diseases (MASLD). Conventional diagnostic models
Confirmed ORR in the China cohort was 26.7% with STRIDE, 10.9%
like the FIB-4, APRI and NFS scores have limitations in sensitivity and
with durvalumab, and 3.6% with sorafenib (Table 1). STRIDE and
specificity, leaving room for improvement. ChatGPT4.0, an artificial
durvalumab were tolerable in both cohorts (Table 2). In the China
intelligence (AI)-driven model, has emerged as a novel tool for clinical
cohort, the frequency of Grade 3 or 4 treatment-related adverse events
predictions. This study evaluates ChatGPT4.0’s potential in predicting
was numerically lower with STRIDE or durvalumab versus sorafenib
advanced liver fibrosis compared to conventional scoring systems,
(Table 2).
with an emphasis on its clinical utility in real-world practice.
Conclusion: In the China cohort, STRIDE and durvalumab improved
Method: We retrospectively analyzed 341 biopsy-confirmed MASLD
efficacy outcomes versus sorafenib, with manageable safety, in
patients from the obesity clinic at King Chulalongkorn Memorial
participants with uHCC. These results demonstrate a favorable benefit-
Hospital, Bangkok. ChatGPT4.0’s predictions were compared to liver
risk profile for STRIDE and durvalumab in participants with uHCC from
biopsy results using the METAVIR scoring System. Input variables
mainland China, consistent with the global HIMALAYA population.
included including ethnicity, MASLD diagnosis, age, sex, body mass
Table and Figure:Figure 1.Table 1. Efficacy in the China and global
index (BMI), diabetes status, albumin, SGOT, SGPT, and platelet
cohorts
levels. It was then required to predict the most likely METAVIR stage.
Figure 2.Table 2. Safety in the China and global cohorts
Performance metrics (accuracy, precision, sensitivity, specificity, PPV,
NPV, and AUROC) were calculated and compared to conventional
OP0103 scores (FIB-4 > 1.3; APRI > 0.5, NFS >-1.455, SAFE > 0) for detecting
Prevotella copri-produced 5-aminopentanoic acid promotes advanced fibrosis (>F2).
pediatric metabolic dysfunction-associated steatotic liver disease Result: Of the 341 patients, 49.6% had diabetes. The mean age was
Lu Jiang1, Qingyang Xu1, Tianyi Ren1, Yongchang Zhou1, Juan Xu1, 41.27+13.32 years, with a median BMI of 38.95 (range 19.14-87.37)
Landuoduo Du1, Qianren Zhang1, Huikuan Chu2, Zhong Peng3, kg/m2. Liver biopsy revealed that 45.2% (n=154) had advanced
Jiangao Fan1 fibrosis. ChatGPT4.0 achieved an accuracy of 76.25% and an AUROC
of 0.763 for advanced fibrosis prediction, with a sensitivity of 65.17%
1
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of
Medicine, 2Union Hospital, 3Huazhong Agricultural University and specificity of 80.16%. Its Cohen’s kappa score (0.424) indicated
moderate agreement with biopsy results, outperforming SAFE (0.095)
Background: Recent studies suggest an association between the and NFS (-0.160) and comparable to FIB-4 (0.409) and APRI (0.406).
expansion of Prevotella copri and the disease severity in children with Notably, ChatGPT4.0 achieved a PPV of 53.7% and an NPV of 86.7%,
metabolic dysfunction-associated fatty liver disease (MASLD). We indicating its strength in balancing predictive values. While APRI
aimed to investigate the causative role and molecular mechanisms of had a higher sensitivity (68.54%) and AUROC (0.798), ChatGPT4.0’s
P. copri in pediatric MASLD. superior specificity supports its utility in reducing false positive in
Method: C57BL/6J mice aged 3 weeks were fed a high-fat diet (HFD) clinical workflows. For fibrosis stages F0-F4, weighted F1 scores
and orally administered with P. copri for 5 weeks. We assessed the further reflected ChatGPT4.0’s balanced performance (0.4439).
key features of MASLD and the gut microbiota profile. By untargeted Conclusion: ChatGPT4.0 demonstrates potential as a clinical decision
metabolomics on mouse fecal samples and the supernatant from P. support tool for predicting advanced liver fibrosis in MASLD patients.
copri culture, we identified P. copri-derived metabolite and tested its Its performance is comparable to widely used conventional models,
effects in vitro. with improved specificity and balanced predictive values, supporting
Result: In HFD-fed mice, administration of P. copri significantly its integration into clinical workflows to enhance diagnostic accuracy.
promoted liver steatosis. Genes associated with inflammation and Table and Figure:Figure 1.Performance of ChatGPT4.0 in predicting
fibrosis were significantly upregulated in the livers from the HFD+P. liver fibrosis
copri group compared with the HFD group. In addition, P. copri reduced Figure 2.Comparison of diagnostic performance between ChatGPT4.0
gut microbial diversity and increased the proportion of Firmicutes while and conventional tools in detecting advanced liver fibrosis
decreasing Bacteroidota. Importantly, 5-aminopentanoic acid (5-
AVA) was significantly enriched in both mouse feces from the HFD+P.
copri group and the culture supernatant of P. copri. In vitro, 5-AVA OP0105
aggravated palmitic acid-induced lipid accumulation in HepG2 cells Regulatory Impact of ATG-125 on Fatty Acid Oxidation and
and primary mouse hepatocytes. Mechanistically, P. copri-produced Farnesoid X Receptor Signaling Pathways, as well as Mitochondria
5-AVA exacerbated hepatic steatosis by promoting lipogenesis Biogenesis Contributing to Metabolic Dysfunction-Associated
and fatty acid uptake, while also reducing hepatic very-low-density Fatty Liver Disease in High-Fat and High-Sucrose Diet Mice
lipoprotein export. Tzung Yan Lee1
Conclusion: Our findings demonstrated that P. copri promotes liver 1
Chang Gung University
steatosis in HFD-fed juvenile mice through its metabolite 5-AVA,
Background: Mitochondrial dysfunction exhibits a pivotal role
suggesting its potential as a therapeutic target for the management of
in metabolic disorder and metabolic dysfunction-associated
pediatric MASLD.
fatty liver disease (MAFLD), therefore, examines the potential
Table and Figure:Figure 1.
mitochondrial biogenesis activators and address their effects on
Figure 2.
hepatic lipid metabolism signaling has been proposed as a convenient
and effective treatment in MAFLD.
OP0104 Method: This study aimed to investigate the effects of a mitochondrial
biogenesis activator, ATG-125, on dyslipidemia and hepatic
steatosis induced by a high-fat and high-sucrose diet (HFSD) in
C57BL/6 (wild type) and farnesoid X receptor knockout (FXR KO) mice.
Result: Compared to the HFSD group, ATG-125 (0.2 mg/kg body 1
Anhui medical university
weight, oral administration) dramatically reduced both of serum Background: H3K27ac, a well-recognized epigenetic marker of
and livers the total triglyceride (TG) and cholesterol (TC) levels active enhancers, has been proved to transcriptionally activate gene
and appeared to decrease the fasting blood glucose and insulin expression by combining with transcription factors and participate
in HFSD-fed wild type and FXR KO mice. In wild type and FXR KO in the progression of metabolic disorder. However, the regulatory
mice fed with HFSD, results indicated that ATG-125 protects against mechanisms of H3K27ac in pathogenesis of metabolic dysfunction-
HFSD-induced hepatic inflammation by reducing the expression associated steatotic liver disease (MASLD) has been rarely studied.
of proinflammatory cytokines, namely IL-6, TNF‐α, IL‐1β, and IL‐1α. Method: Here we performed a genome-wide comparative study on
Additionally, ATG-125 exhibited antioxidative effects on HFSD in mice H3K27ac enhancer activities and the corresponding mRNA profiling of
liver by decreasing the levels of reactive oxygen species (ROS) and liver tissue in NAFLD model rats, and verified the potential mechanism
malonaldehyde (MDA) and downregulation of gluconeogenesis and in vivo and in vitro by gene manipulation, qRT-PCR, Western Blotting,
lipogenesis signaling pathways. Furthermore, ATG-125 was shown to Immunofluorescence Assay, Luciferase Activity Assay, nano-drug
induce the expression of PPARα and its target genes to promote FFA delivery system etc.
oxidation effectiveness. In addition, the FXR activation reduces liver Result: Intriguingly, we observed that a significantly enhanced
steatosis and hyperlipidemia by suppressing de novo lipogenesis and H3K27ac density with abundant alterations of regulatory transcriptome
promoting TG oxidation in wild type mice. was observed in MASLD rats. Based on integrative analysis of ChIP-
Conclusion: In conclusion, our findings suggest that ATG-125 Seq and RNA-Seq, TDO2 was identified as a critical contributor for
exerts protective effects against HFSD-induced dyslipidemia and abnormal lipid accumulation, transcriptionally activated by YY1-
hepatic steatosis, which may be related to an improved inflammatory promoted H3K27ac. Further, TDO2 depletion effectively protected
response, oxidative stress, and hepatic lipid metabolism. The overall against hepatic steatosis. In terms of mechanisms, TDO2 activated NF-
research results show that ATG125 showed up to 80% improvement κB pathway to promote macrophages M1 polarization, representing a
in MAFLD for the wild type group; However, in the FXR KO group, the crucial event in MASLD progression. A bovine serum albumin (BSA)
MAFLD improvement was only 30%, and the precise mechanism is nanoparticles was fabricated to provide sustained release of Allopurinol
worth further exploration. (NPs-Allo) for TDO2 inhibition, possessing excellent biocompatibility
and desired targeting capacity. Venous injection of NPs-Allo robustly
OP0106 alleviated HFD-induced metabolic disorders.
Conclusion: Together this study reveals the pivotal role of TDO2 and
Automated MRI liver segmentation to accurately quantify hepatic
its underlying mechanisms in pathogenesis of MASLD epigenetically
steatosis in MASLD
and genetically. Targeting H3K27ac-TDO2-NF-κB axis may provide
Xiaodie Wei1, Jing Zhang1, Shi Qi2, Lixia Qiu1, Xinxin Wang3
new insights into the pathogenesis of abnormal lipid accumulation and
1
The Third Unit, Department of Hepatology, Beijing Youan Hospital, pave the way for developing novel strategies for MASLD prevention
Capital Medical University, 2BEIJING FENGTAI HOSPITAL, and treatment.
3
Department of Pathology, Beijing Youan Hospital, Capital Medical Table and Figure:Figure 1.Epigenetic profiling of the active enhancer
University
marker H3K27ac in metabolic dysfunction-associated steatotic liver
Background: Magnetic resonance imaging (MRI)-proton density fat disease (MASLD) uncovers TDO2 as a pivotal therapeutic target.
fraction (PDFF) has been used in clinical practice. However, the region Enhanced H3K27ac activity drives TDO2-mediated lipid accumulation
of interest (ROI) method used by radiologists is time-consuming, and NF-κB-induced M1 macrophage polarization. Encapsulating
limiting its broader application. We aimed to develop and validate a Allopurinol within BSA nanoparticles to inhibit TDO2 effectively
whole-liver segmentation (WLS) model to accurately quantify hepatic alleviates metabolic disruptions, presenting a promising therapeutic
steatosis using MRI-PDFF, with liver biopsy as the reference standard. strategy for MASLD.
Method: This study recruited 538 patients diagnosed with metabolic Figure 2.Transcription factor YY1 induced TDO2 upregulation via
dysfunction-associated steatotic liver disease (MASLD) who underwent modulating H3K27ac
MRI-PDFF. An AI-WLS model using the VBB-net algorithm was trained
to segment the liver. The performance of the AI-WLS model was
validated in 166 patients with biopsy-proven MASLD.
OP0108
Result: Dice scores for the training and validation cohorts were 0.94 Long-term Prognosis of Chronic Hepatitis B Patients with
± 0.05 and 0.93 ± 0.04, respectively. The margins of error (MOEs) Nonalcoholic Steatohepatitis from A Multicenter RCT Study
of the PDFF measured by the ROI and WLS were 1.51% and 1.46%, Chang Xiu Juan1, Yang Yong Ping1, Chen Yong Ping2, Shang Qing
respectively. The agreement between the two methods was excellent, Hua3, Yu Zu Jiang4, Tan Lin5, Liu Hua Bao6, Jiang Li7, Xiao Guang
with an ICC of 0.996 (95% CI, 0.995-0.997). The bias was 0.06% Ming 8, Chen Liang 9, Lu Wei 10, Hu Xiao Yu11, Wang Jing12, Wang
(95%CI: -0.14% -0.12%). ROI and WLS showed similar diagnostic Xiao Dong13, Li Zhi Qin 14, Chen Da15
performances for steatosis grading. (AUC: ROI = 0.995, 0.951, 0.924; 1
the Fifth Medical Center of Chinese PLA General Hospital, 2The First
WLS = 0.995, 0.951, 0.928; P = 0.70, 0.83, 0.17, respectively) Affiliated Hospital of Wenzhou Medical University, 3the 960th Hospital
Conclusion: The WLS model exhibited higher agreement, less of Chinese PLA,, 4Department of Infectious Disease, the First Affiliated
variability, and similarly excellent diagnostic efficacy compared to Hospital of Zhengzhou University, 5Department of Liver Disease,
the ROI method. Therefore, it could be an alternative to the ROI for Fuyang 2nd People’s Hospital, 6Traditional Chinese Medicine Hospital
quantifying hepatic steatosis in patients with MASLD. of Chongqing, 7Department of Infectious Diseases, Southwest
Table and Figure:Figure 1.Diagnostic performance of ROI-PDFF and Hospital, Army Military Medical University, 8Guangzhou 8th People‘s
WLS-PDFF in detecting steatosis grades Hospital, 9Department of Hepatic Diseases, Shanghai Public Health
Figure 2.Comparison of proton density fat fraction based on manual Clinical Center, 10Tianjin Second People‘s Hospital, Tianjin Institute
ROI and AI-WLS. A. Linear regression fit plots; B. Bland- Altman plots of Hepatology, 11National Integrative Medicine Clinical Base for
showing smaller bias and limits of agreement Infectious Diseases and Department of Infectious Diseases, Affiliated
Hospital of Chengdu University of Traditional Chinese Medicine,
1
2Affiliated Traditional Chinese Medicine Hospital of Southwest
OP0107 Medical University, 13Department of Infectious and Liver Diseases,
Epigenetic regulation of H3K27ac-Mediated Gene Expression Liver Research Center, the First Affiliated Hospital of Wenzhou
Reveals TDO2 as a Pivotal Therapeutic target in Metabolic Medical University, 14Center of Therapeutic Liver Disease, the 960th
Associated Steatohepatitis Liver Disease Hospital of Chinese PLA, 15Fuzhou Infectious Diseases Hospital
Xuejin Lu1, Jin Peng1, Mingzhu Cui1, Danhong Wang1, Xingyue Pei1, Background: Purpose: Although concomitant nonalcoholic
Fei Zheng1, Yulin Chen1, Yuxuan Yan1, Shulei You1, Yunshu Tang1, steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the
Yaling Zhu1 long-term prognosis of CHB patients concomitant with NASH remain
unclear. We aim to explore the outcomes of CHB patients with NASH traditional anticoagulants.
receiving antiviral treatment.
Method: Methods: This study was based on a 14 centers, prospective,
OP0110
randomized controlled trial (NCT01965418) in China, 1000
CHB patients with biopsy-proven histological significant fibrosis with or Intrahepatic immune cell profiling in advanced chronic liver
without NASH were recruited, and treated them for more than 7 years disease: unraveling etiology-specific patterns with single-cell
with entecavir (ETV)-based therapy (ETV plus Biejiaruangan vs. ETV sequencing analysis
plus Placebo: 1:1). 727 patients received the second (at week 72) liver Jing Liu1, Sumeng Li1, Zibiao Zhong2, Anxiong Liu2, Junming Shi3, Shu
biopsies. The primary endpoint was the incidence of liver cancer, and Sheng3, Fei Deng3, Qifa Ye2, Jun Wu1, Xin Zheng1
the secondary endpoints were decompensated cirrhosis, and death. 1
Department of Infectious Diseases, Institute of Infection and
Result: Results: Among the 1000 CHB patients, 69.9% patients were Immunology, Union Hospital, Tongji Medical College, Huazhong
male, the adverage age of 42 years, 182 CHB patients with NASH, and University of Science and Technology, 2Transplant Center of Wuhan
818 without NASH. At week 72, 136 CHB patients combined with NASH, University, Institute of Hepatobiliary Diseases of Wuhan University,
591 without NASH. After a follow up of 7.5 years, 65(6.5%) , 3(0.3%), Zhongnan Hospital of Wuhan University, 3CAS Key Laboratory of
and 17(1.7%) patients developed hepatocellular carcinoma(HCC), Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese
decompensated cirrhosis, and death. The incidence of HCC in CHB Academy of Sciences
patients with NASH was similar to those without NASH at baseline (6.5% Background: Advanced chronic liver disease (ACLD) is responsible
vs. 6.6%, P = 0.975). In addition, the incidence of HCC in CHB patients for the majority of deaths in patients with cirrhosis. Immune cells appear
with NASH was still similar to those without NASH at week 72 (6.1% to play a crucial role in ACLD; however, the intrahepatic immune cells
vs. 5.9%, P = 0.817). Then, decompensated cirrhosis and death of the may differ and have not been investigated in depth to date in different
CHB patients with NASH was similar to those without NASH at baseline aetiologies.
and week 72. Besides, the resolution of NASH was unrelated with the Method: Liver samples were collected from patients with ACLD and
incidence of HCC (P = 0.475). Furthmore, the LASSO and Multivariable their controls (healthy liver). Specifically, liver tissue samples from
Cox proportional regression analysis indicated that therapy (HR: 0.46, patients with ACLD included those with chronic hepatitis B virus (HBV),
P = 0.003 ), cirrhosis (HR: 2.61, P = 0.017 ), and HBV DNA (HR: 0.72, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH). Single-
P = 0.041 ) were independent factors of the incidence of HCC, while, cell RNA sequencing was used to analyze the immune characteristics
NASH at baseline (P = 0.765 ) and NASH at week 72 (P = 0.784 ) were of 17,746 cells.
not. Result: Single-cell RNA sequencing analysis showed a high
Conclusion: Conclusions: The long-term prognosis of CHB patients percentage of classical monocytes, cDC2, and macrophages
with or without NASH on antiviral treatment were similar, especially, in AIH; FCGR3A+ NK cells, effector CD8+ T cells (CD8Teff) and
for the incidence of HCC. It provides the reliable evidence-based effector memory CD8+ T cells (CD8Tem) in ALD; and FCGR3A+ NK,
evidence for the clinical management of CHB patients with NASH. CD8Tem, CD8+ mucosal-associated invariant T cells (CD8MAIT) and
Table and Figure:Figure 1.Patient flow chart XCL1+ NK cells in the HBV group. Compared to a healthy liver, the
Figure 2.The incidence of hepatocellular carcinoma (HCC) in CHB AIH group had higher levels of classical monocytes, cDC2, and non-
patients with NASH or without NASH classical monocytes. The ALD group had elevated effector memory
CD8+ T cells (CD4Tem), CD8Teff, tissue-resident memory CD8+ T
cells (CD8Trm), FCGR3A+ NK cells, and non-classical monocytes.
OP0109
In the HBV group, CD8Trm and FCGR3A+ NK cells were significantly
Direct Oral Anticoagulants for Budd-Chiari Syndrome Following increased. Monocyte and cDC2 levels were higher in the AIH group
Percutaneous Angioplasty in A Chinese Cohort compared to the ALD and HBV groups. In contrast, the ALD group had
Chengjian Wu1, Zhaoyan Gao1, Yi Shen1, Xuefeng Luo1 significantly higher CD8Teff and CD4Tem subpopulations compared
1
Department of Gastroenterology and Hepatology, Laboratory of to AIH and HBV. The UCell enrichment analysis demonstrated that
Gastrointestinal Cancer and Liver Disease, West China Hospital, the CD4 Tem, CD8 Teff and FCGR3A+ NK cells in the ALD and HBV
Sichuan University groups exhibited augmented cytotoxicity in comparison to the healthy
Background: Direct oral anticoagulants (DOACs) have been widely liver. Conversely, the cCD2 in the AIH group displayed heightened
used to treat various thrombotic disorders. However, data regarding cytotoxicity in contrast to the ALD and HBV groups. In addition,
their use in patients with Budd-Chiari syndrome (BCS) are limited. The classical monocytes in ALD, HBV and AIH groups showed a stronger
present study was designed to assess the efficacy and safety of antigen presentation signature than those in the healthy liver. Further
DOACs in a Chinese population with BCS. analysis showed that CD8Teff and CD4Tem cells were more cytotoxic
Method: Between August 2020 and August 2024, patients with BCS than other immune cells, whereas XCL1+ NK, CD8Trm, and CD8Tem
who received DOACs following percutaneous transluminal angioplasty cells were functionally exhausted. FCGR3A+ NK cells had both
(PTA) were retrospectively evaluated. The primary outcome was the traits. The GO enrichment analysis revealed that FCGR3A+ NK cells
proportion of patients free from restenosis; secondary outcomes were enriched in genes related to the regulation of NK cell-mediated
included bleeding and death. cytotoxicity pathway and T-cell activation, while cCD2 was enriched in
Result: A total of 88 patients who received DOACs following PTA genes associated with the positive regulation of cytokine production.
were included in the analysis, with a mean age of 46.4 ± 13.1 Cellular communication showed that cDC2 and monocytes might
years. 44 patients received rivaroxaban, and the other 44 crosstalk via CD160-TNFRSF14 ligand-receptor interaction, while
patients received dabigatran. 67 patients (76%) had cirrhosis, and FCGR3A+ NK cells and CD8+ T cells receptor-ligand pair via CD55-
11 patients (13%) had a history of variceal bleeding. The median ADGRE5(CD97) interactions.
duration of DOAC therapy was 20.3 (interquartile range, 8.6 to 28.6) Conclusion: Our study reveals the diverse roles of intrahepatic
months. The median follow-up time was 22.6 (interquartile range, 14.4 immune cells and the dysfunctional immune microenvironment in
to 31.6) months. The 1- and 3-year accumulative patency rates were ACLD, providing new insights into its immunopathogenic mechanisms.
77.8% and 68.7%, respectively. 5 major bleedings (5.7%; incidence rate Table and Figure:Figure 1.Single-cell RNA-sequencing (scRNA-
3.4 per 100 patient-years; n = 4 upper gastrointestinal bleeding, n = 1 seq) based on BD Rhapsody and clustering of cells during ACLD.
severe epistaxis with a decrease in hemoglobin by more than 2.0 g/L), T-distributed stochastic neighbor embedding (tSNE) plot of T and NK
9 minor bleedings (10.2%; incidence rate 6.0 per 100 patient-years; (a), mononuclear phagocytes (MPs) (d), clusters were identified by
n = 5 gingival bleeding, n = 2 epistaxis, n = 2 menorrhagia) occurred the integrated analysis, colored by cell cluster. Gene set enrichment
during DOAC therapy. Two patients died during follow-up (one from analysis showed the cytotoxicity signature score of CD4 Tem and CD8
hepatocellular carcinoma and another from hepatorenal syndrome). Teff cells (b),classical monocytes (e). Differentially expressed gene
Conclusion: DOACs are safe and effective in patients with BCS (DEG) of FCGR3A+ NK cells (c) and cDC2 (f).
following PTA. Further study is required to compare them with Figure 2.Cell-cell communication. The net of interactions between
immune cells in the liver (a). Interactions between cDC2 (b), FCGR3A+ OP0112
NK cells (c) and immune cells (C). Circos plot showing the weights/ Study on the indications and prognosis of glucocorticoids in
strength of interactions between ligands and receptors across cell patients with acute-on-chronic liver failure
types.
Jiaxuan Zhou1, Rongkuan Li1, Xiaotong Ai1, Xinmei Chen1
1
The Second Hospital of Dalian Medical University
OP0111
Background: Acute-on-chronic liver failure (ACLF) is a syndrome
National survey of awareness of human serum albumin indications characterized by rapid progression of organ failures with a high short-
and actual practice in decompensated cirrhosis among physicians term mortality rate. Presently, the treatment of ACLF lacks specific
in China drugs. There are different opinions on the use of glucocorticoids
Chenxi Zhang1, Dandan Weng2, Ziqiang Li1, Wanhua Ren3, Ying Guo4, as immune and inflammatory agents in the treatment of liver failure.
Xiaozhong Wang5, Li Shi6, Xiao Lu7, Zhuping Qian8, Baoyan An1, Some studies show that glucocorticoids are effective while others
Haiguang Xin1, Zhujun Cao1, Qing Xie9 think they are ineffective. In order to clarify the therapeutic role and
1
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao clinical indicators of glucocorticoids in patients with ACLF, this study
Tong University School of Medicine, 2Department of Infectious is designed.
Diseases, Yuyao People’s Hospital, 3SHANDONG PROVINCIAL Method: Patients who were admitted to the Second Affiliated Hospital
HOSPITAL, 4Third People‘s Hospital of Taiyuan, 5Traditional Chinese of Dalian Medical University from 2010.01 to 2024.09 were the
Medicine Hospital of Xinjiang Uygur Autonomous Region, 6TIBET subjects. They all met the Asian Pacific Association for the Study of
AUTONOMOUS REGION PEOPLE‘S HOSPITAL, 7Infectious Disease the Liver (APASL) consensus on the management of ACLF. Exclusion:
Center, The First Affiliated Hospital of Xinjiang Medical University, under age 18 or over 80, discharged from the hospital or died within 48
Urumqi, China., 8Department of Nursing, Ruijin Hospital, Shanghai hours of admission, received liver transplantation, had hepatocellular
Jiao Tong University School of Medicine, 9Department of Infectious carcinoma or other organ malignancies, used immunosuppressive
Diseases , Ruijin Hospital, Shanghai Jiao Tong University School of drugs or were infected by HIV. Among 1062 ACLF cases, a total of
Medicine, Shanghai, China 701 meeting the inclusion and exclusion criteria were collected. We
Background: Surveys from European and North American societies randomly selected 213 patients who were divided into survival and
suggested that human serum albumin is commonly prescribed beyond death group according to the 28-day prognostic outcome. Univariate
the evidence-based indications in the management of decompensated and Multivariate COX analysis were performed to determine the
cirrhosis. We aimed to assess the awareness of human serum albumin independent prognostic factors affecting the 28d mortality. The clinical
indications and actual practice among physicians in China. indications for the use of glucocorticoids were analyzed according to
Method: This was a cross-sectional, nation-wide, questionnaire-based the prognosis. ACLF patients who used glucocorticoids were randomly
survey study completed in November 2024. Physicians across China sampled and divided into training and validation group according to
were invited to participate and answer pre-specified questions through the ratio of 7:3. After Univariate and Multivariate COX analysis, we
the wenjuanxing pop-up (a Wechat-powered survey platform). The achieved the independent risk factors and constructed the prediction
questionnaire included information on personal and practice settings model. The area under the ROC curve of CLIF-C ACLFs, AARC, CTP,
of the physicians, their perspective and prescription on albumin use MELD, COSSH-ACLFs and the established prediction model were
and also the knowledge on the mechanisms of albumin in cirrhosis and compared (Figure 1).
potentially expanding indications. Result: Glucocorticoid therapy, PLT, CD3, absolute lymphocyte value,
Result: A total of 1034 physicians across China were invited and 957 IL-6, and PT were independent prognostic factors for the prognosis of
(93%) completed the survey (Figure 1&2). Detailed information on ACLF at 28 days. For patients with hormone therapy, IL-6, IL-10, PLT,
physicians’ experiences and their practice settings were summarized and ALB were independent prognostic factors for 28-day prognosis.
in Table 1. Most of the physicians were sure about the indications of IIPA score was constructed (Logit(P)=18.531+0.244*IL-10+0.377*IL-
albumin in the prevention of circulatory dysfunction after paracentesis, 6-1.211*ALB-0.03*PLT). The area under the ROC curve of IIPA and
but such certainty decreased for HRS treatment and further decreased other scores in the training group were 0.984, 0.824, 0.797, 0.784,
in the treatment of SBP and differential diagnosis for HRS. Beyond 0.735 and 0.718, respectively (Fig. 2a).The area under the ROC
the three established indications, hypoalbuminemia, treatment of curve in the validation group were 0.881, 0.852, 0.776, 0.774, 0.733
ascites and/or hydrothorax and edema were frequently considered and 0.629, respectively (Fig. 2b).
as indications (Figure 3). In real practice, hypoalbuminemia is the top Conclusion: For ACLF patients, the application of glucocorticoids during
condition for which physicians most frequently prescribed albumin, with the treatment can improve their 28d prognosis. The value of IIPA model
other non-indicated conditions also ranking among the top positions is super than CLIF-C ACLFs, AARC, CTP, MELD, and COSSH-ACLFs
on the list (Figure 4). Most respondents considered key limitations of score in evaluating the 28d prognosis of ACLF patients treated with
albumin use were national health insurance policies (92%) and national glucocorticoids.
health assessment policies (94%) and half of the physicians had to Table and Figure:Figure 1.Flowchart of training group and validation
withdraw albumin infusion because of policy limitation. In patients with group cases screening
SBP, 72% of physicians agreed albumin administration with antibiotics Figure 2.Compare the area of ROC curves to determine prognostic
for preventing renal failure, of whom only 32% used albumin strictly accuracy. (a) Training group. (b) Validation group.
according to guideline. 62% and 81% of respondents used albumin
in patients with AKI in suspicion of HRS and treatment of HRS-AKI,
OP0113
respectively. Moreover, 96% physicians agreed patients with ascites
would benefit from long-term albumin infusion attributed to non- Development of a Novel Prognostic Model for Evaluating Survival
oncotic functions. Among those did not support long-term albumin Outcomes in Patients with Acute-on-Chronic Liver Failure
infusion, limitations were high cost (86%), incomplete compliance Wende Li1, Wanshu Liu2, Yihui Rong1, Dongze Li2, Bing Zhu2, Shaobo
(51%), infusion unavailable in outpatient clinic (46%), and insufficient Yang1, Shidong Sun1, Shaojie Xin2, Shaoli You2, Yu Chen3, JUN LI4
evidence (45%). 1
Peking University International Hospital, 2Fifth Medical Center of
Conclusion: In this national survey, albumin is under-dosed for Chinese PLA General Hospital, 3Beijing Youan Hospital, Capital
evidence-based indications but overused for off-label purposes. While Medical University, 4Zhejiang University School of Medicine First
the recognition of its benefits from long-term use is high, barriers such Affiliated Hospital
as cost, accessibility, and insufficient local evidence continue to hinder Background: Acute-on-chronic liver failure (ACLF) is associated with
its practical application. a high rate of short-term mortality, highlighting the need for reliable
Table and Figure:Figure 1.Figure1&2, Table 1 prognostic tools to enhance patient management and optimize liver
Figure 2.Figure3&4 transplant allocation. Current prognostic scores have limitations in
accurately predicting short-term survival in patients with ACLF. This
study aims to identify risk factors and develop new prognostic models Medical Centre, Chuncheon, Republic of Korea, 16302, Military
for this patient population. Hospital, China, 17Dayanand Medical College, Ludhiana, India,
Method: A retrospective analysis was conducted involving 1,386 1
8Department of Gastroenterology and Hepatology Sciences, IMS
patients with ACLF who were admitted to a medical facility between & SUM Hospital, Bhubaneswar, Odisha, India, 19Department of
2010 and 2018. Both univariate and multivariate statistical analyses Medicine, Chulalongkorn University, Bangkok, Thailand, 20Department
were utilized to identify independent predictors of 28-day mortality of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan,
in patients who did not undergo liver transplantation (LT). A novel Armenia, 21Ankara University, 22Department of Medicine, University of
prognostic score was subsequently developed and validated using an Santo Tomas, Manila, Philippines, 23Dr. Ziauddin University Hospital
external test cohort. Clifton Karachi, 24Department of Hepatology, Alka Hospital, Nepal,
Result: Univariate analysis revealed several factors associated with 28-
2
5Humanity & Health Medical Group, 26Fatima University Medical
Center Manila, Manila, Philippines, 27POST GRADUATE INSTIUTE
day mortality. Multivariate analysis identified hepatic encephalopathy
OF MEDICAL EDUCATION AND RESEARCH CHANDIGARH INDIA,
(HE) grade, pulmonary infection (PI), spontaneous bacterial peritonitis 2
8Asian Institute of Gastroenterology, Hyderabad, India, 29AIG
(SBP), age, ACLF subtype, international normalized ratio (INR),
hospitals HYDERABAD INDIA, 30Sir Salimullah Medical College
neutrophil count, and the model for end-stage liver disease (MELD)
Hospital, Bangladesh, 31Chiba University, Japan., 32 CMOSH
score as independent predictors. The newly developed prognostic Medical College, Bangladesh, 33Global Hospitals, Hyderabad, 34Max
score demonstrated superior areas under the receiver operating Super Specialty Hospital, Saket New Delhi, India, 35Department of
characteristic curves (AUROCs) for predicting both 28-day and 90- Gastroenterology and Hepatology, Sir Ganga Ram Hospital New
day mortality compared to existing models such as the ALBI, MELD, Delhi, India., 36Lakeshore Hospital. Kochi (India), 37KGMC, Lucknow
and MELD 3.0 (0.863 and 0.853, respectively; all p < 0.05). The (India), 38Mansoura University, Egypt, 39TN Medical College and BYL
sensitivity and specificity of the MELD-complication score were found Nair Hospital, 40SMS Jaipur, India, 41IGIMS, Patna, India, 42Cipto
to be 77.89% and 77.81%, respectively, with a cut-off value of 2.58, Mangunkusumo Hospital, Indonesia, 43Cipto Mangunkusumo National
indicating significant survival differences between groups above and General Hospital, 44Queen Mary Hospital, The University of Hong
below this threshold. Furthermore, the new model exhibited robust Kong, 45Punjab Institute of Liver and Biliary Sciences, Mohali, India,
performance in external cohorts. 4
6Violeta Medical Centre, Armenia, 47University of Malaya Medical
Conclusion: The newly developed prognostic score offers a more Centre, Malaysia, 48SMNC, Jodhpur, India, 49G.B. Pant Hospital, New
precise assessment of short-term mortality in patients with ACLF Delhi, India, 50SUM Ultimate Medicare, Bhubaneswar, India, 51Linkou
compared to traditional scoring systems such as MELD, MELD 3.0, Chang Gung Memorial hospital, Taiwan, China, 52Aster Medicity,
and ALBI. This score serves as a valuable tool for clinical decision- Kochi, India , 53Institute Of Liver And Biliary Sciences New Delhi
making and prognostic evaluation in this high-risk population. Background: Background Acute-on-chronic liver failure (ACLF)
Table and Figure:Figure 1.Figure 1 is associated with high mortality. The role of therapeutic plasma
Figure 2.Graphical Abstract exchange (TPE) is not clear in the management of ACLF population.
We evaluated the role of TPE in management of patients with steroid
OP0114 ineligible (mDF score &gt;90) severe alcohol-ACLF with no liver
transplant option.
PLASMA EXCHNAGE IN ACLF ALCOHOLIC HEPATITIS PATIENTS
Method: Methods We done the prospective analysis of the
WITH mDF&gt;90 improves 28-day survival but poor 90-day
retrospective collected data of Alcohol- ACLF patients from the AARC
survival.
database as defined by APASL criteria with mDF&gt;90 who received
Vinod Arora1, Ashok Choudhury2, Rakhi Maiwall2, Mohd Rela3, Dinesh TPE. Primary and secondary objectives were to assess the 28-day and
Jothimani3, Mamun Al Mahtab4, Harshad Devar Bhavi5, C E Eapen6, 3-month survival, and efficacy and safety of TPE.
Ashish Goel6, Cesar Yaghi7, Qin NING8, Tao Chen8, Jidong JIA9, Result: Results Of the database of 10306 patients, we evaluated 3400
Zhongping DUANZhongping10, Saeed Hamid11, Amna Subhan Butt12, patients with Alcohol-ACLF of which 840/3400 (24.7%) patients had
Akash Shukla13, Soek Siam Tan14, Dong Joon Kim15, Jinhua Hu16, Alcohol-ACLF with mDF &gt;90, of which 129/840(15.4%) underwent
AJIT SOOD17, Omesh Goyal17, Vandana Midha17, MANOJ SAHU18, TPE. Mean CTP, MELD, DF, AARC score were 12.5  1.8; 27.7  7.4;
SOMBAT TREEPRASERTSUK19, KESSARIN THANAPIROM19, 130.15  24.5; 10.5  1.5. Mean number of TPE sessions given were
Hasmik Ghazinyan20, Abdulkadir Dökmeci21, JOSE SALLANO22, 3.4  1.2. 7-day and 28-day survival was 90/129 (69.7%); 66/129
Zaigham Abbas23, Ananta Shrestha24, George LAU25, Diana (51.1%) patients; 3-month survival was noted in 15/129 (11.6%)
Payawal26, AJAY DUSEJA27, SUNIL TANEJA27, NIPUN VERMA27, PN patients. Mean reduction in CTP and MELD at day 7 was noted {-3.1
RAO28, Anand V Kulkarni29, MITHUN SHARMA29, FAZAL KARIM30,  1.2; 7.5  3.2) however increase in MELD score to almost baseline
Osamu Yokosuka31, Debasis Choudhury32, Chandan Kumar33, Sanjiv was noted at day 28 in 50/66 (75.5%) survivors at day 28 i.e. 3/4 th of
Saigal34, Anil Arora35, Ashish Kumar35, Abraham Koshy36, Ajay Kumar the patients who underwent TPE. Adverse events were seen in 70/129
Patwa37, Mohamed Elbasiony38, Pravin Rathi39, Sudhir Maharshi40, (54.2%) patients. Discontinuation of TPE post first session was seen in
VM Dayal41, Ashish Kumar Jha41, Kemal Fariz Kalista42, Rino Gani43, only 10/129 (7.7%) of the patients. Sepsis was seen in 54/129 (41.8%)
MF Yuen44, Virendra Singh45, Sargsyan Violeta46, Ruveena Bhavani47, of the patients, pneumonia being the commonest in 29/129 (22.5%)
Sunil Dadhich48, Sanjeev Sachdeva49, Ayaskanta Singh50, Chieu Hao patients. Mean duration to sepsis post TPE was not available which
Huang51, Charles Panackel52, SHIV KUMAR SARIN53 remains a limitation of study.
1
Institute of Liver & Biliary Sciences, Vasant Kunj, New Delhi, 2Institute Conclusion: Conclusions TPE remains an effective therapeutic
of Liver and Biliary Sciences, New Delhi, India, 3Dr Rela Institute option in ACLF AH with high DF score; however, it provides short-term
Chennai India, 4Department of Hepatology, Bangabandhu Sheikh benefit. Whether reduction of MELD at day 7 with TPE opens window
Mujib Medical University, Dhaka, Bangladesh, 5Department of for introduction of steroid therapy in patients with no transplant options
Hepatology, St John Medical College, Bangalore, India, 6Department needs to be determined.
of Hepatology, CMC, Vellore, India, 7Saint Joseph University,
Figure 2.PLASMA EXCHNAGE IN ACLF ALCOHOLIC HEPATITIS
Lebanon, Beirut, 8Tongji Hospital, Tongji Medical College,Huazhong
PATIENTS WITH mDF>;90 improves 28-day survival but poor 90-day
University of Science and Technology, 9Tongji Hospital, Wuhan,
survival.
China, 10Hepatology Institute Capital Medical University, China,
1
1Department of Medicine, Aga Khan University Hospital, Karachi,
Pakistan, 12Department of Medicine Aga Khan University Karachi OP0115
Pakistan, 13Department of Gastroenterology, Lokmanya Tilak The Fujian Mobile Application based HBV Screening Program:
Municipal General Hospital and Lokmanya Tilak Municipal Medical Increased Linkage to Care Through Technology?
College, (LTMMC), Mumbai, India.Department of Medicine Aga Khan
University Karachi Pakistan, 14Department of Medicine, Hospital Lai Wei1, Jinlin Hou2, Fuqiang Cui3, Qing Xie4, Devin Razavi-Shearer5,
Selayang, Bata Caves, Selangor, Malaysia., 15Hallym University Homie Razavi5, Jidong Jia6
1
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung
Hospital, Tsinghua University, 2Guangdong Institute of Hepatology, (HBV) infected population diagnosed and 80% antiviral treatment
Hepatology Unit and Department of Infectious Diseases, Nanfang coverage. China has 30% of the global burden of HBV, and recently
Hospital, Southern Medical University, 3School of Public Health, has taken a strong step towards elimination by adopting the most
Peking University, 4Department of Infectious Diseases, Shanghai Ruijin simplified treatment guidelines. Guangdong province has historically
Hospital, Jiaotong University School of Medicine, 5Center for Disease had a high prevalence of HBV and recently implemented a plan to
Analysis Foundation, 6Liver Research Center, Beijing Friendship screen 20 million individuals over the age of 30 in the least developed
Hospital, Capital Medical University parts of the province, reaching 70% coverage by the end of 2026. This
Background: In 2016, the WHO set out to eliminate viral hepatitis study aimed to utilize mathematical modeling to measure the potential
by 2030, proposing specific targets, including 90% of the hepatitis B impact of the Guangdong Plan and how linkage to care rates will be
virus (HBV) infected population diagnosed and 80% antiviral treatment instrumental.
coverage. China, the country with the largest share of HBV burden, Method: The PRoGReSs model was populated with Guangdong
has recently taken a leadership role in HBV elimination by adopting specific population and epidemiological data. The Guangdong Plan
the most simplified treatment guidelines. Fujian province historically was assumed to meet the set targets of 10% diagnosis in 2024,
has had a high prevalence of HBV and recently implemented a plan to 30% in 2025 and 70% by the end of 2026. The counterfactual, Base
utilize a mobile based application system to increase linkage to care 2023, assumed that no Guangdong Plan had been adopted and that
within their large-scale screening program. In 2024, they screened 2 17% of those newly diagnosed were linked to care. The Guangdong
million individuals for HBV. This study aimed to utilize mathematical Plan scenario examined the impact of maintaining a 17% linkage to
modeling to measure the potential impact of the Fujian Plan. care rate, but with the higher levels of diagnoses. Guangdong Plan
Method: The PRoGReSs model was populated with Fujian specific 35% Linkage examined the impact of doubling the linkage to care to
population and epidemiological data. Fujian province was assumed 35%, and the Guangdong Plan Elimination examined the impact of
to meet targets of 10% diagnosis in 2024, 30% in 2025 and 70% by increasing linkage to care to 70%, while also turning attention from
the end of 2026. The counterfactual, Base 2023, assumed that no screening to treatment in 2027 treating 80% of the total diagnosed
Fujian Plan had been adopted and that 17% of those newly diagnosed population by 2030.
were linked to care. The Fujian Plan scenario examined the impact Result: The Guangdong Plan is estimated to save 9,000 lives through
of  increasing diagnoses, while maintaining 17% linkage to care. The 2035, averting 6,000 incident cases of decompensated cirrhosis
Fujian Plan 35% Linkage scenario examined the potential impact of the and 7,000 cases of hepatocellular carcinoma (HCC) (Figure 1).
mobile application increasing linkage to care to 35%. The Fujian Plan Guangdong Plan 35% Linkage is estimated to save 24,000 lives
Elimination examined the impact of increasing linkage to care to 70%, through 2035, averting 17,000 incident cases of decompensated
while also turning attention from screening to treatment in 2027 treating cirrhosis and 19,000 cases of HCC. If Guangdong was able to link
80% of the total diagnosed population by 2030. 70% of those newly diagnosed to care and increase treatment in the
Result: The Fujian Plan is estimated to save 8,000 lives through 2035, previously diagnosed population, meeting the WHO 2030 guidelines,
averting almost 6,000 incident cases of hepatocellular carcinoma 142,000 lives would be saved through 2035, growing to over 641,000
(HCC) (Figure 1). If the mobile application is able to double linkage lives through 2050.
to care to 35%, then the same plan is estimated to save 19,000 lives Conclusion: The Guangdong Plan is estimated to result in Guangdong
through 2035, averting 14,000 cases of hepatocellular carcinoma. If Province meeting the WHO 2030 target of 90% of the infected population
Fujian Province is able to link 70% of those newly diagnosed to care and being diagnosed by 2030. However, linkage to care must be increased
increase treatment in the previously diagnosed population, meeting to have the maximum impact. The new guidelines provide the ability
the WHO 2030 guidelines, 60,000 lives would be saved through for non-specialists to provide treatment for simple HBV cases, which
2035, averting 43,000 incident cases of decompensated cirrhosis and could increase the linkage to care. However, in addition to the large-
47,000 cases of HCC. The impact of the program is projected save scale screening program, there must be concerted efforts to link those
over 229,000 lives through 2050. previously diagnosed to care in order save over half a million lives in
Conclusion: The Fujian Plan is estimated to result in Fujian province the next 25 years.
meeting the WHO 2030 target of 90% of the infected population being Table and Figure:Figure 1.Estimated disease burden of hepatitis B
diagnosed by 2030. The use of a mobile application will likely greatly virus by scenarios in Guangdong Province (2022–2035)
increase linkage to care. While this is a great improvement compared to
the baseline, linkage to care must be increased to maximize the impact OP0117
of the screening program. New Chinese guidelines are simplified
enough to allow non-specialists to provide treatment for simple HBV The cost-effectiveness of albumin in the management of
cases, which could further increase the linkage to care. The screening hepatorenal syndrome in patients hospitalized for decompensated
program combined with the mobile application can provide evidence cirrhosis in urban China
to inform national implementation guidelines. Xiaoyuan XU1, Cristina Coll-Ortega2, Lungen LU3,4, Qing XIE5,4, Liu
Table and Figure:Figure 1.Estimated disease burden of hepatitis B Yang6, Elisabet Viayna2, Cristina Fuster2, Mafalda Ramos7, Mark
virus by scenarios in Fujian Province (2022–2035) Lamotte7
1
Peking University First Hospital, Beijing, China, 2Grifols SA, Sant
Cugat del Valles, Spain, 3Shanghai General Hospital, Shanghai,
OP0116 China, 4Shanghai Jiao Tong University School of Medicine, 5Ruijin
The Guangdong HBV Screening Program: A Template for China? Hospital, Shanghai, China, 6Grifols Pharmaceutical Technology,
Lai Wei1, Jinlin Hou2, Fuqiang Cui3, Qing Xie4, Devin Razavi-Shearer5, Shanghai, China, 7Th(is)²Modeling bv, Asse, Belgium
Homie Razavi5, Jidong Jia6 Background: Human albumin (HA) is an effective adjuvant treatment
1
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung for patients with decompensated cirrhosis (DC) with hepatorenal
Hospital, Tsinghua University, 2Guangdong Institute of Hepatology, syndrome (HRS). Even though, Chinese guidelines recommend HA
Hepatology Unit and Department of Infectious Diseases, Nanfang in patients with DC and HRS, its cost remains a barrier, particularly
Hospital, Southern Medical University, 3School of Public Health, in resource-limited settings. This study aims to assess the cost-
Peking University, 4Department of Infectious Diseases, Shanghai Ruijin effectiveness of HA in patients with DC hospitalized for HRS from the
Hospital,Jiaotong University School of Medicine, 5Center for Disease healthcare provider’s perspective in certain urban areas in China.
Analysis Foundation, 6Liver Research Center, Beijing Friendship Method: A decision-tree model with a short and a long-term time
Hospital, Capital Medical University horizon was developed to assess the cost-effectiveness of the
Background: In 2016, the World Health Assembly approved the vasoconstrictor terlipressin (T) and HA versus T alone in patients with
WHO Global Health Sector Strategy on Viral Hepatitis, which aims DC and HRS (Figure 1). It is assumed that HRS may resolve or not,
to eliminate viral hepatitis as a major public health threat by 2030, and that patients may develop other complications such as severe
proposing specific targets, including 90% of the hepatitis B virus bacterial infections, variceal bleedings, HRS reoccurrence, undergo
liver transplant (LT), and/or die. Clinical inputs were extracted from the In 5,028 patients with HCV genotype 1b, LDV/SOF achieved a 99.6%
literature and included complete response (HA + T versus T alone: sustained virologic response (SVR12), compared to 69.6% in 23
77% vs 25%), occurrence of the aforementioned complications (15% patients with genotype 1a. Baseline Y93H mutation rates impacted
vs 50 %), recurrence of HRS (8% vs 13%), LT (38% vs 0%) and outcomes: SVR12 was achieved in patients with Y93H <1% but failed
mortality (46% vs 88%). Urban Chinese-specific utility and cost inputs in 8 patients with Y93H >90%. Adverse effects included headache
were obtained from the literature representative for at least 13 cities. (9.4%), fatigue (6.2%), and abdominal pain (5.9%).
The dose of HA used in the clinical trial was applied (1 gram/kg on HCC etiology was predominantly HCV (45.6%), followed by HBV
day 1 and 20-40 g/day for the next 14 days). The average weight (34.4%) and HBV co-infection (14.4%). Most patients (74.3%) had
of Chinese males and females was used to calculate the total dose. advanced-stage HCC (TNM stage III/IV). Treatment included surgical
The price of HA was assumed to be 38.6CNY (5.5USD - exchange resection (13.8%), radiofrequency ablation (11.8%), and transarterial
rate Sep 30, 2024: 1 USD = 0.14CNY). Time horizon for the short- chemoembolization (54.9%). Median survival was 19, 11, and 17
term model was 3 months. Patients surviving the first 3 months had months, respectively. Independent predictors of survival included
an extended life expectancy of 10 years for those undergoing LT and tumor size, metastasis, TNM stage, and treatment modality.
2 years for those not undergoing LT (annual discounting of 3% was Conclusion: This study highlights the decline in HBV and HBV/HDV
applied on costs and health outcomes). Outcomes were expressed as superinfection prevalence in Mongolia, with high treatment success
the incremental cost-effectiveness ratio (ICER) reported as CNY/USD rates for HCV genotype 1b using Ledipasvir/Sofosbuvir. Despite
per quality-adjusted life year (QALY). The willingness-to-pay (WTP) progress, behavioral risk factors and advanced liver cancer at
threshold was three times the GDP per capita (268,038CNY/QALY; diagnosis remain significant challenges, underscoring the need for
38,223USD/QALY). One way and probabilistic sensitivity analyses continued prevention and early detection efforts.
were conducted.
Result: HA added to T resulted in an improved survival (41%) and
OP0119
an incremental 0.079QALY gained over the 3-month time horizon and
2.37QALY for the extended time horizon. Addition of HA did also entail Clinical Profile and Patient Reported Outcomes (PROs) in Metabolic
an average incremental cost of 315,326CNY (44,966USD) per treated Dysfunction Associated Steatotic Liver Disease (MASLD) Patients
patient. The resulting ICER is 132,973CNY per QALY (18,962USD/ Enrolled in the Global NASH/MASH Registry from Asian Countries
QALY). One-way sensitivity analysis showed that the ICER was most Zobair M Younossi1,2, Ming Lung Yu1,3, Vincent WaiSun Wong1,4,
sensitive to costs and utilities of LT, both in the acute and long-term Yuichiro Eguchi1,5, Wah Kheong Chan1,6, Jiangao Fan1,7, Andrei Racila
models. The probabilistic sensitivity analyses showed that HA can JR1, Maria Stepanova1,2, Fatema Nader1,2, Saleh A Alqahtani1,8,9
be considered cost-effective in 100% of iterations using the above- 1
The Global NASH/MASH Council, Washington, DC, USA ,
mentioned WTP. 2
Beatty Liver and Obesity Research Center, Inova Health System,
Conclusion: Adjunctive HA may be considered a cost-effective Falls Church, VA, USA, 3Kaohsiung Medical University Hospital,
treatment in patients with DC and HRS in certain urban areas in China. Taiwan,China, 4Department of Medicine and Therapeutics, The
Table and Figure:Figure 1.HRS Decision tree Chinese University of Hong Kong, Hong Kong SAR, China,
5
Locomedical General Institute, Locomedical Medical Cooperation,
Saga, Japan, 6Gastroenterology and Hepatology Unit, Department of
OP0118 Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur,
Genotype distribution, clinical manifestations, therapy and Malaysia, 7Xinhua Hospital, Shanghai Jiatong University School of
molecular genetic peculiarities of virus-related liver diseases in Medicine, Shanghai, China, 8Center for Outcomes Research in Liver
Mongolian population Disease, Washington DC, USA, 9Liver, Digestive & Lifestyle Health
Oidov Baatarkhuu1,2,3, Jazag Amarsanaa3 Research Section, and Organ Transplant Center of Excellence, King
Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
1
Department of Infectious Diseases, School of Medicine, Mongolian
National University of Medical Sciences, Ulaanbaatar, Mongolia, Background: Patients with MASLD from Asia may have a different
2
Mongolian Academy of Medical Sciences, Ulaanbaatar, Mongolia, clinical and PRO profile in comparison to other regions of the world.
3
Mongolian Association for the Study of Liver Disease The aim was to assess overlap between NAFLD and MASLD as well as
Background: Hepatitis B (HBV) and C (HCV) remain major global the clinical and PRO profile of MASLD patients enrolled from real-world
health threats, contributing significantly to liver-related mortality. In practices in several Asian countries.
2019, WHO reported 1.5 million acute HBV cases and 820,000 HBV- Method: Patients from China, Hong Kong SAR of China, Taiwan
related deaths. In Mongolia, high HBV and HCV prevalence is linked Province of China, Japan, and Malaysia with an established diagnosis
to a liver cancer rate of 68.1 per 100,000, eight times the global of NAFLD or NASH enrolled in the Global Liver Registry™ (GLR) were
average. This study analyzes viral hepatitis genotype distribution, included in the study. The presence of at least one cardiometabolic
clinical manifestations, risk factors, treatment outcomes, and genetic risk factor (overweight defined as BMI >24 or clinical diagnoses of
variations, focusing on liver cancer causes and survival. type 2 diabetes, hypertension, or hyperlipidemia) was used to rule
Method: Between 2012 and 2020, 6,071 patients (ages 2–75) were in MASLD/MASH. Clinical and PRO (FACIT-F, CLDQ, and WPAI) data
enrolled across six medical centers in Mongolia. A cross-sectional were analyzed.
study of 546 acute hepatitis patients (2012-2014) assessed genotype Result: Of 8270 patients with the original diagnosis of NAFLD from
distribution. A cohort of 182 patients was followed for one year to 18 countries enrolled in the GLR, 1572 were from Asian countries.
identify behavioral risk factors. Treatment outcomes were evaluated in Of NAFLD patients with sufficient clinical data (n=1457), 90.25%
5,028 HCV patients receiving Ledipasvir/Sofosbuvir (LDV/SOF), with had at least one cardiometabolic risk factor and, therefore, met the
viral load monitored at 4, 12, and 24 weeks. Resistance mutations in criteria for MASLD. Of those with MASLD, 88% were overweight and
HCV genotypes 1a and 1b were studied in 120 patients. A retrospective 55% obese (BMI >28), 34% had type 2 diabetes, 44% hypertension,
study of 198 HCC patients examined clinical features, treatment and 40% hyperlipidemia. The mean (SD) age in MASLD was 53 (14)
modalities, and survival. years, 62% male, 19% with advanced fibrosis (by biopsy or FIB-4 or
Result: Acute hepatitis in Mongolia declined significantly over a transient elastography), 9% with history of anxiety, 7% depression,
decade: HBV (32.7% to 26.2%, p=0.001), HBV/HDV superinfection 23% clinically overt fatigue, 5% abdominal pain, 21% sleep apnea.
(27.3% to 10.8%, p=0.001), and HCV (6.4% to 6.0%). Genotype In comparison to those with MASLD, patients who did not meet the
distribution showed HAV genotype 1a (100%), HBV genotype D criteria for MASLD were younger (mean age 49 [14] years) and less
(98.5%), HCV genotype 1b (100%), and HDV genotype 1 (100%). commonly had advanced fibrosis (8%) or sleep apnea (8%) (p<0.05).
Behavioral risk factors included casual sex (AOR=2.2), tattooing Patients with MASLD and advanced fibrosis were older (mean age
(AOR=1.6), and family members with hepatitis (AOR=1.5). Chronic 61 [11] vs. 51 [14] years), less commonly male (49% vs. 62%), and
disease progression occurred in 6.7%, 40%, and 94.4% of HBV, HBV/ had more type 2 diabetes (61% vs. 33%) and hypertension (62% vs.
HDV co-infection, and HBV/HDV super-infection cases, respectively. 42%) than MASLD patients without advanced fibrosis (p<0.05) despite
similar BMI. There was no significant difference in PRO scores between Figure 2.Tables
MASLD and NAFLD from Asia: total CLDQ-NAFLD 5.75 (0.88) vs. 5.79
(0.80) on a 1-7 scale, total FACIT-F 119.8 (22.7) vs. 120.2 (23.3) on a
OP0121
0-160 scale, all p>0.05. MASLD patients with advanced fibrosis had
lower PRO scores in select domains of CLDQ-NAFLD (p<0.05 for V-001: a novel hepatitis B antiviral drug that regulates HBV DNA,
Activity/Energy and Worry domains). In multiple regression analysis, surface and e antigen by activating the PI3K-AKT-mTOR/4EBP1
independent predictors of lower PRO scores in MASLD patients from axis
Asia included age, female sex, non-hepatic comorbidities (anxiety, XiaoQuan Liu1, ZhiPing Wan1, Hong Deng1
depression, clinically overt fatigue, sleep apnea), advanced hepatic 1
1Department of Infectious Diseases, Third Affiliated Hospital of Sun
fibrosis, and the lack of regular exercise (p<0.05). Yat-sen University
Conclusion: In Asian countries, there is a 90% overlap between Background: Hepatitis B virus (HBV) serves as a primary cause of
MASLD and NAFLD. Impairment of quality of life in MASLD patients cirrhosis and hepatocellular carcinoma, necessitating the development
from Asia is driven by demographic factors, lack of regular exercise, of innovative therapeutic strategies. Our team has successfully
advanced fibrosis, and non-hepatic comorbidities. established an in vitro high-throughput screening system designed to
identify compounds capable of inhibiting the expression of Hepatitis B
OP0120 surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg). Among
the identified compounds, V-001, a drug derived from vitamins,
Human albumin uses in cirrhosis complications in China: a
emerged as a promising inhibitor, demonstrating a reduction in HBV
national questionnaire survey
DNA expression as well. The objective of this study is to evaluate the
Zhan Zeng1, Jinghang Xu1, Yifan Han2, Ning Lin1, Yanyan Yu1, impact of V-001 on the expression levels of HBsAg, HBeAg, and HBV
Xiaoyuan Xu3 DNA, as well as to elucidate its underlying mechanism of action.
1
Department of Infectious Diseases,Peking university first hospital, Method: In our study, we treated HepG2.2.15 and HepG2-NTCP
2
Department of Gastroenterology, Peking university first hospital, cells with V-001 to assess its effects on HBsAg, HBeAg, and HBV
3
Peking university first hospital DNA levels. We analyzed mRNA expression and 4EBP1 levels post-
Background: Human albumin (HA) is widely used for the treatment of treatment. To explore 4EBP1’s role in HBsAg and HBeAg regulation,
hypoalbuminemia caused by various conditions and is recommended we manipulated its expression in HepG2.2.15 cells using siRNA
in guidelines for managing ascites, spontaneous bacterial peritonitis and overexpression plasmids, monitoring changes in viral antigen
(SBP), and hepatorenal syndrome (HRS) related to liver diseases. expression. We also assessed the PI3K-AKT-mTOR pathway activity
Previously, there are survey studies in Europe and the United States following V-001 treatment. For in vivo validation, we used an AAV-HBV-
investigating the application of HA in liver disease, but no relevant infected mouse model and compared V-001’s efficacy to IFN and ETV
studies in China. by measuring HBV DNA, HBsAg, and HBeAg levels in treated animals.
Method: A questionnaire-based survey was conducted among Result: V-001, a novel vitamin-derived drug, demonstrated significant
physicians across 29 provinces in China. The primary objectives of antiviral effects against HBV in both HepG2.2.15 and HepG2-NTCP
the study were to assess HA application behaviors, including HA use cell lines by reducing the expression of HBsAg, HBeAg, and HBV
for indications (ascites, SBP, and HRS), and its application in other DNA. This reduction was accompanied by an increase in 4EBP1,
complications. Besides, HA use across different hospital levels were suggesting its role in mediating V-001’s antiviral activity. The modulation
compared. of 4EBP1 influenced the expression of HBsAg, HBeAg, and HBV DNA,
Result: A total of 531 valid responses were obtained. Among indicating its potential as a therapeutic target. V-001’s mechanism of
responders, 19.8% were chief physicians, 29.5% were associate chief action involves the activation of the PI3K-AKT-mTOR pathway, which
physicians, 34.5% were attending physicians, and 16.2% were resident suppresses AKT phosphorylation and downstream gene expression,
physicians. Of these, 80.0% worked in tertiary hospitals, 20.0% in leading to increased 4EBP1 levels and consequently affecting viral
secondary hospitals. Physicians came from departments including replication. In an AAV-HBV infected murine model, V-001 decreased
infectious disease (37.3%), gastroenterology (23.5%), hepatology the expression of HBsAg, HBeAg, and HBV DNA, reinforcing its
(17.1%), internal medicine (8.7%), and others (13.4%). antiviral potential. The drug also activated the PI3K-AKT-mTOR/4EBP1
Among cirrhotic patients treated by the physicians,50.0% had serum axis, providing insights into its mechanism of action and highlighting
albumin levels <30 g/L, 30.0% between 30 - 35 g/L, and the rest >35 the importance of this pathway in HBV regulation.
g/L. In patients with albumin <30 g/L, 80.0% of physicians treated Conclusion: V-001, a novel therapeutic agent, has shown remarkable
them with HA; for patients between 30 - 35 g/L, 15.0% received HA, efficacy in suppressing HBV surface and e antigens, along with HBV
while those with albumin >35 g/L did not. The top considerations for DNA expression. This achievement is attributed to its ability to activate
initiating HA therapy among physicians were ascites (44.4%) and the PI3K-AKT-mTOR pathway and upregulate 4EBP1 expression,
hypoalbuminemia (<30 g/L, 28.4%). The biggest concern to HA use, which are key regulators in cellular processes and protein synthesis.
as cited by 56.7% of physicians was insurance limitations. V-001’s innovative approach to HBV treatment, through the modulation
A total of 95.7% of physicians utilized HA for treating ascites, with of key cellular pathways and proteins, makes it a promising candidate
rates for SBP and HRS at 75.3% and 87.4%, respectively. Among for further investigation and potential clinical application.
those administering HA, the preferred initial dosage of 10-20 g/day Table and Figure:Figure 1.V-001 Suppresses HBsAg and HBeAg while
was selected by 82.5%, 82.6%, and 79.6% of physicians for ascites, enhancing p-4EBP1 Expression in HepG2.2.15 Cells
SBP, and HRS, respectively. The median duration of HA treatment for Figure 2.V-001 inhibits HBsAg expression in an AAV-HBV mouse model
ascites, SBP, and HRS was 7, 5, and 7 days, respectively.
The use of HA for other complications varied by condition, with 50.0%
OP0122
of physicians using it for shock and pleural effusion, and 30.0% for
gastrointestinal bleeding and non-SBP infections, and 27.0% used it HBx-mediated Epigenetic Reprogramming through the ncBAF
for liver cancer. Complex to Promote HBV cccDNA Transcription
Physicians practicing in tertiary hospitals were more likely to prescribe Xiaoxue Yuan1,2,3, Wenqian Geng1,2,3, Yang Wang1,2,3, Xi Wang1,2,3,
an initial dose of 10 -20 g/day compared to those in secondary hospitals Song Yang4,3,2
(P < 0.001) and were inclined to use HA for treating shock (P < 0.001). 1
National Key Laboratory of Intelligent Tracking and Forecasting for
Conclusion: The primary reasons for Chinese physicians to employ Infectious Diseases, Beijing Ditan Hospital, Capital Medical University,
HA therapy include the treatment of ascites and hypoalbuminemia, Beijing,100015, China, 2Beijing Key Laboratory of Emerging Infectious
with health insurance being the most significant concern. The Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital,
strategies for HA application among Chinese physicians largely align Capital Medical University, Beijing 100015, China, 3National Center for
with guidelines; however, variations exist based on hospital level. Infectious Diseases, Beijing Ditan Hospital, Capital Medical University,
Table and Figure:Figure 1.Figures Beijing 100015, China, 4Center of Liver Diseases Division 3, Beijing
Ditan Hospital, Capital Medical University, Beijing 100015, China through efficiency of ACE-tRNAs. Recombined AAV expressing the
Background: The persistent and stable presence of HBV cccDNA in ACE-tRNA and AAV encoding 1.3×HBV were used to establish mouse
the nuclei of hepatocytes is the primary reason for the chronicity of HBV model and to detect the replication of HBV in vivo. Ribosome profiling
infection, the inability of antiviral treatments to completely eradicate the were used to detect off-target toxicity of ACE-tRNA to host cells.
virus, and the recurrence of hepatitis after discontinuation of therapy. The phosphorylation of L-HBc was tested by IP-MS. A tandem array
HBV replication is based on the transcriptional products of cccDNA, a expressing tRNASUAG and two HBV-specific gRNAs (gHBVs) was
process regulated by multiple factors, including host regulatory factors. created and its effect on HBV replication was detected in vitro and in
However, the molecular mechanisms controlling the chromatinization vivo.
and transcription of cccDNA are still poorly understood. Therefore, Result: All of the three candidate ACE-tRNAs could read through the
elucidating the regulatory mechanisms of cccDNA chromatinization Fluc-PTC reporter. Among them, tRNASUAG had the highest read-
and identifying specific targets that can modulate HBV cccDNA through efficiency and was the only one that significantly reduced
transcription is urgently needed. This is not only a critical challenge in HBc protein. Furthermore, tRNASUAG significantly inhibited HBV
the clinical strategies for curing chronic hepatitis B but also a significant replication in vitro and in vivo without significant off-target read-through
scientific issue related to the pathophysiology, pharmacology, and on the normal stop codon of host genes. The protein level and stability
even the virology of viral replication. of L-HBc was lower than that of wild-type HBc, which is induced by
Method: This Study aims to utilize various techniques, including the increased ubiquitination level and the enhanced proteasomal
cccDNA-ChIP, cccDNA-PCR, MNase-PCR, Southern blot, Northern degradation of L-HBc. The phosphorylation at Ser184 introduced by
blot, and drug interventions, to conduct the following work: 1) To use tRNASUAG was the key site leading to the increased ubiquitination
multiple HBV models to clarify the promoting effect of ncBAF on HBV level of L-HBc. The tandem array of tRNASUAG and HBV-specific
cccDNA transcription; 2) To perform HBV infection experiments using gRNAs (gHBVs) could synergistically inhibit HBV replication by
CRISPR-Cas9 technology and ATPase-dead mutants to explore the combining RNAi and CRISPR/Cas9 technologies in vitro and in vivo.
critical role of the ATPase activity of the ncBAF complex in promoting Conclusion: This is the first study to use an ACE-tRNA to read through
cccDNA transcription; 3) To analyze the binding interactions between the stop codon of HBc and promote the degradation of HBc by
HBx and ncBAF complex subunits, as well as the spatial interactions introducing an amino acid that can be post-translationally modified,
mediated by YY1 between the ncBAF complex and the HBV genome, thereby inhibiting HBV replication. In addition, ACE-tRNA and CRISPR/
to elucidate the mechanism by which HBx specifically recruits the Cas9 technologies can be effectively integrated through ACE-
ncBAF complex. tRNA-gRNA tandem arrays to achieve a combined inhibition of HBV
Result: The ncBAF complex can significantly reduce the transcription replication.
level of cccDNA. HBx directly binds to the ncBAF subunit BAF155, Table and Figure:Figure 1.The diagram of the dual-target inhibitory
and inhibition of the critical ncBAF subunit BRD9 can significantly alter effect on HBV replication mediated by tRNASUAG-gRNAHBV tandem
the acetylation activity of cccDNA. AU15330, a PROTAC of BRG1/ array.
BRM, can significantly inhibit the replication of HBV and markedly
reduce the accessibility of HBV cccDNA. OP0124
Conclusion: This study suggested that HBx specifically recruits
SHBs mitigates sorafenib-induced apoptosis in hepatocellular
the ncBAF complex and overcomes heterochromatin barriers
carcinoma via activation of RAF1/MEK/ERK signaling pathway
by regulating the interaction between BRD9 and histone acetylation,
Shu Xiang Wu1,2, Yu Xiang Hong1,2, Hang Li1,2, Xu Lin1,2
achieving epigenetic reprogramming of cccDNA to promote its
transcription. This research could provide new targets and strategies
1
Key Laboratory of Gastrointestinal Cancer (Fujian Medical
for the prevention and treatment of hepatitis B, and it holds significant University), Ministry of Education, Fuzhou, China, 2Fujian Key
Laboratory of Tumor Microbiology, Department of Medical
importance for controlling the progression of chronic hepatitis B
Microbiology, Fujian Medical University, Fuzhou, China
disease.
Table and Figure:Figure 1.HBx-mediated Epigenetic Reprogramming Background: Hepatocellular carcinoma (HCC) is one of the most
through the ncBAF Complex to Promote HBV cccDNA Transcription prevalent cancers worldwide, with a significant association to
hepatitis B virus (HBV) infection, which has been shown to drive
HCC progression. Sorafenib, a multi-kinase inhibitor, is the first-line
OP0123 treatment for advanced HCC. However, recent studies indicate that
The Mechanism and Application of Regulating Hepatitis B Virus HBV infection may confer resistance to sorafenib treatment. The small
Replication by ACE-tRNA. hepatitis B virus surface antigen (SHBs), the most abundant HBV
Xingwen Yang1,2, Jie Wang1,2, Jie Li1 viral protein, has been implicated in HCC development, yet its role in
1
Department of Microbiology & Infectious Disease Center, School of sorafenib resistance is unclear.
Basic Medical Sciences, Peking University Health Science Center, Method: Cell proliferation and apoptosis in sorafenib-treated HCC
Beijing, China., 2NHC Key Laboratory of Medical Immunology, Peking cells or xenograft tumors were detected with CCK-8 assay, 7-AAD/
University, Beijing, China. Annexin V dual staining and TUNEL assay. The expression and
Background: Hepatitis B virus (HBV) infection remains a major global phosphorylation levels of protein were analyzed with western blot and
health issue.  Current drugs still face challenges in achieving clinical immunohistochemical staining. The protein-protein interactions were
cure for chronic hepatitis B. Therefore, new therapeutic approaches identified by Co-Immunoprecipitation (Co-IP) and LC-MS/MS analysis.
and combination therapy strategies are needed. Anticodon Result: This study demonstrates that SHBs enhances sorafenib
engineered tRNA (ACE-tRNA) technology has been widely applied in resistance in HCC cells and xenograft models by inhibiting apoptosis.
the treatment of genetic diseases caused by nonsense mutations. By Upon sorafenib treatment, SHBs expression was found to enhance
modifying the anticodon loop of tRNA to pair complementarily with the the RAF1/MEK/ERK signaling pathway, as evidenced by increased
stop codon, it allows read-through of premature termination codons phosphorylation of ERK and MEK. Inhibition of ERK activity with
(PTCs) on mRNA. And the production of full-length proteins was U0126 countered SHBs effects on sorafenib-induced apoptosis,
restored. The stop codon of the HBV core protein (HBc) in C ORF is cleaved caspase-3, and cellular proliferation. Mechanistically, SHBs
the highly conserved TAG.As the C and P ORFs partially overlap, and binds to PTPN1, enhancing its phosphorylation, which subsequently
the P ORF is located behind the C ORF, the natural stop codon of the dephosphorylates the scaffold protein PTPIP51. This dephosphorylation
HBcresembles a PTC in some aspects. In this study, we first explored promotes RAF1 recruitment to the 14-3-3β complex, leading to
whether ACE-tRNA could read through the stop codon of the C ORF. activation of the RAF1/MEK/ERK pathway.
Furthermore, we explored the effects of ACE-tRNA on HBV replication Conclusion: SHBs prevents sorafenib-induced apoptosis in HCC
and the underlying mechanisms. cells by binding to PTPN1 and stimulating the formation of the
Method: The Fluc reporter containing a PTC was used to test the read- PTPIP51/14-3-3β/RAF1 complex, thereby activating the RAF1/MEK/
ERK signaling pathway. This mechanism provides insight into HBV-
induced sorafenib resistance in HCC, highlighting SHBs as a potential Shuhong Liu2, Meiling Li2, Yan Li2, Yiyun Jiang2, Meng Li2, Haiyan
target for overcoming treatment resistance in HBV-related HCC. Wei2, Chunmei Bao4, Junqi Niu3, Jingmin Zhao2
Table and Figure:Figure 1.Schematic model illustrating how SHBs 1
Medical School of Chinese People’s Liberation Army (PLA),
reduces sorafenib-induced apoptosis via the PTPN1/RAF1/ERK axis. 2
Department of Pathology and Hepatology, the Fifth Medical Center
of PLA General Hospital, 3Department of Hepatology, The first hospital
of Jilin University, 4The Clinical Laboratory, Fifth Medical Center of PLA
OP0125
General Hospital
Rapid hepatitis B surface antigen reduction: results from a
Background: Although the implementation of hepatitis B virus (HBV)
phase Ⅰb study evaluating multiple ascending doses of HT-102,
mother-to-child blockade plan has significantly reduced the global rate
a neutralizing antibody against HBsAg in chronic hepatitis B
of HBV infection in children, there are still a large proportion of children
patients
infected with HBV every year. In the current study we assessed clinical
Zong Zhang1, Guangming Li2, Bei Zhong3, Guoqiang Zhang4, Lin
predictors of functional cure in pediatric chronic hepatitis B (CHB).
Zheng5, Yunqing Qiu6, Dong Wang7, Shanzhong Zhang7, Yanqin Ma7,
Method: We enrolled 1321 treatment-naive pediatric CHB who had
Zhipeng Zhang7, Lijuan Ding7, Yumei Dong8, Lungen LU8
performed liver biopsy from the Fifth Medical Center of PLA General
1
Shandong Public Health Clinical Center, 2The Sixth People´s Hospital between July 2006 to June 2023. Then they were divided
Hospital Of Zhenzhou, 3Qingyuan People´s Hospital, 4Luoyang into four age groups. Statistical analysis of antiviral response were
Central Hospital, 5Mengchao Hepatobiliary Hospital of Fujian Medical performed to assess the association between clinical predictors and
University, 6The First Affiliated Hospital, Zhejiang University school of
functional cure.
Medicine, 7Hepa thera, 8Shanghai General Hospital
Result: Our cohort were divided into four groups: group 1
Background: HT-102 is a human monoclonal antibody targeting the enrolled 151 (11.43%) pediatric CHB patients aged 0 - 3 years old,
conserved antigenic loop of HBsAg with the potential to functions as group 2 enrolled 732 (55.41%) pediatric CHB patients aged 4 - 7
1) inhibition of hepatitis B virus (HBV) entry into cells, 2) elimination years old, group 3 enrolled 255(19.3%) pediatric CHB patients aged
of virions and sub-viral particles for the treatment of chronic HBV 8 - 12 years old and group 4 enrolled 183 (13.85%) pediatric CHB
infection. Single dose of HT-102 up to 600 mg were well tolerated in patients aged 13 - 18 years old. Among them, 765 pediatric CHB
healthy subjects. Here, we reported phase I b data in subjects with patients were treated with antiviral drugs after liver biopsy. Multivariate
chronic HBV infection (ChiCTR2300072837) regression revealed that younger age (P < 0.001) and baseline
Method: This was a randomized, double-blind, placebo-controlled, HBV surface antigen (HBsAg) levels (P < 0.05) were independent
multiple ascending doses study of HT-102 administered via predictors of functional cure in young children. Children with younger
subcutaneous (SC) injection to subjects with chronic HBV infection. age got higher HBsAg clearance rates than that in older pediatric
The study enrolled subjects who were on nucleos(t)ide reverse CHB (P < 0.001). Further more, younger children achieved HBsAg
transcriptase inhibitor (NRTI) therapy≥2 months and had HBsAg 200- seroclearance and HBeAg seroclearance with shorter time than that
3000 IU/ml with hepatitis B e antigen (HBeAg) negative at screening. in older children (P < 0.001). Besides, younger age predicts more
Eligible patients were assigned to 50mg, 150mg, or 300mg group to positive antiviral response despite in HBeAg positive pediatric CHB
receive 5 SC HT-102 doses, every week for 4 weeks. Eight subjects (P = 0.003) or HBeAg negative pediatric CHB(P = 0.024).
per cohort were randomized (6:2) to receive HT-102 or placebo. All Conclusion: Younger age and lower baseline HBsAg levels predict
patients received NRTI treatment throughout the study. Patients were more positive antiviral response in CHB children with all age groups.
followed-up to Day 70 after the first HT-102 or placebo dosed.
Result: Twenty-four subjects were randomized to receive 5 SC doses
of HT-102 with 50mg, 150mg, 300mg or placebo. Demographic and OP0127
baseline characteristics were well balanced across all cohorts. The Significance of Auto-antibodies in Living Liver Donor Liver
administration of multiple SC doses of HT-102 for up to 300mg in CHB Transplantation: A Scoping Review
subjects demonstrated a favourable safety profile and was well tolerated. Bochao Jiang1, Chanda Kendra Ho1,2,3, Thinesh Lee
No subjects dosed HT-102 discontinued due to AE, no SAE nor death Krishnamoorthy1,2,3
were reported. All adverse event (AE)s were grade 1 or 2. No subjects 1
Singapore General Hospital, 2Duke-NUS Graduate Medical School,
developed clinical or laboratory evidence of immune complex disease. Singapore, 3Duke- NUS Academic Medical Centre Transplant Centre,
All subjects achieved a > 2 log10 IU/mL decline at nadir and rapidly SingHealth Services, Singapore
achieved within approximately 1-week post-dose across 3 cohorts. Background: Living donor liver transplantation (LDLT) is crucial for
Most subjects (11/12) in 150mg and 300mg group achieved <10 IU/ end-stage liver disease, especially in Asia where cadaveric grafts
ml and remained at Week10. (Figure). Pharmacokinetic parameters are limited. Some centers exclude potential donors with positive
(Cmax and AUC0-last) basically increased with dose escalation both autoantibodies (AAbs) due to concerns of occult autoimmune
in HBV-infected patients and HV. The mean peak time (Tmax) ranged hepatitis (AIH) and future risks to donor safety, which has no room
from 71.08 to 107.98 h and half-life (t1/2) ranged approximately from for compromise. An important clinical question, however, exists as
10.1 to 16.1 days in HBV-infected patients, both shorter than in HV, to whether such concerns are truly justified given the lack of robust
which suggestive of target-mediated drug disposition in patients. All evidence. This scoping review seeks to synthesize the currently
samples for ADA test is negative except one sample in 300 mg group available evidence on the impact of positive AAbs on donor safety and
tested ADA positive with titer 1.0 at week 10 and negative for further the natural history of patients with AAbs.
Nab test. Method: A comprehensive search of PubMed, Embase, and Cochrane
Conclusion: Multiple doses of HT-102 in 50-300mg were associated Library was conducted, following PRISMA-ScR (2018) guidelines.
with rapid HBsAg reductions in the HBV-infected patients and slight English articles published from 1st Jan 2000 to 1st March 2024 were
greater HBsAg decline with longer sustained duration was observed included. An experienced librarian was consulted to ensure quality in
in 150mg or 300mg group. HT-102 is generally well tolerated in HBV- search methodology. Two reviewers independently assessed eligibility
infected patients with NRTI with good pharmacokinetics profile. The and extracted relevant data on study characteristics, AAb types, donor
early data support further evaluation of HT-102 as a potential functional demographics, donor screening and evaluation protocol, follow-up
cure for patients with chronic HBV infection. duration, and clinical outcomes particularly relating to donor safety.
Table and Figure:Figure 1.Changes in HBsAg Over Time in CHB Conflicts were resolved by consensus or a third reviewer, if needed.
patients with HT-102 Result: Of 1067 studies retrieved from 3 databases, 26 were shortlisted
as potentially relevant. 19 out of 26 were retrospective descriptions of
OP0126 LDLT donor evaluation protocols and outcomes in centres from a diverse
Predictors of functional cure in pediatric chronic hepatitis B range of geographical backgrounds, and only 2 (from Sindh, Pakistan
and Tel Aviv, Israel) specifically mentioned performing autoimmune
Lin Chen1,2, Lina Jiang2, Bokang Zhao3, Dan Zhao2, Yue Jiang2,
workup in living donors. One group from Turkey described routine liver Conclusion: Pediatric LT offers favourable long-term outcomes,
biopsies in all potential donors but no cases of occult autoimmune especially in children who survive more than a year after surgery. Online
diseases or positive AAbs were highlighted. None reported donor consultations are beneficial for long-term follow-ups. Recognizing poor
rejection based on AAbs; and top cited reasons for rejection were prognostic predictors like pre-LT PELD score and chronic PVT aids in
typically steatosis, inadequate remnant liver volume, thrombophilic risk assessment and optimizing patient care.
conditions or donor reluctance/ psychosocial incompatibility. Table and Figure:Figure 1.Flow chart of patient selection and their
Regarding the natural history of AAbs, 469 studies were retrieved, 11 outcome
studies were relevant, including 3 prospective longitudinal follow-up Figure 2.Univariate and multivariate Cox regression analysis for overall
studies. No conclusive evidence linked AAbs to increased AIH risk in survival in pediatric liver transplant recipients
individuals with normal liver function.
Conclusion: This review has mapped significant gaps in high-quality
OP0129
evidence regarding AAbs in donor safety and their natural history,
highlighting areas for future research. Screening practices vary across Long-term results of patients undergoing liver transplantation due
institutions, but AAbs are neither routinely screened nor considered to celiac disease
an exclusion criterion in most, if not all, centres. In asymptomatic MURAT HARPUTLUOGLU1, Caner Altun2, Sezai Yilmaz3
individuals with normal liver function and AAbs, there does not seem 1
INONU UNIVERSITY MEDICAL FACULTY LIVER TRANSPLANT
to be an elevated risk for developing AIH and hence sheds light on the INSTITUTE TRANSPLANT HEPATOLOGY DEPT. MALATYA/TURKEY,
utility (or lack thereof) of following up as well. Future research should 2
INONU UNIVERSITY MEDICAL FACULTY DEPT. OF INTERNAL
focus on prospective studies specifically designed to assess the long- MEDICINE MALATYA/TURKEY, 3INONU UNIVERSITY MEDICAL
term safety of living liver donors with positive AAbs. FACULTY LIVER TRANSPLANT INSTITUTE DEPT. OF SURGERY
Table and Figure:Figure 1.Figure 1: Flowchart on the overall process of MALATYA/TURKEY
screening and evaluation for this Scoping Review Background: Celiac disease (CD) is a T-cell autoimmune disorder
of the small intestine characterized by malabsorption resulting from
OP0128 the ingestion of gluten, the main protein fraction in wheat, rye, and
barley, in genetically predisposed individuals. Although there are a
Long-Term Survival in Pediatric Living Donor Liver Transplant few studies reporting transplantation for CD (6), there are no studies
Recipients who have Survived the First Year of Surgery: reporting long-term outcomes after transplantation in CD patients.
Experience from India Therefore, we aimed to report the long-term outcomes of patients
Vipul Gautam1, Phani Kumar Nekarakanti2, Vikram Kumar1, Shaleen who underwent liver transplantation for CD in our high-volume liver
Agarwal2, Subhash Gupta2 transplantation center.
1
Department of Pediatric hepatology, Max Centre for Liver and Biliary Method: Our study was a single-center, retrospective study, and
Sciences, New Delhi, 2Department of Liver Transplant Surgery, Max included 28 patients who underwent liver transplantation due to CD at
Centre for Liver and Biliary Sciences, New Delhi Inonu University Liver Transplantation Institute between January 2004
Background: Understanding long-term post-liver transplant (LT) and December 2023. Celiac disease diagnosis was made based on
outcomes is crucial for families when consenting to LT. While India anti-tissue transglutaminase (anti-TTG) or anti-endomysium antibody
possesses expertise, it lacks a well-organized healthcare system. positivity and/or duodenal biopsy results. Clinical and laboratory data
This study analysed children who survived beyond one-year post-LT, of patients were obtained by reviewing the patients’ electronic files.
focusing on pre-LT clinical parameters, surgical procedures, delayed This study was carried out with the permission of the Inonu University
complications, follow-up challenges and long-term outcomes within a Scientific Research and Publication Ethics Committee with the decision
living donor program in a developing country. Further, this data will be number 2024/5649.
meaningful for healthcare planners in other resource limited countries. Patients’ age, gender, transplantation type, anti-TTG levels before
Method: This retrospective study was carried out at the Centre and after transplantation, presence of iron deficiency anemia and
for Liver and Biliary Sciences in New Delhi using a prospectively osteoporosis, body mass index, immunosuppressive treatment
maintained database spanning from September 2006 to January used after transplantation, survival time, causes of death, presence
2023. The study included all pediatric LT (pLT) recipients, aged 1 of diarrhea after transplantation, development of recurrence and
month to 17 years, who survived for more than a year following rejection, relationship with other malignancies, presence of second and
LT. Children with inadequate follow-up care were excluded. Pre-LT third transplantation, cytomegalovirus infection, biliary complication
clinical parameters, donor characteristics, surgical procedures, and frequency and feature, type of bile duct anastomosis, and liver biopsy
long-term complications/outcomes were analysed. results (acute rejection, chronic rejection, antibody-mediated rejection,
Result: During the study, 480 pLTs were performed, with 448 children disease recurrence), if any, were recorded.
surviving beyond one year. Of these, 358 compliant pLT recipients with Result: A total of 28 patients were included in the study, 12 (42.9%) male
sufficient follow-up data formed the study cohort (Figure 1). Biliary and 16 (57.1%) female. Two (7.1%) of the transplants were deceased
atresia was the most common indication (40%) of LT. Twenty-three donor and 26 (92.9%) were living donor liver transplantation. In our
percent necessitated intervention within three-months of the surgery, study, we found the 1, 3, 5 and 10-year survival rates in patients who
however, it had no impact on occurrence of late complications or underwent transplantation due to celiac disease to be 92.9%, 92.9%,
overall survival. Out of 358 children, 30 died and 23 survived following 84.4% and 75%, respectively One of the most striking results was the
late radiological or surgical intervention, while the remaining 305 had high frequency of biliary complications. Another important finding was
an uneventful long-term course with a median follow-up of 62 (IQR:31- the significant difference in BMI between pre-transplant and post-
112) months. Due to India’s extensive geographical expanse, the transplant. (p<0.001). In addition, while 77.8% of the patients had
majority (232, 65%) of patients utilized online/web consultations via high anti-TTG levels before transplantation, this rate became 10.5%
platforms like WhatsApp and email, along with physical consultations after transplantation, and the rate of normality increased significantly
as deemed necessary based on clinical indications. Regular in-person (p<0.001). In our study, CD recurrence, post-transplant acute and
outpatient visits were attended by 45% (n=160) of the patients, while chronic rejection rates were 7.1%, 7.0% and 21.4%, respectively.   
video consultations were utilized by 12.2% (n=44). It’s important Conclusion: Our results suggest that liver transplantation provides
to note that the data overlaps since patients often utilized multiple significant benefits on weight gain and anti-TTG levels in CD.
communication channels. The 15-year survival probability was 72.4%
as per Kaplan Meier Curve. Univariate and multivariate Cox regression OP0130
analysis for overall survival in pLT recipients has been shown in table
1. PELD score and post-LT chronic portal vein thrombosis (PVT) were Biliary complications after liver transplantation: Single center
independent prognostic factors for overall survival. Each unit increase experiences
in PELD correlated with a 4% increase in the likelihood of death. Abdulkadir Dökmeci1, Deniz Nalci1,2
1
Ankara University, 2Bahcesehir University management of AS and in whom guidewire could not be negotiated
Background: Biliary complications develop in approximately 30% of were subjected to TP-CANAS using single operator cholangioscope
the liver transplant patients. Living donor liver transplantation (LDLT) (SpyGlass™ DS II, Boston Scientific Inc. USA). Patients with
has some advantages over to deseased donor liver transplantation coagulopathy, thrombocytopenia, and cholangitis were excluded.
(DDLT) and widely accepted in many countries, although it has more In most cases, a 0.035-inch guidewire was used to negotiate AS.
biliary complications than DDLT. Biliary complications following LT Patient demographic data, technical success rate (reaching up to AS),
remain a major problem. in different transplantation centers. The procedure success rate (negotiation of guidewire through AS), and
aim of this study were to analized biliary complications according to clinical success rate (placement of stent) were noted along with the
donor type in liver transplant recipients. peri procedure complication rate.
Method: Totally 412 recepients underwent liver transplantation (LT) in Result: From June 2020 to December 2024, 48 patients underwent
Ankara University in two period from 1994 to 2010 and from 2014 to TP-CANAS. Of these, 35 (79.2%) were males, with a mean age of 44.6
2021. We excluded 119 recepients as a result of death within the first years (15-68). The most common indication of the transplant was HCV
30 days of transplantation and insufficient medical follow-up records. in 21 (43.8%), HBV+HDV in 10 (20.8%), and HBV 7 in (14.6%). All
So, we enrolled 293 ( first period: 119, second period:174) recipients patients received a right lobe graft, 47 without middle hepatic vein
to this study. The patients were predominantly male (62.8%), and their (MHV) and one with MHV. One-third of patients presented after two
mean age was 53,1 ± 13.4 years. Biliary complications were identified years of transplant (16/48), while a quarter presented within 6 months
based on the clinical signs, biochemical findings, US, MRCP and (13/48). Single bile duct anastomosis was present in 22 (45.8%), two
ERCP.   LDLT and DDLT rates were determined as 60% and 40% in ducts in 25 (52.1%), and one had three ducts (2.1%) anastomosis.
the 1st period and 87% and 13% in the 2nd period respectively. Two Technical success was achieved in all 48 (100%) patients. The
biliary reconstruction methods, duct-to-duct and Roux-en-Y procedure success rate was 34/48 (70.8%) patients. The reasons
anastomosis are used in our institute. for failure to negotiate were mainly acute angulations, tortuousness,
Result: In the last three decades, LDLT has emerged as a clinically complete closure, long length, and inability to visualize the AS
safe addition to DDLT. So, percentage of LDLT increased from 60% landmarks. The clinical success rate was achieved in 32/48 (66.7%).
in first period to 87% in second period in our study. We analized The reasons for failure, apart from the failure of guidewire negotiation
biliary complications according to donor type (DDLT and LDLT). The in 14 (29.1%) patients, was the inability to pass the accessories in 2
percentage of biliary complications were lower in second period (30%) (4.1%) patients due to very tight AS. Stricture dilation was performed in
than the first (39%). Biliary strictures were shown higher in second 28 (58.3%) patients, mostly using 8-10 mm dilation balloons. No deaths
period (52%9) than first period (46%) because of higher percentage or major complications occurred. Minor complications occurred in
of LDLT (Figure 1). Biliary leakage was higher in first period (29%) than 4/48 (8.3%) including fever, shivering, abdominal distension, nausea,
in second period (16%). Also, biliary stricture + leakage were seen at vomiting, minor bleeding, and leukocytosis.
the same percentage in both period. But, biliary stricture + stone was Conclusion: This study presents the largest real-world dataset on TP-
higher in second period (13%) than in first period (7%).  Two biliary CANAS in LDLT recipients. The procedure is safe and has promising
reconstruction methods, duct-to-duct and Roux-en-Y anastomosis, are results. It has huge potential to be incorporated into the routine non-
widely used in our center. surgical management protocol.
Conclusion: According to our concequent 2 studies in Ankara University
, we demonstrated that percentage of biliary complications were lower OP0132
in second period (30%) than the first period (39%). Anastomotic biliary
BOLD, A Phase 3, Randomized, Placebo-Controlled Trial to
strictures were the most common biliary complications in both periods
Evaluate the Efficacy and Safety of Odevixibat in Infants With
, although biliary strictures were shown higher in second period than
Biliary Atresia After Kasai Portoenterostomy – Study Design and
first period because of higher percentage of DLT. Biliary leakage were
Current Status
shown higher in DDLT than LDLT. Biliary stones were present especially
Saul J Karpen1, Greg Wright2, Bailey Peck2, Qingqing Li3, Shan
in the patients with anastomotic biliary stenosis and were shown
Zheng, Danielle Dray2, BOLD study group
in higher percentage in recepients underwent LDLT. Finally, bliary
strictures were demonstrated  higher in LDLT than in DDLT, as a
1
Stravitz-Sanyal Institute for Liver Disease and Metabolic Health,
contrast biliary leakages were shown higher percentage in DDLT. Virginia Commonwealth University School of Medicine, 2Ipsen, 3Ipsen
(Shanghai) Pharmaceutical Co., Ltd
Table and Figure:Figure 1.Biliary stenosis. Stenosis was treated by
ERCP and plastic stent placed. Background: Biliary atresia is a severe progressive fibroinflammatory
Figure 2.Biliary leakage was seen at anastomosis and treated by ERCP cholangiopathy of infants. Current treatment options are surgical—
either Kasai portoenterostomy (KPE) or liver transplantation. It is
proposed that post-KPE, infants with biliary atresia have ongoing liver
OP0131 injury from excessive retained intrahepatic bile acids, suggesting that
The Role of Transpapillary Cholangioscopy-Assisted Negotiation any means to reduce bile acid hepatic load may limit this damage. By
of Anastomotic Strictures in Living Donor Liver Transplant diverting bile acids away from the liver, the ileal bile acid transporter
Recipients in Post Failure ERCP: Groundbreaking Findings from (IBAT) inhibitor odevixibat has the potential to reduce liver damage in
the Largest Global Real-World Dataset patients with biliary atresia.
Syed Mujahid Hassan1, Nasir Mehmood1, Rani Tulsi1, Abdul Wahab Method: BOLD (NCT04336722) is the first phase 3 trial in biliary
Dogar1, Mohsin Hussain Khoso1, Yousuf Memon1, Asmat Ullah1, atresia aimed at targeting disease pathogenesis using an IBAT
Nadim Bajkani1, Irbaz Memon1 inhibitor. Eligible patients (age ≤90 days at KPE and eligible to start
1
Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences treatment within 3 weeks post-KPE) will be randomized to once-daily
Background: Endoscopic Retrograde Cholangiopancreatography odevixibat or placebo. Study endpoints are shown in the Figure. Short-
(ERCP) is the primary treatment for post-transplant anastomotic term safety was demonstrated in a Sentinel Cohort (1:1 randomization
strictures (AS). However, its failure rate is higher in living donor liver to odevixibat 40 µg/kg/day or placebo for 1 month). Currently, patients
transplant (LDLT) recipients compared to non-transplant patients, are enrolling in the Primary Cohort (1:1 randomization to odevixibat
primarily due to challenges in guidewire negotiation through AS. 120 μg/kg/day or placebo). Following study completion, patients may
Although transpapillary cholangioscopy-assisted negotiation of continue receiving odevixibat through an open-label extension study
anastomotic strictures (TP-CANAS) has been proposed to address (NCT05426733).
these ERCP failures, existing literature is limited to case reports and Result: Accrual is ongoing in 19 countries (target enrollment, n=245).
small case series. We present our extensive experience with TP- The study is estimated to be completed in mid-2026.
CANAS, representing the largest dataset of its kind. Conclusion: Early intervention is critical for slowing or preventing
Method: All consecutive patients who underwent ERCP for the complications of biliary atresia and improving the success of KPE.
In patients with biliary atresia with a draining KPE, IBAT inhibition via
odevixibat has the potential to lessen hepatic bile acid accretion and identify the contribution of microbiota to the phenotype alterations of
improve liver function. CB2R-/- mice. The NAFLD patients and healthy controls were recruited
Table and Figure:Figure 1.Figure. Primary, secondary and exploratory and the demographic and clinical parameters were analyzed. The 16S
endpoints in the BOLD trial of odevixibat in patients with biliary atresia rRNA gene sequencing was performed for structural and functional
analysis of gut microbiota. Serum metabolomics approaches were
conducted and correlation network was built to explore the microbial
OP0133
effector of CB2R in mediating MAFLD development. Administration
Causal association of cholesterol metabolism-related proteins of associated microbiota-derived metabolites was performed to
with Hepatocellular Carcinoma (HCC) and Metabolic Dysfunction- determine its effect on MAFLD phenotypes.
Associated Steatotic Liver Disease (MASLD): a Mendelian Result: We found that hepatic CB2R expression was decreased in
randomization study MAFLD mice and CB2R-/- mice with normal chow developed MAFLD.
Shitao Jiang1, Dianzhe Tian1,2,3, Yaoge Liu1, Han Zheng1, Lei Zhang1, Interestingly, cohousing with or transplanted microbiota from wild type
Yiyao Xu1, Xin Lu1 (WT) mice ameliorated the MAFLD phenotype of CB2R-/- mice. The
1
Department of Liver Surgery, State Key Laboratory of Complex gut dysbiosis including increased Actinobacteriota and decreased
Severe and Rare Diseases, Peking, Union Medical College Hospital, Bacteroidota of CB2R-/- mice was similar to that of MAFLD patients
Chinese Academy of Medical Sciences and Peking Union Medical, and mice. Notably, the microbial functional analysis and metabolomics
2
Eight-year Medical Doctor Program, Chinese Academy of Medical profiling pointed out obviously disturbed tryptophan metabolism
Sciences and Peking Union Medical College, 3School of Life in MAFLD patients and mice, which were also exhibited in CB2R-
Sciences, Tsinghua University /- mice. Correlation network showed that the disordered tryptophan
Background: Aberrations in cholesterol metabolism are crucial in metabolites such as indolelactic acid (ILA) and xanthurenic acid in
developing liver diseases such as hepatocellular carcinoma (HCC) CB2R-/- mice were modulated by gut dysbiosis and related to MAFLD
and metabolic dysfunction-associated steatotic liver disease (MASLD). severity indicators. Furthermore, the in vitro and in vivo validation
More studies are needed on the causal relationship between circulating experiment showed that enriched tryptophan metabolites ILA
cholesterol metabolism-related proteins and these liver diseases. aggravated NAFLD phenotypes.
Method: This study utilized Mendelian randomization (MR) to identify Conclusion: These results demonstrated the involvement of CB2R
the role of cholesterol metabolism-related proteins in HCC and MASLD. in NAFLD which were related to gut microbiota-mediated tryptophan
We systematically investigated the causal associations of these metabolites indole-3-lactic. Our novel findings highlighted CB2R and
proteins with HCC and MASLD and their roles in disease progression the associated microbes and tryptophan metabolites as promising
using circulating proteomic databases and bioinformatics tools. In targets for NAFLD.
addition, network-based drug repositioning techniques and molecular Table and Figure:Figure 1.Cannabinoid-2 Receptor Depletion
docking experiments were utilized to assess the interactions of the Contributes to Metabolic Dysfunction-Associated Fatty Liver Disease
above biomarkers with known drugs to discover drugs with potential via Regulating Microbiota
therapeutic effects. Figure 2.Cannabinoid-2 Receptor Depletion Contributes to Metabolic
Result: MR analysis identified several proteins linked with significant Dysfunction-Associated Fatty Liver Disease via Regulating Microbiota-
risk for HCC and MASLD. Notably, apolipoprotein E (APOE) expression derived Tryptophan Metabolites Indole-3-lactic
was significantly increased in tissues from HCC and MASLD
patients, closely correlating with elevated disease risk. Meta-analysis OP0135
demonstrated a significant causal relationship between APOE and
increased risk of HCC (OR: 1.710, 95% CI: 1.220-2.400; P<0.01) and Phase 3 ESSENCE Trial: Semaglutide in metabolic dysfunction-
MASLD (OR: 1.490, 95% CI: 1.280-1.740; P < 0.01). Additionally, associated steatohepatitis (MASH)
network analysis revealed extensive interactions between APOE and Jidong Jia1, Philip Newsome2, Arun Sanyal3, Iris Kliers4, Laura
other disease-related proteins, suggesting that APOE may contribute Harms Østergaard4, Michelle Long4, Mette Skalshoi Kjær4, Anna
to liver disease progression through its influence on complex protein Cali4, Elisabetta Bugianesi5, Mary Rinella6, Michael Roden7,8,9, Vlad
networks. Ratziu10
Conclusion: Our findings underscore the potential role of cholesterol 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
metabolism-related proteins, particularly APOE, in the pathogenesis University, 2Roger Williams Institute of Liver Studies, Faculty of Life
of HCC and MASLD. This study provides new insights into the Sciences and Medicine, King’s College London, Foundation for Liver
molecular mechanisms of these liver diseases and highlights potential Research, and King’s College Hospital, 3Stravitz-Sanyal Institute
therapeutic targets. for Liver Disease and Metabolic Health, VCU School of Medicine,
Table and Figure:Figure 1.Schematic of the study design
4
Novo Nordisk A/S, 5Department of Medical Sciences, University of
Turin, 6Department of Medicine, University of Chicago, 7Department
of Endocrinology and Diabetology, Medical Faculty and University
OP0134 Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 8Institute
Cannabinoid-2 Receptor Depletion Contributes to Metabolic for Clinical Diabetology, German Diabetes Center, Leibniz Center for
Dysfunction-Associated Fatty Liver Disease via Regulating Diabetes Research at Heinrich Heine University Düsseldorf, 9German
Microbiota-derived Tryptophan Metabolites Indole-3-lactic Center for Diabetes Research, Partner Düsseldorf, München-
Neuherberg, 10Sorbonne Université, Institute for Cardiometabolism
Cheng Weiting1, Pei Siya1, Huang Yan1, Wu Li1, Huang Zebing1
and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC
1
Department of Infectious Diseases, Xiangya Hospital, Central South
University Background: Semaglutide, a glucagon-like peptide-1 receptor
agonist, is a candidate for the treatment of metabolic dysfunction-
Background: Metabolic dysfunction-associated fatty liver
associated steatohepatitis (MASH). Semaglutide is being investigated
disease (MAFLD) has been the leading cause of liver-related
for its potential to treat MASH in the phase 3 ESSENCE trial.
morbidity and mortality worldwide. Lipid disorders was the hallmark
Method: ESSENCE, an ongoing multi-center, phase 3 randomized,
of MAFLD, which was known to be modulated by gut microbiome.
double-blind, placebo-controlled outcome trial involving 1200
Cannabinoid-2 receptor (CB2R) is the receptor of endocannabinoids
participants with biopsy-defined MASH and fibrosis stage F2/
mainly expressed in immune cells. Whereas our preliminary study
F3, randomized participants 2:1 to once-weekly subcutaneous
revealed the preventative role of CB2R in liver injury related to lipid
semaglutide 2.4 mg or placebo for 240 weeks. A planned interim
metabolism. Thus, we aimed to explore the role of CB2R in MAFLD and
analysis at week 72 of the first 800 participants evaluated the trial’s
the underlying mechanism relating to microbial community.
primary endpoints: resolution of steatohepatitis with no worsening of
Method: Here, the high-fat diet-induced model mice and CB2R-
liver fibrosis, and improvement in liver fibrosis with no worsening of
/- mice were used to reveal the role of CB2R in MAFLD. Co-housing
steatohepatitis.
experiment and fecal microbiota transplantation were carried out to
Result: Among the 800 participants (semaglutide [n=534; 169 F2, to be 0.78–0.94. MRE had the best AUROC of 0.937–0.95, but only 2
365 F3] or placebo [n=266; 81 F2, 185 F3]), mean (standard deviation studies were identified with relatively small sample sizes (72 and 77
[SD]) age was 56.0 (11.6) years and body mass index was 34.6 (7.2) respectively). 25 studies reported evidence for serological biomarkers,
kg/m2. Most participants were White (67.5%), female (57.1%) and scoring tools or algorithms in identifying advanced fibrosis in general
55.9% had type 2 diabetes at baseline; 250 (31.3%) participants had MASLD population, among which FIB-4, NFS, and APRI (≥15 studies
F2 and 550 (68.8%) had F3. Resolution of steatohepatitis with no for each) had the most abundant evidence, but a highly scattered
worsening of fibrosis was achieved by 62.9% of participants in the distribution of AUROC. However, when using the recommended cut-off
semaglutide group vs 34.1% receiving placebo, with an estimated value, FIB-4 had high negative predictive value (range: 89.6%-91.5%,
difference in responder proportions (EDP) of 28.9% (95% CI, 21.3 cut-off value 1.3) in ruling out advanced fibrosis, as well as NFS (NPV
to 36.5; P<0.0001). Improvement in liver fibrosis with no worsening range: 88%-94.8%, cut-off value −1.455). Similar analysis has been
of steatohepatitis was achieved by 37.0% (semaglutide) and 22.5% conducted for significant fibrosis (≥F2) and cirrhosis (F4).
(placebo) (EDP, 14.4%; 95% CI, 7.5 to 21.4; P<0.0001), while 32.8% Conclusion: FIB-4, NFS and TE have been extensively studied in the
(semaglutide) and 16.2% (placebo) achieved combined resolution of Chinese population. The performance of FIB-4 and NFS as ruling out
steatohepatitis with improvement in liver fibrosis (EDP, 16.6%; 95% CI, tools and TE as a diagnostic tool was similar to that reported in the
10.2 to 22.9; P<0.0001). There were improvements in liver enzymes Western population. The risk stratification pathway recommended by
and non-invasive fibrosis markers. As expected, improvements in western guidelines might also be applicable to the Chinese population.
body weight and cardiometabolic parameters were also observed.
The incidence of serious adverse events in the safety analysis set was OP0137
similar in both arms.
Conclusion: In participants with MASH and moderate to advanced liver Adverse outcomes and HBsAg seroclearance of chronic hepatitis
fibrosis, semaglutide 2.4 mg once-weekly demonstrated superiority vs B complicated with metabolic dysfunction-associated steatotic
placebo for improvement of histological activity and fibrosis markers, liver disease: A cohort study
thus meeting both primary endpoints after 72 weeks of treatment. In Jialan Wang1, Airong Hu2, Suwen Jiang2, Ken Lin3, Ying Fan4,
addition, semaglutide improved MASH injury and fibrosis biomarkers Menghan Jin3, Haojin Zhang4, Shiyang Fang4, Shiqi Yang1
and cardiometabolic features. 1
Graduate School, Wenzhou Medical University, 2Liver Diseases
(Jia Jidong (Chinese speaker) is not part of the original author team Center, Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital,
and will only report on behalf of Philip N. Newsome, Arun J. Sanyal,
3
Ningbo University Health Science Center, 4School of Medicine,
Iris Kliers, Laura Harms Østergaard, Michelle T. Long, Mette Skalshøi Shaoxing University
Kjær, Anna Cali, Elisabetta Bugianesi, Mary Rinella, Michael Roden, Background: To explore the influence of metabolic dysfunction-
Vlad Ratziu.) associated steatohepatopathy (MASLD) on the risks of adverse events,
including cirrhotic complications and hepatocellular carcinoma, and
OP0136 on the hepatitis B surface antigen (HBsAg) clearance among patients
with chronic hepatitis B (CHB).
The non-invasive assessment of liver fibrosis in metabolic Method: From January 2015 to January 2024, consecutive patients
dysfunction associated steatotic liver disease (MASLD) in the with CHB and had undergone liver biopsy were enrolled at Ningbo
Chinese population: a scoping review No. 2 Hospital, Ningbo, China. Upon enrollment, participants
Qianqian Zheng4, Lai Wei1,2, Di Cao3, Xuan Qi3, Ying Wang3, Yuemin underwent blood, imaging tests and physical examinations. To assess
Nan4 the presence of MASLD, metabolic dysfunction, steatohepatitis and
1
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung steatosis in relation to the cumulative incidence of related adverse
Hospital, 2School of Clinical Medicine, Tsinghua University, 3Novo events (cirrhotic complications and hepatocellular carcinoma) and
Nordisk (China) Pharmaceuticals Co., Ltd, 4Department of Traditional serum HBsAg clearance.
and Western Medical Hepatology, Hebei Medical University Third Result: Our cohort was included 827 patients. The median follow-up
Hospital time for adverse events as an outcome was 4.62 years (3.08 - 6.76),
Background: Non-invasive tests (NITs)-based risk stratification and for HBsAg seroclearance, it was 4.72 years (3.23 - 7.10) , There
pathways have been recommended in growing numbers of MASLD were 81 adverse events, including 13 of HCC and 68 of hepatic
guidelines. However, the current guidelines in China do not include dysfunction, as well as 33 HBsAg antigen-clearance events. In the
the aforementioned pathways, and the awareness, acceptance and PSM analysis, the presence of MASLD in 151 patients was associated
clinical practice of NITs among Chinese physicians are relatively low. with increased adverse outcomes (PSM-adjusted HR, 2.095; 95%
Therefore, we carried out a scoping review to evaluate the sufficiency CI, 1.098 - 3.996), and HBsAg clearance (PSM-adjusted HR, 3.475;
of NITs related evidence in China, scrutinize their performance and 95% CI, 1.279-9.439). In patients with MASLD, the presence of
identify potential data gap. steatohepatitis and metabolic burden (P> 0.65) was not associated
Method: We followed the Arksey and O’Malley framework for scoping with adverse outcomes. Compared with the steatosis, activity, fibrosis
reviews. A search was conducted in 3 English and 4 Chinese databases (SAF) scores <5 group (42.38%), the SAF≥5 group (57.62%) was
from Jan 2012 to Mar 2023. Eligible studies must target liver fibrosis significantly associated with adverse event rates (HR: 6.812, 95%CI:
assessment in Chinese patients with MASLD (previously known and 2.528-18.354). Multifactorial analysis demonstrated that aspartate
studied as NAFLD or MAFLD), use liver biopsy as the gold standard, aminotransferase (AST) and gamma-glutamyl transferase (GGT) were
and report at least AUROC for diagnostic performance. independent risk factors for disease progression in CHB patients with
Result: Out of 12, 714 retrieved articles, 81 studies were included, MASLD (P< 0.05). The non-invasive diagnostic models, with AST and
involving 35, 260 subjects. The majority of the studies (66) focused GGT, developed accordingly were more effective than the aspartate
on the general MASLD population, one on children, and the remaining aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) in
14 investigated MASLD patients with comorbidities such as chronic predicting adverse events in patients with MASLD combined with CHB
hepatitis B, diabetes/prediabetes, or obesity. Furthermore, several (AUC=0.700).
confounders of the diagnostic performance have been tested, Conclusion: The existence of MASLD was related to higher rates
including BMI, age, the degree of hepatic steatosis, HBV infection, of adverse events and HBsAg seroclearance in patients with CHB.
AST level, genetic polymorphism of PNPLA3 and the diabetes status. In addition to MASLD, metabolic dysfunction can also increase the
Advanced fibrosis (≥F3) is generally recommended to be screened incidence of adverse events in CHB patients, but there is no cumulative
as the high-risk stage. 35 studies reported diagnostic performance in effect. Non-invasive models based on AST and GGT had good
identifying advanced fibrosis in general MASLD population. 15 studies accuracy in predicting the risk of adverse events in this population.
reported imaging diagnostic methods, 9 of which included evidence Table and Figure:Figure 1.Cumulative incidence of (A) adverse
of transient elastography (TE), AUROC ranging 0.71–0.94. In 3 with outcomes and (B) HBsAg seroclearance. Patients with concurrent
more substantial sample sizes in China (>200), AUROCs was reported MASLD had higher incidence of adverse outcomes and HBsAg
seroclearance than those without MASLD. Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a
Figure 2.Cumulative incidence of (A) adverse outcomes and (B) HBsAg minimally invasive interventional procedure to relieve the symptomatic
seroclearance. These CHB patients were also classified into the four complications of portal hypertension, and HE is the most common and
groups of data presented, namely patients with MASLD, those with only often severe complication following TIPS, previous research had found
steatosis, those with only metabolic dysfunction, and no steatosis (only that polytetrafluoroethylene (ePTFE) stents and bare stents had a
with HBV). Patients with MASLD had increased incidence of adverse comparable post-TIPS HE rates. The Fluency (Bard, Murray Hill, USA)
outcomes and HBsAg seroclearance than those with steatosis only. and the Viatorr (W.L. Gore & Associates, Flagstaff, AZ, USA) are two
types of ePTFE-covered stents, Despite the ePTFE-covered stent was
OP0138 widely recommended by the guidelines, the effect of different ePTFE-
covered stents on patients` outcomes remains controversial. This
The relationship between the ratio of red blood cell distribution study aimed to investigate the incidence of hepatic encephalopathy
width to albumin concentration and the incidence and mortality (HE) following transjugular intrahepatic portosystemic shunt (TIPS)
risk of metabolic dysfunction-associated fatty liver disease. using different types of stent grafts in patients with cirrhosis.
Zixuan Qiu1, Zilong Wang1, Bo Feng1 Method: Consecutive patients with cirrhosis who underwent TIPS from
1
Peking University People‘s Hospital January 2012 to December 2022 in our center were considered to
Background: The red blood cell distribution width-to-albumin ratio be included in the study. Patients were divided into the Viatorr group
(RAR) has emerged as a potential negative regulatory factor in various and Fluency group. Case-control matching was performed to control
metabolic disorders. However, its precise relationship with both the potential confounding variables at baseline. Kaplan-Meier and Cox
incidence and all-cause mortality risk in individuals afflicted with regression analyses were used to identify the cumulative rates and
metabolic-associated fatty liver disease (MAFLD) remains insufficiently independent risk factors of post-TIPS HE.
elucidated. Result: 1077 patients were included in this study, 340 patients
Method: This investigation utilizes data from the National Health and in the Viatorr group and 737 in the Fluency group. The 2-year
Nutrition Examination Survey III (NHANES III). Employing logistic cumulative incidence of HE was significantly lower in the Viatorr group
regression and Cox proportional hazards models, we scrutinize the compared with Fluency group (26.4% vs. 34.3%, p =0.018). The 2-year
association between RAR and the incidence and mortality risk of cumulative rate of shunt dysfunction was also lower in the Viatorr group
MAFLD, respectively. Additionally, restricted cubic spline regression is (2.2% vs. 7.5%, p=0.037). However, the 2-year cumulative rate of
applied to probe the nonlinear dynamics between RAR and all-cause transplant-free survival (93.4% vs. 90.1%, p = 0.428) was comparable
mortality within the MAFLD framework. between two groups.
Result: The logistic regression analysis revealed a significant Conclusion: TIPS creation using the Viatorr stent-grafts showed a
correlation between the Risk Assessment Rate (RAR) and both the lower risk of HE and better patency compared with the Fluency stent-
prevalence of Metabolic Associated Fatty Liver Disease (MAFLD) and grafts. Therefore, dedicated stent-graft should be preferred for the
all-cause mortality. Specifically, the unadjusted logistic regression TIPS creation in patients with cirrhosis.
model identified a notable positive trend between higher quartiles of
RAR and MAFLD risk (P for trend < 0.001). Within the multivariable OP0141
logistic regression framework, the odds ratios (OR) for the second,
The Potential Mechanism of Action and Active Ingredients of
third, and fourth quartiles were calculated as 1.12, 1.24, and 1.25,
Ruangan Granules Against Liver Fibrosis
respectively (P values of 0.006, < 0.001, and < 0.001), underscoring a
progressive escalation in MAFLD risk concomitant with increasing RAR Xiaofei Shang1,2,3, Yand Liu1, Qianqian Niu1, Huan Chen1,2, Xiuhui Li1
levels. When assessed as a continuous variable, RAR demonstrated
1
Beijing YouAn Hospital, Capital Medical University, Beijing, P.R.
an OR of 1.19 (95% CI 1.08-1.30), further substantiating the positive China., 2Beijing Institute of Hepatology, Beijing Youan Hospital,
correlation. In terms of all-cause mortality, multivariable Cox regression Capital Medical University, Beijing, China., 3Lanzhou Institute of
analysis affirmed that elevated RAR indices were significantly linked Husbandry and Pharmaceutical Sciences, Chinese Academy of
Agricultural Sciences, Lanzhou 730050, P.R. China.
to increased mortality risk in MAFLD patients. The hazard ratios
(HR) for the second, third, and fourth quartiles were 1.07, 1.15, and Background: Ruangan granules (RGG) have been used to treat
1.84, respectively, with the association maintaining significance even liver fibrosis with good clinical efficacy for many years. The anti-liver
after adjustment for additional confounders. To further interrogate fibrosis activity of RGG was proven in vivo in our previous study. In this
the non-linear relationship between continuous RAR levels and all- study, we aimed to explore the potential mechanism corresponding to
cause mortality in MAFLD patients, we employed restricted cubic mitophagy and investigate its active ingredients against liver fibrosis.
spline analysis. Results revealed that at an RAR value of 3.90, the Method: LPS was used to induce inflammatory response and oxidative
HR reached a zenith of 1.61 (p for overall < 0.0001, p for nonlinear stress in HL-7702 cells, and then α-SMA was detected in LX-02 cells
< 0.0026). Remarkably, prior to this inflection point, HR exhibited a in the coculture model. The effect on the Pink1-parkin-mediated
pronounced increase with rising RAR, while post-inflection, it showed a mitophagy pathway was investigated using Western blotting, PCR
tendency towards stabilization. and other technologies. After using UPLC-ESI-Q-TOF/MS and other
Conclusion: These findings propose that RAR may serve as a viable analytical tools to determine the chemical constituents, the SI index
biomarker for MAFLD, illustrating a robust positive association with (the toxicity against HL-7702/LX-2 cells) of each compound was
both disease incidence and all-cause mortality in affected individuals. evaluated.
Such insights may hold significant implications for clinical practice and Result: RGG inhibited the release of inflammatory cytokines and
patient management. ameliorated the oxidative stress of HL-7702 cells in a concentration-
Table and Figure:Figure 1.The relationship between RAR and the dependent manner, especially at 1000 μg/ml (P<0.01). The activation
incidence of MAFLD and the overall mortality risk of LX-02 cells was prevented and the release of α-SMA was inhibited.
Figure 2.The nonlinear relationship between RAR and all-cause RGG improved mitochondrial morphology and function and inhibited
mortality risk in MAFLD the overexpression of proteins and genes associated with mitophagy.
PINK1-Parkin is the key pathway mediating mitophagy and attenuating
the inflammatory response, contributing to the anti-liver fibrosis effect
OP0140 of RGG in vivo and in vitro. Finally, 27 compounds were identified from
Dedicated stent decreases the risk of hepatic encephalopathy RGG. Among them, the SI index of salvianolic acid A (SAA) is the best,
after transjugular intrahepatic portosystemic shunt in cirrhotic which can alleviate inflammation and oxidative stress of HL-7702 cells
patients induced by LPS and inhibit α-SMA release by LX-2 cells in a coculture
Xuefeng Luo1, Shu Du Mei1 with HL-7702 cells.
1
West China Hospital of Sichuan University Conclusion: RGG exerted anti-liver fibrosis activity by attenuating the
inflammatory response via Pink1/Parkin-mediated mitophagy, and SAA
is the main active ingredient of RGG against liver fibrosis. This study Safety and Efficacy of Xiaozhi Formula in Patients with Metabolic
provides an overall view of the mechanism underlying the protective Dysfunction-Associated Fatty Liver Disease: A Randomized,
effect of RGG against liver fibrosis, and the potential target of SAA Controlled, Placebo Clinical Trial
should be further investigated. Tao Wang1, Liping You1, Jinghao Zhang1, Lihong Qu2, Yueqiu Gao1,
Table and Figure:Figure 1.The determination of autophagic flux in Xuehua Sun1
HL-7702 cells induced by LPS using mRFP-GFP-LC3 adenovirus 1
Department of Hepatology, Shuguang hospital affiliated to shanghai
infection (A, B), the western blot analysis of the Parkin-Pink1 mediated university of traditional chinese medicine, Shanghai,201203, China,
mitophagy (C), and PCR analysis of the relative gene expression of 2
Department of Infectious Diseases, East Hospital, Tongji University,
Dnm1 (D), Mfn1 (E), Mfn2 (F), Timp1(G), Pink1 (H) and Parkin (I) in HL- Shanghai, 200120, China
7702 cells induced by LPS. (Data represent the mean ± SD of three
Background: Clinical formula Xiaozhi formula (XZF) has been shown to
independent experiments, ###represent the significant difference
be effective in the metabolic dysfunction-associated fatty liver disease
between control group and model group, p<0.001; *p<0.05 represent
(MAFLD) rodent model, while there is a lack of high-quality evidence-
the significant difference between model group and RGG-treated
based clinical evidence for XZF in the treatment of MAFLD patients.
group; ** for p<0.01; *** for p<0.001).
Method: 100 patients with metabolism-related fatty liver
disease (MAFLD) were randomized 1:1 into the XZF group and the
OP0142 placebo group on the basis of dietary and exercise interventions for
Cryptotanshinone targets PPARγ to reduce nonalcoholic fatty a period of 12 weeks. The primary outcome was the relative change
liver disease in liver fat content, as measured by liver magnetic resonance proton
density fat (MRI-PDFF) from baseline to 12 weeks. The two key
Tao Wang1, Xuehua Sun1
secondary endpoints included absolute change in liver fat content and
1
Department of Liver Diseases, Shuguang Hospital Affiliated to
proportion of patients with hepatic fat reduction ≥ 30% from baseline to
Shanghai University of Traditional Chinese Medicine, Shanghai,
12 weeks measured by MRI-PDFF. Safety assessments encompassed
2
01203, China
vital indications, blood counts, Electrocardiogram (ECG) and renal
Background: Non-alcoholic fatty liver disease (NAFLD) has a high function.
prevalence, complex pathomechanisms, and an increasing burden Result: A total of 97 patients with MAFLD completed the trial. In the
of cardiovascular events and end-stage liver disease.Mechanistic intention-to-treat (ITT) analysis, XZF treatment significantly decreased
investigations and drug development of NAFLD still have a long way to relative and absolute hepatic fat content measured by MRI-PDFF
go. Chinese herbal medicines are rich in skeleton and biocompatible, (-32.57% vs -14.75%, least squares mean difference -17.82%, 95%Cl
and they are potential drug libraries for small molecules. -26.51 to -9.13, P < 0.001) and (-6.12% vs -2.72%, least squares mean
Method: Animal models of NAFLD induced by HFD were constructed to difference -3.40%, 95%Cl -4.99% to -1.80, P < 0.001) compared to
analyze the effects of cryptotanshinone on serum and liver liver enzymes placebo. Furthermore, the proportion of patients with a decrease in liver
and lipid metabolism-related indexes; its effects on insulin resistance fat content of 30% or more was significantly higher in the XZF group
were detected using glucose tolerance and insulin tolerance assays; compared to the placebo group (44.68% vs 6.12%, odd ratio (OR) =
and its effects on glucose-lipid metabolism, lipoatrophy were observed 8.70, 95%Cl 2.69 to 28.09, P < 0.001). Additionally, 12 weeks of XZF
using histological assays such as HE, Oil Red O , Wolf Scarlet Red treatment led to greater reductions in ALT, AST, body mass index (BMI),
and PAS, inflammation and fibrosis; predicting the potential molecular triglyceride (TG) and fasting plasma glucose (FPG) levels. Notably, no
mechanism based on transcriptome sequencing technology, using rt- adverse events were reported in either group. Approximate results can
PCR, Western blot and immunohistochemistry to verify the changes also be derived in the per-protocol (PP) analysis
in the molecular and protein levels of the relevant pathways; using ex Conclusion: A 12-week treatment with the herbal formula XZF was
vivo and in vivo reversion experiments to verify that the drug exerts its demonstrated to be safe in MAFLD patients. Moreover, XZF effectively
anti-NAFLD effect through this pathway; and using molecular docking reduced hepatic fat content and currently improved various clinical
to explore the target of the action of cryptotanshinone. parameters, including ALT, AST, BMI, TG, and FPG levels.
Result: In the HFD model, cryptotanshinone reduced body weight,
liver weight and fat weight, lowered ALT levels, improved insulin
resistance, and attenuated inflammation and liver fibrosis in mice. OP0144
Transcriptomics results showed that cryptotanshinone could inhibit Study on the key pharmacodynamic components of Total
the pathway related to lipid synthesis and liver fibrosis; rt-PCR and Astragalus saponins (TAS) in improving Cholestatic Liver Disease
Western blot confirmed that it could inhibit the expression of factors (CLD)
related to the hepatic fat de novo synthesis pathway, such as Fasn Linzhang Zhang 1, Jiewen Shi1, Shenglan Qi1, Gaofeng Chen1, Ping
and Scd1, and reduce the phosphorylation level of Acc; it could Liu1, Wei Liu1
inhibit the expression level of the fibrosis-related genes, Co1a1 and 1
Shanghai University of Traditional Chinese Medicine
αSma, and inhibit the phosphorylation level of Smad3 .In an in vitro
Background: Previous studies have found that Total Astragalus
hepRG cell line, the effects of cryptotanshinone on improving steatosis
saponins (TAS) could significantly improve Cholestatic Liver Disease
and lowering TG were reversed by the combined use of the PPARγ
(CLD), but it is unclear which specific components play a key role.
agonist rosiglitazone, and rt-PCR and Western blot confirmed that the
The aim of this study is to investigate the effects of compound A or
expression levels of PPARγ and CD36 were significantly regulated
B absence on the efficacy of TAS for CLD by component elimination
by rosiglitazone. Molecular docking experiments suggested that the
method.
minimum docking energy of cryptotanshinone and PPARγ was -9.106
Method: The chemical analysis of the TAS, TASA-/- (TAS after removing
Kcal/mol and was located in the pocket structure of PPARγ.
compound A), TASB-/- (TAS after removing compound B) and TASAB-/-
Conclusion: Verification that cryptotanshinone ameliorates hepatic
(TAS after removing compound A and B) were first identified by
steatosis, corrects insulin-associated dyslipidemia, and blocks
UHPLC-Q-Exactive Orbitrap HRMS technology; then were assessed in
the progression of inflammation and fibrosis through inhibition
vivo on 3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD
of the PPARγ/CD36 pathway by different dietary models using
mouse model. Liver injury and collagen deposition were evaluated
transcriptomics techniques in conjunction with in vitro and ex vivo
by serum biochemistry and histopathological assay. The mRNA and
replication experiments
protein expressions of cytokeratin 19 (CK19) and α-smooth muscle
actin (α-SMA) were assessed to evaluate ductular reaction and liver
OP0143 fibrosis by qRT-PCR assay, western blot assay, immunohistochemistry
assay and immunofluorescence assay.
Result: As shown in Figure 1, TASA-/-, TASB-/- and TASAB-/- were
identified by UHPLC-Q-Exactive Orbitrap HRMS, and they do not
contain compounds A, B or A and B, respectively. In vivo study, obvious serum markers (%) in the hospitalized population (n=73 165) in
changes of the liver pathology and a several-fold increase in ALP, TBA, Taizhou, China.
TBIL, ALT, AST and SR positive area levels were significantly improved Figure 2.Figure 2 Changes in HBsAg positive rate of all age groups in
following TAS treatment, whereas these improvements was vanished in Taizhou, China in 2023, the countries in 1982, 1992, 2006, 2020 and
TASA-/-, TASB-/- and TASAB-/- treatments, except TBA level in TASA-/- Jiangsu in 2010
treatment. And in Figure 2, the contents of Hyp, the mRNA and protein
expression of CK19 and α-SMA were improved after TAS treatment,
OP0146
while these improvements were also vanished in TASA-/-, TASB-/- and
TASAB-/- treatments. The application of aMAP risk score for predicting hepatocellular
Conclusion: In summary, this study revealed that compound A or B carcinoma development among individuals with hepatitis B virus-
could significantly affect the efficacy of TAS in CLD, indicating that infection in community
compound A or B was indispensable to the efficacy of TAS. Mingfang Ji1, Xia Yu1, Yun Du2, Shifeng Lian1, Fugui Li1, Biaohua Wu1,
Table and Figure:Figure 1.the effects of compound A or B absence on Jiyun Zhan3, Xuejun Liang3, Zhiheng Liang1, Yanling Zhou4, Rong
the efficacy of TAS in hepatic injury Fan5, Jinlin Hou5
Figure 2.the effects of compound A or B absence on the efficacy of 1
Zhongshan City People‘s hospital, 2Department of Oncology,
TAS in ductular reaction and liver fibrosis Southwest Hospital, Army Medical University, 3Xiaolan Public Health
Service Center, 4Xiaolan People‘s Hospital of Zhongshan, 5Department
of Infectious Diseases, Nanfang Hospital, Southern Medical University
OP0145
Background: The aMAP (age–male–ALBI–platelets) score has
Prevalence of Hepatitis B Virus (HBV) Infection Based on Routine
been demonstrated to be a useful non-invasive tool for assessing
Screening of Hospitalized Patients
hepatocellular carcinoma (HCC) risk in chronic hepatitis patients in
Sun Hongzhan1, Yang Lili1, Wang Xinru2, Wang Bo2, Xiao Li2, Xian hospital settings. However, its application among individuals infected
Jianchun2 with hepatitis B virus (HBV) in community has been insufficiently
1
Obstetrics and Gynecology, The Affiliated Taizhou People‘s Hospital studied.
of Nanjing Medical University, 2Department of Hepatology, The Method: We conducted a prospective community-based liver cancer
Affiliated Taizhou People‘s Hospital of Nanjing Medical University screening project in Zhongshan, China in 2012. A total of 2,893 hepatitis
Background: The prevalence of hepatitis B virus (HBV) serum B virus surface antigen (HBsAg)-positive individuals were enrolled
markers (HBV-M) varies based on factors such as geographical and followed biannually with alpha-fetoprotein (AFP) and abdominal
location and age. This study aimed to assess the seroepidemiology of ultrasonography. All participants were followed-up until December 31,
HBV in Taizhou, China, based on routine HBV-M screening results from 2021. We collected data on age, sex, albumin, bilirubin, and platelet
hospitalized patients, and to explore its correlation with age, sex, and levels to calculate the aMAP score, categorizing participants into low-,
hepatitis B vaccination (HepB) status. medium-, and high-risk HCC groups. Cumulative HCC incidence rates
Method: Data were obtained from hospitalized patients who underwent were then calculated.
HBV-M testing at Taizhou People’s Hospital in 2023. Patients with Result: Among 1,040 HBsAg-positive individuals with complete data
incomplete or conflicting data, as well as those who tested positive for for aMAP score calculation, 76 (7.3%) were categorized as high-risk,
HIV, hepatitis C virus (HCV), or Treponema pallidum (TP) antibodies, 402 (38.7%) as medium-risk, and 562 (54.0%) as low-risk. Over a
were excluded. Based on the presence of HBsAg, anti-HBc, and median follow-up period of 7.6 years, 35 participants developed HCC.
anti-HBs antibodies, patients were classified into four categories: (1) The 3-year, and 5-year cumulative HCC incidence rates were 0% and
current HBV infection (HBsAg+), (2) previous HBV infection (HBsAg- 0.18% in the low-risk group, compared with 3.0% and 4.0% in the
but anti-HBc+), (3) immune individuals (anti-HBs+ and negative medium-risk group, and 6.6% and 12% in the high-risk group (P<0.001
HBV-M), and (4) susceptible individuals (negative for all HBV markers). for 3-year, P<0.001 for 5-year). The corresponding hazard ratios (HR)
Previous and current infections were collectively referred to as HBV- were 19.1 (95% CI: 7.8–46.0) for the high-risk group and 7.6 (95% CI:
infected individuals. Age groups were divided into 5-year intervals, 3.4–17.0) for the medium-risk group, compared to the low-risk group.
with individuals born before 1991 included in the pre-HepB vaccination Conclusion: The aMAP risk score could be a promising tool for
cohort. identifying high-risk individuals for HCC development among HBV
Result: A total of 73,165 eligible patients were included, with a median infected individuals in community. Further studies using prospective,
age of 57 years and 48.6% male. The rates of current infection, previous community-based screening cohorts are warranted.
infection, susceptibility, and immunity were 6.66%, 46.40%, 28.19%,
and 18.56%, respectively. (1) The HBV infection rate increased with OP0147
age, peaking between 45 and 55 years, after which the current
infection rate gradually decreased, while the previous infection rate Novel Subtypes of Non-alcoholic Fatty Liver Disease and their
continued to rise. (2) The male population had a higher HBV infection Distinct Adverse Outcomes and Genetic Profiles
rate and a lower proportion of susceptible individuals, but sex did Li Wang1, Shutong Wu1, Shiqi Hu1, Yang Zhou2, Shuohua Chen3, Ying
not significantly affect immunity status. (3) The current infection rates Lu1, Jiangao Fan4, Shouling Wu3
for individuals born before and after the implementation of the HepB 1
Department of Epidemiology and Biostatistics, Institute of Basic
vaccination program, as well as for children aged 1–5 years, were Medical Sciences Chinese Academy of Medical Sciences; School
7.49%, 3.42%, and 0.10%, respectively. The corresponding previous of Basic Medicine Peking Union Medical College, 2Institute of
infection rates were 53.10%, 3.42%, and 2.00%. (4) In the post-HepB Basic Medical Sciences Chinese Academy of Medical Sciences,
vaccination cohort, the proportion of susceptible individuals remained
3
Department of Cardiology, Kailuan General Hospital, 4Department
high and varied significantly by age. of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong
Conclusion: In Taizhou, China, the prevalence of HBsAg positivity University School of Medicine
remains relatively high. HBV infection rates increase with age up to Background: The complex interaction among the demographic,
45–55 years, after which the current infection rate begins to decline. metabolic, and liver function-related factors may determine the sub-
HepB vaccination has significantly reduced the HBV infection rate phenotypes of non-alcoholic fatty liver disease (NAFLD). We aimed
in the population, but a substantial proportion of individuals remain to reclassify NAFLD and validate the classification via outcomes and
susceptible, with notable fluctuations in susceptibility across age genetic profiles.
groups. Comprehensive, population-wide management—including Method: Latent class analysis was applied to identify subgroups
screening, diagnosis, treatment, and follow-up—will be crucial in using demographic and clinical features among 11,467 adult men
achieving the WHO’s goal of eliminating viral hepatitis as a public with incident NAFLD who occurred in the Kailuan cohort from 2006 to
health threat. 2013 in China. Then, we compared risks of incident all-cause mortality,
Table and Figure:Figure 1.Figure 1 Age-specific prevalence of HBV cancers, cardiovascular diseases (CVDs), and genetic associations
among subgroups. A validation was conducted on 17,197 adult males 22% of iterations and cost-effective in 75% of cases using the above-
with incident NAFLD enrolled between 2014 and 2019 in the same mentioned WTP. It should be noted that in daily practice often a dose
cohort. of 10-20 g/day for 5-7 days is used in China. Assuming that the dose
Result: We identified five clusters with significantly different used in the actual clinical practice would lead to similar clinical results,
characteristics and risk of outcomes: three obese clusters (age-related likelihood of HA being a cost-effective adjuvant treatment would be
with normal triglyceride [ARO], metabolic syndrome-associated [MET], even higher since the total dose of HA used as standard of care is
and early-onset severe obese [ESO]) and two nonobese NAFLD lower.
clusters (hypertension-related [HRN] and with modest metabolic Conclusion: Adjunctive HA may be a cost-effective treatment in
derangements [LEAN]). ESO had the lowest risk of all events. patients with DC and SBP in certain urban areas in China.
Compared to ESO, the HRN group exhibited the highest risk of cancers Table and Figure:Figure 1.SBP Decision tree
(hazard ratio [HR] 2.12; 95% CI 1.22–3.69) risk, while MET remained Figure 2.SBP Model outcomes
the highest risk for CVDs (HR 2.86; 95% CI 1.96–4.19) and death (HR
2.14; 95% CI 1.41-3.24) after covariates adjusted. The ARO group had
OP0149
similar outcomes to those of MET except for CVDs. In addition, the
HRN group had a higher chance of CVDs than the ARO and LEAN Lipid metabolism indicators provide tools for the diagnosis of
group (HR 1.72; 95% CI 1.22–2.44). In support of the sub-phenotypes, nonalcoholic fatty liver disease: Results of a nationwide survey
22 NAFLD progression-related SNPs are distinct among clusters. The Chang Fu1, Xiaocong Li2, Kai Liu1
subtypes was confirmed in the validation cohorts. 1
Department of Hepatobiliary and Pancreatic Surgery, General
Conclusion: We identified NAFLD sub-phenotypes with distinct Surgery Center, The First Hospital of Jilin University, 2Department of
metabolic characteristics, disease progression, and genetic profiles. Pharmacy, China-Japan Friendship Hospital
This new stratification would predictably facilitate the development of Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic
precision-targeted therapies for NAFLD. liver condition marked by excessive lipid accumulation in hepatocytes
except alcohol and other definite liver injury factors. Cardiometabolic
OP0148 index (CMI), visceral adiposity index (VAI), and lipid accumulation
product (LAP) are lipid-related parameters that reflect central obesity,
The cost-effectiveness of albumin in the management of
which is closely associated with the development of NAFLD. The aim
spontaneous bacterial peritonitis in patients with decompensated
of this study is to investigate the effectiveness of these lipid-related
cirrhosis in urban China
parameters in diagnosing NAFLD and to compare their predictive
Liu Yang1, Cristina Coll-Ortega2, Xiaoyuan XU3, Lungen LU4,5, Qing abilities.
XIE6,5, Elisabet Viayna2, Cristina Fuster2, Mafalda Ramos7, Mark Method: This population-based study extracted datasets from the
Lamotte7 National Health and Nutrition Examination Survey (NHANES) 2017–
1
Grifols Pharmaceutical Technology, Shanghai, China, 2Grifols SA, 2020. Vibration controlled transient elastography using a FibroScan®
Sant Cugat del Valles, Spain, 3Peking University First Hospital, Beijing, system (model 502, V2 Touch) with controlled attenuation parameter
China, 4Shanghai General Hospital, Shanghai, China, 5Shanghai Jiao measurements identifed NAFLD at a threshold of ≥ 274 dB/m. CMI,
Tong University School of Medicine, 6Ruijin Hospital, Shanghai, China, VAI, and LAP were included in the multivariate logistic model as
7
Th(is)²Modeling bv, Asse, Belgium both continuous and categorical variables to assess the relationship
Background: Human albumin (HA) is an effective adjuvant treatment between different lipid-related parameters and NAFLD. To further
for patients with decompensated cirrhosis (DC) who develop elucidate this connection, we utilized restricted cubic splines and
spontaneous bacterial peritonitis (SBP). Addition of HA to antibiotic conducted subgroup analysis. Additionally, the receiver operating
treatment is recommended in clinical guidelines for the management characteristics (ROC) curve was employed to evaluate the predictive
of cirrhotic patients with SBP. However, the cost remains a barrier in effectiveness of CMI, VAI, and LAP for NAFLD.
certain resource-limited settings. This study aims to assess the cost- Result: This study included 2,878 participants with an average
effectiveness of HA and antibiotics compared to antibiotics alone in age of 52.3 ± 16.9 years, of whom 52.3% were female. Among the
cirrhotic patients hospitalized due to SBP from the healthcare provider’s study population, 1,263 participants were diagnosed with NAFLD,
perspective in certain urban areas in China. resulting in a prevalence rate of 48.9%. Generally, individuals with
Method: A decision-tree model was developed (Figure 1). Clinical NAFLD tend to be older, more frequently male, and show a higher
data were gathered from published literature. Clinical inputs included prevalence of diabetes and hypertension. As components of lipid-
infection resolution (assumed 100% in both arms), duration of antibiotic related parameters, BMI, WC and TG were significantly increased in
therapy (HA + cefotaxime versus cefotaxime alone: 5 vs 6 days), renal participants with NAFLD, while HDL-C was significantly decreased.
impairment (9.52% vs 33.33%), length of stay (14 vs 13 days) and When lipid-related parameters were analyzed as continuous variables,
in-hospital (9.52% vs 28.57%) and post hospital discharge (12.70% they showed a positive correlation with NAFLD. The OR(95%CI) were
vs 12.70%) mortality. Urban Chinese-specific utility and cost inputs 2.29(1.81,2.89) for CMI (per 1-unit), 1.40(1.28,1.52) for VAI (per 1-unit)
were obtained from literature representative for at least 13 cities. The and 1.15(1.11,1.20) for LAP (per 10-units). This correlation remains
dose of HA from the Chinese guidelines for the treatment of DC was statistically significant when the lipid-related parameters are analyzed
applied (1.5 g/kg on day 1 and 1 g/kg on day 3). The average weight of as categorical variables. In descending order of diagnostic capability
Chinese males and females, as well as the estimated sex distribution, for NAFLD, the AUC values are as follows: LAP (0.794), CMI (0.752),
was used to calculate the total dose. The price of HA was 38.6 CNY and VAI (0.719).
(5.5 USD - exchange rate Sep 30, 2024: 1 USD = 0.14 CNY). Time Conclusion: CMI, VAI, and LAP are important clinical indicators
horizon was 3 months (no discount rate was applied). Outcomes were for identifying NAFLD, with LAP demonstrating the best predictive
expressed as incremental cost-effectiveness ratio (ICER) reported as ability among them. This study provides practical indicators from the
CNY/USD per quality-adjusted life year (QALY). The willingness-to-pay perspective of lipid metabolism for the prevention and early intervention
(WTP) threshold was three times the GDP per capita (268,038CNY/ of NAFLD development. Future prospective cohort studies are needed
QALY; 38,223USD/QALY). One way and probabilistic sensitivity to further validate these findings.
analyses (PSA) were conducted. Table and Figure:Figure 1.Figure 1 Association between lipid-related
Result: HA added to antibiotics resulted in an improved survival (19%) parameters and NAFLD. The red solid line represents the smoothed
and an incremental 0.03 QALY gained over the 3-month time horizon. curve fit between the variables, while the black dashed lines indicate
It also increased the cost over 3 months in 2,767CNY (395 USD) per the 95% confidence interval of the fit.
patient, on average (Table 1). The resulting ICER was 97,023CNY/ Figure 2.Figure 2 ROC curves for different lipid-related parameters to
QALY (13,836USD/QALY). Key drivers of the model results were in- predict NAFLD.
hospital mortality, incidence and utility of renal impairment, cost of renal
impairment, and cost of DC. The PSA showed that HA was dominant in
 OP0150 negative CHB patients with suppressed viral loads were enrolled and
Cost-effectiveness of different strategies in achieving a functional assigned to NA (NA alone for 36 weeks, n=62), NAs+Peg-IFNα (NA
cure in CHB plus Peg-IFNα for 36 weeks, n=26), NA+αPD-1 (NA plus αPD-1 for 24
weeks followed by NA alone for 12 weeks, n=30), or NA+αPD-1/Peg-
Jing Chen1, Eliza Wong1, Ji Dong Jia2, Jin Mo Yang3, Tawesak
IFNα (NA plus αPD-1 for 24 weeks followed by NA plus Peg-IFNα for
Tanwandee4, Diana Payawal5, Saeed Hamid6, Shiv K SARIN7, Masao
12 weeks, n=6). For patients with CHB, αPD-1 (sintilimab, 100mg) was
Omata8, George LAU9,10
intravenously administered once every 3 weeks.
1
JC School of Public Health and Primary Care, Chinese University Result: After 4-week treatment for AAV-HBV mice, liver and
of Hong Kong, Hong Kong SAR, China, 2Liver Research Center,
plasma HBsAg levels decreased similarly in EA and EP groups,
Beijing Friendship Hospital, Capital Medical University, Beijing, China,
and decreased more in triple-drug combination groups, with a
3
Department of Internal Medicine, St. Vincent‘s Hospital, College of
significant difference between EA/P and MC groups (P=0.023). No
Medicine, The Catholic University of Korea, Seoul 06591, Korea. ,
adverse events (AEs) were observed except for hair loss in chest
4
Division of Gastroenterology, Department of Medicine, Faculty of
Medicine Siriraj Hospital, Mahidol University, Thailand, 5Department of and abdomen in one mouse from EAP group. Frequencies of HBV
Medicine, Cardinal Santos Medical Center, Mandaluyong, Philippines, surface-specific IL-4+/IL-21+/IFN-γ+/TNF-α+ CD8+T cells increased
6
Aga Khan UniversityAga Khan University, Karachi-74800, Pakistan. significantly in liver and blood in EA/P group (P<0.05). Frequencies
, 7Institute of liver and biliary sciences, 8Yamanashi Central and Kita of PD-1+CD8+ T cells in liver increased significantly in EA/P
Hospitals, University of Tokyo, 9Humanity & Health Medical Group, group and positively correlated with frequencies of CD38+CD8+ T
1
0Zhongshan Hospital, Fudan University, Shanghai, China cells (P<0.05). Furthermore, HBsAg decrease values correlated with
frequencies of surface-specific IL-21+CD8+ and PD-1+CD8+ cells
Background: Chronic hepatitis B (CHB) remains a major global health
(P<0.05). In patients with CHB, the overall incidences of AEs and
challenge, requiring effective and cost-efficient treatment strategies.
serious AEs (SAEs) were lower in NA+αPD-1 group than in NA+Peg-
This study evaluated the impact and cost-effectiveness of three
IFNα group (AEs: 70.0% vs 100.0%, P=0.007; SAEs: 6.7% vs 30.8%,
therapeutic strategies on HBsAg loss, related complications, and
P=0.046), with no significant difference between NA+Peg-IFNα and
associated costs from a healthcare provider’s perspective in the Asia-
NA+αPD-1/Peg-IFNα groups (P>0.05). Baseline HBsAg levels were
Pacific (AP) region.
similar across all groups (NA: 263.6 IU/mL, NA+Peg-IFNα: 251.8 IU/
Method: A Markov state-transition model was developed to assess
mL, NA+αPD-1: 283.1 IU/mL, NA+αPD-1/Peg-IFNα: 306.7 IU/
the cost-effectiveness of three antiviral treatment strategies: (1)
mL, P=0.784). From 0 to 24 weeks, HBsAg reductions were similar
indefinite nucleos(t)ide analogue (NA, entecavir) treatment, (2)
in NA+Peg-IFNα, NA+αPD-1 and NA+αPD-1/Peg-IFNα groups
Pegylated interferon (PegIFN) add-on to NA followed by NA cessation
(P=0.361), with all greater than HBsAg reduction in NA group (P<0.05).
(PegIFN+NA), and (3) NA cessation upon achieving stopping criteria
From 24 to 36 weeks, NA+αPD-1/Peg-IFNα group had the greatest
(STOP). The model simulated 10,000 CHB patients (aged 50+, NA-
HBsAg reduction (P<0.05). Additionally, αPD-1 treatment enhanced
suppressed, HBeAg-negative) and included virological and clinical
HBsAg-specific T cell response and T cell activation (P<0.05).
relapse and retreatment scenarios. Health outcomes and costs were
Conclusion: In a finite treatment, compared with NA plus Peg-IFNα,
discounted at 3.5%. Sensitivity analyses explored parameter and
NA plus αPD-1 may have a lower risk of AEs and similar efficacy in
model uncertainties.
reducing HBsAg levels. Sequential NA plus Peg-IFNα after NA plus
Result: By 2050, the STOP strategy is projected to reduce
αPD-1 can further reduce HBsAg levels.
hepatocellular carcinoma (HCC) and HBV-related mortality by 50%
Table and Figure:Figure 1.Figure 1 Study design and results (AAV-HBV
and 41%, respectively, compared to indefinite NA treatment, and was
mice).
cost-saving across the AP region, particularly in high-income settings.
Figure 2.Figure 2 Study design and results (Patients with chronic
The PegIFN+NA strategy was cost-effective, with incremental cost-
hepatitis B).
effectiveness ratios (ICERs) below one GDP per capita across all
settings. ICERs were sensitive to rates of HBsAg loss, seroreversion,
and therapy costs. Both STOP and PegIFN+NA strategies had a >90% OP0152
probability of being cost-effective compared to indefinite NA treatment. Efficacy and safety of xalnesiran in combination with the
Conclusion: Utilizing currently available drugs can significantly checkpoint inhibitor PD-L1 LNA in virologically suppressed
improve clinical outcomes for CHB patients. The most cost-effective participants with chronic hepatitis B: results from the Piranga
strategies differ by country income level in AP regions, indicating the phase 2, randomized, controlled, adaptive, open-label platform
need for tailored treatment approaches to align with the economic study
context of each country. Karen Doucette1, Deian Jelev2, Jia Horng Kao3, Luis Enrique Morano
Amado4, Kosh Agarwal5, Tarik Asselah6, Anchalee Avihingsanon7,
OP0151 Rozalina Balabanska8, Wan Long Chuang9, Apinya Leerapun10, Tien
Anti-PD-1 antibody combined with nucleos(t)ide analogue and Huey Lim11, Young Suk Lim12, Wei Wen Su13, Sheng Shun Yang14,
peg-IFNα enhances anti-HBV efficacy and T cell response in AAV- Ed Gane15, Gemma Attley16, Maria Teresa Catanese17, Farouk
HBV mice and patients with chronic hepatitis B Chughlay17, Anna Maria Geretti17,18, Gregory Hooper19, Remi Kazma17,
Yukun Liang20, Sijie Lu21, Ruchi Upmanyu19, Jeffrey Xu20, Wen
Taiyu He1, Min Chen1, Maoying Liu1, Huanyu Xiang1, Li Zhang1,
Zhang21, Man Fung Yuen22, for the Piranga Study Group
Huidan Sun1, Lu Zhang1, Mingli Peng1, Peng Hu1, Dachuan Cai1,
Dazhi Zhang1, Yinghua Lan1, Hong Ren1
1
Division of Infectious Diseases, University of Alberta, Edmonton,
Alberta, Canada, 2Clinic of Gastroenterology, St. Ivan Rilski University
1
Department of Infectious Diseases, Key Laboratory of Molecular
Hospital, Medical University of Sofia, Sofia, Bulgaria, 3Hepatitis
Biology for Infectious Diseases (Ministry of Education), Institute for
Research Center, National Taiwan University Hospital, Taipei, Taiwan,
Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical
China, 4nfectious Diseases, University Hospital Álvaro Cunqueiro,
University, Chongqing, China.
Galicia Sur Health Research Institute (IISGS), Vigo, Spain, 5Institute of
Background: This study aimed to explore the safety, efficacy and Liver Studies, King‘s College Hospital NHS Foundation Trust, London,
immune mechanism of therapeutic strategies based on anti-PD-1 United Kingdom, 6Université de Paris-Cité, Department of Hepatology,
antibody (αPD-1), nucleos(t)ide analogue (NA) and pegylated AP-HP, Hôpital Beaujon, Centre de recherche sur l’inflammation,
interferon-alpha (Peg-IFNα) for chronic hepatitis B (CHB). Inserm UMR1149, Paris, France, 7HIV-NAT, Thai Red Cross AIDS
Method: In the mouse study, adeno-associated virus (AAV)-hepatitis Research Centre and Center of Excellence in Tuberculosis, Faculty
B virus (HBV) mice were divided into model control (MC), entecavir, of Medicine, Chulalongkorn University, Bangkok, Thailand, 8Clinic
ETV+αPD-1 (EA), ETV+Peg-IFNα (EP), triple-drug sequential of Gastroenterology, Acibadem City Clinic Tokuda Hospital, Sofia,
combination (EA/P), and triple-drug initial combination (EAP) Bulgaria, 9Kaohsiung Medical University Hospital, Kaohsiung Medical
groups. Based on results from the mouse study, HBV e antigen (HBeAg)- University, Kaohsiung, Taiwan, China, 10Department of Internal
Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Claire McGeown1, for the Piranga Study Group
Thailand, 11Middlemore Hospital, Auckland, New Zealand, 12Asan 1
F. Hoffmann-La Roche Ltd, Basel, Switzerland, 2Roche R&D Center
Medical Center, University of Ulsan College of Medicine, Seoul, (China) Ltd, Shanghai, China, 3Roche Products Ltd, Welwyn Garden
Republic of Korea, 13Department of Internal Medicine, Changhua City, United Kingdom, 4Roche Innovation Center New York, Little Falls,
Christian Hospital, Changhua, Taiwan, 14Division of Gastroenterology NJ, USA, 5Roche (China) Holding, Ltd, Shanghai, China
& Hepatology, Department of Internal Medicine, Taichung Veterans
Background: In the Piranga (NCT04225715) phase 2 platform study,
General Hospital, Taichung, Taiwan, China, 15New Zealand Liver
the efficacy and safety of the HBsAg-targeting siRNA, xalnesiran,
Transplant Unit, Auckland City Hospital, Auckland, New Zealand,
1
6Roche Innovation Center New York, Little Falls, NJ, USA, 17F. was assessed alone or in combination with 3 immunomodulators: the
Hoffmann-La Roche Ltd, Basel, Switzerland, 18University of Rome checkpoint inhibitor, PD-L1 LNA; the TLR7 agonist, ruzotolimod; or
Tor Vergata, Rome, Italy (current affiliation), 19Roche Products Ltd, peginterferon α. Relative to the nucleos(t)ide analogue control arm as
Welwyn Garden City, United Kingdom, 20Roche (China) Holding, common comparator (HBsAg loss 24 weeks after the end of treatment
Ltd, Shanghai, China, 21Roche R&D Center (China) Ltd, Shanghai, [EOT] = 0%), xalnesiran combinations with ruzotolimod or with
China, 22Department of Medicine and State Key Laboratory of Liver peginterferon α performed best (12% and 23%, respectively); while
Research, Queen Mary Hospital, The University of Hong Kong, Hong xalnesiran monotherapy or combinations with PD-L1 LNA had limited
Kong, China efficacy(0 to 7%). In this exploratory post-hoc analysis, similarities
Background: Piranga (NCT04225715) is a phase 2 platform study and differences between these xalnesiran-based combinations were
designed to evaluate the efficacy and safety of finite duration therapies evaluated, shedding light on findings that may explain the observed
to achieve functional cure in virologically suppressed chronic primary results.
hepatitis B (CHB) participants (pts). Here, we report the primary and Method: Data originated from 158 nucleos(t)ide analogue-treated
selected secondary and exploratory endpoint results of xalnesiran participants (pts) randomized to 5 arms: xalnesiran alone (n=30) or
(RO7445482), a GalNAc-conjugated small interfering ribonucleic acid with an immunomodulator: PD-L1 LNA administered concurrently
(siRNA) targeting HBsAg transcripts, in combination with PD-L1 LNA (n=33) or sequentially (n=31), ruzotolimod (n=34), or peginterferon
(RO7191863), a GalNAc-conjugated locked nucleic acid inhibiting the α (n=30). HBsAg change from baseline was evaluated in subgroups
expression of the programmed death-ligand 1. stratified by baseline HBsAg level. For each arm, the association of
Method: Virologically suppressed CHB pts on nucleos(t)ide analogue on-treatment ALT elevations with the maximum HBsAg reduction or
(NA) therapy for at least 12 months were randomized to two arms: HBsAg loss at EOT was evaluated using scatter plots and Spearman
concurrent or sequential. In both arms, xalnesiran 200mg was correlation coefficient.
administered every 4 weeks from week 1 to 24. PD-L1 LNA 2.0 mg/ Result: In all arms, the nadir of HBsAg level was observed at EOT
kg was administered weekly for 12 weeks: either from week 13 to 24 with HBsAg reductions of 1.9 log10 IU/mL for xalnesiran monotherapy
(concurrent arm) or from week 25 to 36 (sequential arm). NA therapy vs. 2.1 log10 IU/mL for both arms of xalnesiran with PD-L1 LNA and
continued in all pts during the treatment period and until NA stopping 2.2 log10 IU/mL for both arms of xalnesiran with ruzotolimod or with
criteria were met at the end of treatment (EOT) or during the follow-up peginterferon α. The HBsAg reduction was consistently larger in pts
period. The primary endpoint was the proportion of pts with HBsAg loss with low (≤ 1,000 IU/mL) than in pts with high (> 1,000 IU/mL) HBsAg
at week 24 post-EOT. Secondary and exploratory endpoints included at baseline. The largest HBsAg reduction at EOT in the group of pts
changes in viral markers, safety, and analyses stratified by individual with low baseline HBsAg level was observed for the combination
baseline characteristics such as HBsAg level, HBeAg status, or HBV with peginterferon α (3.0 log10 IU/mL), while this reduction was
genotype. comparatively smaller in all other arms (2.1 to 2.4 log10 IU/mL). On-
Result: A total of 33 and 31 pts were enrolled in the concurrent and treatment ALT elevations of DAIDS Grade 2 or more were observed
sequential arms, respectively. Across both arms, the mean (SD) age in 13% of pts treated with xalnesiran monotherapy vs. 15% to 33% of
was 49.3 (8.6) years and the majority of pts were male (75.0%), Asian pts treated with xalnesiran with an immunomodulator. Correlation of
(68.8%), and HBeAg-negative at baseline (78.1%). At EOT, HBsAg on-treatment ALT elevations with the maximum HBsAg reduction was
loss had occurred in 2 (6.1%) and 4 (13.3%) pts in the concurrent modest across all arms (r ≤ 0.3) and statistically not significant. HBsAg
and sequential arms, respectively, with no cases of seroconversion. loss occurred both in presence and absence of ALT elevations with no
At the primary endpoint, HBsAg loss was sustained in only 2 pts from clear association. All ALT elevations resolved without sequelae.
the sequential arm. All pts with HBsAg loss had a baseline HBsAg Conclusion: These findings suggest that the combination of xalnesiran
≤ 168.3 IU/mL. The mean HBsAg reductions in the concurrent and with peginterferon α achieved high rates of HBsAg loss through an
sequential arms were, respectively, 2.12 and 2.08 log10 IU/mL at EOT increase in depth of HBsAg reduction, specifically in pts with low
and 1.30 and 1.46 log10 IU/mL at week 24 post-EOT. The mean HBsAg baseline HBsAg. Moreover, the absence of association between on-
reductions were higher for pts with baseline HBsAg levels ≤ 1000 IU/ treatment ALT elevation and the HBsAg reduction or loss indicates that
mL than those with baseline HBsAg levels > 1000 IU/mL, and for pts ALT flares may not be required to achieve HBsAg loss with xalnesiran-
with HBV genotype B than those with HBV genotypes C or D. Adverse based combination regimen.
events (AEs) were primarily Grade 1 or 2, with no serious AEs reported. Table and Figure:Figure 1.Design of the Piranga phase 2 platform
Maximum ALT elevations of DAIDS Grade 2 and 3 were observed in 22 study
(34.4%) and 3 (4.7%) of all 64 pts, respectively. All ALT elevations were Figure 2.Results for the combination of xalnesiran with peginterferon α
associated with preserved liver synthetic and excretory functions, and
resolved without sequelae. OP0154
Conclusion: The combination of xalnesiran with the checkpoint Targeted enrichment long-read single-cell transcriptomics reveal
inhibitor PD-L1 LNA, either concurrently or sequentially, achieved the clonal expansion of hepatocytes infected with HBV
limited efficacy on HBsAg loss and its durability. Xalnesiran with PD-L1
Yanfang Huang1, Miaoqu Zhang1, Yongping Liu2, Hongyuan Xue1,
LNA was generally safe and well-tolerated.
Qiran Zhang1, Jinhang He1, Zhengxin Wang1, Wenhong Zhang1, Chao
Table and Figure:Figure 1.
Qiu1
Figure 2. 1
Huashan Hospital, Fudan University, 2Hangzhou Xixi Hospital
Background: HBsAg derived from integrated HBV DNA poses a
OP0153 considerable challenge in defining the functional cure of chronic HBV
Similarities and differences of xalnesiran-based combination infection and elevates the risk of hepatocarcinogenesis. Previous
regimens aimed to achieve functional cure in the Piranga phase studies have failed to distinguished between HBV integrations and
2 platform study cccDNA at the single-cell level. Long-read sequencing is capable
Remi Kazma1, Cong Cheng2, Sudip Das3, Gemma Attley4, Annabelle of identifying full-length chimeric transcripts. Hence, we employed
Lemenuel-Diot1, Ethan Chen5, Ruchi Upmanyu3, Farouk Chughlay1, targeted enrichment long-read single-cell sequencing to disclose
HBV integration and analyze the impacts of HBV integration on tenofovir that has been widely used in mainland China for the treatment
transcriptomics. of chronic hepatitis B (CHB). The previous registrational study
Method: Single-cell long-read PacBio single molecule real-time (SMRT) (NCT03903796) has established the non-inferior virologic efficacy of
sequencing was established through the utilization of customized TMF to tenofovir disoproxil fumarate (TDF), while demonstrating higher
HBV beads to enhance the abundance of captured HBV sequences rates of alanine aminotransferase (ALT) normalization and improved
by means of specific HBV probes capture and PCR amplification. bone and renal safety profiles. This study presented the long-term
Subsequently, we carried out the sequencing on liver tissues from efficacy and safety of TMF in a phase IV study.
patients at various disease stages, including four patients with chronic Method: Participants from the Phase III registrational trial of TMF
hepatitis B (CHB), one with decompensated cirrhosis (DC), and two were enrolled and followed for another seven years, starting at week
with liver failure (LF). Sequencing reads were aligned with both the 144 in the Phase III study as the baseline. All participants continued
HBV genome (NC_003977.1) and the Human Reference Genome a daily 25 mg oral dose of TMF. The primary efficacy endpoint was
(GRCh38) to identify HBV-human chimeric transcripts. the percentage of patients with serum HBV DNA levels below the
Result: A total of 36,345 hepatocytes and 4,718 HBV-positive quantification limit at week (144+) 96. This report presents the findings
hepatocytes from seven individuals were identified, among which 5.7% at week (144+) 96.
(269/4,718) contained HBV integration. Nearly 80% of HBV integration Result: Totally, 639 (63.8 %) participants were enrolled: 436 patients
was located in genic regions (including introns, promoters, and exons), received TMF for 144 weeks and 203 patients had 96 weeks of TDF
suggesting that the transcription of HBV integration is initiated by host followed by 48 weeks of TMF. By week (144+) 96, the TMF group
genes rather than HBV promoters. and the TDF-to-TMF group achieved HBV DNA <20 IU/mL rates of
There were 110 unique integration sites included in the analysis. 95.2% and 94.1%, respectively, increasing by 5.5% (P<0.05) and
HBV integration was present in 4.31% (128/2,971) of HBV-positive 7.3% (P<0.05) from week 144 (Figure 1). Also, there are 91.9% and
hepatocytes from five patients, and HBV DNA was integrated into 92 91.5% patients in each group achieved a HBV DNA <10 IU/mL.
host genes, indicating that HBV DNA was randomly integrated into The HBeAg loss was still increasing during the studied period and
chromosomes without selective amplification. reached 50% by week 144+96 in both groups (Figure 2). Meanwhile,
It is notable that clonal expansion of hepatocytes with HBV integration the HBeAg seroconversion rates rose by 8.5% in the TMF group and
was observed in the two HBeAg-positive patients. In these cases, 9.9% in the TDF-to-TMF group. For the ALT normalization rate, the
17.95% (100/557) and 5.04% (60/1,190) of HBV-positive hepatocytes TDF-to-TMF group had a further increase by 4.8% during the study.
harbored HBV integration, with HBV predominantly integrating into No new drug-related adverse events were noted and only one case
the FN1 gene (93%, 93/100) and the UGP2 gene (53.3%, 32/60), of hepatocellular carcinoma was observed over 96 weeks. At week
respectively. (144+) 96, the proportion of patients with osteopenia (by spine bone
Conclusion: We have developed a targeted enrichment long-read mineral density) in both groups was numerically lower than that at 144
single-cell sequencing technology to identify HBV integration, track weeks, while the proportion of patients with osteoporosis remained
the clonal expansion of hepatocytes. unchanged. The accumulated incidence of an estimated glomerular
Table and Figure:Figure 1. filtration rate<60 ml/min/1.73 m2 remained low for five years (0.2% vs
1.0%, respectively). Both groups maintained stable weight and lipid
profiles during the study period.
OP0155
Conclusion: Five-year TMF treatment in CHB patients demonstrates
5-Year Efficacy and Safety of Tenofovir Amibufenamide in Chronic excellent efficacy and safety. Sustained benefits were achieved across
Hepatitis B Patients multiple efficacy endpoints, particularly in terms of virological response
Jinlin Hou1, Zhihong Liu1, Junqi Niu2, Min Zhang3, Guicheng Wu4, and serological conversion. Additionally, parameters of bone, renal,
Lihua Sun5, Daokun Yang6, Yan Huang7, Lvfeng Yao8, Enqiang and lipid safety remained stable over the study period. This study is
Chen9, Yawen Luo10, Shufang Yuan11, Jia Shang12, Xiaoqing Fu13, ongoing, and further follow-up results are anticipated.
Lihua Zhong14, Liang Chen15, Peng Hu16, Fengmei Wang17, Yao Xie18, Table and Figure:Figure 1.Figure 1. Achievement of virological
Xuebing Yan19, Wenhong Zhang20, Huazhong Chen21, Minghua Su22, response of TMF group and TDF-to-TMF group at week 144 and week
Min Xie23, Jidong Jia24, Jie Li25, Xiaorong Mao26, Mingqin Lu27, Qin (144+) 96
Zhang28, Desheng Xie29, Xingxiang Yang30, Qing Xie31, Caiyan Zhao32, Figure 2.Figure 2. Proportion of patients with HBeAg loss, and change
Zhizhen Hu33, Lei Shu33, Fanru Nie33 in HBeAg seroconversion rate from baseline in TMF group and TDF-to-
1
Nanfang Hospital, Southern Medical University, 2The First Hospital of TMF group at week (144+) 96. The denominator of HBeAg loss was the
Jilin University, 3Sencond Xiangya Hospital of Central South University, number of HBeAg- positive patients at 144 weeks. The denominator of
4
Chongqing University Affiliated Three Gorges Hospital, 5The First HBeAg seroconversion was the number of HBeAg positive and anti-
Affiliated Hospital of Xinjiang Medical University, 6The First Affiliated HBe negative persons at 144 weeks
Hospital Of Xinxiang Medical University, 7Xiangya Hospital, Central
South University, 8Mengchao Hepatopiliary Hospital of Fujian Medical
University, 9West China Hospital of Sichuan University, 10Affiliated OP0156
Hospital of Zunyi Medical University, 11Liuzhou People‘s Hospital, Decanoylcarnitine improves liver mitochondrial dysfunction in
1
2Henan Provincial People‘s Hospital, 13Hangzhou Xixi Hospital, 14The HBV infection by enhancing fatty acid β-oxidation
Fourth Affiliated Hospital of Harbin Medical University, 15Shanghai Ye Sun1, Chuanlong Zhu1
Public Health Clinical Center, 16The Second Affiliated Hospital of 1
Department of Infectious Disease, The First Affiliated Hospital of
Chongqiong Medical Uniwersity, 17Tianjin Third Central Hospital , Nanjing Medical University
1
8Beijing Ditan Hospital Capital Medical University, 19The Affiliated
Hospital Of Xuzhou Medical University, 20Huashan hospital affiliated Background: Occurrence of metabolic-associated steatotic liver
to Fudan University, 21Taizhou Hospital Of Zhejiang Province, 22The disease in patients with chronic hepatitis B is increasing annually, but
First Affiliated Hospital of Guangxi Medical University, 23Guangzhou the interaction between hepatitis B virus infection and lipid metabolism
Eighth People‘s Hospital,Guangzhou Medical University, 24Beijing is still unclear. Our study aims to clarify whether fatty acid metabolism
Friendship Hospital Capital Medical University, 25Nanjing Drum Tower regulation could alleviate mitochondrial dysfunction causing by
Hospital, 26The First Hospital of Lanzhou University, 27 The First HBV infection.
Hospital of Wenzhou Medical University, 28Tongren Hospital, Shanghai Method: We analyzed public gene set of the human livers and
Jiao Tong University School Of Medicine, 29Shanghai Fifth People‘s conducted a proteomic analysis on mice livers for exploring metabolism
Hospital, 30Sichuan Provincial People‘s Hospital, 31Ruijin Hospital, disorder and the affected organelles associated with HBV infection. The
Shanghai Jiao Tong University School of Medicine, 32Hebei Medical effect of decanoylcarnitine on fatty acid β-oxidation and mitochondria
University Third Hospital, 33Jiangsu Hansoh Pharmaceutical Group was investigated both in vivo and vitro. Pathways involved were shown
Co., Ltd. with proteomic analysis and confirmed with western blot.
Background: Tenofovir amibufenamide (TMF) is a novel prodrug of Result: The study showed that HBV infection could cause fatty acid
β-oxidation disorder and mitochondrial dysfunction in vivo and vitro. achieve statistical cure following hepatectomy, with cure probabilities
Overexpression of CPT1A could improve mitochondrial function in varying substantially based on risk stratification. This model provides
hepatocytes. Furthermore, supplementation of decanoylcarnitine could valuable prognostic information for treatment decision-making and
also activate CPT1A expression, thus improve fatty acid metabolism post-operative surveillance.
and repair mitochondrial dysfunction. Additionally, proteomic analysis Table and Figure:Figure 1.Virtual Abstract
of the mice livers suggested that decanoylcarnitine was working by
stimulating the PPAR signaling pathway and PPARα pathway was the
OP0158
most important among PPARs.
Conclusion: The disorder of fatty acid metabolism and mitochondrial Characterization of CD8+ MAIT cells in Liver Transplant Immunity
dysfunction in hepatocytes caused by HBV infection could be partially Hailun Cai1, Xinqiang Li2, Jinzhen Cai2, Bin Wu1
restored by exogenous supplement of decanoylcarnitine. It showed a 1
Fujian Medical University Union Hosptial, 2The Affiliated Hospital of
light in the therapeutic potential of decanoylcarnitine in HBV infection Qingdao University
and provided a new approach for mitochondrial dysfunction related Background: Mucosal-associated invariant T (MAIT) cells represent
diseases. one of the most abundant subsets of unconventional T cells and have
Table and Figure:Figure 1.Abstract been shown to play a significant role in regulating immune responses.
Figure 2.Decanoylcarnitine improves HBV-related mitochondrial However, the regulatory functions of MAIT cells in the context of liver
dysfunction. transplant immunity remain unknown.
Method: In this study, we conducted single-cell RNA sequencing,
OP0157 flow cytometry, and multiplex immunofluorescence (mIHC) assays
to identify the proportion and characteristics of CD8+MAIT cells in
Cure Probability After Hepatectomy for Patients with HBV-
humans and mice following liver transplantation.
Associated Hepatocellular Carcinoma: A Multi-institutional
Result: CD8+ MAIT cells were prominently featured in the single-
Analysis
cell CD8 profiles of human livers following liver transplantation,
Yifan Li1,2, Lanqing Yao1, Hong Ren3, Jinbo Gong2, Han Wu1, Lihui demonstrating strong signaling associations with macrophages.
Gu1, Yingjiang Liang4, Han Liu5, Kongying Lin6, Ziqiang Li7, Lei Cai8, Notably, the fractional populations of MAIT1 and MAIT17 were
Tinghao Chen9, Yahao Zhou10, Hong Wang11, Hongwei Guo12, Qixuan distinctly clustered in transplanted livers. The expression of CD8+
Zheng13, Feng Shen1, Zhong Chen2, Tian Yang1 MAIT markers was downregulated in acutely rejected livers. In parallel,
1
Eastern Hepatobiliary Surgery Hospital, Second Military Medical the percentage of CD8+ MAIT cells was significantly elevated in
University (Naval Medical University), 2Affiliated Hospital of Nantong a mouse liver transplant model, indicating a clear trend in the liver.
University, 3Department of Viral Hepatitis Control and Prevention, Furthermore, MAIT cells exhibited high expression of PD1 on their
Shanghai Municipal Center for Disease Control and Prevention, surface, suggesting that they could serve as a target for PD1/PDL1
4
Department of Hepatobiliary Surgery, the First Affiliated Hospital
modulation, providing a novel approach to enhance transplantation
of Harbin Medical University, 5First Hospital of Jilin University,
immunity.
6
Mengchao Hepatobiliary Hospital, Fujian Medical University,
Conclusion: CD8+ MAIT cells represent a promising predictive
7
The First Affiliated Hospital of Shandong First Medical University
biomarker for liver transplant rejection and may serve as potential
& Shandong Provincial Qianfoshan Hospital, 8Chongqing General
Hospital, Chongqing University, 9Department of General Surgery, targets for PD-1/PD-L1 therapies. This finding lays the groundwork
Ziyang First People’s Hospital, 10Department of Hepatobiliary Surgery, for further investigations into the role of these cells in transplantation
Pu’er People’s Hospital, 11Department of General Surgery, Liuyang immunity.
People’s Hospital, 12The Second Department of General Surgery, The Table and Figure:Figure 1.Characterization of CD8+ MAIT cells in Liver
Second People’s Hospital of Changzhi, 13Department of Hepatobiliary Transplant Immunity
Surgery, Shandong Provincial Hospital Affiliated to Shandong First Figure 2.Characterization of CD8+ MAIT cells in Liver Transplant
Medical University Immunity
Background: Statistical cure implies that a treated patient achieves
the same life expectancy as an individual without the disease. While OP0159
cure models have been applied to various malignancies, no specific Safety and efficacy of tenofovir alafenamide in liver transplant
model exists for hepatitis B virus (HBV)-associated hepatocellular recipients
carcinoma (HBV-HCC).
YingHong Shi1, WeiRen Liu1, Jia Fan1, ZhenBin Ding1, XiaoWu
Method: Patients who underwent curative-intent hepatectomy for
Huang1, Jian Zhou1
HBV-HCC between 2011 and 2022 were retrospectively analyzed 1
Department of Liver Surgery and Transplantation, Liver Cancer
using a multi-institutional database. Univariable and multivariable Cox-
Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and
regression analyses were performed to identify independent prognostic
Cancer Invasion of Ministry of Education, Fudan University, Shanghai,
factors of disease-free survival. X-tile analysis was employed to stratify China
patients into three risk groups. A spline-based cure model was applied
to compare cure probability against matched Chinese HBV carriers Background: Tenofovir alafenamide (TAF) can be considered a viable
with data provided by the Shanghai Center for Disease Control and alternative for prophylaxis against HBV reactivation because favorable
Prevention, as well as Chinese general population with the data renal safety profile without the need for dose adjustment in patients
obtained from the China National Bureau of Statistics. with renal impairment. Although TAF is established as a treatment for
Result: Among 740 patients, high viral load, poor liver function, HBV patients, data regarding the efficacy and safety of administering
multiple tumors, large tumors, satellite nodules, macrovascular TAF to liver transplant (LT) recipients is still limited. We report the
and microvascular invasion, intraoperative blood transfusion, and Chinese experience with TAF as treatment for LT patients.
postoperative HBV reactivation were identified as independent risk Method: This study prospectively analyzed data from 66 LT patients
factors of decreased disease-free survival. The cure probability after who were treated with TAF 25mg once daily as prophylaxis against
hepatectomy was 21.2% compared to those matched HBV carriers HBV recurrence. Demographic and clinical data were documented.
and 11.1% compared to Chinese general population. Risk stratification Additionally, clinical status was assessed at baseline and clinical
identified three distinct groups with varying cure probabilities. Low- findings, including AEs and cause of therapy interruption were
risk patients (63.2%) demonstrated favorable outcomes, with initial documented every 12 weeks during 48 weeks of follow up period. The
cure probabilities of 30.1% versus HBV carriers and achieved 95% analysis was conducted in accordance with the Helsinki Declaration
cure certainty by 8.6 years, while high-risk patients (15.2%) showed of 1975 and was approved by the ethics committee of the Zhongshan
negligible cure probability. Hospital, Fudan University.
Conclusion: A subset of patients with HBV-associated HCC can Result: In total, the study included 66 LT patients who were treated
with TAF as prophylaxis against HBV recurrence. Before transplant, function in patients with HM.
4.5%(3/66) were not on antiviral therapy. At the time of transplant, Table and Figure:Figure 1.Figure 1. A patient at the age of 46 developed
the median HBV DNA level was <50 IU/mL (range, <50-738), with HM 1 year after TIPS. When we attempted to embolize a GRS, GRS
83.3%(55/66) patients having undetectable levels of HBV DNA. The to PVS was observed (Blue and red circle) (1A). We embolized
virology status and liver biochemistry at the time of liver transplant PVS (Green circle) (1B), and the symptoms of HM was successfully
are shown in Table 1. 59 out 66 patients were included in week 48 revealed. HM, hepatic myelopathy; TIPS, transjugular intrahepatic
analyses (4 patients had died of disease progression, 3 patients had portosystemic shunt; GRS, gastro-renal shunt; PVS, paraspinal vein
discontinued therapy because of unscheduled injection of hepatitis B shunt.
immunoglobulin). Figure 2.Figure 2. Nomogram to predict the HM. To use, locate ‘ascites’
At 48 weeks of treatment with TAF, 93.2% patients (55/59) tested axis; draw a line straight up to the ‘Points’ axis to determine the score
seronegative for HBsAg; 100% patients (59/59) had undetectable associated with the variables. Repeat for the other two variables. Sum
levels of HBV DNA. No patients had reactivation of HBV. No side effects the scores and locate the total score on the ‘Total points’ axis. Draw a
attributable to TAF were noted during the 48 weeks follow-up period. line straight downward to the ‘HM’ axis to obtain the HM occurrence
Conclusion: Tenofovir alafenamide exhibits high antiviral efficacy and probability. *p < 0.05; ***p < 0.001; PVS, paraspinal vein shunt; HE,
a good safety profile for LT recipients. Still, the safety and tolerability of hepatic encephalopathy; HM, hepatic myelopathy.
TAF for organ transplant patients should be evaluated through larger
cohorts.
OP0161
Table and Figure:Figure 1.
Survival benefit from neoadjuvant transarterial chemoembolization
with tyrosine kinase and immune checkpoint inhibitors for
OP0160 resectable intermediate or advanced hepatocellular carcinoma
Paraspinal Vein Shunt (PVS): A Potential Key Factor Leading to (GUIDANCE002): a multicenter, retrospective study
Hepatic Myelopathy DaLong Yang1, Chuang Qin2, Ning Peng3, ShaoPing Liu4, YaQun Yu5,
Yuhong Suo1, Lixue Xu2, Chenyue Zhang1, You Deng1, Yu Wang1, JunLiang Nong6, FanJian Zeng7, Ze Su8, YongYu Yang9, FuQuan
Xinyan Zhao1, Hongqi Zhang3, Fuliang He1, Jidong Jia1 Yang10, MianJing Li11, MingSong Wu12, XueYao Wang13, YongRong
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical Liang14, FuXing Li15, ShuChang Chen16, YongCheng Lai17, QingQing
University, The Nation Clinical Research Center for Digestive Pang18, TengMeng Zhong19, YiHe Yan20, YingYu Zhang2, Lin Ye5,
Diseases, Beijing, China, 2Department of Radiology, Beijing XiaoFeng Dong9, WenFeng Li10, Jie Liu11, HongBing Yao13, PeiSheng
Friendship Hospital, Capital Medical University, The Nation Clinical Wu14, XianShuang Mao15, JunJie Ou16, YaoZhi Chen17, GuoDong
Research Center for Digestive Diseases, Beijing, China, 3Department Wang18, Kang Chen20, XiuMei Liang1, XueMei You1, Yi Zhang1,
of Neurosurgery, Capital Medical University Affiliated Beijing xuanwu ChangYang Chen1, WenXuan Liu1, JiaNan Shao1, Xuan He1, BangDe
Hospital, Beijing, China Xiang1, Liang Ma1, JianHong Zhong1
Background: Hepatic myelopathy (HM) is a rare neurological 1
guangxi medical university cancer hospital, 2Liuzhou People’s
manifestation of patients with chronic liver diseases whose exact Hospital, 3First Affiliated Hospital of Guangxi Medical University,
etiology remains unclear. It has been previously reported to be 4
Eighth Affiliated Hospital of Guangxi Medical University, 5Affiliated
associated with surgical or spontaneous portosystemic shunt Hospital of Guilin Medical University, 6Hengzhou City People’s
(SPSS) like gastro-renal shunt (GRS) and splenorenal venous shunt Hospital, 7Wuzhou Red Cross Hospital, 8First People’s Hospital
(SRS). However, of those pathways which is the key shunt for HM of Nanning, 9People‘s Hospital of Guangxi Zhuang Autonomous
occurrence remains unclear. Region, 10First People’s Hospital of Yulin, 11Guilin People‘s Hospital,
When we attempted to embolize a GRS in a patient with HM in 2023
1
2People’s Hospital of Beiliu, 13Second Affiliated Hospital of Guilin
to reverse symptoms of HM, we found that the patient had coexisting Medical University, 14First People’s Hospital of Qinzhou, 15People‘s
Hospital of Hezhou, 16Wuzhou People’s Hospital, 17Beihai People’s
GRS to paraspinal vein shunt (PVS). Surprisingly, the symptoms of HM
Hospital, 18Liuzhou Workers Hospital, 19Baise People‘s Hospital,
patient were substantially reversed by further embolizing of the PVS, 2
0Second Affiliated Hospital of Guangxi Medical University
suggesting that PVS might be a key factor in the process of HM. Thus,
the aim of this study was to review all patients with HM and matched Background: Introduction: The efficacy and safety of
non-HM patients in our center and to observe the correlation of PVS neoadjuvant transarterial chemoembolization with tyrosine kinase and
and HM. immune checkpoint inhibitors (neoadjuvant triple therapy) for patients
Method: We retrospectively reviewed all patients diagnosed with HM with resectable intermediate or advanced hepatocellular carcinoma
in Beijing Friendship Hospital, Capital Medical University. As well, are unclear.
44 non-HM patients with portal hypertension (PHT) were randomly Method: Methods: Patients who received neoadjuvant triple therapy
enrolled during the same period. Multivariate logistic regression models (n = 205) or who underwent hepatectomy directly (n = 378) at 20
were used to identify the predictors of HM, and nomogram model medical centers in China between January 2019 and June 2023
incorporating PVS were developed. A risk score model was established were retrospectively compared in terms of overall survival, event-
for the prediction of HM. The receiver operating characteristic (ROC) free survival, recurrence-free survival, adverse events related to
curve, calibration curve and decision curve analysis (DCA) were neoadjuvant therapy, and postoperative complication. Subgroup
used to evaluate the utility of the prediction models. A 1:2 propensity- stratified comparisons also included 106 patients who received
score matching (PSM) was performed to reduce potential confounding neoadjuvant triple therapy followed by hepatectomy or 99 patients
factors and selection bias. who received neoadjuvant therapy without subsequent hepatectomy
Result: 19 patients with HM, from May 2016 to January 2024 were because they preferred to continue loco-regional/systemic therapy or
included. Of these patients, PVS was found in 13 patients because their cancer progressed to an unresectable state.
(68.4%). The PVS, ascites and hepatic encephalopathy (HE) Result: Results: Compared to patients who underwent hepatectomy
were identified as independent risk factors for HM patients by directly, patients who received neoadjuvant triple therapy showed
multivariate analysis. Blood ammonia was defined as intermediate significantly higher overall survival (HR 0.70, 95%CI 0.53–
factors, thus was not included into the regression analysis. The 0.92) and significantly longer median event-free survival (19.7 vs
area under the ROC curve of the established model according 10.9 months, p < 0.001). Similar results were obtained after propensity
to above three factors were 0.937 (95% confidence interval, score matching. Among patients who underwent hepatectomy,
0.876-0.997) for the total 63 patients, and 0.917 (95% confidence those who underwent prior neoadjuvant triple therapy had
interval, 0.846-0.989) for the 54 post-PSM patients, respectively. significantly better overall (HR 0.45, 95%CI 0.31–0.66) and event-
Conclusion: PVS, ascites and HE were independently predictive free survival (HR 0.49, 95%CI 0.38–0.63) than those who underwent
factors of HM. PVS might be a key shunt in the development of HM hepatectomy directly. Similar results were obtained after propensity
and embolization of PVS might be effective for improving the motor score matching. Among patients who received neoadjuvant triple
therapy, overall survival was significantly better among those who Table and Figure:Figure 1.Figure 1. A. Trajectories of acute kidney
subsequently underwent hepatectomy (HR 0.40, 95%CI 0.24- injury in liver transplantation patients. B. different AKI severity among
0.67). Neoadjuvant therapy led to a complete pathologic response different graft dysfunction groups. C. comparions of graft survival
rate of 34.0% and major pathologic response rate of 43.4%. However, between different severity of liver and renal dysfunction
neoadjuvant therapy was associated with high rates of serious adverse Figure 2.Table 1 and 2. 1.Kidney Function During Hospitalization
events and postoperative complications, including bile leakage, Stratified by L-GrAFT risk group. 2.Clinical Outcomes Stratified by
ascites and hepatic insufficiency. Graft Function and Postoperative Kidney Function Trajectories
Conclusion: Conclusions: Neoadjuvant triple therapy offers
overall and event-free survival benefits for patients with initially
OP0163
resectable intermediate or advanced hepatocellular carcinoma, but
associated with increasing risk of adverse events and postoperative INSR Exists on the Mitochondria of Hepatocytes and Correlates
complications. with the Severity of MAFLD
Yifei Qi1, Qinghong Yu1, Shijin Bai1, Shiyu Wang1, Tianhui Liu1
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
OP0162
University, State Key Lab of Digestive Health, National Clinical
The Impact of Early Graft Dysfunction On Renal Dysfunction After Research Center of Digestive Diseases
Orthotopic Liver Transplantation: A Multicenter, Retrospective,
Background: Background and Aims Insulin receptor (INSR) plays a
Longitudinal Cohort Study
key role in physiology, as well as the most prevalent chronic diseases,
Nie Yu1, Huang Jin Bo2, Lai Ye Hua3, Zhao Qiang2 including T2D, obesity, and metabolic dysfunction associated fatty liver
1
Department of Hepatobiliary Surgery II and Transformation Center for disease (MAFLD). Ligand-activated INSR undergoes internalization
Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, and traffic inside. However, there is still a lack of knowledge on INSR
Southern Medical University, Guangzhou 510220, People’s Republic trafficking to different organells and subsequent response. It has been
of China., 2Organ Transplant Center, The First Affiliated Hospital, reported that INSR translocates to the mitochondria in corneal epithelial
Sun Yat-sen University, NO.58 Zhongshan Er Road, Guangzhou cells and maintains the functional stability of mitochondria. This study
510080, China, 3Department of Transplantation, The People’s Hospital
aims to explore whether INSR is present on the mitochondria of
of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi,
hepatocytes and its relationship to the severity of MAFLD.
China.
Method: Methods Mitochondrial proteins were extracted from both
Background: The relations and trajectories of liver graft dysfunction the liver tissue of normal male C57BL/6 mice and the hepatic cell
and renal dysfunction is not fully described after orthotopic liver line AML12. The expression of INSR was detected by Western Blot.
transplantation(OLT). We performed a quantitative analysis to Double immunofluorescence staining of mitochondria and INSR was
evaluate the impact of graft dysfunction on clinical trajectories of performed in AML12 cells. Male C57BL/6 mice were randomly divided
acute kidney injury(AKI) and long-term renal function using the most into control group and MAFLD group. The control group were fed
recent continuous Liver Graft Assessment Following Transplantation chow diet and the MAFLD group were fed methionine and choline
(L-GrAFT) risk-score that could stratified graft dysfunction severity. deficient diet (MCD) diet or choline-deficient, L-amino acid-defined
Method: This retrospective multicenter observational study included (CDAA) diet, respectively. Haematoxylin and eosin (H&E) staining
1098 consecutive primary OLT patients from Guangdong cohort(n=788), was performed for determination of steatosis, ballooning and lobular
Guangxi cohort(n=115) and public INSPIRE cohort(n=195) between inflammation. Sirius Red staining was performed for determination of
January 2015 and December 2022. L-GrAFT risk-score was used to liver fibrosis. The expression of INSR in mitochondria was detected by
classify the severity of early graft dysfunction: good function(n=316), Western Blot, and was compared between control and MAFLD group.
mild dysfunction (n=542), moderate dysfunction (n=170) and severe Result: Results Western Blot results revealed that INSR was detected
dysfunction (n=70). AKI was graded using KDIGO criteria. Patients in the mitochondrial protein of both normal mouse liver tissue and
were divided into different groups according to post-OLT renal and AML12 cells. Immunofluorescence results showed the co-localization
graft dysfunction. Perioperative renal-associated outcomes long-term of mitochondria and INSR in AML12 cells. These data indicates that
survival were compared among different trajectories of AKI and graft INSR exists on the mitochondria of hepatocytes. Compared with control
dysfunction. group, H&E staining results showed steatosis, hepatic ballooning,
Result: 51.2% (n=562) recipients developed AKI. 87.9% AKI occurred lobular inflammation in the liver of MAFLD group, and Sirius Red staining
within 48 hours after OLT, with 40.2% AKI episodes developed during showed pericellular fibrosis in the liver of MAFLD group. Compared
surgery. AKI rates in good, mild, moderate and severe graft dysfunction with control group, the protein level of INSR on mitochondria of liver
group were 41.5%, 48.5%, 60.0% and 94.3%. Renal-related outcomes tissue in MAFLD group was significantly lower (P<0.05). These data
including peak creatinine, AKI duration, AKI severity and rates of indicates that mitochondrial INSR decreased in the liver of MAFLD.
persistent AKI, RRT and MAKEs all significantly deteriorated as graft Conclusion: Conclusions INSR exists on the mitochondria of
function deteriorated(P<0.001). Mild(OR 2.92 and OR 2.80), moderate hepatocytes, and decreased in the context of MAFLD. Mitochondrial
(OR 9.31 and OR 7.19) and severe (OR 83.2 and OR 120.7) graft INSR is related to the severity of MAFLD and might play a role in the
dysfunction were independent predictors of RRT requirement and progression of MAFLD.
MAKEs(P<0.001). Patients combining both liver and renal dysfunction
had significant inferior graft survival and increased MAKEs compared to
those with only liver dysfunction(P<0.001). After adjusting for recipient, OP0164
donor and surgical parameters, Simultaneous severe impairment of Distribution of estimated glomerular filtration rate in MASLD
liver function and renal function(group 6, liver-renal function stage across continents and according to country
VI) was independently associated with worst adjusted 3-month graft Jing Zhao1, Ferenc E Mózes2, Xinyu Xu1, Dong Ji3, Huiqing Liang4,
failure(adjust HR 73.73, CI: 35.26-154.14, P<0.001) and one-year Xiaoling Chi5, Jinjun Chen6, Takeshi Okanoue7, Toshihide Shima7,
graft survival (adjust HR 24.50, CI: 15.49-38.75, P<0.001) compared Yongfen Zhu8, Christian Labenz9, Bihui Zhong10, Masato Yoneda11,
to other groups, while severe graft dysfunction with preserved renal Atsushi Nakajima11, Junping Shi12, Jing Zhang13, Sanjiv Mahadeva14,
function achieve an unexpectedly good prognosis(one-year graft Wah Kheong Chan14, Fangping He15, Chunyan Ye16, Su Lin17,
survival 58.3%) Adele Delamarre18, Victor De Lédinghen18, Monica Lupsor-Platon19,
Conclusion: Different severities of graft dysfunction graded by Zhonghua Lu20, Hong TANG21, Jidong JIA22, Peter J Eddowes23,
L-GrAFT score were associated with distinct clinical trajectories of Liang Xu24, Yiling Li25, Yuemin Nan26, Hong Deng27, Junqi Niu28,
renal dysfunction and survival outcomes. Simultaneous impairment Xuebing Yan29, Qing Ye30, Qinglei Zeng31, Yongjian Zhou32, Jeremy FL
of graft and renal function synergistically exacerbated OLT outcomes Cobbold33, Chenghai Liu34, Jie Li35, Lei Li36, Jing Wang37, Fanpu Ji38,
while preserved renal function could counteract the adverse effects of Jin Chai39, Yongning Xin40, Giovanni Targher41, Christopher D Byrne42,
severe graft dysfunction. Yuchen Fan43, Jiahui Zhang44, Geraldine Ooi45, Jacob George46,
Michael Pavlides47, Danqin Sun1, Minghua Zheng48 Background: With the rising global prevalence of metabolic
1
Urologic Nephrology Center, Jiangnan University Medical Center, dysfunction-associated steatotic liver disease (MASLD), a significant
2
Radcliffe Department of Medicine, University of Oxford, 3The Fifth association between this common liver disease and chronic kidney
Medical Center of Chinese PLA General Hospital, 4Hepatology disease has become evident. This retrospective multinational study
Unit, Xiamen Hospital of Traditional Chinese Medicine, 5Department aims to illustrate the distribution of estimated glomerular filtration
of Hepatology, The Second Affiliated Hospital of Guangzhou rate (eGFR) levels in people with biopsy-confirmed MASLD and to
University of Chinese Medicine, 6Hepatology Unit, Department of investigate the association between eGFR and liver fibrosis in different
Infectious Diseases, Nanfang Hospital, Southern Medical University, countries and regions
7
Department of Gastroenterology and Hepatology, Saiseikai Suita Method: 3308 participants with biopsy-proven MASLD from 34 centers
Hospital, 8Department of Hepatology and Infection, Sir Run Run Shaw were enrolled in the study. eGFR was calculated using the CKD-EPI
Hospital, Affiliated with School of Medicine, Zhejiang University,, equation and eGFR < 90 ml/min/1.73m2 was defined as the declined
9
Department of Internal Medicine I, University Medical Centre eGFR group
of the Johannes Gutenberg-University Mainz, 10Department of Result: European participants were older, had higher adiposity
Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, measures, and a greater prevalence of metabolic comorbidities than
1
1Department of Gastroenterology and Hepatology, Yokohama
Asian. Europeans also had lower eGFR levels (92.21±20.65 vs.
City University School of Medicine, 12Department of Hepatology,
104.71±17.31 ml/min/1.73 m2, P<0.001) and more severe liver
The Affiliated Hospital of Hangzhou Normal University, Hangzhou,
fibrosis (61.35% vs. 32.46%, P<0.001). In Asia, Chinese participants
1
3The Third Unit, Department of Hepatology, Beijing Youan Hospital,
had the highest mean eGFR level at 105.78 ml/min/1.73m2, while
Capital Medical University,, 14Gastroenterology and Hepatology
Unit, Department of Medicine, Faculty of Medicine, University of Malaysian participants had the lowest at 87.3 ml/min/1.73m2. In
Malaya, 15Department of Hepatobiliary Pancreatic Surgery, Eighth Europe, French participants had the highest mean eGFR level at 95.33
Hospital Affiliated to Sun Yat-sen University, 16Institute for the Study ml/min/1.73m2, while Romanian participants had the lowest at 81.08
of Liver Diseases, The Third People‘s Hospital of Changzhou, ml/min/1.73m2. The mean eGFR level was 94.3 ml/min/1.73m2 in
Changzhou, Jiangsu Province, 17Department of Hepatology, Germany and 94.9 ml/min/1.73m2 in the UK, respectively. Moreover,
Hepatology Research Institute, The First Affiliated Hospital of Fujian the eGFR level was inversely associated with liver fibrosis in China,
Medical University, 18Centre d’Investigation de la Fibrose Hépatique, Japan, and France
Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, Conclusion: The European population with biopsy-confirmed MASLD
France, 19Department of Medical Imaging, “Prof. Dr. Octavian has lower eGFR levels and more severe liver fibrosis than the Asian
Fodor“ Regional Institute of Gastroenterology and Hepatology, “Iuliu population. Furthermore, eGFR levels are inversely associated with
Hațieganu“ University of Medicine and Pharmacy, Cluj-Napoca, liver fibrosis in Asians, even after adjusting for traditional renal risk
Romania, 20Clinical Laboratory Center, The Fifth People‘s Hospital of factors
Wuxi, 21Center of Infectious Diseases, West China Hospital, Sichuan Table and Figure:Figure 1.Epidemiological distribution map of eGFR
University, 22Liver Research Center, Beijing Friendship Hospital, level in global multinational centers
Capital Medical University, Beijing, 23National Institute for Health Figure 2.Trend chart and association between eGFR and liver fibrosis
Research Nottingham Biomedical Research Centre, Nottingham score in different regions
University Hospitals NHS Trust and University of Nottingham,
2
4Department of Hepatology, Tianjin Second People‘s Hospital,
Tianjin, China, 25Department of Gastroenterology, First Affiliated OP0165
Hospital of China Medical University, 26Department of Traditional and Global Burden, Temporal Trends, and Future Predictions of
Western Medical Hepatology, The Third Hospital of Hebei Medical Alcohol-Related and Non-Alcoholic Steatohepatitis-Related
University, 27Department of lnfectious Diseases, The Third Affiliated Hepatocellular Carcinoma From 1990 to 2050: A Population-Based
Hospital of Sun Yat-sen University, 28Department of Hepatology, Analysis of GBD 2021 Data
Center of Infectious Diseases and Pathogen Biology, The First Zixuan Xing1, Jingyue Tan2, Yujiao Deng3, Jian Zu2, Yue Zhang2,
Hospital of Jilin University, 29Department of Infectious Disease, The
Zhanpeng Yang2, Xinyuan He1, Enrui Xie1, Yue Zhang1, Xindi Huang1,
Affiliated Hospital of Xuzhou Medical University, 30Department of
Fanpu Ji1,4,5
Hepatology of The Third Central Hospital of Tianjin, 31Department
of Infectious Diseases, The First Affiliated Hospital of Zhengzhou
1
Department of Infectious Diseases, The Second Affiliated Hospital
University, 32Department of Gastroenterology and Hepatology, of Xi’an Jiaotong University, Xi’an, China, 2School of Mathematics
Guangzhou First People‘s Hospital, 33Translational Gastroenterology and Statistics, Xi’an Jiaotong University, Xi’an, China, 3Division of
Unit, University of Oxford, 34Institute of Liver Diseases, Shuguang Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong
Hospital affiliated to Shanghai University of Traditional Chinese University, Xi’an, China, 4Key Laboratory of Environment and Genes
Medicine, 35Department of Infectious Disease, Nanjing Drum Tower Related to Diseases (Xi‘an Jiaotong University), Ministry of Education
Hospital, The Affiliated Hospital of Nanjing University Medical School, of China, Xi‘an, Shaanxi, China, 5Key Laboratory of Surgical Critical
3
6Department of Infectious Disease, The First Affiliated Hospital of Care and Life Support (Xi‘an Jiaotong University), Ministry of
Anhui Medical University, 37Department of Hepatobiliary Diseases, Education of China, Xi‘an, Shaanxi, China
Affiliated Traditional Chinese Medicine Hospital of Southwest Background: Hepatocellular carcinoma (HCC) is a leading cause of
Medical University, 38Department of lnfectious Diseases, The Second cancer-related mortality worldwide. With effective antiviral therapies
Affiliated Hospital of Xi‘an Jiaotong University, Xi‘an, 39Department reducing viral hepatitis-related HCC, the focus has shifted to alcohol-
of Gastroenterology, Southwest Hospital, Army Medical University, related HCC (AL-HCC) and non-alcoholic steatohepatitis-related
Chongqing, 40Qingdao Municipal Hospital, 41Department of Medicine, HCC (NASH-HCC) due to the increasing burden of alcohol use and
University of Verona, 42Southampton National Institute for Health and metabolic disorders. This study aims to evaluate the global burden,
Care Research Biomedical Research Centre, University Hospital temporal trends, and future projections of AL-HCC and NASH-HCC
Southampton, and University of Southampton, Southampton General from 1990 to 2050.
Hospital, 43Department of Hepatology, Qilu Hospital of Shandong Method: We utilized data from the Global Burden of Disease Study
University, 44Department of Paediatrics, The Affiliated Wuxi Children‘s (GBD) 2021 to assess the epidemiology of AL-HCC and NASH-
Hospital of Jiangnan University, 45Centre for Obesity Research and HCC from 1990 to 2021. Age-standardized rates for mortality were
Education, Department of Surgery, Monash University, 46Storr Liver
calculated. Joinpoint regression models were used to determine the
Centre, Westmead Institute for Medical Research, Westmead Hospital
Average Annual Percentage Change (AAPC) and to identify trends.
and University of Sydney, 47Oxford Centre for Clinical Magnetic
We conducted a decomposition analysis to evaluate the impact of
Resonance Research, Radcliffe Department of Medicine and Oxford
demographic changes on mortality trends and projected future trends
NIHR Biomedical Research Centre, University of Oxford, 48MAFLD
Research Center, Department of Hepatology, the First Affiliated until 2050 using a forecasting model.
Hospital of Wenzhou Medical University Result: Both AL-HCC and NASH-HCC showed increasing age-
standardized mortality rates (ASMRs) from 1990 to 2021, with AAPCs
of 0.35 (95% Confidence Interval [CI]: 0.22-0.48) for AL-HCC and 0.82 in this research. The cross-sectional study enrolled 500 participants,
(95% CI: 0.63-1.02) for NASH-HCC. The highest ASMR increases for including 446 patients with MASLD and 54 healthy volunteers. Among
AL-HCC and NASH-HCC were both seen in Region of the Americas the patients with MASLD, 164 underwent liver biopsy. A total of 136
(AL-HCC: AAPC=1.78, 95% CI: 1.45-2.11; NASH-HCC: AAPC=2.03, MASLD patients was subjected to a 24-weeks follow-up in longitudinal
95% CI: 1.76-2.30), while the African Region and Western Pacific study. All subjects underwent abdominal MRI, and general,
Regions had the lowest ASMR increases. Although ASMRs for AL- biochemical, and imaging parameters were collected. The muscle fat
HCC and NASH-HCC will decrease during 2021-2050, the ASMR will content was measured in the psoas muscle at the level of the 3rd lumbar
increase in males and in the Eastern Mediterranean Region and South- vertebra by PDFF (L3-PDFFPsoas). L3-PDFFPsoasresponse was
East Asia Region. Our projections indicate that global deaths from AL- defined by Cohen’s d (responding group, Cohen’s d ≥ 0.2).
HCC and NASH-HCC will continue to rise, driven predominantly by Result: MASLD patients exhibited higher L3-PDFFPsoas compared
age structure. to healthy volunteers [median (IQR): 4.8(1.6) % vs. 6.6(2.6) %,
Conclusion: Although the global age-standardized mortality rate P < 0.001]. L3-PDFFPsoas was higher in metabolic dysfunction-
(ASMR) is projected to decline by 2050, demographic changes associated steatohepatitis (MASH) than in MASL (P = 0.0048) and
will continue to drive an increase in overall deaths. Regional increased with the severity of MASH (early MASH, fibrotic MASH, and
disparities persist, with significant increases projected in the Eastern MASH cirrhosis) (P = 0.013). Subjects with more severe ballooning
Mediterranean and Southeast Asia regions, highlighting the need for or fibrosis had higher L3-PDFFPsoas (all P < 0.05). Also, in total
targeted public health interventions. These findings highlight a shift in participants, L3-PDFFPsoas was significantly  related to FIB-4 score
HCC epidemiology from viral hepatitis to alcohol use and metabolic and liver stiffness measurement (LSM), respectively (r = 0.349 and
disorders, requiring a reorientation of prevention strategies and 0.264, all P < 0.05). After adjustment for multiple confounders, L3-
healthcare policies to address this increasing burden. PDFFPsoas was robustly associated with liver fibrosis (odds ratio =
Table and Figure:Figure 1.Figure 1. Spatial distribution of the AAPC of 1.320, 95% CI: 1.039-1.678, P = 0.023), while L3-PDFFPsoas was not
ASMR for AL-HCC and NASH-HCC during 1990-2021 and 1990-2050 significantly associated with MASLD and MASH. After 24-weeks follow-
in 204 countries and territories. (A) NASH-HCC from 1990 to 2021, (B) up, there are significant reductions in L3-PDFFPsoas (all P < 0.05) in
NASH-HCC from 1990 to 2050, (C) AL-HCC from 1990 to 2021, (D) patients with a 30% relative decrease in MRI-PDFF, 17 IU/L decrease
AL-HCC from 1990 to 2050. in alanine aminotransferase (ALT) or over 2 kPa decrease in LSM.
Figure 2.Figure 2. Contributions of population growth, age structure, Between-group analysis showed greater reduction in MRI-PDFF, ALT
and epidemiological changes to the increase in deaths from AL-HCC and LSM in favor of L3-PDFFPsoas responders (all P < 0.05).
and NASH-HCC worldwide and in six WHO regions, 1990-2021 and Conclusion: Muscle fat content is significantly correlated to MASLD,
2022-2050. (A) NASH-HCC in 1990-2021, (B) NASH-HCC in 2022- especially liver fibrosis. Alterations in muscle fat content correspond
2050, (C) AL-HCC in 1990-2021, (B) AL-HCC in 2022-2050. Black dots with MASLD improvement. These data underscore the potential utility
representing the growth in deaths between the two time periods. The of muscle fat content as a biomarker in the diagnostic and management
magnitude of a positive value indicates a corresponding increase in of MASLD.
deaths attributed to the component, and the magnitude of a negative Table and Figure:Figure 1.Figure 1. L3-PDFFPsoas is significantly
value indicates a corresponding decrease in deaths attributed to the associated with histological MASH characteristics. (a) L3-PDFFPsoas
related component. in patients with MASL and MASH. (b) L3-PDFFPsoas in patients
with MASL, early MASH, fibrotic MASH and MASH cirrhosis. (c-d)
L3-PDFFPsoas values based on histological scores for steatosis,
OP0166
inflammation, ballooning, and fibrosis. All data are median (IQR).
Muscle fat content quantified by L3-PDFFPsoas is strongly Abbreviations: L3-PDFFPsoas, 3rd lumbar vertebra of psoas muscle
associated with fibrosis in patients with metabolic dysfunction- by PDFF; MASL, metabolic-associated steatotic liver; MASH, metabolic
associated steatotic liver disease dysfunction-associated steatohepatitis. IQR: interquartile range.
Ziming An1,2,3, Wuxing Cai1, Qihan Zhu4, Qiaohong Liu2, Zen Tu2, Xin Figure 2.Table 1. Univariate and multivariate analysis producing ORs
Xin1, Yuhan Nie5, Zhongwei Chen6, Caiyun Wen6, Liyou Lian7, Suidan for liver fibrosis among MASLD patient with histology according to L3-
Chen8, Jiangao Fan9, Yiyang Hu1, Yu Zhao1, Minghua Zheng7,10,11, Qin PDFFPsoas.
Feng1,2,3
1
Key Laboratory of Liver and Kidney Diseases, Shanghai University of
OP0167
Traditional Chinese Medicine, Ministry of Education, Shanghai, China,
2
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai Advanced Glycation End Products (AGEs) Promote Inflammation
University of Traditional Chinese Medicine, Shanghai, China, 3Central in Metabolic Associated Fatty Liver Disease (MAFLD) by
Laboratory, Shuguang Hospital Affiliated to Shanghai University Downregulating miR-9-5p Expression and Up-regulating EGR1 in
of Chinese Traditional Medicine, Shanghai, China, 4Department Kupffer Cells
of Endocrinology, the First Affiliated Hospital of Wenzhou Medical Qingyun Sun1,2, Xu Fan3, Jidong Jia3
University, Wenzhou, China, 5Shanghai University of Traditional 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
Chinese Medicine, Shanghai, China, 6Department of Radiology, the University, 2State Key Laboratory of Digestive Health and National
First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Clinical Research Center of Digestive Disease, 3Beijing Friendship
China, 7MAFLD Research Center, Department of Hepatology, the Hospital, Capital Medical University
First Affiliated Hospital of Wenzhou Medical University, Wenzhou,
China, 8Department of Pathology, the First Affiliated Hospital of Background: Inflammatory processes play key roles in the progression
Wenzhou Medical University, Wenzhou, China, 9Center for Fatty of Metabolic-associated steatohepatitis (MASH). Our previous work
Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated demonstrated a crucial role for Kupffer cells (KCs) in diet-induced
to Shanghai Jiao Tong university School of Medicine, Shanghai, MASH mouse model. However, the specific mechanisms by which KCs
China, 10Institute of Hepatology, Wenzhou Medical University, drive the progression of MAFLD remain to be elucidated.
Wenzhou, China, 11Key Laboratory of Diagnosis and Treatment for Method: We identified candidate signaling pathway that regulated
the Development of Chronic Liver Disease in Zhejiang Province, KCs inflammatory activity by whole-transcriptome sequencing and
Wenzhou, China functional enrichment analysis of the differentially expressed mRNAs
Background: The relationship between muscle fat content and and target gene sets of differentially expressed miRNAs in KCs of
metabolic dysfunction-associated steatotic liver disease (MASLD) has MASH vs. MAFL mice. Dual-luciferase reporter assay was employed to
not been well investigated. Here, we aim to elucidate the association further investigate whether the miRNA whose target gene set were also
between muscle fat content quantified by magnetic resonance significantly enriched in the candidate signaling pathway interacted
imaging-proton density fat fraction (MRI-PDFF) and MASLD severity. with the key regulatory molecule in the pathway. Finally, the potential
Method: Cross-sectional and longitudinal studies were conducted regulatory mechanisms on the progression of MAFLD was assessed
by overexpression and interventions in vitro and vivo.
Result: MASH mice had significantly enriched differentially expressed Hospital, 16he Key Laboratory of Hepatic Fibrosis Mechanisms
genes in the AGE-RAGE signaling pathway compared to MAFL of Chronic Liver Diseases in Hebei Province, Hebei International
mice. and showed elevated serum AGE levels and RAGE, IL-1B, IL- Science and Technology Cooperation Base -- Hebei International
6, TNF-α, and MCP-1 expression in KCs, with more severe liver lipid Joint Research Center for Molecular Diagnosis of Liver Cancer
accumulation, ballooning change, and inflammation; In vitro, primary Background: Metabolic dysfunction-associated fatty liver disease
KCs exposed to AGE-BSA showed increased RAGE and inflammatory (MAFLD) encompasses a diverse population with significant
cytokines expression, which were reduced by siRAGE or FPS-ZM1 heterogeneity in demographic and metabolic profiles. This study aimed
treatments. We also found the target gene set functions of miR-9-5p to establish a novel clustering approach to stratify clinical phenotypes
were significantly enriched in the AGE-RAGE signaling pathway, and for the MAFLD population and investigate their associations with long-
miR-9-5p itself was markedly downregulated in the MASH mouse term mortality outcomes across multiple cohorts.
KCs(Fig1); Dual-luciferase reporter assay confirmed the 3’UTR Method: This study included individuals with MAFLD from five cohorts
region of early growth factor-1(EGR1) specifically binded to miR-9- spanning China and the United States. Participants from three medical
5p, leading to the inhibition of EGR1 translation, which was a known centers in China were divided into a training cohort (n = 8,114) and an
key regulatory molecule in the pathway. In MASH mice, AAV-miR-9- internal validation cohort (n = 3,478) in a 7:3 ratio. External validation
5p agomir treatment effectively alleviated liver steatosis, inflammation, cohorts included the National Health and Nutrition Examination Survey
and ballooning degeneration and reduced Kupffer cell infiltration III (NHANES III, n = 2,162) in the United States and the Kailuan cohort
and inflammatory response. In contrast, AAV-miR-9-5p antagomir (n = 23,410) in China. K-means clustering was performed in the training
intervention exacerbated these liver pathological manifestations and cohort, and Euclidean distance was employed for cluster assignment
enhanced the inflammatory activity of KCs.(Fig2) In vitro, compare to in the validation cohorts. Cluster characteristics were visualized using
AGEs-stimulated group, cultured primary KCs with miR-9-5p agomir radar charts, and Cox proportional hazards models were applied to
before AGEs-stimulation inhibited EGR1 expression and reduced evaluate mortality risks in the external validation cohorts.
inflammatory factor levels; with miR-9-5p antagomir distinctly Result: A total of 37,164 individuals were analyzed. Three distinct
increased the expression of EGR1 as well as the inflammatory factors, clusters emerged in the training cohort via K-means clustering. Cluster
whereas the results were reversed after siEGR1 interference. And we 1 featured the youngest participants with favorable metabolic profiles
found down-regulated miR-9-5p promoting inflammatory response by and the lowest fasting blood glucose levels. Cluster 2 was defined
up-regulating EGR1 through STAT pathway in KCs. by intermediate anthropometric and metabolic measures, while
Conclusion: AGEs inhibited miR-9-5p levels in Kupffer cells via RAGE, Cluster 3 consisted of the oldest individuals with the poorest metabolic
enhanced EGR1 expression, and activated the STAT pathways, driving health. These cluster profiles were reproducible across validation
the progression of MAFLD. cohorts (Figure 1). In NHANES III, Cluster 2 (HR: 2.246, 95% CI: 1.173–
Table and Figure:Figure 1.Figure 1. The target gene set functions of 2.945, P < 0.001) and 3 (HR: 8.798, 95% CI: 7.241–10.689, P < 0.001)
miR-9-5p were significantly enriched in the AGE-RAGE signaling showed elevated risks of all-cause mortality compared to Cluster 1.
pathway Similar trends were observed for cardiovascular mortality (Cluster 2:
Figure 2.Figure 2. MiR-9-5p reduced hepatic inflammatory infiltration in HR: 2.206, 95% CI: 1.291–3.770, P = 0.004; Cluster 3: HR: 15.941,
MASH mouse model. 95% CI: 11.054–22.990, P < 0.001) and cancer mortality (Cluster 2:
HR: 4.051, 95% CI: 2.383–6.886, P < 0.001; Cluster 3: HR: 14.573,
OP0168 95% CI: 9.548–22.243, P < 0.001) (Figure 2). Consistent findings were
noted in the Kailuan cohort and across gender-based subgroups.
Cluster analysis-based novel phenotypes for metabolic
Conclusion: This clustering approach uncovered distinct phenotypes
dysfunction-associated fatty liver disease population and their
within the MAFLD population, each with unique mortality risks. These
associations with long-term adverse outcomes
insights provide a foundation for phenotype-specific management
Wenjing Ni1,2,3, Weihong Zhou4, Fuqiang Chen5,6, Jingli Gao7, YeeHui strategies and precision medicine in MAFLD care.
Yeo8, Yixuan Zhu9,3, Qianqian Chen1,2,3, Shanghao Liu10,11, Fajuan Table and Figure:Figure 1.Figure 1. Distribution of feature variables by
Rui1,2,3, Xue Bai1,3, Nan Geng1,3, Rui Jin1,3, Zhiwen Fan12, Wenjian clusters. Note: (A) Training cohort; (B) Internal validation cohort; (C)
Qin5, Xiaolong Qi10,11, Chao Wu13,3, Junping Shi14, Yuemin NAN15,16, Jie External validation cohort 1; (D) External validation cohort 2
Li1,2,3 Figure 2.Figure 2. Associations between different clusters and
1
Department of Infectious Disease, Nanjing Drum Tower Hospital, mortalities in NHANES III (the external validation cohort 1). Note: (A) All-
Affiliated Hospital of Medical School, Nanjing University, 2Department cause mortality; (B) CVD mortality; (C) Cancer mortality. Note: Model
of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College 1: adjust for sex and race; Model 2: model 1 ＋ adjust for poor income
of Nanjing University of Chinese Medicine, 3Institute of Viruses and ratio; Model 3: model 2 + adjusted for daily alcohol consumption.
Infectious Diseases, Nanjing University, 4Department of Health
Management Center, Nanjing Drum Tower Hospital Clinical College
of Nanjing Medical University, 5Shenzhen Institute of Advanced OP0169
Technology, Chinese Academy of Sciences, 6Shenzhen College of Assessing Significant Liver Fibrosis in Psoriasis Patients with
Advanced Technology, University of Chinese Academy of Sciences, MASLD: Predictors and the Role of Non-invasive Tests
7
Kailuan General Hospital, 8Karsh Division of Gastroenterology and Kanteera Sriyudthsak1, Pranapda Chowanutsavettakul2, Panarat
Hepatology, Department of Medicine, Cedars-Sinai Medical Center,
Thaimai1, Nipaporn Siripon1, Einapak Boontaveeyuwat3, Pravit
9
Department of Infectious Diseases, Nanjing Drum Tower Hospital,
Asawanonda3, Sombat Treeprasertsuk1, Piyawat Komolmit1,4,5,
Affiliated Hospital of Medical School, Nanjing University, 10Liver
Kessarin Thanapirom1,4,5
Disease Center of Integrated Traditional Chinese and Western
Medicine, Department of Radiology, Zhongda Hospital, Medical
1
Division of Gastroenterology, Department of Medicine, Faculty
School, Southeast University, Nurturing Center of Jiangsu Province for of Medicine, Chulalongkorn University and King Chulalongkorn
State Laboratory of AI Imaging & Interventional Radiology (Southeast Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand,
University), 11Basic Medicine Research and Innovation Center of
2
Department of Medicine, Faculty of Medicine, Chulalongkorn
Ministry of Education, Zhongda Hospital, Southeast University; University, Bangkok, Thailand , 3Division of Dermatology, Department
State Key Laboratory of Digital Medical Engineering, 12Department of Medicine, King Chulalongkorn Memorial Hospital and Faculty of
of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medicine, Chulalongkorn University, Bangkok, Thailand, 4Center of
Medical School, Nanjing University, 13Department of Infectious Excellence in Liver Fibrosis and Cirrhosis, Chulalongkorn University,
Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical Bangkok, Thailand, 5Excellence Center in Liver Diseases, King
School, Nanjing Universit, 14Department of Infectious Diseases and Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok,
Hepatology, The Affiliated Hospital of Hangzhou Normal University, Thailand
1
5Hebei Medical University Third HospitalDepartment of Traditional Background: Metabolic dysfunction-associated steatotic liver
and Western Medical Hepatology, Hebei Medical University Third disease (MASLD) is prevalent in patients with psoriasis. However,
there is limited data on factors associated with significant fibrosis (SF) of retinoid acid receptor α (RARα). Trehalose or its hydrolysis-resistant
and the use of non-invasive tests (NITs) for assessing fibrosis in this derivative lactotrehalose exhibited potent anti-fibrotic activity in vitro
population. Recently, the novel Steatosis-Associated Fibrosis Estimator and in vivo by functioning as an HSC-specific autophagy inhibitor,
(SAFE) and AGILE 3+ score have been validated for identifying liver which accounts for the antifibrotic effect of CYP1B1 inhibition.
fibrosis in MASLD patients. Therefore, this study aims to identify factors Conclusion: Our study thus reveals an endobiotic function of CYP1B1 in
associated with SF and evaluate the diagnostic accuracy of various liver fibrosis mediated by liver-intestine crosstalk and trehalose. At the
NITs in patients with psoriasis and MASLD. translational level, pharmacological inhibition of CYP1B1 or the use of
Method: We prospectively enrolled 80 psoriasis patients with trehalose/lactotrehalose may represent therapeutic strategies for liver
confirmed MASLD, diagnosed using a controlled attenuation fibrosis.
parameter (CAP)(Fibroscan) value ≥ 248 dB/m, during 2022-2023
from Chulalongkorn University, Bangkok, Thailand. SF was defined as
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a transient elastography (TE) value ≥ 7.1 kilopascals. AST to Platelet
Ratio Index (APRI), BARD, Fibrosis-4 (FIB-4), NAFLD Activity Score Deficiencies of micronutrients in potential liver transplant
(NAS), SAFE and AGILE 3+ were evaluated for diagnostic accuracy candidates- A Cross-sectional study
using the TE as the reference standard. Manesh Kumar1, Zaigham Abbas2
Result: Overall, 24 patients (30%) had SF. Prevalence of diabetes 1
Dr Ziauddin Hospital Karachi, 2Dr. Ziauddin University Hospital Clifton
mellitus (DM) was 29%, and 75% received methotrexate. Multivariate Karachi
analysis revealed that diabetes mellitus (DM) was an independent risk Background: Decompensated liver disease is a debilitating
factor for SF (Adjusted OR= 4.17, 95%CI=1.24-13.97, p=0.02). In condition often accompanied by significant micro- and macronutrient
contrast, neither methotrexate use nor body mass index were associated deficiencies, which can worsen disease prognosis and complicate
with SF. The area under the receiver operating characteristic curve treatment, particularly in patients awaiting liver transplantation.
(AUROC) of APRI, SAFE and AGILE 3+ scores in determining SF was Method: This prospective, cross-sectional, single-center study
0.66 (95%CI: 0.52-0.80, p=0.03), 0.73 (95%CI: 0.62-0.84, p=0.001), included consecutive patients. These patients were enrolled from
and 0.87 (95%CI: 0.78-0.96, p≤0.001), respectively. Among these, both outpatient and inpatient settings. Comprehensive blood tests
AGILE 3+ showed the highest accuracy in detecting SF compared were performed to measure levels of key micronutrients, including
to the SAFE and APRI scores (p≤0.05). FIB-4, NAS and BARD scores vitamin D3, zinc, calcium, magnesium, phosphorus, and iron. Nutrient
showed no significant discriminatory ability for SF. For identifying SF, deficiencies were compared in patients with a MELD score ≥ 15, Child
an AGILE 3+ ≥ 0.28 provided 75% sensitivity, 85.7% specificity, and score B and C.
88.9% negative predictive value (NPV). In addition, a SAFE score ≥ Result: The cohort comprised of total 78 patients, which included 51
6.5 exhibited 91.7% sensitivity, 57.1% specificity, and 94.1% NPV. (64.6%) males and 28 (35.4%) females. Among these patients, 36
The AGILE 3+ score showed a good correlation with the SAFE score (45.6%) were treated on an outpatient basis, while 43 (54.4%) were
(r=0.75, p≤0.001). admitted to the ward. The primary etiologies of CLD were Hepatitis
Conclusion: DM is an independent risk factor for SF in psoriasis C 27 (36.0%), non-alcoholic fatty liver disease 24 (32.0%), alcoholic
patients with MASLD. The novel SAFE and AGILE 3+ scores liver disease 14 (18.7%), Hepatitis B 6 (8.0%), and autoimmune liver
demonstrate good diagnostic accuracy and may be recommended as disease 4 (5.3%). Additionally, 44 (61.1%) of patients had MELD score
NITs for identifying SF in this patient population. ≥ 15. The study identified higher frequencies of deficiencies in zinc
(88.7%), vitamin D3 (deficient 56.4%, insufficient 29.5%), calcium
OP0170 (22.2%), folate (19.4%), iron (116.9%), and magnesium (14.1%),
phosphorus (9.9%), and vitamin B12 (4.3%) across the entire cohort.
Inhibition of heme-thiolate monooxygenase CYP1B1 prevents
Lower levels of vitamin D (12.61 ± 13.72, p = 0.010) were found in
hepatic stellate cell activation and liver fibrosis by accumulating
Child Class C compared to Child Class B. Vitamin D and magnesium
trehalose
deficiencies become more frequent in Child Class C compared to B
Wen Xie1, HungChun Tung1, Jongwon Kim1 (p<0.001 and p = 0.001) and MELD score ≥ 15 (p = 0.008 and p =
1
University of Pittsburgh 0.004).
Background: Liver fibrosis often results from chronic liver injuries, Conclusion: The high prevalence of deficiencies of crucial
leading to inflammation, matrix deposition, and cell death. Unmanaged micronutrients, such as vitamin D3, zinc, magnesium, and iron,
fibrosis can progress to cirrhosis, which may result in liver failure or underscores the necessity of comprehensive nutritional assessment
even liver cancer. Currently, there are no FDA-approved treatments and targeted intervention in patients with decompensated liver disease.
for liver fibrosis. Hepatic stellate cells (HSCs) are liver-specific Effective management of micronutrient levels could potentially reduce
mesenchymal cells that control vitamin A homeostasis. However, complications, improve patient health, and enhance outcomes in these
when the liver is injured, HSCs become activated, losing their vitamin potential liver transplant candidates.
A storage capacity and transforming into myofibroblast-like cells,
which contribute to fibrosis, making them key targets for anti-fibrosis OP0172
therapies. CYP1B1 is a cytochrome P450 enzyme best known for its
function in metabolizing xenobiotic substances. While typically more Assessment of Micronutrient Status and Its Association with
abundantly expressed in extrahepatic tissues, the role of CYP1B1 in Clinical Outcomes in Adult Patients with Compensated and
HSC activation and liver fibrosis remains unclear. Decompensated Liver Cirrhosis Seen at a Tertiary Institution: A
Method: CYP1B1 expression was measured in both fibrotic human and Single-arm Retrospective Cohort Study
mouse livers. HSC-specific Cyp1b1 knockout mice (Cyp1b1ΔHSC) Kathleen Madera Monfort1, Ira Inductivo Yu1
were subjected to thioacetamide (TAA)-, carbon tetrachloride (CCl4)-, 1
NKTI
and bile duct ligation (BDL)-induced mouse models to study the role Background: Micronutrient deficiencies are common in patients with
of CYP1B1 in mice liver fibrosis. Metabolomic analysis was performed liver cirrhosis, affecting their vitamin stores and catabolism. These
to determine the metabolic basis by which CYP1B1 ablation inhibits deficiencies are exacerbated by malnutrition, poor digestion, and
HSC activation and liver fibrosis. diuretic use. This study aims to determine the micronutrient status of
Result: The expression of CYP1B1 was elevated in human and mouse adult Filipino patients with liver cirrhosis, focusing on the prevalence
fibrotic livers and activated HSCs. Systemic or HSC-specific ablation of micronutrient deficiencies, and its association with poorer clinical
as well as pharmacological inhibition of CYP1B1 attenuated HSC outcomes, namely mortality and decompensation, as well as with
activation and protected mice from liver fibrosis. Metabolomic severity of liver cirrhosis in terms of child Pugh score. Further
analysis revealed an increase of the disaccharide trehalose in investigation is needed to fully understand these deficiencies.
CYP1B1-deficient HSCs due to intestinal suppression of the trehalose Method: Clinical and demographic characteristics of adult Filipino
metabolizing enzyme trehalase, whose gene was found to be a target
patients with liver cirrhosis at the National Kidney and Transplant ginger EVs activated the RIG-1-like receptor pathway, upregulating Ahr-
Institute from 2018 to 2023 were examined in the study. The baseline IL-22 (p<0.05) for anti-inflammatory effects. Turmeric EVs specifically
biochemical profiles, vitamins and trace element levels, and the promoted Lachnoclostridium (>1.5-fold; p<0.05) potentiating the
prevalence of micronutrient deficiencies were recorded. The study phosphotransferase system, improved butyrate production and
also examined the percentage of patients who experienced particular support gut homeostasis.
clinical outcomes. The association between specific micronutrient Conclusion: Ginger EVs enhance Lactobacillaceae growth and
deficiencies and poor clinical outcomes was determined using strengthen intestinal immunity, while turmeric EVs promote the PTS
univariate logistic regression. system and butyrate production by Lachnoclostridium, improving
Result: Among 461 patients who were assessed for any micronutrient gut homeostasis. Combination of the two EVs may give better gut
deficiencies, 234 (50.76%) had at least one deficiency. The most modulation. Dietary EVs based gut microbiome modulation can be an
common deficiencies were vitamin D (79.21%) and zinc (86.36%). important tool in managing hepatic injury and disease.
Other micronutrient deficiencies noted were iron deficiency (41.18%), Table and Figure:Figure 1.Graphical representation
hypocalcemia (25.41%), hypophosphatemia (17.27%), and
hypomagnesemia (8.16%). In contrast, vitamin B12 deficiency was rare
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with only 3.70% among the patients tested. Among the vitamins and
minerals examined, vitamin D levels showed that there’s a statistically Attenuation of Gut Urease Activity and Ammonia Production by
significant difference between Child-Pugh classes. While the rest of the Melittin in Experimental Cirrhosis
vitamins and minerals did not show statistically significant levels across DEEPIKA JAKHAR1, Pinki Juneja1, Aarti Sharma1, Bhaskar Sharma1,
the spectrum of liver cirrhosis. Univariate logistic regression analysis Dinesh Mani Tripathi1, Shiv Kumar Sarin1, Savneet Kaur1
revealed associations between specific micronutrient deficiencies 1
Institute of liver and biliary sciences
and poorer clinical outcomes in patients with liver cirrhosis. Vitamin D Background: Antimicrobial peptides (AMPs) are a vital part of innate
deficiency was significantly associated with poorer outcomes, showing immune response. Urease expressing bacteria, predominantly gram
a 351% increased odds compared to those without deficiency. negative, are increased in cirrhotic gut and contribute significantly
Conversely, calcium and phosphorus deficiencies were associated to endogenous ammonia production. Here we investigated a novel
with 48% and 82% decreased odds of poorer outcomes, respectively. hypothesis of using AMPs as a therapeutic to target gut urease bacteria
Zinc, iron, and magnesium deficiencies did not show any statistically and studied the potential of one of the identified AMPs to reduce gut
significant associations with clinical outcomes. urease activity and ammonia production.
Conclusion: The study found a significant association between Method: Urease expressing bacteria were screened using BactPepDB
vitamin D deficiency and poorer liver cirrhosis outcomes, emphasizing database. AMPs were computationally identified and validated through
the importance of routine vitamin D screening. However, the study’s databases (DBAASP.v3, DRAMP, APD) and CAMPR3 predictive models,
small sample size and limitations call for further research on broader employing support vector machines, random forests, discriminant
micronutrients and prospective studies to better understand their analysis to ensure selection of potential AMPs. A natural AMP derived
impact. from bee venom, melittin was selected. Invitro studies with varying
concentrations of melittin were performed with urease expressing
OP0173 bacteria, Klebsiella pneumoniae(kp 1.5 x 109) for reducing bacterial
urease activity and ammonia release. In vivo studies, ethyl cellulose
A Comparative Study of Ginger and Turmeric-Derived Edible
nanoparticles loaded with melittin using double emulsion method were
Extracellular Vesicles (EVs) in Alleviating Liver Injury
prepared. Nanoformulated melittin(NM) was administered orally at 10
PDebishree Subudhi1, Shruthi Chalil Sureshan1, Anupama Parasar1, μg/kg twice weekly in a 10week thioacetamide induced cirrhosis rat
Shivani Gautam1, Chhagan Bihari1, Shiv Kumar Sarin1, Sukriti model and compared with a vehicle group with empty ethyl cellulose
Baweja1 nanoparticles. Impact of melittin on gut microbiome, bacterial urease
1
Institute of liver and biliary sciences activity, ammonia metabolism in organs, plasma ammonia levels and
Background: Edible extracellular vesicles (EVs) are known to restore liver disease progression was assessed.
gut commensals and intestinal integrity. Hence, this study explores Result: In vitro studies demonstrated that melittin at 390 μg/
their role in gastro-hepatic alignment and their potential to ameliorate ml significantly reduced Kp urease activity(2folg) and ammonia
liver diseases. levels(4.9fold). NM exhibited a spherical morphology, 303nm size,
Method: Ginger and turmeric EVs (52–300 nm, zeta potential -17 ± 2.4 76.3% encapsulation efficiency, demonstrating potential for controlled
mV) characterised by metabolomics, tested for stability in simulated oral delivery with good stability. In animal study, in comparison to
digestion. Orally administered (10¹¹ particles) in a TAA liver injury rat controls, NM led to a decrease in portal ammonia 1.4fold (p=0.007),
model, effects were analyzed via 16S rRNA metagenomics, PICRUSt, peripheral ammonia levels 2.6fold (P=0.02), stool ammonia 1.3fold
histopathology and qRT-PCR, validated with in vitro co-culture of (p=0.1), stool and colonic urease activity by 3fold (p=0.05) and 1.4fold
Lactobacillus(LGG). (p=0.05) respectively. No significant changes were observed in
Result: Metabolomic profiling (572 metabolites) revealed that edible glutaminase gene expression in kidney, colon, duodenum, or glutamine
EVs are rich in bioactive phytochemicals with health benefits. Ginger synthetase expression in muscles and liver. 16S rRNA sequencing
EVs were enriched in hepatoprotective silymarin, epicatechin, ellagic revealed reduced species diversity (Shannon index p=0.44) and
acid, and gingerol, while turmeric EVs contained anti-inflammatory/ significant alterations in gut microbiome composition (87%variance
cancer agents such as scopoletin, curcumin, diosgenin, and corilagin. p=0.33), notable decrease in urease expressing taxa (Escherichia coli,
Both EVs retained biological integrity post- stomach/intestine-like Streptococcus) and increased abundance of commensal Prevotella
digestion in vitro, confirming suitability for oral delivery. In a TAA- copri in NM treated vs vehicle. NM treated also showed a significant
induced acute liver injury model (AST: 83.05±4.58 IU/L; ALT: 45.21±8.6 reduction in hepatic fibrosis and immune infiltration as compared to
IU/L; bilirubin: 0.36±0.05 mg/dL; albumin: 1.97±0.09 g/dL;p<0.01), vehicle
edible EVs reduced AST, ALT (ginger: 22.33 IU/L; turmeric: 26.36 Conclusion: Nanoformulated melittin demonstrates a promising
IU/L;p<0.005), and bilirubin (0.17±0.03 mg/dL;p<0.005). Edible EVs therapeutic approach to modulate gut microbiota, ammonia production
improved hepatic cholestasis and inflammation. Ginger EVs effectively and also disease progression by targeting urease expressing bacteria
resolved hepatic necrosis, while turmeric EVs restored albumin levels in cirrhosis
(2.47±0.22 g/dL;p=0.004). Edible EVs improved gut flora diversity, Table and Figure:Figure 1.summary figure
enhancing Firmicutes and inhibiting pathogenic taxa Escherichia-
Shigella (p<0.03). Edible EVs from the Zingiberaceae family similarly
OP0175
promoted Lactobacillaceae growth in the gut. Ginger EVs efficiently
enhanced LGG growth (p=0.01) by upregulating lexA (>1.5-fold;
p<0.05) in vitro compared to turmeric EVs. PICRUSt analysis showed
A mHealth-assisted multifaceted lifestyle intervention for life years (DALYs) for liver cancer attributable to MASH across 204
childhood obesity and NAFLD: A cluster randomized clinical trial countries. We provided counts and rates per 100,000 population,
(the SCIENT study) including 95% uncertainty intervals.
Hui Wang1 Result: In 2019, there were 46.8 thousand cases of MASH-related
1
School of Public Health, Health Science Centre, Peking University HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs
globally. While the prevalence increased by 19.8% since 1990, the
Background: IMPORTANCE Lifestyle modification is the primary
death and DALY rates decreased by 5.3% and 15.1%, respectively.
treatment for pediatric obesity and nonalcoholic fatty liver disease.
The highest prevalence was in High-income Asia Pacific, with the
However, an effective lifestyle intervention strategy for these diseases
greatest increases observed in Australasia, Central Asia, and High-
remains underdeveloped.
income North America. Southern Sub-Saharan Africa reported the
OBJECTIVE This study aimed to evaluate the effects of mHealth-
highest death rate, while the lowest rates were in parts of Latin America,
assisted multifaceted lifestyle interventions on the improvement of BMI
Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the
and nonalcoholic fatty liver disease in children with overweight and
highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin
obese.
America.
Method: DESIGN, SETTING, AND PARTICIPANTS A cluster randomized
Conclusion: The burden of MASH-related HCC is expected to rise
clinical trial was conducted involving 331 students with overweight/
slightly over the next decade. This disease, which is not associated
obese from six primary schools in Ningbo, China, randomized at a 1:1
with the SDI, remains a major public health problem. In addition,
ratio at school level. The primary analyses were based on intention-
the escalating rates of obesity, demographic shifts, and an aging
to-treat analyses principle. ClinicalTrials.gov Identifier: NCT05482191
population could position MASH as a leading factor in liver cancer
INTERVENTIONS The comprehensive lifestyle intervention was
cases, surpassing viral hepatitis. It is imperative, therefore, that the
involved by four stakeholders, including schools, clinics, families, and
forthcoming years see the implementation of strategic interventions
students, to participate in students’ weight management, supported
aimed at the early detection and prevention of liver cancer associated
by mHealth technology.
with MASH.
MAIN OUTCOMES AND MEASURES The primary outcomes were
Table and Figure:Figure 1.Fig.1Global prevalence, death, and DALY
changes in BMI, controlled attenuation parameter and liver stiffness
numbers of MASH-related HCC for male, female, and both sexes from
measurement at the end of trial. Secondary outcomes included
1990 to 2019. (A) Prevalence. (B) DALYs. DALY, disability-adjusted life
alterations in obesity or nonalcoholic fatty liver disease indicators,
year. (C) Death.(D) Global prevalence, deaths, and DALYs attributable
metabolic profiles, and other obesity-related markers. Differences
to MASH for both sexes combined in 2019 and percentage change
between the two groups were analyzed by generalized linear mixed
from 1990 to 2019.
models.
Figure 2.Fig.2 Age-standardized prevalence, death, and DALY
Result: A total of 331 overweight/obese students (mean [SD] age,
rates attributable to MASH for both sexes combined in 2019. (A)
8.5 [0.3] years; 120 girls [36.3%]; mean [SD] BMI, 20.4 [2.2]) from six
Prevalence. (B) Deaths. (C) DALYs. Age-specific numbers and rates of
schools were randomly assigned to the intervention (three schools, 145
prevalence, deaths, and DALYs attributable to MASH by sex, in 2019.
children) or the control group (three schools, 186 children). Compared
(D) Prevalence. (E) Deaths. (F) DALYs. Age-standardized DALY rates
to the control group, the mean differences in BMI, controlled attenuation
attributable to MASH across 21 GBD regions by sociodemographic
parameter, and liver stiffness measurement were significantly
index for both sexes combined, 1990–2019. (G) For each region,
decreased by -0.38 (-0.59 to -0.16, P < 0.001), -15.06 (-22.04 to -8.09,
points from left to right depict estimates from each year from 1990 to
P < 0.001), and -0.67 (-0.88 to -0.46, P < 0.001) in the intervention
2019. (H) Age-standardized DALY rates attributable to MASH across
group, respectively. In the mediation analyses, changes in BMI and
195 countries and territories by sociodemographic index for both
BMI Z score mediated 11.3%, 11.2% of the effect of intervention on
sexes combined in 2019.(I) High fasting plasma glucose and smoking
controlled attenuation parameter (both P < 0.05), respectively. The
age-standardized DALYs attributable to MASH and cancer by region
intervention also led to improvements in several metabolic indicators,
for women and men in 2019. (J) ASDR by sex from 1990 to 2030. (K)
lifestyle knowledge and behaviors. No adverse events were reported
YLLs by sex from 1990 to 2030. (L) YLDs by sex from 1990 to 2030. (M)
in the intervention group.
ASMR by sex from 1990 to 2030.
Conclusion: This intervention effectively reduced BMI, liver steatosis
and liver stiffness in primary school children, highlighting the potential
of implementing mHealth-assisted multifaceted lifestyle interventions OP0177
in large-scaled population. Burden of pancreatic cancer and its attributable risk factors in
Table and Figure:Figure 1. Intervention effects on primary outcomes 204 countries and territories, 1990-2021: results from the Global
according to intention-to-treat analyses Burden of Disease Study 2021
Figure 2.Table 1. Mediating role of BMI/BMI Z score indicators in the Zhifeng Zhao1, Kai Jiang1
effect of intervention on CAP and LSM changes 1
First Medical Center, Chinese PLA General Hospital
Background: To analyze the global epidemiological characteristics,
OP0176 trends, and variations in pancreatic cancer from 1990 to 2021, based
Worldwide burden of liver cancer due to metabolic dysfunction- on data from the Global Burden of Disease (GBD) Study 2021. This
associated steatohepatitis from 1990 to 2019: insights from the study also aims to identify and characterize risk factors attributable to
Global Burden of Disease study pancreatic cancer across different regions and socioeconomic levels.
Minshan Huang1, Chen Hang1, Ma Lan Qing1 Method: The Global Burden of Disease (GBD) Study 2021,
1
The First Affiliated Hospital of Kunming Medical University encompassing data from a diverse array of sources such as surveys,
clinical records, and scholarly publications, has amassed data from
Background: Metabolic dysfunction-associated steatohepatitis
204 countries and territories to assess the disease burden attributed
(MASH) is increasingly becoming a prevalent cause of hepatocellular
to pancreatic cancer over the period from 1990 to 2021.Pancreatic
carcinoma (HCC). Our study examines the burden of MASH-related
cancer cases were classified according to ICD-10 codes C25.0 to
HCC globally, regionally, and nationally, along with associated risk
C25.9. The Bayesian meta-regression tool DisMod-MR 2.1 was used
factors from 1990 to 2019, considering variables such as age, sex,
to estimate incidence and mortality rates. Age-standardized rates
and socioeconomic status.We aimed to report the global, regional, and
(ASRs) and estimated annual percentage changes (EAPCs) were
national burden of liver cancer due to MASH and its attributable risk
calculated to assess temporal trends. Risk factors were evaluated
factors between 1990 and 2019, by age, sex, and sociodemographic
using a comparative risk assessment framework.
index (SDI).
Result: In 2021, there were approximately 508,533 new cases of
Method: Utilizing the Global Burden of Disease 2019 project, we
pancreatic cancer worldwide, with an age-standardized incidence rate
analyzed data on prevalence, mortality, and disability-adjusted
(ASIR) of 6.0 per 100,000 population. The global age-standardized
mortality rate (ASMR) was 5.9 per 100,000, with 505,752 deaths. The Analysis of the Present Research Landscape on Non-
highest ASIRs and ASMRs were observed in high-income regions such Governmental Organizations: Emphasizing Fundamental
as Asia Pacific, North America, and Western Europe. Conversely, the Development Challenges and Solutions
lowest rates were in Sub-Saharan Africa and South Asia. Between Cunduo Jin1, AYTIKIN OMER2, Lai WEI3, Mingyang Li4
1990 and 2021, significant increases in pancreatic cancer burden 1
Seventh Medical Center, PLA General Hospital, 2CHINA LIVER
were noted, especially in regions with lower Socio-Demographic Index HEALTH, 3Beijing Tsinghua Changgung Hospital, 4China Liver Health
(SDI) levels. High fasting plasma glucose and smoking were identified (CLH)
as the most significant risk factors globally.
Background: Non-governmental organizations play an important role
Conclusion: The global burden of pancreatic cancer has increased
in social development. Their operation and development are affected
significantly from 1990 to 2021, with notable regional variations
by various factors, presenting diversified characteristics in different
influenced by socioeconomic factors. High fasting plasma glucose and
regions. Research on them involves multiple fields and levels and is
smoking are key modifiable risk factors. These findings highlight the
significant for understanding their roles and development laws.
need for targeted public health interventions and policies, particularly
Method: Systematically review relevant research on non-governmental
in regions with rising pancreatic cancer burdens. Further research
organizations, covering influencing factors in their development,
is necessary to understand the complex epidemiology of pancreatic
roles, and characteristics in different regions, relevant social culture
cancer and to develop effective prevention strategies.
and behavioral characteristics, and deep-seated problems in their
Table and Figure:Figure 1.Age-standardized incidence rate (A),
development. Cite a large number of previous research studies and
mortality rate (B), and DALY rate (C) of pancreatic cancer per 100,000
viewpoints of different scholars to support the analysis.
population in 2021, by country
Result: 1. Influencing Factors of the Development of Non-Governmental
Figure 2.Global numbers of incident cases (A), deaths (B), and DALYs
Organizations
(C) for pancreatic cancer in 2021, along with the incidence, mortality
Government Policies: Government policies (support or restriction)
rate, and DALY rate per 100,000 population, stratified by age and sex.
significantly impact relief supplies and fund preparation. For example,
in India, government documents improved local NGOs’ fundraising
OP0178 ability; in China, due to the “big government, small society” background,
Novel Phenotypes of Lean Male Metabolic Dysfunction-associated NGOs are subject to certain restrictions.
Fatty Liver Disease and Their Long-term Outcomes: A Data-driven Organizational Operation and Supply and Demand Characteristics:
Cohort Study The supply of emergency supplies by NGOs shows professional
Shutong Wu1, Yang Zhou1, Chenlu Yang1, Qingfeng Ye1, Li Wang1 characteristics. Order decisions are made by the coordination center,
which may lead to information delays. The demand satisfaction rate
1
Department of Epidemiology and Biostatistics, Institute of Basic
of relief supplies is high, and supply and transportation factors are
Medical Sciences Chinese Academy of Medical Sciences; School of
Basic Medicine Peking Union Medical College complex.
2. Roles and Characteristics of Non-Governmental Organizations in
Background: The substantial heterogeneity is a barrier to effective Different Regions
interventions for Metabolic Dysfunction-associated fatty liver disease Middle East Region: NGOs in Egypt play an important role in
(MAFLD), especially in lean patients. We aimed to reclassify lean national stability and make up for government deficiencies in social
MAFLD patients and validate the classification via outcomes and governance. After registration, they enjoy preferential policies, and
genetic profiles to inform the precision medicine and personalized enterprises donating to them can get tax exemptions.
management. China: There is a two-way embedding and cooperative relationship
Method: A swap-stepwise variable selection algorithm incorporated between NGOs and the state. There is also a relationship of “institutional
into latent class analysis was applied to identify subgroups for 2,573 interdependence” between NGOs and the government. Different
lean adult men (body mass index (BMI) < 23 kg/m2), aged 18-65 years theoretical perspectives show distinct characteristics of China’s civil
old, with MAFLD in Kailuan cohort in 2006-2013 (discovery cohort). society development.
Validation was performed in 4,617 lean male MAFLD in the Kailuan 3. Social Culture and Behavioral Characteristics Related to Non-
cohort in 2014-2019, and NHANCES 1999-2018 (n=1512). Then, we Governmental Organizations
compared risks of incident all-cause mortality, cancers, cardiovascular 4. Deep-Seated Problems in the Development of Social Organizations:
diseases (CVDs), and chronic kidney diseases (CKD), as well as Many deep-seated problems are related to the lack of stable institutional
genetic associations among subgroups expectations. For example, the lack of professionals in NGOs is due to
Result: We identified four sub-phenotypes with significantly different insufficient expectations for future development space.
characteristics, risk of outcomes and genetic polymorphisms in 5. Challenges and Future Prospects of the Development of Social
discovery cohort: impaired VLDL-triglyceride (TG) secretion (IVT), Organizations: There are systematic differences in NGOs in multiple
metabolic syndrome-associated (MET), hypertension-related (HTR) dimensions. Social organizations are expected to be an important
and modest metabolic derangements (LEAN) group. LEAN had the structural force in national governance.
lowest risk of all events. Compared to LEAN, HTR exhibited the highest Conclusion: The development of non-governmental organizations is
risk of cancers (hazard ratio [HR] 1.53; 95% CI 1.12-2.09), while IVT affected by various factors and faces some deep-seated problems.
remained the highest risk of all-cause mortality (HR 2.68; 95% CI Future research can explore solutions to promote their healthy
1.31-3.56) after covariates adjusted. HTR and MET shared the higher development for better social service.
risks of CVDs. In support of this clustering, IVT exhibited the highest
frequencies of TM6SF2 (rs58542926) risk alleles, whereas variants
in angiotensin-related genes showed higher mutation frequencies in OP0181
HTR. The classification was further confirmed in external validation Identification of an effective HBV cccDNA inhibitor BAY87-2243
cohorts. and its potential anti-HBV mechanisms
Conclusion: Via machine learning, this study determined four Sihui Li1, Binlin Mao1, Ailong Huang1, Yong Lin1
distinct replicable MAFLD phenotypes with different outcome risk 1
Chongqing Medical University
and genetic profiles. This new stratification would predictably impact
Background: Hepatitis B virus (HBV) infection is a major global public
the development of precision-targeted therapies and improve the
health concern, with infected individuals facing the risk of developing
population-level MAFLD surveillance.
severe liver diseases, including HBV-related chronic hepatitis, cirrhosis,
Table and Figure:Figure 1.Cluster characteristics in discovery cohort
and hepatocellular carcinoma. The persistent presence of hepatitis B
virus (HBV) covalently closed circular DNA (cccDNA) is one of the
OP0180 primary challenges in achieving a cure for HBV infections. Currently,
there are no effective therapeutics specifically targeting cccDNA in
clinical practice, making the discovery of such agents a critical area efficiency overall, particularly for high-risk populations. These findings
for advancements in anti-HBV research. confirm the high diagnostic efficiency and reliability of the GADA
Method: We screened a variety of small-molecule compounds for their model, highlighting its clinical value in HCC diagnosis and providing
ability to inhibit HBsAg production using enzyme-linked immunosorbent a novel tool for early screening and management of HBV-related HCC.
assay. The antiviral activity of the candidate compound BAY87-2243, Conclusion: The GADA model shows exceptional promise for
along with its underlying mechanisms affecting cccDNA expression diagnosing HBV-related HCC, and its clinical utility is supported by
and transcription, was evaluated in HBV-infected hepatoma cells and robust validation.
primary human hepatocytes (PHHs), as well as in a humanized Hu- Table and Figure:Figure 1.Figure 1. Performance of the GADA and
URG liver mouse model. GALAD models for HBV-HCC detection.
Result: BAY87-2243 exhibited potent anti-HBV activity, significantly Figure 2.Figure 2. Performance of the GADA model for the detection of
reducing secreted HBsAg/HBeAg and intracellular levels of HBV RNA, early-stage HBV-HCC.
DNA, and cccDNA across various HBV-infected cell models, including
the humanized liver mouse model. Mechanistic studies revealed that
OP0183
BAY87-2243 not only inhibited the transcriptional activity of cccDNA
but also lowered the levels of critical factors required for cccDNA A single post-treatment LSM measured at various timepoints
formation by suppressing the expression of DNA ligase 1 (LIG1) and shows predictive value for liver-related clinical outcomes
DNA polymerase δ (POLD1). Yameng Sun1, Shuyan Chen, Xiaoqian Xu, Hongxin Piao, Guofeng
Conclusion: In summary, we identify BAY87-2243 as a novel and Chen, Wei Jiang, Yongpeng Chen, Mingyi Xu, Huiguo Ding, Wen
effective inhibitor that reduces cccDNA level, providing a potential new Xie, Xiaoyuan Xu, Hui Ma, Anlin Ma, Tongtong Meng, Jialing Zhou,
strategy for the complete elimination of chronic HBV infection. Bingqiong Wang, Xiaoning Wu, Hong You
1
95 Yong-an Road, Xi-Cheng District, Beijing 100050, China
OP0182 Background: There is limited evidence on the effectiveness of
longitudinal LSM dynamics versus post-treatment LSM in predicting
The GADA model for diagnosing HCC in Chinese hepatitis B
clinical outcomes in patients undergoing treatment for primary liver
patients was developed and validated across multiple centers
disease. This study aimed to assess the prognostic value of both serial
Yamei Wei 1,2, Mingjie Yao3, Mei Zhang1, Lin Wang2, Xiangmei Chen2, LSM measurements and post-treatment LSM in patients with chronic
Fengmin Lu2 hepatitis B (CHB) receiving ongoing antiviral therapy.
1
Department of Preventive Medicine, School of Medicine, Shihezi Method: Patients with significant fibrosis or cirrhosis who were
University, North 4th Road, Shihezi City, Xinjiang 832003, P.R. China, regularly followed up were included in this analysis. Clinical outcomes
2
Department of Microbiology & Infectious Disease Center, School of were defined as hepatic decompensations, liver transplantation, or
Basic Medicine, Peking University Health Science Center, 38 Xueyuan
all-cause mortality. We analyzed the association between LSM and
Road, Beijing 100191, P.R. China, 3Department of Anatomy and
clinical outcomes, focusing on baseline LSM, LSM changes over time,
Embryology, School of Basic Medical Sciences, Peking University
and post-treatment LSM, through Kaplan-Meier survival analysis and
Health Science Center, Beijing 100191, China
time-dependent AUROC to assess predictive accuracy.
Background: Chronic hepatitis B virus (HBV) infection accounts for Result: A total of 875 (78.4%) cirrhotic and 241 (21.6%) non-cirrhotic
more than 40% of hepatocellular carcinoma (HCC) cases worldwide. patients were enrolled.     During a median follow-up of 7.5 (2.5 – 9.5)
The GALAD model demonstrates the potential for enhancing HCC years after antiviral therapy, there were 78 cases of decompensation
diagnosis. However, its diagnostic performance in HBV-associated and 37 deaths. The AUROC ranged from 0.71 to 0.77 for post-treatment
HCC requires further optimization. This study aims to establish a LSM at 1 to 3 years of antiviral therapy, compared with a range from
diagnostic model for HBV-associated HCC. 0.59 to 0.65 for baseline LSM, and from 0.53 to 0.69 for the absolute
Method: We analyzed data from 2,190 patients with HBV-related liver and relative changes in LSM from baseline. LSM <10 kPa after 1,
diseases, including chronic hepatitis B (CHB), liver cirrhosis, and 2, or 3 years of antiviral therapy have a much lower risk of clinical
HCC. The GADA model was developed by omitting AFP-L3 in GALAD outcomes, with a 5-year cumulative incidence of 2.5%, 2.9%, and
model for improved accessibility, and its performance was assessed 3.3%, respectively. This conclusion held true in the cirrhosis subgroup,
via the area under the receiver operating characteristic curve (AUC). in the validation cohort, and when predicting decompensation alone.
Validation was performed on 20,908 patients across 10 hospitals. Notably, patients with an LSM <10 kPa showed better restoration of
Result: The simplified GADA model demonstrated exceptional lobular architecture in histology compared to those with an LSM ≥10
diagnostic performance in identifying HBV-related HCC within the kPa.
modeling group, achieving an AUC of 0.940 (95%CI: 0.927-0.952; P Conclusion: Post-treatment LSM measured 1 to 3 years after antiviral
< 0.001), with a sensitivity of 82.57% and a specificity of 91.53%. This therapy offers superior predictive accuracy for clinical outcomes
performance surpassed that of the original GALAD model, which compared to baseline or LSM changes, with LSM <10 kPa indicating
had an AUC of 0.907 (95% CI: 0.891–0.921), with a sensitivity a significantly lower risk, likely due to improved lobular architecture.
81.92% and a specificity 83.33%. In the internal validation cohort,
the AUC of the GADA model in identifying HBV-related HCC is 0.935
(95%CI: 0.914-0.953; P < 0.001), with a sensitivity of 82.04% and OP0184
a specificity of 92.65%, consistently outperforming the original Use of Sodium-Glucose Co-Transporter-2 Inhibitors and Risk of
GALAD model (AUC: 0.899, 95% CI: 0.873-0.921; sensitivity: 76.05%, Hepatocellular Carcinoma in Patients with Chronic Hepatitis B,
specificity: 84.08%). Further for early-stage HCC detection, the AUC Type 2 Diabetes, and Varying Fibrosis Status
modeling group of the GADA model was 0.858 (95%CI, 0.837-0.877) Xianhua Mao1,2, Ka Shing Cheung1,2, Jing Tong Tan1, Lung Yi Mak1,3,
and the internal validation group was 0.868 (95%CI: 0.836-0.895), Chi Ho Lee1,3, Ho Ming Cheng1,3, Rex WanHin Hui1,3,3, Man Fung
with sensitivities of 68.03% and 70.91% and specificities of 87.90% Yuen1,3, Wai Kay Seto1,2,3
and 87.76%, respectively. There performances were significantly 1
Department of Medicine, School of Clinical Medicine, The University
higher than that of the original GALAD model (P < 0.001). In external of Hong Kong, Hong Kong SAR, China, 2Department of Medicine, The
validation involving 20,908 participants, the GADA model achieved University of Hong Kong-Shenzhen Hospital, Shenzhen, China, 3State
an AUC of 0.919 (95% CI: 0.916-0.923) for identifying HBV-related Key Laboratory of Liver Research, The University of Hong Kong,
HCC, with a sensitivity of 86.00% and specificity of 81.88%. For Hong Kong SAR, China
early-stage HCC detection, the model achieved an AUC of 0.903 Background: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i)
(95% CI: 0.898-0.907), with a sensitivity of 88.16% and specificity may prevent liver disease progression in individuals with type 2 diabetes
of 74.50%, demonstrating a significantly improved sensitivity for (T2D). However, the impact of SGLT-2i on the risk of hepatocellular
early detection. Although specificity slightly declined for early-stage carcinoma (HCC) in chronic hepatitis B (CHB), especially with varying
HCC detection, the GADA model exhibited superior screening
degrees of liver fibrosis, remains under-investigated. of Liver, First Hospital of Jilin University, Changchun, China, 5Liver
Method: This was a retrospective and population-based cohort study. Research Center, Beijing Friendship Hospital, Capital Medical
Patients with T2D and CHB who received SGLT-2i (empagliflozin, University, Beijing, China, 6Beijing Youan Hospital, Capital Medical
dapagliflozin, canagliflozin or ertugliflozin) or sulfonylureas between University, Beijing, China, 7Department of Infectious Diseases, The
2015 and 2021 were enrolled from Hong Kong and all patients were First Affiliated Hospital of Xi‘an Jiaotong University, Xi‘an, China,
followed from the first prescription of study medication till 2022. Liver
8
Peking University Hepatology Institute, Peking University People‘s
fibrosis status was examined by Fibrosis-4 (FIB-4) score, categorized Hospital, Beijing, China, 9Beijing Ditan Hospital, Capital Medical
into low (<1.45), indeterminate (1.45-3.25), and high (>3.25) grade of University, Beijing, China, 10Department of Infectious Diseases,
fibrosis. In addition, cirrhosis and its complications were also defined Xiangya Hospital, Central South University, Changsha, China,
as the high grade of fibrosis. The association between SGLT-2i vs
1
1The Sixth People‘s Hospital of Shenyang, Shenyang, China,
1
2Ji‘nan Infectious Diseases Hospital, Ji‘nan, China, 13Department
sulfonylureas and the risk of HCC was evaluated using multiple Cox
of Infectious Diseases, First Hospital of Peking University, Beijing,
regression models, described as adjusted hazard ratio (aHR) and 95%
China, 14Department of Infectious Diseases, Wuhan Tongji Hospital
confidence interval (CI).
affiliated to Huazhong Technology University, Tongji Medical College,
Result: Among 11939 patients (mean [SD] age: 62.9; 7543 [63.2%]
Wuhan, China, 15Department of Infectious Disease, The First
male) with T2D and CHB, there were 3197 SGLT-2i users and 8742 Affiliated Hospital of Kunming Medical University, Kunming, China,
sulfonylureas users. 4432 (37.1%) were on nucleoside analogue 1
6Department of Infectious Disease, Changhai Hospital, Shanghai,
therapy for a median duration of 48.0 (18.0-89.4) months. Among China, 17Department of Infectious Diseases, First Hospital of Shanxi
untreated patients, the mean HBV DNA was 3.8 log10 IU/mL. The Medical University, Taiyuan, China, 18Department of Gastroenterology,
distribution of low, indeterminate and high FIB-4 scores were 5339 Tongji Hospital, Tongji Medical College, Huazhong University of
(44.7%), 4333 (36.3%), and 2267 (19.0%) respectively. During a mean Science and Technology, Wuhan, China, 19Department of Hepatology
(SD) follow-up of 4.6 (2.6) years, 714 patients were diagnosed with and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China
HCC. Compared with the sulfonylureas group, SGLT-2i users had
Background: The GOLDEN model is designed to predict hepatitis
a significantly lower risk of HCC (aHR 0.53, 95%CI 0.39-0.70) after
B surface antigen (HBsAg) loss based on chronic hepatitis B (CHB)
adjusting for detailed information regarding demography, lifestyle,
patients receiving nucleos(t)ide analogues therapy. Given that
comorbidities, medications, and laboratory results (Table). The
interferon-alpha (IFN-α) has demonstrated greater efficacy than
benefits of SGLT-2i were consistent across almost all subgroups (aHR:
nucleos(t)ide analogues in reducing quantitative HBsAg (qHBsAg)
0.37-0.64). Of note, the protective effect of SGLT2i was significantly
levels, we aimed to validate the GOLDEN model’s effectiveness in
demonstrated in individuals with high (aHR 0.64, 95%CI 0.42-0.98)
predicting HBsAg loss or decline in IFN-α-treated CHB patients.
and indeterminate (aHR 0.47, 95%CI 0.28-0.80) FIB-4 scores, but not
Method: IFN-α-treated patients were enrolled from EXCEL study, a
in low FIB-4 scores (aHR 0.53, 95%CI 0.25-1.03, p=0.062).
randomized controlled trial included hepatitis B e antigen-positive,
Conclusion: In this population-based cohort study, use of SGLT-
non-cirrhotic, treatment-naïve CHB patients, as well as Search-B
2i, compared with sulfonylureas, decreased the risk of HCC among
cohort, a prospective real-world observational cohort of CHB. Utilizing
individuals with T2D and CHB especially in more severe liver fibrosis,
multiple qHBsAg measurements, the GOLDEN model was employed
suggesting a potential chemopreventive role of SGLT-2i in patients with
to calculate patient’s probability of achieving HBsAg loss or decline.
both chronic diseases.
Result: Among 264 patients in EXCEL study and 1041 patients from
Table and Figure:Figure 1.Table. Association between SGLT-2i use and
Search-B cohort, the corresponding cumulative incidence of qHBsAg
the risk of hepatocellular carcinoma in patients with type 2 diabetes
<100 IU/mL or HBsAg loss was 17.0% and 6.7%, after the median
and chronic hepatitis B. *adjusted for demographic data (age and
follow-up of 18.0 (IQR, 18.0-30.0) and 66.7 (IQR, 48.8-84.7) months,
sex), lifestyle factors (alcohol, smoking, and body mass index),
respectively. In EXCEL study, the median of qHBsAg levels declined
comorbidities (hypertension, hyperlipidemia, heart failure, coronary
from 4.0 log10 IU/mL at enrolment to 3.2 log10 IU/mL at end of
heart disease, stroke, atrial fibrillation, and chronic kidney disease),
treatment followed by a slight rebound, then reached 3.4 log10 IU/
HBV medications (adefovir, entecavir, lamivudine, tenofovir disoproxil,
mL at end of follow-up, finally decreased to 2.8 log10 IU/mL at end of
tenofovir alafenamide, and telbivudine), HBV follow-up duration
extension follow-up. While in Search-B cohort, qHBsAg levels remained
and HBV treatment duration, diabetes medications (metformin,
consistently low (2.7-2.8 log10 IU/mL) during follow-up. The GOLDEN
Dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor
model achieved an area under the curve of 0.841 (95% CI: 0.770-
agonist, thiazolidinediones, and insulin), diabetes duration, common
0.912) for predicting qHBsAg <100 IU/mL in EXCEL study and 0.964
medications (aspirin, statins, and non-steroidal anti-inflammatory
(95% CI: 0.953-0.974) for predicting HBsAg loss in Search-B cohort,
drugs), and laboratory test (albumin, alanine aminotransferase,
and maintaining robust performance across subgroups. The favorable
aspartate transferase, bilirubin, gamma-glutamyl transferase, platelet,
group defined by the GOLDEN model showed higher cumulative
triglyceride, HbA1c, Hepatitis B e antigen, and HBV DNA).
incidences of qHBsAg <100 IU/mL (EXCEL study: 40.3% vs. 2.7%,
p<0.001) or HBsAg loss (Search-B cohort: 37.2% vs. 0%, p<0.001)
OP0185 than the unfavorable group, along with significantly lower qHBsAg
External Validation of the GOLDEN Model for Predicting HBsAg levels and faster qHBsAg decline rates. When stratified by qHBsAg
Loss in Non-cirrhotic Chronic Hepatitis B Patients with Interferon- levels at enrolment (cutoffs: 1000 or 3000 IU/mL), the GOLDEN model
alpha Based Therapy still showed excellent discrimination performance. Moreover, the
Xingmei Liao1, Qing Xie2, Xiaoguang Dou3, Junqi Niu4, Hong Ma5, favorable group defined by the GOLDEN model and qHBsAg levels at
Yali Liu6, Shumei Lin7, Huiying Rao8, Song Yang9, Jianping Xie10, enrolment were confirmed as independent predictors for HBsAg loss
Mingxiang Zhang11, Qiang Li12, Yanyan Yu13, Qin Ning14, Wu Li15, or decline.
Chengzhong Li16, Liaoyun Zhang17, Zhengang Zhang18, Tao Han19, Conclusion: The GOLDEN model is a robust and reliable tool for
Jian Sun1, Jinlin Hou1, Rong Fan1, Chronic Hepatitis B Study predicting HBsAg loss or decline in CHB patients received IFN-α
Consortium based therapy, offering valuable support for clinicians in developing
personalized, effective management strategies for CHB patients.
1
Guangdong Provincial Key Laboratory for Prevention and Control
Table and Figure:Figure 1.Figure 1. Evaluation of predictive performance
of Major Liver Diseases; Guangdong Provincial Clinical Research
of GOLDEN model in EXCEL study. (A) ROC curve to predict qHBsAg
Center for Viral Hepatitis; Key Laboratory of Infectious Diseases
Research in South China, Ministry of Education; Department of <100 IU/mL at EOF. (B) Cumulative incidence of qHBsAg <100 IU/mL
Infectious Diseases, Nanfang Hospital, Southern Medical University, at EOF in overall patients, (C) patients with qHBsAg levels <3000 IU/
Guangzhou, China, 2Department of Infectious Diseases, Ruijin mL at enrolment, and (D) patients with qHBsAg levels ≥3000 IU/mL at
Hospital, Shanghai Jiao Tong University School of Medicine, enrolment. AUC, area under curve; EOF, end of follow-up; qHBsAg,
Shanghai, China, 3Department of Infectious Diseases, Shengjing quantitative hepatitis B surface antigen; ROC, receiver-operating
Hospital of China Medical University, Shenyang, China, 4Department characteristic curve.
Figure 2.Figure 2. Evaluation of predictive performance of GOLDEN Technical Improvements and Outcomes in Pediatric Living Donor
model in Search-B cohort. (A) ROC curve to predict HBsAg loss during Liver Transplantation
follow-up. (B) Cumulative incidence of HBsAg loss during follow- Yuhua Deng1, Xiaoke Dai1, Mingman Zhang1
up in overall patients, (C) patients with qHBsAg levels <1000 IU/mL 1
children’s hospital affiliated to chongqing medical university
at enrolment, and (D) patients with qHBsAg levels ≥1000 IU/mL at
Background: This study aims to compare the clinical efficacy and
enrolment. AUC, area under curve; qHBsAg, quantitative hepatitis B
prognosis of pediatric living donor liver transplantation before and after
surface antigen; ROC, receiver-operating characteristic curve.
specific improvements at a single center.   
Method: The clinical data from 255 pediatric cases of living donor liver
OP0186 transplantation conducted at the Children’s Hospital of Chongqing
Results of Nucleos(t)ide Analog Treatment Discontinuation in Medical University between January 2021 and December 2024
Hepatitis B e-Antigen-Negative Chronic Hepatitis B: NUCSTOP were retrospectively analyzed. These cases were stratified into an
Study early-stage group (January 2021 to August 2023), comprising 179
Sercsn Kiremitci1, Gulseren Seven2, Koray Kochan3, Elmas Biberci patients, and a late-stage group (September 2023 to December 2024),
Keskin1, Gulay Okay1, Yasemin Akkoyunlu1, Bilge Sumbul1, Meliha encompassing 76 patients. When comparing the early-stage group
Meric Koc1, Hakan Senturk1 with the late-stage group, notable technical advancements in the latter
1
Bezmialem Vakıf University, 2Medicana Zincirlikuyu Hospital, 3Liv included: transitioning from a previous two-point anastomosis of the
Hospital hepatic vein to a three-point anastomosis, aligning more closely with
physiological anatomy; enhancing the outer membrane suture fixation
Background: Chronic hepatitis B still maintains its importance all over during biliary-enteric anastomosis to mitigate anastomotic tension;
the world despite effective vaccination programs.Especially in the last and optimizing Roux-en-Y biliary anastomosis by minimizing intestinal
10-15 years, with the use of potent first-line nucleos(t)ide analogs (NAs) branch length to maintain it within the range of 15-20 cm, thereby
in treatment, the prognosis of chronic hepatitis B has shown significant facilitating immunosuppressant absorption.
improvement.However, since these drugs act at a later phase of the Result: The postoperative immunosuppression regimen was the same
hepatitis B viral cycle and cannot directly inhibit covalently closed for both groups of patients. The average age at surgery of the 76
circular DNA, the likelihood of a functional cure remains low despite patients in the late stage group was 5 months (3-96 months),and one
long-term use. According to the literature data, the likelihood of a case of cross-sectional bile leakage was repaired by another surgery.
functional cure under treatment is reported to be between 0.5% and During the follow-up period, the children had no hepatic vein stenosis
2.3%. There are recommendations in the Asian Pacific Association or biliary stenosis. The immunosuppressant drug concentration was
for the Study of Liver (APASL) and European guidelines stating that significantly improved compared with the previous group, and the
in patients with sustained response who meet criteria, treatment can drug concentration was maintained at 4~10ng/ml. After statistical
be discontinued without achieving a functional cure,and HBsAg loss analysis, there was no significant difference in operation time, blood
may occur during observation. Following the recommendations in the loss, and incidence of hot and cold ischemia time between the two
APASL guidelines, we aimed to investigate the functional cure and the groups (P>0.05). However, 8 children with bile leakage in the early
potential relapses during follow-up by discontinuing treatment in non- group improved after surgery. In the later follow-up of 8 children with
cirrhotic HBeAg-negative patients. bile leakage, 3 cases had severe biliary stenosis and recovered after
Method: This is a prospective, single-center, and observational interventional treatment. Six cases had obvious hepatic vein stenosis,
study. Eligible fifty-seven patients were identified, the treatment and five of them had obvious pleural effusion. Their condition was
was discontinued and the patients have been started to follow-up relieved after interventional vasodilator treatment. Thirty children had
prospectively. NAs was discontinued in accordance with the treatment unstable FK506 concentrations, which were maintained at 1 to 3 ng/
discontinuation recommendations in the APASL guideline. All ml for a long time. Among them, 3 of them had to switch to hormone
participants enrolled the study were HBeAg- negative status at + sirolimus because their FK506 concentration was too low. The
NAs initiation. concentration gradually stabilized and their liver function recovered.
Result: The median age of the patients was 49 (29-72) years and 24 Conclusion: Improvements in pediatric living donor liver
(42%) were females. The median treatment duration was 96 (36- 276) transplantation technology can help reduce postoperative vascular
months and patients were followed for a median duration of 42 months. and bile duct complications, maintain the stability of post-operative
Sixteen patients had a previous history of NAs switch, and thirteen of immunosuppressant blood concentrations.
these patients had a history of lamivudine resistance. Thirty-eight of
57 patients (66%) developed an elevated HBV-DNA level of >2000 IU/
mL at least once, defined as virological relapse and 23 (60%) of them, OP0188
experienced clinical relapse.Forty-one of 57 patients were retreated Beta-catenin/Sirtuin 1/Farnesoid X Receptor Pathway Promotion
with the previously used antiviral agents during the follow-up. In a of Portal Vein Ligation and Parenchymal Transection-Induced
portion of the patients, treatment was restarted during the follow-up Rapid Liver Regeneration
due to previously defined severe flare criteria, while others restarted Yifan Tong1, Zheyong Li1, Xiujun Cai1
NAs with their own decision. HBsAg loss occurred among 4 (7%) 1
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
patients. All patients who experienced HBsAg loss had a history of
Background: Background By accelerating the regeneration of
lamivudine resistance (p= 0.002).
the future liver remnant (FLR), portal vein ligation and parenchymal
Conclusion: Despite receiving NAs suppression therapy for a long
transection (PVLT) allow for more extensive hepatectomy. Given that
time, HBsAg loss occurs rarely. Although it was not life-threatening,
the mechanism remains poorly understood, the aim of this study was
most patients experienced relapses and treatment should be restarted
to investigate the mechanism of PVLT-induced liver regeneration (LR).
(72%). In our study, whether it is a coincidence that all patients with
Method: A PVLT-induced LR mouse model was established, followed
HBsAg loss are patients in whom NAs are used sequentially due to
by RNA microarray analysis to identify candidate molecules. Genomic
lamivudine resistance is an issue that needs to be further investigated.
deletion and chemical manipulation of target molecules were used to
Table and Figure:Figure 1.Characteristics of included patients at the
explore their functions in PVTL-induced LR. Validation was conducted
time of NAs cessation
using a diseased liver model and human samples.
Figure 2.Comparison of the patient groups with and without history of
Result: PVLT-induced LR was significantly accelerated compared with
lamivudine resistance
that in sham-operated mice (p<0.05). An RNA microarray revealed that
Sirtuin 1 (SIRT1) is a crucial molecule in the proliferation of the FLR.
OP0187 Regardless of whether SIRT1 is inhibited chemically or through genetic
deletion, PVLT-induced LR is distinctly attenuated. Further investigation
revealed that SIRT1 promoted PVLT-induced LR via the farnesoid X
receptor (FXR). Additionally, beta-catenin (CTNNB) was also found to mitochondrial function. However, the role of GPX3 in liver regeneration
participate in the process of FLR proliferation. Chemical inhibition of remains unclear. In this study, we explored the impact of GPX3 on
CTNNB was markedly impaired but activation of WNT/CTNNB mildly mitochondrial function and its regulatory influence on liver regeneration.
enhanced PVTL-induced LR (p<0.05). Deletion of SIRT1 blocked the Method: GPX3 was identified as a potential target through transcriptome
facilitating effect of CTNNB on PVTL-induced LR. These findings were sequencing. We generated liver cell-specific GPX3 knockout mice
validated in diseased liver models and patient samples, confirming and subjected 8-week-old GPX3fl/fl albcre and GPX3fl/fl mice to 70%
the correlation between the CTNNB/SIRT1/FXR pathway and PVLT- partial hepatectomy (PH). Samples were collected at designated time
induced LR. points post-surgery. Primary hepatocytes were isolated using a two-
Conclusion: Activation of the CTNNB/SIRT1/FXR pathway offers step collagenase perfusion technique. Immunoprecipitation coupled
critical mechanistic insights into accelerating PVLT-induced LR. with mass spectrometry was employed to identify potential interacting
Modulation of CTNNB/SIRT1/FXR may therefore improve clinical proteins of GPX3. Additionally, GPX3 truncation mutants were created
outcomes in patients receiving staged hepatectomy. to investigate specific binding sites between GPX3 and downstream
Table and Figure:Figure 1.Beta-catenin/Sirtuin 1/Farnesoid X proteins.
Receptor Pathway Promotion of Portal Vein Ligation and Parenchymal Result: In the 70% partial hepatectomy model, GPX3 expression
Transection-Induced Rapid Liver Regeneration significantly increased at 48 hours post-surgery. GPX3 knockout
Figure 2.CTNNB/Sirt1/FXR pathway and liver proliferation in human mice exhibited a marked reduction in liver-to-body weight ratio
and a delayed expression of key proliferative proteins involved in
liver regeneration, indicating an impaired regenerative response.
OP0189
Furthermore, GPX3 knockout resulted in enhanced mitochondrial
Circulating Tumor-specific Cell-free Tumor DNA is Useful oxidative stress, compromised mitochondrial membrane potential,
in Monitoring Recurrence of HBV-related HCC after Liver and diminished mitochondrial respiratory function, collectively
Transplantation suggesting mitochondrial dysfunction. Further investigation revealed
Shiou-Hwei Yeh1, Chiao-Ling Li1, Yi-Hsiang Hsiao2, You-Yu Lin3, mitochondrial quality control dysfunction, evidenced by increased
Sheng-Tai Tzeng4, Chin-Fang Huang4, Ting-Jie Chang4, Ya-Chun mitochondrial fission and reduced fusion. Investigation into the
Wang4, Pei-Jer Chen5, Ming-Chih Ho2 underlying mechanisms revealed that GPX3 interacts with VDAC1,
1
Graduate Institute of Microbiology, National Taiwan University thereby regulating mitochondrial homeostasis through the modulation
College of Medicine, Taipei, Taiwan., 2Department of Surgery, National of VDAC1 function.
Taiwan University Hospital, Taipei, Taiwan., 3Graduate Institute of Conclusion: Our findings suggest that GPX3 modulates mitochondrial
Clinical Medicine, National Taiwan University College of Medicine, function through its interaction with VDAC1, thereby playing a critical
Taipei, Taiwan., 4TCM Biotech International Corp., Taipei, Taiwan, role in the regulation of liver regeneration. This suggests that GPX3
5
Hepatitis Research Center, National Taiwan University Hospital may serve as a promising therapeutic target for treating acute liver
Background: HCC recurrence after liver transplantation (LT) poses injury.
a significant challenge to patient outcomes. Since high AFP levels Table and Figure:Figure 1.GPX3 deficiency impairs liver regeneration
could disqualify patients from LT, a new biomarker is urgently needed Figure 2.GPX3 deficiency exacerbates mitochondrial dysfunction
for post-LT recurrence monitoring. This study aims to investigate the during liver regeneration
possibility of cell-free circulating tumor DNA (ctDNA) as tumor marker
in this clinical setting. OP0191
Method: Fifteen HBV-related HCC patients undergoing LT were
enrolled in this study. Capture-NGS analysis was used to identify the Study of overall survival and factors affecting outcomes in
virus-host chimeric DNA (vh-DNA) derived from HBV integration and chronic hepatitis C patients undergoing liver transplantation: A
TERT promoter mutations for each HCC. These mutations were then single-centered cohort study
selected as signature ctDNA markers for individual HCCs and their Chitchai Rattananukrom1, Kongpob Yongrattanakit1, Tanita
levels in plasma samples were analyzed by mutation-specific ddPCR Suttichaimongkol1, Witsarut Manasirisuk1, Kookwan Sawadpanich1,
assays. Apichart Sangchan1, Kawin Tangworapongchai1, Pisaln Mairiang1,
Result: Vh-DNA and TERT promoter mutations were found in 84.6% Wattana Sukeepaisarnjareon1
of HCC, with 90.9% being detected in baseline plasma samples by 1
Division of Gastroenterology and Hepatology, Department of
ddPCR, superior to the detection rates of AFP (36%) and PIVKAII Medicine, Faculty of Medicine, Srinagarind Hospital, Khon Kaen
(64%). The ddPCR was then applied to plasma samples obtained University, Khon Kaen, Thailand
during two-year follow-up after LT. No ctDNA was detected in plasma Background: Chronic hepatitis C virus (HCV) infection is a significant
of all recurrence-free patients. In contrast, ctDNA from residual tumor global health concern. It can lead to progressive liver diseases such
cells was detected in the follow-up plasma of all recurrent patients, as cirrhosis and hepatocellular carcinoma (HCC). Liver transplantation
even prior to diagnostic imaging and better than AFP. (LT) is recognized as the curative treatment for early-stage HCC and
Conclusion: Considering that most HCC recurrence in LT patients decompensated cirrhosis. However, LT recipients with chronic HCV
originates from primary HCC, tumor-specific vh-DNA or TERT promoter infection tend to have lower survival rates compared to those with
mutations show promise as valuable ctDNA markers for detecting other indications. While studies in Western countries have explored
most recurrence, especially in HBV-related HCC that cannot be various factors influencing outcomes, including HCC, similar research
monitored by AFP or PIVKA-II. The results highlight the importance of is lacking in Asia. This study aims to examine overall survival and
incorporating ctDNA testing into clinical practice to improve prognosis factors affecting outcomes in chronic hepatitis C patients undergoing
of recurrence after LT. liver transplantation at Srinagarind Hospital.
Method: The medical records of adult LT recipients with HCV infection,
OP0190 transplanted between January 2008 and May 2023, were reviewed.
Survival curves were generated using the Kaplan-Meier method
GPX3 regulates liver regeneration by preserving mitochondrial
and compared using the log-rank test. Univariate Cox proportional
quality control
hazard models were employed to calculate hazard ratios for variables
Yuechen Wang1, Jian Xu1, Haoran Hu1, Haoming Zhou1 associated with death. The primary outcome was the overall survival
1
The First Affiliated Hospital of Nanjing Medical University of LT recipients with chronic HCV infection and secondary outcomes
Background: The liver’s unique regenerative capacity enables it to were factors affecting overall survival, the rate of HCV recurrence,
respond effectively to various diseases and injuries. The maintenance cirrhosis recurrence, and HCC recurrence.
of mitochondrial function is essential for sustaining the liver’s robust Result: The medical records of 81 adult LT recipients with chronic
regenerative potential. Glutathione peroxidase 3 (GPX3), a member hepatitis C transplanted at Srinagarind Hospital. HCV recurrence
of the glutathione peroxidase family, is closely associated with was observed in nearly all cases (98.6%) where HCV viral load was
detectable prior to liver transplantation. Subsequently, approximately host metabolism interaction mechanism in MAFLD
72% of patients underwent HCV treatment after LT, with a 100% Method: Participants from Yunnan were divided into two groups:
success rate in achieving sustained virological response (SVR). At MAFLD (N=150) and controls (N=150). Serum, fecal samples, and
the last follow-up, 76.8% of patients were SVR. Cirrhosis recurrence lifestyle data (physical activity, sleep, diet) were collected. LC-MS
occurred in 4.9% of cases, while HCC recurrence was noted in 7.4% of analyzed fecal and plasma metabolites, while 16S rRNA sequencing
cases. The 5-year overall survival rate was 75.3%. For factors affecting analyzed gut microbiota. MAFLD was assessed using the FAST score.
patient outcomes, HCC recurrence (HR= 26.55; 95% CI= 5.14-137.21; Result: There were significant differences between the MAFLD
P< 0.001) and cirrhosis recurrence (HR= 9.05; 95% CI=1.79-45.87; group and the control group in fecal microbiota structure (Figure
P=0.008) were also found to be correlated with an increased risk 1A-B), microbial metabolites, and serum metabolites. Thirty-six
of mortality. On the other hand, both HCV treatment after LT (HR= differential microbial species were identified, such as Akkermansia
0.09; 95% CI= 0.03-0.3; P< 0.001) and achieving SVR status at the muciniphila_D_776786 (Figure 1C). Eighteen differential metabolites in
final follow-up visit (HR= 0.13; 95% CI= 0.05-0.35; P< 0.001) were serum, represented by cholesterol sulfate, and fifty-three differential
significantly associated with a reduced risk of death. metabolites in feces, represented by retinol, were found (Figures 1D-E
Conclusion: Over the 16-year period, the 5-year overall survival rate and 1F-G).
of LT recipients with chronic HCV infection was 75.3%. The recurrence Unhealthy lifestyle and dietary habits (high salt, high fat
of HCC and cirrhosis were the significant risk factors for reducing diet, and poor sleep quality) were negatively correlated with microbial
overall survival. Conversely, LT patients who underwent HCV treatment α-diversity (Figure 2A).
and achieved SVR status at the final follow-up visit demonstrated a There was a correlation between fecal microbiota and
good factor to improve overall survival. microbial metabolites, suggesting that the hypothesized mechanistic
Table and Figure:Figure 1.the overall survival outcomes among 81 liver relationship between microbes and microbial metabolites could
transplant recipients with HCV infection, become a target for modulating gut microbiota (Figure 2B).
Figure 2.the overall survival rates of patients stratified by their sustained Microbial functions enriched in MAFLD were positively
virologic response (SVR) status at the final follow-up visit. correlated with overall disease characteristics (such as hepatic
steatosis, inflammation, blood lipids, blood glucose, BMI, and
blood pressure), while microbial functions depleted in MAFLD were
OP0192
negatively correlated with these disease characteristics (Figure 2C).
The Impact of Sarcopenia on Early Postoperative Mortality in In the disease state, approximately 41.7% of the enriched
Living Donor Liver Transplant Recipients with End-Stage Liver pathways in serum metabolism overlapped with microbial-enriched
Disease metabolic pathways (Figures 2D-E).
Alp Atasoy1, Abdulbaki Agackiran2,2, Emre Aray2, Kubra Vardar3,2, Eda Both host metabolism and microbial metabolism enriched in
Nur Yildiz2, Abdulkadir Dökmeci4,2, Kaan Karayalcin4,2, Deniz Balci2 MAFLD was negatively correlated with key disease features such as
1
Medical Park Goztepe Hospital, 2Bahcesehir University Medical Park insulin resistance, hepatic steatosis, and inflammation. (Figures 2F-G).
Goztepe Hospital, 3Istanbul Kent University, 4Ankara University Cholesterol sulfate has therapeutic potential for MAFLD.
Background: Sarcopenia, a common complication in end-stage liver Supplementation of cholesterol sulfate in HepG2 cells reduced lipid
disease (ESLD), has been associated with poor outcomes in liver deposition (Figure 2H).
transplantation. This study aimed to evaluate the relationship between Conclusion: This study revealed significant changes in gut microbiota,
sarcopenia, assessed by psoas muscle thickness-to-height ratio microbial metabolites, and serum metabolites in MAFLD. The findings
(PMTH), and early postoperative mortality in recipients of living donor suggest that changes in microbial structure in MAFLD may influence
liver transplantation (LDLT). disease characteristics through alterations in function. The microbial
Method: From June 2022 to December 2024, 112 ESLD patients (74 metabolism and host metabolism exhibit synergistic effects on the
males, 38 females) undergoing LDLT at Istanbul Bahçeşehir University disease across multiple metabolic pathways, and early changes in
Medical Park Hospital were included. Sarcopenia was measured metabolism may offer protective mechanisms. Supplementing key
using PMTH, and early mortality (within 1 month post-transplant) metabolites like cholesterol sulfate showed therapeutic promise,
was assessed. Gaussian distribution testing was performed, and providing scientific evidence for MAFLD intervention.
correlations were analyzed using point-biserial and Pearson correlation Table and Figure:Figure 1.Figure1 captions: A: Gut microbiota
tests. composition at the phylum level in central Yunnan (KM), eastern
Result: The mean BMI and MELD score were 27.78 ± 4.6 and 18.98 ± Yunnan (HZ), western Yunnan (LC, YJ), and southern Yunnan (BN). B:
6.8, respectively. A significant negative correlation was found between β-diversity analysis of gut microbiota between the MAFLD group and
PMTH and early mortality (p = 0.0198, p < 0.05*), indicating that lower the control group. C: LEfSe differential analysis between the MAFLD
PMTH values were associated with higher early mortality risk. However, group and the control group. D: PLS-DA analysis of serum metabolites
no significant correlation was observed between PMTH and hospital between the MAFLD group and the control group. E: Heatmap of
stay duration (p = 0.1166, p > 0.05). differential serum metabolites between the MAFLD group and the
Conclusion: Sarcopenia, as measured by PMTH, is significantly control group. F: PLS-DA analysis of fecal metabolites between the
associated with increased early postoperative mortality in LDLT MAFLD group and the control group. G: Heatmap of differential fecal
recipients. These findings underscore the importance of preoperative metabolites between the MAFLD group and the control group.
sarcopenia assessment to identify high-risk patients and improve Figure 2.Figure2 captions: A: Correlation analysis between lifestyle
outcomes in LDLT. Further studies are needed to explore targeted and dietary habits and microbial α-diversity. B: Correlation analysis
interventions for sarcopenia in this population. between fecal microbiota and microbial metabolites, with the x-axis
representing microbial metabolites and the y-axis representing fecal
microbiota. C: Correlation analysis between fecal microbiota functions
OP0193 and biochemical indicators, with the x-axis representing biochemical
The Gut Microbiota-Metabolite-Host Metabolism Interaction indicators and the y-axis representing fecal microbiota functions. D:
Mechanism in MAFLD: From Multidimensional Analysis to KEGG enrichment pathway analysis of serum metabolites. E: KEGG
Precision Intervention enrichment pathway analysis of microbial metabolites. F: Correlation
Huang Min Shan1,2, Chen Hang1,2, Ma Lan Qing1,2, The First Affiliated analysis between serum metabolites and biochemical indicators,
Hospital of Kunming Medical University with the x-axis representing biochemical indicators and the y-axis
1
The First Affiliated Hospital of Kunming Medical University, 2Chinese representing serum metabolites. G: Correlation analysis between
Society of Hepatology, Collaborative Group on Hepatology-Related microbial metabolites and biochemical indicators, with the x-axis
Digestive Diseases representing biochemical indicators and the y-axis representing
Background: This study aims to reveal the gut microbiota-metabolite- microbial metabolites. H: Oil Red O staining.
 OP0194 subjected with HFHD.
Insulin-Like Growth Factor Binding Protein 7 as a Biomarker
for Hepatic Fibrosis and Cardiac Dysfunction in Metabolic OP0195
Dysfunction-Associated Fatty Liver Disease Mechanistic Study of Resmetirom in Treating MAFLD Mouse
Wenjing Ni1,2,3, Qianqian Chen1,2,3, Yixuan Zhu1,3, Fajuan Rui1,2,3, Model: Gut Microbiota Remodeling and Metabolic Regulation
Zhiwen Fan4, Shengxia Yin1,3, Qianwen Zhao1,3, Jie Li1,2,3 Chen Hang1,2, Huang Min Shan1,2, Ma Lan Qing1,2
1
Department of Infectious Disease, Nanjing Drum Tower Hospital, 1
The First Affiliated Hospital of Kunming Medical University, 2Chinese
Affiliated Hospital of Medical School, Nanjing University, 2Department
Society of Hepatology, Collaborative Group on Hepatology-Related
of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College
Digestive Diseases
of Nanjing University of Chinese Medicine, 3Institute of Viruses and
Infectious Diseases, Nanjing University, 4Department of Pathology, Background: The pathogenesis of metabolic associated fatty liver
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, disease (MAFLD) is closely related to gut microbiota, but its specific
Nanjing University mechanisms remain unclear. Resmetirom, as the first drug approved
for the treatment of MASH with fibrosis, has not yet been studied in
Background: Individuals with metabolic dysfunction-associated
relation to gut microbiota. This study aims to investigate the role and
fatty liver disease (MAFLD) face an elevated risk of liver-related
mechanisms of gut microbiota in Resmetirom’s treatment of MAFLD
complications and cardiovascular diseases. However, the interplay
using multi-omics approaches.
between liver fibrosis and cardiac function in MAFLD remains
Method: We established a MAFLD mice model with a high-fat diet
unknown. This study aims to investigate the role of insulin-like growth
(HFD) and treated mice with Resmetirom for 8 weeks. An FMT model
factor binding protein 7 (Igfbp7) in the process of liver fibrosis and its
was also constructed. Liver fat and lipid deposition were evaluated with
association with cardiac dysfunction.
HE and Oil Red O staining. Blood serum indicators were measured,
Method: Single-cell sequencing data from Gene Expression Omnibus
and ileal contents were analyzed for metagenomics and untargeted
(GEO) datasets (GSE145154, GSE156057, GSE192740, GSE174748)
metabolomics.
were analyzed to identify potential targets in liver fibrosis and heart
Result: 1.Resmetirom and FMT Alleviate Metabolic Disorders and
failure. Circulating Igfbp7 levels and liver tissue expression were
Hepatic Steatosis
examined in patients with liver fibrosis. Male C57BL/6J mice (6 weeks
Resmetirom and FMT improved glucose intolerance, insulin resistance
old) were fed a high-fat, high-fructose diet (HFHD) or a control diet for
(Fig1 A-C), hepatic steatosis, lipid deposition (Fig1 D-E), serum
20 weeks to induce MAFLD-associated liver fibrosis. Igfbp7 depletion
indicators (ALT, AST, TG, TC, LDL-C, HDL-C, Fig1F-K), liver weight, fat
in mature myofibroblasts was achieved using Igfbp7-targeting shRNA
distribution, and adipose tissue weights (Fig1 L-Q). They also restored
under the Postn promoter, packaged into AAV6 (AAV-shIgfbp7).
ZO-1 and Occludin levels in intestinal tissues (Fig2 Q-S).
Echocardiography was performed to assess left ventricular ejection
2.Fecal Microbiota Composition and Key Taxa
fraction (LVEF) and fractional shortening (FS). Liver histology was
Significant differences were found among groups (Fig2 A-B). Lefse
analyzed with hematoxylin-eosin (HE) staining. In vitro studies utilized
identified 62 taxa between Control and HFD (Fig 2C), 53 between HFD
TGF-β-activated human hepatic stellate cells (LX-2) to explore Igfbp7-
and Resmetirom (Fig 2D), and 49 between HFD and FMT (Fig 2E).
associated mechanisms.
Parabacteroides was enriched in HFD but reduced in Resmetirom and
Result: Reanalysis of single-cell sequencing data identified Igfbp7 as
FMT groups (Fig 2F).
a significantly differential expressed gene implicated in liver fibrosis
3.Fecal Metabolites and Metabolic Pathways
and heart failure. Among patients with liver fibrosis and concurrent
3,475 metabolites across eight classes were identified (Fig 2G).
heart failure, circulating IGFBP7 levels correlated positively with liver
Significant differences in fecal metabolites were observed among the
stiffness measurements (LSM), and immunohistochemical staining
Control, HFD, Resmetirom, and FMT groups (Figure 2H). The metabolic
confirmed IGFBP7 expression was proportionally associated with liver
pathways involved in the differential metabolites between the HFD and
fibrosis severity (Figure 1). HFHD-fed MAFLD mice exhibited increased
Resmetirom or FMT groups were distinct (Figure 2I-N). Resmetirom
liver fibrosis and reduced cardiac function (LVEF and FS), which were
increased butyric acid, indole derivatives, and deoxycholic acid but
alleviated by Igfbp7 depletion. Igfbp7 mRNA levels were elevated
reduced palmitic and stearic acid (Fig 2O). FMT increased rosmarinic
alongside myofibroblast markers (Acta2, Postn, Col1a1) in MAFLD mice
acid, citric acid, and indole-3-methyl acetate but reduced dimethyl
but decreased following Igfbp7 depletion. Glucose tolerance test
hexasulfide, methyl methylthio selenide, and uracil (Fig 2P).
and insulin tolerance test showed an improved performance in mice
Conclusion: This study explored the role and mechanisms of
with Igfbp7 depletion (Figure 2). Consistent findings were observed
Resmetirom in treating MAFLD using a HFD mice model and FMT
in primary hepatic stellate cells (HSCs) from wild-type mice, where
experiments. Resmetirom improved glucose intolerance, insulin
Igfbp7 expression increased during spontaneous activation. TGF-β-
resistance, hepatic steatosis, blood lipid profiles, body weight,
activated LX-2 cells displayed enhanced Igfbp7 expression, migration,
and fat tissue distribution. Its therapeutic effects were mediated by
proliferation, and contraction, effects that were mitigated by Igfbp7
regulating specific bacterial taxa, restoring gut microbiota balance,
knockdown.
and reversing MAFLD progression. Resmetirom also modulated key
Conclusion: IGFBP7 serves as a promising biomarker for assessing
metabolic pathways linked to gut microbiota, enhancing host metabolic
liver fibrosis severity and cardiac dysfunction in MAFLD. Targeting
regulation. This study offers new molecular insights and preclinical
IGFBP7 could offer therapeutic potential for managing liver and
evidence for Resmetirom in MAFLD treatment.
cardiovascular complications in MAFLD patients.
Table and Figure:Figure 1.Figure 1 Resmetirom and FMT Alleviate
Table and Figure:Figure 1.Figure 1. IGFBP7 was identified as a potential
Metabolic Disorders and Hepatic Steatosis in HFD Mice (A) Body
target in the interplay between liver fibrosis and heart failure. (A) GEO
weight curves. (B) Glucose tolerance test (GTT) results. (C) Insulin
analysis from different databases; (B) Immunohistochemical staining
tolerance test (ITT) results. (D-E) Representative Oil Red O and H&E-
and quantitative analysis of IGFBP7 along with myofibroblast markers
stained liver sections (200× magnification; scale bar: 50 μm). (F-K)
in patients with fibrosis; (C) The association between liver stiffness
Serum ALT, AST, TG, TC, HDL-C, and LDL-C levels. (L-Q) Liver weight,
measurement and IGFBP7 in patients with liver fibrosis concurrent with
hip breadth, height, and adipose tissue weights. Data are expressed
heart failure.
as mean ± SEM (n = 5-10). Statistical significance: *P < 0.05, **P <
Figure 2.Figure 2. IGFBP7 aggravated liver fibrosis and cardiac
0.01, ***P < 0.001, ****P < 0.0001.
dysfunction in MAFLD. (A) Protocol of establishment of Igfbp7
Figure 2.Figure 2 Effects of Resmetirom and FMT on Gut Microbiota
depletion mouse model; (B) Glucose tolerance test and insulin
and Fecal Metabolites in MAFLD Mice (A) Alpha diversity of gut
tolerance test; (C) The mRNA levels of Igfbp7 and myofibroblast
microbiota. (B) Beta diversity clustering. (C-E) Lefse analysis of key
markers in mice subjected with HFHD; (D) Echocardiography and
taxa: (C) Control vs. HFD, (D) HFD vs. Resmetirom, (E) HFD vs. FMT.
analysis of left ventricular ejection fraction and fractional shortening
(F) Differential genera among groups. (G) Metabolite class distribution.
in mice subjected with HFHD; (E) Hematoxylin-eosin staining of mice
(H) OPLS-DA of differential metabolites. (I-N) KEGG pathway
enrichment of metabolites. (O) Heatmap of metabolites: Control, HFD, machine learning models (Random Forest, XGBoost, LightGBM) and
and Resmetirom. (P) Heatmap: Control, HFD, and FMT. (Q-S) ZO-1 two deep learning models (FT Transformer, GANDALF) in the MAFLD
and Occludin protein expression normalized to actin. Data are mean population. (D-G) Radar charts showing the Brier score, MCC, Recall,
± SEM (n = 5-10). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. and Log-loss values for the five models. (H) SHAP analysis providing
localized interpretability, illustrating the prediction of the MDD risk
score for the specific sample. (I-P) RCS curves exploring the nonlinear
OP0196
relationships between risk factors and MDD risk, offering deeper
A Personalized Risk Score and Predictive Model for Stratifying insights into complex associations.
High Depression Risk in Patients with Metabolic Dysfunction-
Associated Fatty Liver Disease: A 5-Year Follow-Up Study of
103,954 Patients from the UK Biobank OP0197
Junrong Li1, Zhongwen Feng1, Taolong Zhou2, Xiaobing Zhai1, Turicimonas muris Disrupts Treg/Th17 Balance through CXCL9 to
Xiaoliang Li2, Tao Luo2, Kefeng Li1, Mingxing Huang2 Promote the Progression of MAFLD
1
Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Longyun Wu1, Qiaoyun Xia1, Xiaolan Lu1
Applied Sciences, Macao Polytechnic University, Macau SAR, China, 1
Department of Gastroenterology, Fudan University Pudong Medical
2
Zhuhai Third People’s Hospital, Zhuhai, Guangdong, China Center
Background: Metabolic dysfunction-associated fatty liver disease Background: Metabolic-associated fatty liver disease (MAFLD) has
(MAFLD) affects 38% of adults globally and poses higher mortality emerged as the second leading cause of end-stage liver disease and
risks when combined with major depressive disorder (MDD). Limited the second most common cause of hepatocellular carcinoma among
research exists on the risk factors for MDD onset in MAFLD patients. adults awaiting liver transplantation in the United States.
This study aims to address these gaps by identifying key risk factors Method: We initially identified the enterobacterium Turicimonas muris
for MDD in MAFLD patients through a comprehensive analysis of (T. muris) in NAFLD mouse models using 16S rRNA sequencing,
a large-scale, five-year longitudinal cohort from the UK Biobank. followed by isolation and cultivation of T. muris through fecal bacterial
By employing advanced machine learning and deep learning isolation techniques. Subsequently, we predicted the functional profile
methodologies, this study systematically compares multiple predictive of T. muris via TELL-Seq whole genome sequencing. Finally, we re-
algorithms to identify significant predictors of MDD risk and develop introduced T. muris into mice to validate its role in MAFLD.
robust predictive models. Additionally, an individualized risk scoring Result: 1. Compared with the normal diet control group, fecal alpha
formula is constructed to provide personalized risk assessments for diversity in mice fed a high-fat diet decreased, while the abundance
MAFLD patients. of T. muris significantly increased (Figure 1A). 2. Using TELL-Seq
Method: This study analyzed data from 103,853 MAFLD patients in whole-genome sequencing, we identified that T. muris may play a role
the UK Biobank cohort, followed for five years, with 1,241 developing in nutrition and metabolism (Figure 1B). 3. For the T. muris reinfusion
MDD. A total of 81 features spanning demographic, lifestyle, experiment, mice were divided into three groups: the normal chow diet
anthropometric, clinical, and biochemical domains were examined. (NCD) group, the 45% high-fat diet (HFD) group, and the T. muris+45%
Feature selection involved LightGBM-based bootstrap screening and HFD group. During the intervention period, mice in the T. muris+45%
sequential forward selection. Machine learning models (LightGBM, HFD group exhibited greater weight gain compared to those in the
XGBoost, Random Forest) and deep learning models (FT Transformer, 45% HFD group (Figure 1C), and this difference was statistically
GANDALF) were trained and validated using 5-fold cross-validation significant at the end of the intervention (Figure 1D). Biochemical
and evaluated on metrics including AUC, MCC, F1-score, Brier score analysis revealed that the DB level in the T. muris+45% HFD group was
and Log-loss. SHapley Additive exPlanations (SHAP) and restricted significantly higher than in the 45% HFD group (P < 0.01), although
cubic splines (RCS) provided insights into feature contributions and ALT, AST, and TB levels were also elevated, these differences were
nonlinear relationships. not statistically significant (Figures 1E-H). Additionally, LDL-C levels
Result: Among 317,065 MAFLD participants (mean age 57, 62.1% in the T. muris+45% HFD group were significantly higher than in the
male), 1,241 (1.19%) were newly diagnosed with MDD over five years, 45% HFD group (P < 0.05) (Figures 1I-L). 4. Flow cytometry analysis of
with women exhibiting a higher incidence (1.54% vs. 0.98% in men) spleen samples from the three groups showed that the percentage of
(Figure 1). Feature selection (Figure 2A-B) identified 15 significant Th17 cells in the T. muris+45% HFD group was significantly increased
predictors for model development, including BMI, RBC levels, and compared to the 45% HFD group (P < 0.01), while the percentage of
physical activity. Machine learning models demonstrated excellent Treg cells was decreased, though not significantly (P > 0.05) (Figures
predictive performance, with LightGBM achieving the highest 2A-B). 5. Further analysis using Olink proteomics revealed that liver
AUC (0.98) and superior calibration (Brier score: 0.049). Nonlinear inflammatory factor levels, including Adam23, Cdh6, Cxcl9, Tnfrsf12a,
relationships between MDD risk factors were revealed through RCS Tpp1, and Wisp1, were significantly higher in the T. muris+45% HFD
analysis (Figure 2I-P), emphasizing the protective effects of moderate group compared to the 45% HFD group. Conversely, Dlk1 levels were
activity and RBC levels and the risk-enhancing roles of obesity and significantly reduced (Figure 2C). KEGG pathway analysis suggests
inflammation. SHAP analysis provided individualized risk scores that cytokine-cytokine receptor interaction may be an important
(Figure 2H), showcasing the model’s ability to predict and stratify MDD signaling pathway involved (Figure 2D).
risk among MAFLD patients effectively. Conclusion: In this study, T. muris is demonstrated to potentially
Conclusion: This study developed a highly accurate model for exacerbate the progression of NAFLD through the upregulation of
predicting MDD risk in MAFLD patients, achieving an AUC of 0.98 Cxcl9 and the aggravation of Treg/Th17 imbalance.
using data from the UK Biobank cohort. By identifying 15 key predictors Table and Figure:Figure 1.Figure 1 Separation and Transfusion of
through robust feature selection, the model enables individualized risk Turicimonas muris.
assessment and supports precise treatment planning. This approach Figure 2.Figure 2 Turicimonas muris Exacerbates Inflammation in Mice
facilitates early detection and targeted interventions, improving clinical with Non-Alcoholic Fatty Liver Disease (NAFLD).
outcomes for high-risk MAFLD patients.
Table and Figure:Figure 1.A) Table 1. Baseline characteristics and
OP0199
5-year follow-up comparison of MAFLD patients with and without MDD.
B) Figure 1. Study population. EVALUATING IMPACT OF WEIGHT CHANGES ON HISTOLOGICAL
Figure 2.Figure 2. (A) The top 80% of features preliminarily selected PATTERNS OF LIVER FIBROSIS IN MASH: IMPLICATIONS FOR
based on their frequency ranking after 1000 bootstrap iterations. (B) SPATIAL INTERROGATION
The 15 predictive factors identified through forward selection using Kutbuddin Akbary1, Nicholas Syn2,3, EnYing Tan4, Ethan JooWei
the LightGBM model. The left y-axis represents feature importance, Quek5, Daniel Huang4, Jonathan Lee4, Yayun Ren1, Cheng Han Ng4,
while the right y-axis shows the cumulative AUC. (C) Comparison of Aileen Wee2, Gwyneth Soon2, NurHalisa Binte Jumaat4, Yock Young
ROC values for MDD risk prediction models constructed using three Dan4, Mark Muthiah4
1
HistoIndex Pte Ltd, 2Department of Pathology, National University ELISA. The difference in progerin and the interaction with APRI and
Health System, 3Division of Biomedical Informatics, Yong Loo Lin FIB-4 between cases and controls were explored. The wild type
School of Medicine, National University of Singapore, 4Division of (WT) and progeria mice (LmnaG609/G609) were administrated with
Gastroenterology and Hepatology, Department of Medicine, National 40%CCl4 using intraperitoneal injection for 4 weeks to construct the
University Hospital, 5Yong Loo Lin School of Medicine, National hepatic fibrosis model, which were divided into the four groups: WT-
University of Singapore CTR, WT-CCl4, LmnaG609/G609-CTR, and LmnaG609/G609-CCl4.
Background: The mechanisms by which weight loss influences Moreover, primary hepatocyte was isolated from the above groups.
hepatic fibrosis and the role of pre-surgery weight dynamics in The degree of hepatic fibrosis was evaluated by histopathological
predicting fibrosis outcomes are not well understood. This study aims staining. The expression of progerin, hepatic fibrosis markers, and the
to evaluate the correlation between pre-surgery weight changes and cGAS-STING pathway, as well as SASPs in liver tissue and primary
patterns of fibrosis changes using Second Harmonic Generation/Two hepatocytes were detected by western blotting and RT-qPCR.
Photon Excitation (SHG/TPE) imaging with AI analysis-based collagen Result: Plasma progerin in patients with hepatic fibrosis was higher
parameters (qF) in liver biopsies of bariatric surgery patients with than that in controls. There was no significant difference in plasma
MASH. progerin level among patients with hepatic fibrosis of different etiology.
Method: Sixty-nine patients scheduled for bariatric surgery were Spearman correlation analysis showed that the level of plasma
evaluated for weight changes over six months preceding surgery progerin in the fibrosis group was positively correlated with AST, DBIL,
when they were placed on a Very Low Caloric Diet (VLCD), and TBA, and was negatively correlated with ALB and HB. Plasma progerin
were categorized as either weight loss (n=60) or weight gain (n=8). was an independent risk factor for hepatic fibrosis (OR=42.250,
Relative weight changes were assessed as percentage changes from 95%CI:11.501-155.204, P<0.001). The area under the curve (AUC)
baseline. Unstained core liver biopsies, obtained at time of surgery, of plasma progerin combined with APRI and FIB-4 in the diagnosis
were analysed, and quantified using qF. Spearman correlation of liver fibrosis was 0.995. In vivo, compared to the WT-CCl4 group,
analyses were conducted between relative weight changes and qF- progerin in liver tissue and primary hepatocytes remarkably increased
derived collagen morphological parameters, with results presented as in the LmnaG609/G609-CCl4 group. The inflammatory infiltration and
r-values. collagen fiber deposition were increased in the LmnaG609/G609-
Result: Weight loss correlated with significant alterations in overall qF CCl4 group compared to the WT-CCl4 group. And the activation of the
parameters, particularly in regions exhibiting “chicken wire” fibrosis cGAS-STING pathway and the high levels of SASPs (e.g. IL-6, IL-8, IL
(r = -0.4), pericentral region (r = -0.42), and overall hepatic region (r 1-β, and TNF-α,) were exhibited in the LmnaG609/G609-CCl4 group
= -0.49). Weaker correlations were observed in zone 2 parameters (r compared to WT-CCl4 group.
= -0.32). Conversely, weight gain demonstrated positive correlations Conclusion: Progerin in combination with APRI and FIB-4 significantly
with qF parameters in the same regions. These NASH-CRN zonal improve the diagnostic efficiency of liver fibrosis, and the underlying
parameters were selected due to their high r-values, highlighting a mechanism of these effects may induce liver premature senescence
strong correlation between weight change and the extent of overall via activating the cGAS-STING pathway.
and chicken wire fibrosis. Table and Figure:Figure 1.
Conclusion: This study reveals that relative weight loss prior to Figure 2.
bariatric surgery is strongly associated with reductions in overall
hepatic fibrosis, especially chicken wire fibrosis. These highlight OP0201
the spatial importance of zones of “chicken wire” fibrosis in disease
regression with weight loss targeted therapies. This would further MSC-derived exosomes attenuates periductal fibrosis by inhibiting
enhance our understanding of responders and non-responders and Th 17 differentiation in human liver multi-lineage organoids and
open up avenues for precision medicine in MASH. Mdr2-/- mice models
Table and Figure:Figure 1.Figure 1: Demonstrates the correlations Hongcui Cao1,2,3, Wenyi Chen1,2, Qiaoling Pan1,2, Jiong Yu1,2,3, Qigu
between qF parameters, based on zonal classification as per the Yao1,2, Lanjuan LI1,2
NASH-CRN system, with pre-surgery weight loss and weight gain. [A]
1
State Key Laboratory for the Diagnosis and Treatment of Infectious
Shows the correlation of qF-based parameters with weight loss and Diseases, The First Affiliated Hospital, Zhejiang University School of
weight gain, categorized according to the NASH-CRN zonal system. Medicine, 2National Clinical Research Center for Infectious Diseases,
[B] Presents scatter plots and correlations of relative weight change National Medical Center for Infectious Diseases, 3Zhejiang Key
with individual zonal qF parameters, highlighting those with high Laboratory for Diagnosis and Treatment of Physic-chemical and
r-values. Aging-related Injuries
Background: Primary sclerosing cholangitis (PSC) is characterized by
progressive periductal fibrosis of the hepatic bile ducts and chronic
OP0200
inflammation, leading to characteristic “beaded” appearance of the
Progerin-Induced Premature Senescence Aggravates Hepatic bile ducts as detected by cholangiography , and fibroinflammatory
Fibrosis by Activating the cGAS-STING Pathway destruction of bile ducts appearance as “onion skinning” like
Bingxin Lu1, Rui Wang1, Xianxi Li1, Xingyuan Yang1, Yanqin Yue1, fibrosis histopathologically. No radical therapy exists making liver
Xiaoli Ma1, Wang Guo1, Jian Hou2, Xiaoying Luo*1 transplantation inevitable for end-stage patients. The pathogenic
1
People’s Hospital of Zhengzhou University, Department of mechanism of PSC is complex and is influenced by a multitude of
Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou factors, including immunity, genetics, and bile duct pathology. An
450003, China, 2Department of Epidemiology and Biostatistics, ideal model for in-depth study of the pathogenic mechanisms and
College of Public Health, Zhengzhou University, Zhengzhou 450003, therapeutic approaches involved is still lacking.
China Method: We constructed novel liver-derived multi-lineage organoids
Background: Abnormal progerin accumulation induces liver (Mulorgs) from PSC patients and co-cultured them with human T
premature senescence to aggravate hepatic fibrosis. However, the helper 17 (Th17) cells to mimic the Th17-associated intrahepatic
involvement mechanisms of progerin-related premature senescence microenvironment, in conjunction with PSC model mice (Mdr2-/- mice),
in hepatic fibrosis remains largely unclear. Activation of the cyclic to investigate the pathogenic mechanism of Th17-promoted hepatic
GMP-AMP synthase (cGAS)-interferon gene stimulating factor (STING) fibrosis in more depth, and to further explore the mechanism by which
pathway is involved in regulating cellular senescence. Thus, this study mesenchymal stem cell-derived exosomes (ExoMSC) regulate Th17
aimed to elucidate the interplay of progerin, the cGAS-STING pathway differentiation to ameliorate liver fibrosis in PSC.
and hepatic fibrosis. Result: In the Mulorgs model, IL-17A was found to increase the
Method: We conducted a case-control study, which included fifty-five expression of inflammatory chemokines, fibrosis-related genes and
patients with hepatic fibrosis and fifty-five age and sex-matched healthy collagens, which could be ameliorated by ExoMSC, and further
controls. The plasma progerin of the individuals were determined by verified in Mdr2-/- mice that hepatic “onion-skinning” like fibrosis could
be ameliorated by ExoMSC through inhibition of Th17 differentiation. Medical School, Southeast University,
MiRNA microarray, cell function analyses, establishment of a Th17- Background: Minimal hepatic encephalopathy (MHE) significantly
FibHOs (fibrotic Mulorgs) co-culture system and Cut-tag analysis affects the clinical outcomes and quality of life (QOL) of patients with
revealed that highly expressed miR-7977 by ExoMSC reduced the cirrhosis. However, timely diagnosis and intervention are challenging
expression of the transcription factor IKBζ via targeting NFKBIZ, due to sophisticated diagnostic methods.
attenuated the chemotaxis of Th17 to the fibrosis-associated Method: This study analyzed 660 healthy controls and 757 patients
microenvironment and reduced gene peaks of IKBζ-targeted IL-17A. with cirrhosis enrolled from 27 hospitals in China, divided into the test
Conclusion: Collectively, our data demonstrate the significant potential (292 patients) and validation (465 patients) cohort. The multivariate
of Mulorgs in modelling the in vivo microenvironment of diseases, and linear regression was performed to construct a diagnostic model of
uncover the deep-rooted mechanism of ExoMSC-derived miR-7977 in the Stroop test (Stroop-CN) according to the results of healthy controls
inhibiting Th17 differentiation and ameliorating intrahepatic fibrosis in and then used to diagnose MHE in patients with cirrhosis at different
PSC. disease severity. The EuroQol 5-D questionnaire was used to evaluate
Table and Figure:Figure 1.MSC-derived exosomes attenuates the QOL.
periductal fibrosis by inhibiting Th 17 differentiation in human liver Result: A diagnostic model of the Stroop test (Stroop-CN) was
multi-lineage organoids and Mdr2-/- mice models constructed by multivariate linear regression based on the results of
healthy controls. The prevalence of MHE and the comparison results
OP0202 with psychometric hepatic encephalopathy score through the Stroop-
CN model were stable in the test and validation cohorts. Moreover, the
RBM25 promotes liver fibrogenesis by regulating chondroitin
prevalence of MHE remained significantly higher in patients with worse
sulfate E metabolism in macrophages
disease conditions marked as high Child-Pugh grades and MELD-Na
Gong Shiming1,2,3, Wang Bo1,2,3, Ma Lijie1,2,3, Duan Xuewen1,2,3, Cheng
scores in the test and validation cohort (Figure 1). The EuroQol 5-D
Meng1,2,3, Zhan Zhenzhen1,2,3, Xia Qiang1,2,3
questionnaire revealed that patients with MHE had a worse QOL than
1
Department of Liver Surgery, Renji Hospital, School of Medicine, those without MHE both in the test and validation cohort.
Shanghai Jiao Tong University, 2Shanghai Institute of Transplantation, Conclusion: An easy and practical Stroop-CN model for MHE
3
Shanghai Engineering Research Center of Transplantation and
diagnosis based on the EncephalApp is established, and a significant
Immunology
proportion of Chinese patients with cirrhosis suffer from MHE, which
Background: Liver macrophages can promote liver fibrogenesis negatively affects patients’ QOL.
by directly activating hepatic stellate cells (HSCs). Interfering with Table and Figure:Figure 1. Prevalence of MHE in different groups of
the crosstalk between macrophages and HSCs may be an effective patients with cirrhosis.(A-B) Comparison results of MHE prevalence
therapeutic strategy for liver fibrosis. RNA binding motif protein 25 among different Child-Pugh in patients with cirrhosis of test and
(RBM25) is a key component of the U1 spliceosome, but its role in validation cohort, respectively; (C-D) Comparison results of MHE
liver fibrosis remains unknown. The aim of this study is to investigate prevalence among different MELD-Na score classifications in patients
how RBM25 promotes liver fibrogenesis by regulating macrophage with cirrhosis of test and validation cohort, respectively. MHE, minimal
metabolism. hepatic encephalopathy.
Method: In this study, we systemically investigated the expression
of RBM25 in liver cirrhosis, including patients with different clinical
aetiologies and three preclinical models induced by carbon
OP0204
tetrachloride (CCl4), bile duct ligation and methionine/choline-deficient HIF-1α/LTBP2 axis activate HSCs to promote liver fibrosis by
diet. Macrophage-specific RBM25 knockout (RBM25-cKO) mice were interacting with LOXL1 via the ERK pathway
generated to investigate the function of macrophage RBM25. Cross- Mengxin Lu1, Shuai Tao1, Conglin Zhao1, Yuxian Huang1, Liang
talk between macrophages and HSCs was investigated in vitro. Chen1
Result: RBM25 expression was significantly increased in both human 1
Shanghai Public Health Clinical Center (affiliated with Fudan
and murine cirrhotic livers, particularly in macrophages. Macrophage- University)
specific RBM25 deficiency significantly attenuated the progression of Background: LTBP2 is a multi-domain exocrine protein present
liver fibrosis. In vitro conditioned medium experiments showed that in the ECM and associated with the fibrosis of numerous organs.
macrophages promote HSC activation in a paracrine manner. Further Nevertheless, the function of LTBP2 in liver fibrosis remains poorly
studies showed that macrophage RBM25 promotes the stability comprehended. This study aims to investigate the role and mechanism
of Chst15 mRNA, which is subsequently translated into a type II of LTBP2 in liver fibrosis.
transmembrane glycoprotein that acts as a sulfotransferase to produce Method: The expression of LTBP2 was assessed via public
chondroitin sulfate-E (CS-E). Furthermore, we demonstrated that CS-E databases and validated by immunohistochemistry. The migration and
could promote HSC activation in a TGF-β-dependent manner. Finally, proliferation of HSCs were determined through wound healing, CCK-8
pharmacological inhibition of Chst15 reduced HSC activation and and cell cycle assays. Epithelial-mesenchymal transition and MAPK
showed therapeutic value in liver fibrosis. pathway markers were evaluated using Western blotting. Chromatin
Conclusion: Macrophage RBM25 promotes liver fibrosis through the immunoprecipitation was employed to detect DNA-protein interactions.
Chst15/CS-E axis which has a role in activation of HSCs. Chst15 may The interaction between LTBP2 and LOXL1 was discovered through
be a promising therapeutic target for the treatment of patients with liver database prediction and molecular docking. RNA sequencing was
fibrosis. utilized to identify the pathways of LTBP2.
Result: The expression of LTBP2 is positively correlated with the
OP0203 severity of liver fibrosis and significantly increased in fibrotic liver
Detection of minimal hepatic encephalopathy in Chinese patients tissues in both human and mice. More importantly, in vivo LTBP2
with cirrhosis based on the Stroop-CN model: A prospective inhibition significantly alleviates CCL4-induced liver fibrosis by
multicenter study reducing collagen accumulation and HSCs activation in mice. In
vitro, knockdown or overexpression of LTBP2 inhibits or enhances the
Xiaoyan Li1, Shanghao Liu2, Ying Guo3, Hongmei Zu4, Huiling Xiang5,
proliferation, migration and expression of fibrotic genes in LX-2 cells.
Jasmohan S Bajaj6, Fusheng Wang7, Junliang Fu1, Xiaolong Qi8
Then, HIF-1α promoted LTBP2 expression by directly binding to the
1
5th medical center of PLA, 2Zhongda Hospital, Medical School,
LTBP2 promoter. Moreover, western blot results showed that LTBP2
Southeast University, 3the Third people’s Hospital of Taiyuan, 4The
promoted HSCs activation and EMT. Mechanically, LTBP2 interacting
Fourth People’s Hospital of Qinghai Province, 5Tianjin Third Central
with LOXL1 via ERK1/2 signaling pathway to promote the EMT and
Hospital , 6Division of Gastroenterology, Hepatology and Nutrition,
HSCs activation.
Virginia Commonwealth University and Central Virginia Veterans
Healthcare System, 7 5th medical center of PLA, 8Zhongda Hospital, Conclusion: HIF-1α/LTBP2 axis promoted HSCs activation and EMT
by interacting with LOXL1 via ERK signaling and may be a potential misdiagnosed. This study emphasizes the significance of awareness
target in liver fibrosis. among healthcare workers about the increasing incidence of acute
Table and Figure:Figure 1.The effect of LTBP2 in liver fibrosis. hepatitis A among this group to ensure accurate diagnosis and
Figure 2.Schematic diagram of the role of LTBP2 in liver fibrosis appropriate management.
Method: A hospital-based retrospective cross-sectional study was
employed. Fifty-eight confirmed acute HAV patients who visited
OP0205
Adera Medical and Surgical Center (AMSC) between August 2023
Inverse Correlation of Th2-Specific Cytokines with Hepatic Egg and January 2024 were enrolled. Sociodemographic, clinical, and
Burden in S. mansoni-Infected Hamsters laboratory parameters and documented management data, including
Verena Von Buelow1, Lena Russ1, Frederik Stettler1, Gabriele hospitalization and any trial of antibiotic treatment before considering
Schramm2, Franco Harald Falcone3, Christoph Gero Grevelding3, HAV or in the course of the illness, were collected. The data were
Martin Roderfeld1, Elke Roeb1 entered and analyzed using SPSS (SPSS, Version 26.0).
1
Department of Gastroenterology, 2Research Center Borstel, 3Institute Result: The sex ratio was similar, with a slight male predominance
of Parasitology (M/F = 1.07). The mean age [± SD] of the patients was 19.3[± 8.8]
Background: Schistosomiasis is a parasitic disease caused by years. Thirty-nine (67.2%) of the patients were students, and all of the
Schistosoma spp. that affects over 250 million individuals globally. The patients were from Addis Ababa. Vomiting (82.8%), anorexia (70.7%)
species S. mansoni particularly impacts the gastrointestinal tract and and yellowish discoloration of the eyes (62.1%) were the most common
elicits a Th2 immune response through its eggs, leading to granuloma presenting symptoms, while icteric sclera 44 (75.9%) and epigastric
formation. The relationship between the quantity of parasitic eggs tenderness 17 (29.3%) were the most common physical findings.
and the immune response remains poorly understood. This study More than half of the patients (55.2%) were initially misdiagnosed with
investigated whether the amount of parasitic eggs influences the typhoid fever (TF) (46.8%), peptic ulcer disease (PUD) (31.2%) or
immune response in S. mansoni-infected hamsters. urinary tract infection (UTI) (15.6%). All patients recovered fully, and
Method: Hamsters were infected with S. mansoni cercariae by the liver function tests (LFTs) normalized with supportive care within 2-4
paddling method at the age of 8 weeks. Bisex and monosex worm weeks.
populations were produced by poly-miracidial and mono-miracidial Conclusion: This study revealed the shift in the age of HAV susceptibility
intermediate-host infections, respectively. The hepatic and intestinal and subsequent infection towards adolescents and young adults
egg burden was assessed, and cytokine expression as well as (mean [± SD] age 19.31 [± 8.8] years) in our cohort, with more than
the expression of three key egg-derived proteins were analyzed half of the patients (55.2%) initially being misdiagnosed with TF, PUD or
in monosex- and bisex-infected animals via qRT-PCR. Statistical UTI, causing diagnostic and treatment challenges. This necessitates
correlations between egg burden or egg-derived factors Ipse/alpha-1, heightened awareness among healthcare workers and the public.
kappa-5, and omega-1, and the immune response were analyzed in Early HAV diagnosis through targeted laboratory investigations and
liver and colon tissue. avoiding unnecessary antibiotics are crucial for effective management
Result: Notably, the Th1 cytokine response induced by S. mansoni and prevention via hygienic and immunization strategies.
infection was independent of the hepatic egg burden, while the Th2
cytokines IL-4, IL-5, and IL-13 exhibited an inverse correlation in the OP0207
liver. A modest cytokine expression was observed in the monosex-
Late Onset Encephalitis in a Young Indian Male with Acute Liver
infected group, whereas bisex-infected animals showed up to 4.6-fold
Failure Due to Hepatitis A
(IL-4), 10-fold (IL-5), and 30-fold (IL-13) increased expression levels.
Furthermore, hepatic IL-4 and IL-13 expression correlated inversely Manish Kumar1, Simi Tahiliani1, Kishore S1
with egg-derived factors of S. mansoni eggs, such as IPSE/alpha-1,
1
ABVIMS and Dr RML Hospital
kappa-5, and omega-1. In contrast, the induction of IL-4, IL-5, and IL- 1. Introduction Less than 1% of hepatitis A cases progress to acute liver
13 mRNA expression in the colon tissue demonstrated no dependence failure. Extra-hepatic manifestations may include transient arthralgia,
on the intestinal egg burden. hemolytic anemia, maculopapular rash, and neurological symptoms.
Conclusion: The data indicate an inverse relationship between egg Impaired liver detoxification can lead to seizures, and encephalitis may
burden and soluble egg factors on one side, and the Th2 immune rarely occur due to direct viral invasion of the CNS. We present a case
response on the other, but only in the liver and not in the colon of of late onset encephalitis due to hepatitis A with atypical clinical, CSF,
infected hamsters. This suggests the host may have developed a and imaging findings. 2. Case Description A 21-year-old male from
protective mechanism to limit the Th2 response when faced with a high New Delhi, India, presented with a 10-day history of fever, jaundice,
egg burden, potentially due to the prolonged embryogenesis of the and altered sensorium. He was deeply icteric, exhibited a generalized
parasitic eggs in the liver. This hypothesis is supported by the lack maculopapular rash, had tender hepatomegaly, and ecchymosis on
of any correlation between egg burden and immune response in the the right flank. The pupils were normal, meningeal signs were absent,
colon, where the intestinal transit of the eggs is more rapid. and plantars were extensor. Arterial blood gas indicated compensated
Table and Figure:Figure 1.Strategy to attenuate hepatic Th2 immune metabolic acidosis with a high anion gap. The patient had renal AKI
response in the face of a substantial parasite egg burden and hepatocellular jaundice, with an INR of 4.18. Ultrasound showed
Figure 2.The hepatic Th2 cytokines IL-4, IL-5, and IL-13 exhibit an an enlarged liver and a 13 cm spleen. Non-contrast CT, fundus, and
inverse relationship with egg load CSF analyses were normal. Tests for dengue, malaria, scrub typhus,
and Leptospira were negative. Procalcitonin was positive (> 0.5 ng/dL),
OP0206 while cultures were sterile. HIV and Hepatitis serologies (B, C, E) were
negative. Hepatitis A IgM was positive. On day 2, he was electively
Hepatitis A Beyond Childhood Causing Diagnostic and Therapeutic intubated and received high bowel washes with lactulose. Fresh
Challenges in Addis Ababa, Ethiopia frozen plasma transfusion was required due to endotracheal bleeding.
Abate Bane Shewaye1,2, Kaleb Assefa Berhane2, Amsalework Daniel Antibiotics were added for secondary infections, and an episode of AV
Fanta2 nodal re-entry tachycardia was treated with adenosine. By day 5, he
1
Addis Ababa University , 2Adera Medical and Surgical Center was extubated and moved out of ICU on day 7. He later experienced
Background: Hepatitis A is an acute viral infection of the liver caused high-grade fever, confusion, and a generalized tonic-clonic seizure. A
by hepatitis A virus (HAV) that is acquired through the feco-oral route. repeat non-contrast CT head revealed focal hypodensity in the right
It is ranked first in terms of incidence rate among the four major acute occipital lobe. MRI showed focal edema in the right parieto-occipital
forms of viral hepatitis (A, B, C, and E) and usually occurs in early lobe, likely consistent with post-ictal edema. CSF Gram stain, culture,
childhood. However, the prevalence acute hepatitis A has recently viral PCR, and CBNAAT for tuberculosis were negative. Ceruloplasmin,
increased among teenagers and young adults, and it is usually urinary copper, and iron profiles were normal, as were autoimmune
panels. EBV, HSV, and CMV PCRs were negative. His encephalitis-like
presentation was linked to hepatitis A; he was treated conservatively Liao1, Zhe Xie1, Jennifer Robb3,4, Clarissa Prazeres da Costa3,2,4,
and discharged on levetiracetam after 3 days. A follow-up LFT after one Ulrike Protzer1,2
month indicated relapsing hepatitis, with subsequent ultrasound ruling 1
Institute of Virology, Technical University of Munich / Helmholtz
out extra-hepatic obstruction. Serial LFTs showed a gradual return to Munich, Munich, Germany, 2German Center for Infection Research
baseline, and the anti-epileptic drug was tapered and stopped. Our (DZIF), Munich partner site, Munich, Germany, 3Institute for Medical
patient presented with acute liver failure due to hepatitis A, complex Microbiology, Immunology and Hygiene, Technical University of
extra-hepatic manifestations, and delayed encephalitis, with a relapse Munich, Munich, Germany, 4Center for Global Health, Technical
during follow-up. It’s crucial to exclude other causes of encephalitis, as University of Munich, Munich, Germany
imaging and EEG findings are not specific. Confirmation is achieved Background: Schistosoma are helminth parasites that infect around
by demonstrating viral RNA in the CSF. These manifestations are 250 million humans worldwide. The parasite matures in the liver,
typically self-limiting and have a good prognosis. causes liver damage, and influences host immune responses. The
SARS-CoV-2 pandemic led to the development of various vaccine
OP0208 strategies, including the first licensed mRNA-based vaccines and
classical protein-based vaccines. However, the efficacy of these
Post COVID Condition and long-term COVID-19 Impact on hepatic
vaccines among individuals with existing hepatic parasite infections
decompensation and survival in Cirrhosis: a propensity matched
remains uncertain. Here, we aimed to explore how the SARS-CoV-2
observational study
vaccination was influenced by an underlying helminth infection using
PRERNA SHARMA1, MADHUMITA PREMKUMAR1, RASHMI an experimental Schistosoma mansoni-infection mouse model.
RANJAN GURU1, ANCHAL SANDHU1, KAMAL KAJAL1, AJAY Method: Naïve mice and mice chronically infected with S. mansoni
KUMAR DUSEJA1, VIRENDRA SINGH1, SUNIL TANEJA1, NIPUN were immunized with mRNA-based Comirnaty vaccine or aluminum
VERMA1, SAHAJ RATHI1, ARKA DE1 adjuvanted spike protein, and boosted after four weeks. Vaccine-
1
Post Graduate Institute of Medical Education & Research, induced humoral and cellular immune responses were evaluated one
Chandigarh week after boost immunization.
Background: Patients with cirrhosis are susceptible to decompensation Result: Comirnaty vaccination induced comparable spike-specific
events including ascites, acute variceal bleeding(AVB), hepatic IgG titers and virus-neutralization capacity in both naïve and helminth-
encephalopathy(HE), or death after COVID-19. Patients may infected mice. However, spike-specific IgG subclass profiles differed
experience post-COVID condition(PCC) with multisystem(cardiac, between the groups. In naïve mice, the IgG2c subclass predominated,
neurological or musculoskeletal) involvement that persists for at least reflecting a Th1 response, while in helminth-infected mice, the
2 months. IgG1 subclass predominated, indicating a Th2-prone response. In
Method: Hospitalized patients with cirrhosis and COVID-19 between comparison, spike protein immunization resulted in significantly lower
January 2021 and January 2023 were assessed for hepatic levels of IgG responses than Comirnaty vaccination, with the IgG1
decompensation events and mortality and were compared to a subclass predominating in both naïve and helminth-infected mice,
propensity matched cohort of those with cirrhosis and nonCOVID-19 likely due to the aluminum adjuvant. Beyond antibody responses,
sepsis. Patients who survived COVID-19 were followed for PCC and Comirnaty vaccination induced robust spike-specific CD4+ and CD8+
cirrhosis-related events or death over 1 year. T-cell responses. These responses were significant compared to the
Result: Of 252 patients with Cirrhosis+COVID-19(73% men, weaker T-cell responses observed with spike protein immunization. In
aged48.9± 13.7years, 31%-diabetes, 44%-hypertension, 35%-alcohol- helminth-infected mice, Comirnaty vaccination elicited strong, dose-
associated, 34.5%-MASLD), 72(28.6%) died in hospital and dependent spike-specific IFNγ+ CD4+ T-cell responses comparable
180(71.4%) were discharged following recovery, similar to in hospital to those detected in naïve mice. However, spike-specific IFNγ+
mortality in Cirrhosis+non-COVID-sepsis(58/214,27.1%). During CD8+ T-cell responses were significantly lower in helminth-infected
follow-up, 60(33.3%) met criteria for PCC, 19(10.5%) had no sequelae mice compared to naïve counterparts. Moreover, helminth infection
and 101(56.1%) patients died(N=45) or were lost to follow up(N=56). significantly impacted the polyfunctionality of vaccine-induced CD8+
Late Mortality was higher in Cirrhosis+COVID-19than non-COVID- T cells. In helminth-infected mice, there was a marked reduction in
sepsis (56.1% vs 35.3%,P=0.026). Causes of death post-COVID spike-specific IFNγ+ TNFα+ IL-2+ CD8+ T cells. This was accompanied
recovery(N=45) were 12-ACLF;4-sepsis;20-liver failure,2-AVB,7- by a notable increase in spike-specific PD-1+ Lag3+ CD8+ T cells,
hepatocellular carcinoma. Patients with PCC were aged 47.6years, indicating functional suppression of CD8+ T cells.
63.3%-men,Charlson Comorbidity Index>4(51.7%), 45%-diabetes, Conclusion: Immunization with the mRNA-based Comirnaty vaccine
56.7%- hypertension, with 33.3%, 23.3% and 43.3% in Child-Pugh induced significantly stronger antibody and T-cell responses compared
class A,B&C respectively. PCC symptoms reported were persistent to spike protein immunization. While chronic helminth infection had
dyspnea(34,43%), mild cognitive complaints(20,25.3%), and anxiety minimal impact on SARS-CoV-2 protein immunization, it altered the
(47,59.4%). On multivariable Cox Proportional-Hazards analysis, characteristics of antibody responses and substantially reduced
predictors of PCC were baseline MELDNa(HR 1.12,95%CI:1.05- the magnitude and functionality of CD8+ T-cell responses elicited by
1.17,P<0.001), and age(HR0.9,95%CI-0.91-0.99,P=0.012). Predictors SARS-CoV-2 mRNA vaccination.
of mortality following COVID-19 recovery were MELDNa(HR
1.03,95%CI:1.01-1.05,P=0.008), age(HR 1.2, 95%CI 1.1-1.5,P=0.002)
OP0210
and hypertension(HR 1.63,95%CI 1.07-2.49,P=0.025).
Conclusion: COVID-19 is associated with significant long-term Etiology and Diagnostic Roadmap in Patients with Non-viral
mortalityand Long-COVID is seen in a third of patients with cirrhosis Chronic Liver Injury
who survive COVID-19. Yanfei Feng1, Jianning Jiang1
Table and Figure:Figure 1.GRAPHICAL ABSTRECT 1
Gaungxi
Figure 2.Table 1: Cox Proportional Hazards for Predictors of Background: Nonviral chronic liver injury refers to chronic liver
Development of Post COVID Condition after Recovery from Covid-19 diseases caused by non-viral infectious factors, and its incidence
following hospital discharge. Table 2: Cox Proportional Hazards for is increasing year by year. The diagnosis time and accuracy vary
Predictors of Mortality after Recovery from Covid-19 and hospital greatly due to the influence of regional, hospital, and clinician level of
discharge. medical care. This study aims to explore a suitable clinical diagnostic
and treatment pathway by retrospectively analyzing the causes and
OP0209 diagnostic methods of chronic liver function abnormalities caused by
nonviral liver injury in our hospital, in order to improve the diagnosis
Hepatic helminth infection modulates the immune responses
rate and shorten the diagnosis time, avoid delaying the condition and
induced by different types of SARS-CoV-2 vaccines
ineffectively occupying medical resources.
Jinpeng Su1,2, Youssef Hamway3,2,4, Julia Schluckebier3,4, BoHung
Method: A retrospective analysis was conducted on 356 patients with radiomics features. Radiomics model were developed using Logistic
non-viral chronic liver injury admitted to our hospital from June 2020 to Regression (LR), Random Forest and Extra Trees algorithms. Finally,
December 2022, aiming to analyze the etiology and main diagnostic a new nomogram model was built by integrating the super-
methods, as well as explore the clinical diagnostic pathway. resolution model with COSSH-ACLFs, a widely used clinical prognosis
Result: General Information: A total of 572 patients with non-viral model for HBV-ACLF .
liver injury diagnosed and treated in our hospital from June 2020 to Result: Eight key radiomic features were identified through the LASSO
December 2022 were collected. 163 patients (28.5%) with recurrent process to built super-resolution model. The super-resolution technique
liver dysfunction < 3 months or unknown course of disease and 53 demonstrated superior predictive power for 28 and 90-day survival
patients (9.3%) with incomplete data were excluded. A total of 356 compared to traditional radiomics model [AUC of Random Forest
patients (62.2%) with non-viral chronic liver injury with disease course model for 90 day survival: 0.881 vs. 0.860 in train cohort, 0.876 vs. 0.791
≥3 months were included. There were 356 patients with non-viral in validation cohort, 0.741 vs. 0.703 in test cohort]. Super Resolution
chronic liver injury, including 183 males (53.4%) and 173 females model is comparable with clinical models. In the training cohort, the
(46.6%). The age ranged from 15 to 84 (46.8±15.7) years. super-resolution models surpassed most clinical models, including
The common causes of non-viral chronic liver injury were MELD (28-day AUC: 0.821; 90-day AUC: 0.784), CLIF-C ACLFs (28-
autoimmune liver disease (AILD) in 71 cases (19.9%), non-alcoholic day AUC: 0.846; 90-day AUC: 0.868), and CLIF-C OFs (28-day AUC:
fatty liver disease (NAFLD) in 64 cases (18.0%) and alcoholic liver 0.858; 90-day AUC: 0.803). The nomogram model, integrating Super
disease (ALD) in 57 cases (16.0%). The main diagnostic methods Resolution with the classic clinical model COSSH-ACLFs, yielded the
were medical history (26.5%), liver biopsy (25.5%), and imaging highest predictive accuracy across all cohort.
examinations (15.5%). (Table 1) Conclusion: The super-resolution model performed exceptionally
Combined with the common types of diseases and the well as a prognostic biomarker and was significantly correlated with
operability of examination in actual clinical work, the following multi-organ failure. By integrating super-resolution radiomics with
clinical diagnosis paths were summarized: First-line screening: clinical models, we achieved the highest AUC in survival prediction,
1.medical history collection and physical examination; 2. liver highlighting the utility of this approach in optimizing clinical decision-
function; 3.screening of hepatotropic and non-hepatotropic viruses; 4. making for HBV-ACLF patients.
autoimmune antibodies; 5. immunoglobulin; 6. blood lipid; 7. abdominal Table and Figure:Figure 1.Compare of AUC among clinical model,
ultrasound examination; Second-line screening: 1. rare pathogen; 2. traditional radiomics and Super-Resolution radiomics model in
thyroid function; 3. serum ceruloplasmin and K-F ring; hepatic CT/MRI; predicting prognosis of ACLF patients.
Three-line screening: 1. gene testing; 2. liver biopsy. For patients who Figure 2.Construction and Validation of the Nomogram Based on
are not strongly interested in second or third-line screening, follow- COSSH-ACLF Scores and the Super-Resolution Model
up can be conducted to observe whether liver function can improve
after discontinuation of special drugs, alcohol withdrawal, diet control, OP0212
deworming or treatment of primary disease, and if so, it is related to the
above conditions. (Figure 1) FIB-5 and/or FIB-4 index for hepatic fibrosis evaluation in chronic
Conclusion: The diagnostic pathway map for non-viral chronic liver hepatitis B.
injury is efficacious, straightforward, feasible, and merits clinical Mohamed Abdel-Samiee1, Maha Elsabaawy1, Khaled Metwally1,
implementation. Wessam Morad1, Nermin Ehsan1, Eman Abdelsameea1
Table and Figure:Figure 1.Figure1 Diagnostic pathway of non-viral 1
National Liver Institute
chronic liver injury Background: Chronic hepatitis B virus (HBV) infection is one of
Figure 2.Table1 Analysis of main diagnostic methods in 310 cases of the major health problems worldwide. Use of non-invasive tests for
non-viral chronic liver injury with definite etiology assessment of hepatic fibrosis such as the FIB-4 index could be used
to avoid liver biopsy. Another promising noninvasive test, FIB-5, could
OP0211 also be used to detect a significant hepatic fibrosis. The aim of the
study was to compare the use of FIB-5 and FIB-4 as noninvasive
Deep Learning-Based Super-Resolution CT Radiomics Enhances
markers to assess chronic HBV-related hepatic fibrosis.
Prognosis prediction for Patients with Hepatitis B virus related
Method: This cross-sectional study was conducted on 176 chronic
Acute-on-Chronic Liver Failure
HBV patients who underwent liver biopsy. Grading and staging of liver
Xueyun Zhang1, Shiman Wu2, Yuxian Wu1 fibrosis was done according to the METAVIR scoring system. FIB-5
1
Huashan Hospital Fudan University Department of Infectious and FIB-4 scores were calculated for all patients. Exclusion criteria
Diseases, 2Huashan Hospital Fudan University Department of of the study included patients co infected by hepatitis C virus (HCV),
Radiology hepatitis D virus (HDV) or human immunodeficiency virus (HIV),
Background: Hepatitis B virus related acute-on-chronic liver failure patients with primary or secondary liver tumors, patients who received
(HBV-ACLF) is a severe and life-threatening condition, requiring timely any previous antiviral or immunosuppressive medications, and also
prognosis prediction. Despite the availability of several prognostic patients who refused liver biopsy or having any contraindication to
scoring models, they primarily rely on peripheral blood markers and undergo liver biopsy and patients with decompensated cirrhosis.
rarely analyze liver characteristics in ACLF patients directly. Due to the Result: As regards FIB-4 for differentiation between non-significant
risks associated with liver biopsies, imaging techniques like liver CT fibrosis (group I) and significant fibrosis (group II), at a cutoff level
scans offer a non-invasive alternative for liver evaluation. Radiomics, of 1.28 with positive predictive value (PPV) 41.4% and specificity
an advanced image analysis method, extracts and statistically 48% while at a cutoff level of 7.08 with PPV 98.8% and specificity
analyzes quantitative data from medical images, offering insights 98% for FIB-5. There was a significant relationship between fibrosis
beyond what the naked eye can detect. Deep learning-based super- stages and both serum indices. There was a significant increase in
resolution reconstruction techniques provide an end-to-end approach the level of FIB-4 as fibrosis progressed from non-significant (F0-1) to
to enhancing image resolution. significant fibrosis (F2-4). A significant decrease in the level of FIB-5 (p
Method: A retrospective study was conducted on 181 HBV-ACLF = 0.00001) was observed with the progression of fibrosis stages from
patients who underwent CT scans across two medical centers. The non-significant to significant fibrosis.
cohort from 146 patients from Huashan Hospital was divided randomly Conclusion: FIB-5 score was more specific than FIB-4 for diagnosing
into train cohort (n = 102) and validation cohort (n =44), while an significant from non-significant hepatic fibrosis in patients with chronic
external test cohort (n = 35) patients were sourced from Shanghai HBV infection.
Public Health Clinical Center. Super-resolution CT images were Table and Figure:Figure 1.
reconstructed using Aenerative adversarial network (GAN) hosted on
the OnekeyAI Platform. Radiomics features were extracted using ITK-
OP0213
SNAP, and a multi-task LASSO model was employed to select non-zero
Unexpected Low Prevalence of Hepatitis Delta Virus Infection in conducted to explore the relationships between miRNA expression
Southern Viet Nam profiles and intrahepatic cell types.
Thuy Thu Nguyen1, Van Huy Vo2, An Bac Luong3, Chuong Dinh Result: Immune cell infiltration patterns varied across the four phases
Nguyen2, Phong Tien Quach2, Thuy ThiThanh Trinh2, Sang The of CHB, with distinct changes in frequencies of CD8+ T cells and
Phan2, Tuan Ngoc Cao2, Chi Bich Mai4, Vu Anh Hoang3, Frank follicular helper T cells. Differential expression analysis identified 273
Maldarelli1, Hoang Huu Bui2 significantly altered miRNAs, with 66 showing a fold change >1.5. The
1
HIV Dynamics and Replication Program, NCI, Frederick, United 66 miRNAs with notable differences were upregulated during the IA
States, 2Department of Gastroenterology, University Medical Center, phase compared to the IT and IC phases. Among them, miR-155-5p,
Ho Chi Minh City, Vietnam, 3Center for Molecular Biomedicine, miR-150-5p, miR-132-3p, miR-142-5p, miR-21-3p, and miR-146b-5p
University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam, were also consistently upregulated in the ENH phase. Additionally,
4
Diagnostic Laboratories, University Medical Center, Ho Chi Minh City, a clustered heat map illustrated distinct miRNA expression patterns
Vietnam associated with different phases. Most immune cell markers were
Background: HBV/HDV co-infection is the most severe form of viral upregulated during the IA phase, while non-immune cell markers
hepatitis, but HDV screening has not received adequate attention. showed minimal or no variation across the phases. These upregulated
Despite Vietnam having one of the highest rates of viral hepatitis-related miRNAs in the IA phase were significantly associated with the
hepatocellular carcinoma (HCC), the role of HDV in contributing to this upregulated immune cell markers in this phase.
burden remains poorly understood. Conclusion: The intrahepatic miRNA profiles across different phases
Method: We used the standardized assay (LIAISON® XL Anti-HDV) to of CHB are generally stable, with limited changes significantly
detect HDV antibodies (anti-HDV) in 721 patients with stable chronic associated with immune cell infiltration, particularly in the IA phase.
hepatitis B (CHB) (n=175), hepatitis flare (HF) (158), liver cirrhosis (LC)
(181), and HCC (207). Socio-demographic and clinical parameters OP0215
were collected from patients’ records. Long-Term Clinical Outcomes in Hepatitis B Patients Achieving
Result: The median ages of patients with CHB, HF, LC, and HCC Clinical Cure with Interferon or Nucleos(t)ide Analog Therapy
were 47, 44, 56, and 61 years, respectively. Men comprised 52%,
Daqiong Zhou1, Jianru Jia2, Feng Zhao2, Jiangyu Liu1, Zichen Zhang1,
77.2%, 60.7%, and 82.1% of the patients in these groups. HF patients
Zhenhuan Cao1
exhibited significantly elevated ALT levels (336-1248 U/L) and HBV 1
Beijing Youan Hospital, 2Baoding People‘s Hospital
DNA concentrations (4.17-8.00 log IU/mL), mainly due to treatment
discontinuation (22.15%) or spontaneous HBV reactivation (70.25%). Background: Large-scale data on the long-term prognosis of
HBeAg positivity rates were 20% in CHB, 45% in HF, 21.3% in LC, and hepatitis B patients achieving clinical cure remain limited, particularly
26.7% in HCC. Anti-HDV antibodies were rare, detected in 0% (0/175) regarding potential differences in long-term clinical outcomes between
of CHB cases, 0.63% (1/158) of HF cases, 2.76% (5/181) of LC cases, patients cured with interferon versus nucleos(t)ide analog therapy. This
and 2.42% (5/207) of HCC cases. While HDV infection was observed study followed 886 clinically cured patients over an extended period to
more frequently in HF, LC, and HCC patients (2.01%) compared to investigate the incidence and risk factors of hepatocellular carcinoma
CHB patients (0%), the difference was not statistically significant. (HCC) and liver cirrhosis, focusing on analyzing the differences in
Conclusion: We observed an unexpectedly lower rate of HDV these outcomes based on the therapeutic approach used to achieve
prevalence in the South of Vietnam suggesting the heterogeneous clinical cure.
geographic distribution of HDV or variability in anti-HDV detection Method: This study analyzed HBsAg-positive patients who visited
methods. HDV infection might be associated with advanced liver Beijing You’an Hospital between February 2008 and January 2023.
disease but did not contribute to its high burden in Southern Vietnam. Patients included were those who completed antiviral therapy and met
Table and Figure:Figure 1.Patient Characteristics the following criteria: HBsAg <0.05 IU/mL, HBeAg negative, HBV DNA
Figure 2.Unexpected Low HDV Infection Rates <10 IU/mL, and no liver cirrhosis or hepatocellular carcinoma (HCC).
Comprehensive clinical data were collected, including demographic
information and liver and renal biochemical markers. The primary
OP0214
endpoint was liver cirrhosis. We estimated cumulative incidence using
The Profiles and Signatures of miRNAs in Different Phases of the Kaplan-Meier method and calculated hazard ratios with Firth bias-
Natural History of Chronic HBV Infection corrected Cox regression analysis.
QIONG WANG1, Fahong Li2, Jiming Zhang2, Mengji Lu1 Result: A total of 886 patients who achieved clinical cure through
1
Institute of Virology, University Hospital of Essen, University of interferon or nucleos(t)ide analog therapy were included in this study.
Duisburg-Essen, Essen, Germany, 2Department of Infectious The median age of the patients was 38 years (31–47), and 65% were
Diseases, Huashan Hospital, Fudan University, Shanghai, China male. Patients in the interferon treatment group were younger at the time
Background: Chronic Hepatitis B Virus (HBV) infection (CHB) can lead of therapy cessation (37 [30–46] vs. 44 [36–53], P<0.001) and had a
to severe liver diseases like cirrhosis and hepatocellular carcinoma. higher HBsAb positivity rate (50.9% vs. 37.9%, P=0.001). The median
MicroRNAs (miRNAs) are crucial post-transcriptional regulators follow-up duration after therapy cessation was 2.4 years (1.2–4.6
influencing HBV replication and host antiviral responses. The years). During follow-up, 3 patients (0.3%) developed hepatocellular
intrahepatic miRNA expression profiles remain poorly characterized carcinoma (HCC), and 6 patients (0.7%) developed liver cirrhosis.
across different phases of natural history of CHB. In this study, we The cumulative risk of cirrhosis at 5 and 10 years after therapy
addressed the question what the characteristics of hepatic miRNA cessation was 1.4% and 2.7%, respectively. Age was identified as an
expression profiles are and how hepatic miRNA expression profiles independent risk factor for the development of cirrhosis, particularly in
are associated with host immune responses. patients aged 50 years and older, who had a significantly higher risk of
Method: 43 patients with CHB were included and classified into four progression to cirrhosis (HR: 7.663, 95% CI: 1.699–43.969, P=0.009).
groups based on the phases of CHB: immune tolerance (IT), immune No significant differences in the risk of cirrhosis development were
active (IA), inactive carrier state (IC), and HBeAg-negative active observed between patients treated with interferon versus nucleos(t)
chronic hepatitis (ENH). Liver biopsies were collected from these ide analogs.
patients and subjected to miRNA microarray profiling and mRNA-seq Conclusion: The cumulative incidence of hepatocellular carcinoma
analysis. Differential miRNA expression analysis was conducted across (HCC) and liver cirrhosis following clinical cure of hepatitis B is very
the four groups. Immune cell infiltration was analyzed using the Cell- low and shows no significant correlation with the antiviral therapy used.
Type Identification by Estimating Relative Subsets of RNA Transcripts The only risk factor associated with the development of cirrhosis after
(CIBERSORT) algorithm. Additionally, 92 markers representing 12 clinical cure is the patient’s age at the time of cure, underscoring the
intrahepatic cell types were analyzed to assess their expression importance of achieving clinical cure at an earlier stage.
patterns across the four phases. Finally, correlation analyses were Table and Figure:Figure 1.Cumulative Incidence of Liver Cirrhosis in
Chronic Hepatitis B Patients with HBsAg Seroclearance. (A) Overall
Cohort; (B) Comparison Between Interferon and Nucleos(t)ide Analog -related HCC.
Groups. Method: Patients with CHB-related cirrhosis (with or without HCC)
Figure 2.Cumulative Risk of Liver Cirrhosis by Age. (A) Overall Cohort; admitted to Tianjin Second People’s Hospital from February 2017
(B) Interferon Group; (C) Nucleos(t)ide Analog Group. to April 2023 were enrolled. N-glycomics test was performed on all
patients, and N-glycomics related diagnostic models were established
using machine learning methods. The performance of the diagnostic
OP0216
model was evaluated by decision curve analysis (DCA) and calibration
Characteristics of HBV integration in pediatric patients with curve analysis. Cox regression analysis was used to establish a
chronic hepatitis B infection N-glycomics-related prognostic model for CHB-related HCC after
Na Wu1, Zhiwei Chen1, Yan Han1, Jing Tang1, Hong Ren1 radical resection. N-glycomics was detected several times in patients
1
the Second Affiliated Hospital of Chongqing Medical University with CHB related HCC after surgery to monitor the recurrence of the
Background: HBV integration plays a pivotal role in HBsAg production model.
and the development of hepatocellular carcinoma; however, the Result: A total of 226 patients with CHB-related cirrhosis were
characteristics of HBV integration in children with chronic hepatitis B included in the diagnostic model, including 70 patients with HCC and
(CHB) remain unclear. 156 patients without HCC. In the training set, the AUC of random forest
Method: Liver biopsies from 26 pediatric CHB patients at the Children’s model and support vector machine model were 1.000 (95%CI: 1.000-
Hospital of Chongqing Medical University and 28 adult CHB patients 1.000) and 0.949 (0.912-0.986), respectively. 0.967 (95%CI: 0.930-
at Chongqing University Three Gorges Hospital were collected 1.000) and 0.908 (0.840-0.976) in the test set, respectively. Subgroup
for HBV integration analysis. A probe-based capture strategy was analyses were also performed. In the prognostic model, 136 patients
employed to analyze HBV DNA in a subset of 18 pediatric and 28 adult with CHB-related HCC after radical treatment were included, and the
CHB patients. Additionally, spatial transcriptome sequencing was N-glycomics related model was established and verified in the training
conducted on samples from 8 pediatric CHB patients, while spatial set population. Multivariate Cox regression analysis model was an
transcriptome data from 3 adult CHB patients obtained from previous independent marker for predicting the risk of postoperative recurrence
studies served as the control group. of HCC (P < 0.05). During the follow-up period, it was found that the
Result: All patients were HBeAg positive and treatment-naïve. Among prognostic model was related to the clinical status of the patients,
the 26 CHB children, the median age was 8.0 years (IQR 6.0-10.8), which could detect the recurrence of HCC in all recurrent patients
with 50.0% being female (13/26). The mean levels of HBV DNA, (n=12), significantly better than AFP (n=7) and PIVKA-II (n=9), and
HBsAg, pgRNA, and HBcrAg were 7.85 log10 IU/mL, 4.52 log10 IU/ could detect recurrent lesions earlier than imaging.
mL, 7.09 log10 copies/mL, and 8.4 log10 U/mL, respectively. The Conclusion: Our findings explain the clinical application value of
median number of HBV DNA integration events in CHB children N-glycomics in CHB-related HCC. Relevant diagnostic and prognostic
was 28.00 (IQR 10.00-49.25), which did not significantly differ from models have been identified. Glycomics models can effectively
that in adults (median 43.50, IQR 23.00-55.50). The integration predict the occurrence and recurrence of HCC, which is conducive to
breakpoints of the two groups were similar in terms of chromosomal improving the efficiency of clinical decision-making and promoting the
location, gene structure, and viral gene distribution. However, the precision medicine of HCC.
sequencing depth at these breakpoints was significantly higher in the Table and Figure:Figure 1.Fig. 1: Outline of studies and study
adult group compared to the pediatric group. Spatial transcriptome participants. Overview of the study design. A total of 397 individuals
sequencing data revealed that most liver tissues from children lacked were included in the study, and their serum samples underwent
transcriptionally active HBV integration events. The spots containing targeted N-glycomics analysis.
integrated HBV were sparsely distributed, and the percentage of Figure 2.Fig. 2: Comparison of N-glycomics prognostic models and
spots with viral integration was comparable to that observed in the protein biomarkers for HCC surveillance. A-B. Patients P35 and P18
adult HC group (median 18.02% vs 9.45%). Interestingly, the abnormal in prognostic cohort 2 during the entire follow-up period after radical
ALT group showed significantly higher transcriptionally active HBV surgery. The horizontal axis represents the time of postoperative
integration events and scores for effector T cells, aDCs, Kupffer cells, follow-up, and the dots represent the glycomics model values tested,
Type I IFN response, and inflammation-promoting factors compared to with blue indicating no recurrence and red indicating recurrence (see
the normal ALT group. Within the abnormal ALT group, the scores for the Supplementary Material for follow-up maps of all patients). C-D.
aDCs, NK cells, monocytes, Kupffer cells, Type I IFN response, APC The categorization of imaging results, glycomics model status, serum
co-stimulation, inflammation-promoting factors, and CD4 Tcm were biomarker (AFP and PIVKA-II) results during each patient’s clinical
significantly higher in regions containing integrated HBV compared to course are shown in each color-code plot. Red indicated positive,
regions without HBV integration. This phenomenon was not observed yellow indicated equivocal, while blue indicated negative. E. The
in the normal ALT group. proportion of the time of HCC recurrence detected earlier by glycomics
Conclusion: HBV integration events were comparable between model, AFP and PIVKA-II than imaging, respectively.
children and adults at both the DNA and RNA levels, suggesting
that HBV integration occurs during the early stages of infection. OP0218
This highlights the importance of early treatment and intervention for
Effectiveness and Safety of Atezolizumab Combined with
children with CHB.
Lenvatinib as Conversion Therapy for Initially Unresectable
Hepatocellular Carcinoma: a Retrospective Study
OP0217 Yongwei Chen1, Jiye Chen1, Ying Luo1, Wenbo Ji1, Xin Xiang1, Qiang
Early screening, diagnosis and recurrence monitoring of Yu1
hepatocellular carcinoma in chronic hepatitis B patients based on 1
Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General
serum N-glycomics analysis: A cohort study Hospital
Xuemei Tao1, Liang Xu1, Yuqiang Mi1, Rui Su1, Wentao Kuai1 Background: The IMbrave150 study showed the efficacy of
1
The Second People‘s Hospital Affiliated to Tianjin Medical University atezolizumab combined with bevacizumab in patients with initially
Background: Hepatocellular carcinoma (HCC) is a heavy burden of unresectable hepatocellular carcinoma (iuHCC), with an objective
cancer worldwide, and hepatitis B virus (HBV) is the leading cause of response rate (ORR) of 30%. The REFLECT study demonstrated that
HCC in China. It is very important to develop early detection strategies lenvatinib achieved an ORR of up to 24.1% as a first-line treatment of
and precise postoperative interventions. However, the commonly used iuHCC. The IMbrave251 study is investigating the efficacy and safety
detection indicators are not sensitive and specific enough. The aim of of the combination of atezolizumab and lenvatinib as a second-line
this study is to develop and validate N-glycomics-based diagnostic treatment in advanced HCC patients who have previously received
and prognostic models for the detection of chronic hepatitis B (CHB) atezolizumab and bevacizumab. This study aims to evaluate the
effectiveness and safety of atezolizumab in combination with lenvatinib
as conversion therapy in patients with iuHCC. (15 /20:75%) and CT (6/8: 75% ) were more frequent in NASH; MaT
Method: This retrospective study enrolled patients with untreated HCC (4/8: 50%) was associated with HBV etiology and had highest
locally advanced or metastatic iuHCC who received a conversion AFP levels (>100 mg/L). MaT variant showed higher p53 expression
therapy of atezolizumab (1200 mg, q3w) and lenvatinib (8 mg or 12 (6/8: 75%), EPCAM positivity (8/8: 100%), and MSS status (7/8:
mg qd) between September 2020 and March 2024. The radiological 87.5%); while nuclear β-catenin expression was more predominant in
assessment was conducted after 3-4 cycles treatment to identify MiT (8/20: 40%) and CK19 positivity was most frequent in PG pattern
resectable patients, followed by the maintenance therapy until 1 year (2/2: 100%). Both CT (4/8: 50%) and MiT variant (9/20: 45%) had high
after the surgeries or intolerable toxicity. Clinical data were collected immune scores (IRS>5) compared to MaT (5/8: 62.5%, IRS: 1-4).
from medical records. The outcomes were objective response rate Genomic landscape of NC-HCC (2 Micro, 2 Macro, 1 PSG) had
(ORR), disease control rate (DCR) and conversion rate. Adverse germline TERT promoter mutation (rs2853669) in 80%; Somatic
events (AEs) were also collected. mutation in TFP12 promoter in all; TERT (C228T) mutation in one, a
Result: A total of 42 patients were analyzed using Response Evaluation novel ELF3 pathogenic mutation in MaT, and AZIN1 pathogenic variant
Criteria in Solid Tumors version 1.1 in the study. The mean age was in MiT.
58.17±10.81 years, with a predominance of male patients (n=35, Conclusion: NC-HCC had underlying NASH and HBV etiologies with
83.33%) and Barcelona Clinic Liver Cancer stage C (n=39, 92.86%). MaT variant more frequent in the HBV. Macrotrabecular dominant
17 (40.48%) patients were absent from portal vein tumor thrombus pattern in HCC was associated with aggressive clinic-phenotypic as
alongside 12 (28.57%) VP 1-2 and 13 (30.95%) VP 3-4. 11(26.2%) well as molecular characteristics. MiT (β Cat+) and CT -HCC (p53+)
patients had extrahepatic metastasis. 8, 19 and 6 patients achieved were hot tumors with exhausted immune markers (PD1, CTLA4). MaT
complete response, partial response and stable disease, respectively. variant (p53+, HBV) had stem cell phenotype and were cold tumors.
The ORR was 64.29% (n=27) and the DCR was 78.57% (n=33). Germline TERT promoter mutation and somatic TFPI2 promoter
Notably, the surgical conversion rate was 33.33% (n=14). However, mutation were hallmark of NC-HCC.
postoperative recurrences occurred in 2 patients at 3 and 8 months Table and Figure:Figure 1.Immunohistochemistry and Heatmap
after resection. AEs were reported in 40.48% (n=17) of patients. Most depiction of correlation of morphology with clinical and genetic
common AEs were hand-foot syndrome, loss of appetite, fatigue, characteristics in HCC occuring in non-cirrhotic liver
and hypertension. One death occurred due to cerebral hemorrhage.
A total of 3 patients discontinued treatment due to AEs. One patient
OP0220
experienced severe dermatological toxicity, and two others withdrew
treatment following severe gastric hemorrhage. AI-Enhanced Tumor Volume Assessment for Hepatocellular
Conclusion: The findings of this study underscored the potential Carcinoma Treatment Efficacy: A Superior Alternative to Diameter-
benefits of atezolizumab combined with lenvatinib as conversion Based Evaluation Criteria
therapy for patients with unresectable HCC. Further prospective Lei Zhang1, Shitao Jiang1, Dianzhe Tian1,2,3, Xinting Sang1, Xin Lu1,
studies are warranted to validate these results and explore long-term Yiyao Xu1, Haitao Zhao1
benefits. 1
Department of Liver Surgery, State Key Laboratory of Complex
Table and Figure:Figure 1.Table 1 Baselines characteristics of patients Severe and Rare Diseases, Peking, Union Medical College Hospital,
Figure 2.Table 2. Effectiveness Chinese Academy of Medical Sciences and Peking Union Medical,
2
Eight-year Medical Doctor Program, Chinese Academy of Medical
Sciences and Peking Union Medical College, 3School of Life
OP0219 Sciences, Tsinghua University
Hepatocellular carcinoma in non-cirrhotic hepatectomy Background: Hepatocellular carcinoma (HCC) is a significant
specimens: Morpho-molecular characterisation with prognostic contributor to global cancer mortality. There is an urgent need for
relevance improved methods to assess the efficacy of treatments for inoperable
KHUSHBOO AGRAWAL1, Gayatri Ramakrishna1, Archana Rastogi2, HCC. This study introduces an artificial intelligence (AI)-augmented
Shiv K Sarin1 approach that emphasizes tumor volume over the traditional diameter-
1
Institute of Liver & Biliary Sciences, 2Institute of Liver & Biliary focused RECIST 1.1 criteria.
Sciences, New Delhi, India Method: Our system utilizes automated lesion segmentation and a
Background: Non-cirrhotic hepatocellular carcinoma (NC-HCC) three-dimensional reconstruction algorithm, enabling real-time and
is characterised by unique pathophysiological characteristics and dynamic monitoring of HCC lesion volumes. This approach provides
represents 20% of HCC. Several recent studies of HCC in cirrhotic insights into how lesion growth patterns correlate with patient prognosis.
background have demonstrated that tissue characteristics and Result: Volume-centric assessments of growing lesions demonstrated
morphology based correlates of molecular subtypes provide valuable a statistically significant p-value of 0.039, indicating the superiority of
information for management and prognosis. However, studies on this method over traditional diameter-based measures. There was also
morpho-molecular characteristics of HCC in non-cirrhotic liver are a notable increase in efficiency in lesion labeling times; the system-
scarce. Present study aims to assess association of morphological assisted segmentation method required an average of 12.35 minutes
phenotypes with molecular traits of prognostic importance. (standard deviation: 2.80 minutes), compared to the manual methods,
Method: Paraffin-embedded tissue blocks (5 each) of NC-HCC which took an average of 37.42 minutes (standard deviation: 4.60
(N=40) resection specimens were assessed for four histologic minutes).
patterns. Immunohistochemistry- IRS scoring was performed for the Conclusion: Integrating AI into the assessment of HCC offers a
signaling pathways (p53, β-catenin), stem cell markers (EpCAM, transformative and streamlined strategy for monitoring treatment
CK19), Microsatellite marker panel (MSI), and immune markers (PD1, responses, potentially leading to improved clinical outcomes and
PDL1, CTLA4). For MSI: nuclear reactivity for MLH1, PMS2, MSH2, patient prognoses. As AI becomes more integrated into healthcare,
MSH6 were recorded to label MSI-stable or MSI high. A combined IRS its role in modern HCC treatment paradigms is increasingly crucial.
score of PD1 and CTLA4 > 5 was considered hot tumor; 1-4 as cold Future research should focus on refining and validating this AI-
tumors. DNA from cases with >80% dominance of single histologic enhanced system across various clinical settings and diverse patient
pattern was analyzed for targeted somatic mutation analysis by Next populations.
Generation Sequencing. In addition, clinic-pathologic correlation and Table and Figure:Figure 1.Main steps of the study
tumour heterogeneity with respect to the histologic patterns was also
assessed. OP0221
Result: NASH was most predominant etiology (23/40: 57.5%) followed
by HBV (9/40: 22.5%). Histological pattern dominance (>50%):
Microtrabecular (MiT) (20/40;50%), Pseudoglandular (PG) (2/40;5%),
Macrotrabecular (MaT) (8/40;20%), compact (CT) (8/40;20%).MiT
Alpha-fetoprotein combined with initial tumor shape irregularity Result: The results demonstrated that serum AKR1B10 levels were
in predicting the survival of patients with advanced hepatocellular significantly elevated in HCC patients (1,769.5 ± 171.0 pg/mL)
carcinoma treated with immune-checkpoint inhibitors: a multi- compared to healthy controls (80.6 ± 5.0 pg/mL) (p < 0.0001). In the
center cohort study ROC curve analysis, AKR1B10 achieved an area under the curve
Zhang Feng1, Wang Yong Shuai1, Wang Ji Zhou1 (AUC) of 0.896, with sensitivity at 72.7% and specificity at 95.7% at
1
The First Affiliated Hospital of University of Science and Technology the cutoff of 267.9 pg/mL, while AFP had the AUC of 0.816, sensitivity
of China of 65.1%, specificity of 88.9%. Postoperative monitoring revealed
a dramatic drop in serum AKR1B10 levels after surgery, returning
Background: Immune checkpoint inhibitors (ICIs) are playing a
to normal in 3-5 days. The follow-up assessment revealed that the
significant role in the treatment of hepatocellular carcinoma (HCC).
elevated serum AKR1B10 (≥267.9 pg/mL) associated with a short
This study aims to explore the prognostic value of alpha-fetoprotein
median survival time (25 vs. 34 months, p < 0.001). Univariate and
(AFP) combined with initial tumor shape irregularity in predicting the
multivariate COX regression analysis indicated that AKR1B10 is an
prognosis of patients treated with ICIs.
independent predictor of poor prognosis in HCC (HR 1.830, 95% CI
Method: In this retrospective, multi-center cohort study, 296 HCC
1.312-2.552, p < 0.001). AFP showed prognostic value at a cutoff of
patients received ICIs. Patients were randomly divided into the training
400 ng/mL. In cirrhotic tissues, IHC showed upregulated AKR1B10
set and the validation set in a 3:2 ratio. The training set was used
in a subgroup of hepatocytes accompanied with increased serum
to evaluate the impact of baseline factors on overall survival (OS)
AKR1B10.
using the Cox model and to develop an easily applicable ATSI (AFP
Conclusion: AKR1B10 is a novel serum marker of HCC and holds
and Tumor Shape Irregularity) score, which was then verified in the
the promise for postoperative monitoring and prognostic prediction.
validation set.
The expression of AKR1B10 in a subgroup of hepatocytes in cirrhotic
Result: The ATSI score was developed from two independent
tissues indicates its potential as a serum marker for screening and
prognostic risk actors: baseline AFP ≥ 400 ng/ml (HR 1.71, 95% CI 1.08
diagnosis of early HCC.
~ 2.73, P =0.023) and initial tumor shape irregularity (HR 1.66, 95% CI
Table and Figure:Figure 1.Figure 1. Serum AKR1B10 levels in HCC,
1.01 ~ 2.75, P =0.048). The median OS was not reached in patients
HC, BLT, CHB, LC and early HCC.
who met no criteria (95% CI 28.20 ~ NA), 25.80 months (95% CI 14.17
Figure 2.Figure 2. Prognostic values of serum AKR1B10 in HCC
~ NA) in patients who met one criterion, and 17.03 months (95% CI
patients. Serum AKR1B10 was used for survival analysis in HCC
11.73 ~ 23.83) in patients who met two criteria (P =0.001). The median
patients (A) stratified by TNM stage (B) or BCLC stage (C). Cumulative
progression-free survival (PFS) was 10.83 months (95% CI 9.27 ~
survival differences across groups were statistically evaluated using
14.33) for 0 points, 8.03 months (95% CI 6.77 ~ 10.57) for 1 point,
the Log-Rank test.
and 5.03 months (95% CI 3.83 ~ 9.67) for 2 points (P <0.001). The
validation set effectively verified these results (median OS, 37.43/
24.27/ 14.03 months for 0/ 1/ 2 points, P =0.028; median PFS, 13.93/ OP0223
8.30/ 4.90 months for 0/ 1/ 2 points, P <0.001). EXPLORING PREDICTORS OF RAPID PROGRESSION TO MAJOR
Conclusion: The easily applicable ATSI score based on the baseline ADVERSE LIVER OUTCOMES IN METABOLIC DYSFUNCTION-
AFP levels and initial tumor shape can effectively predict efficacy and ASSOCIATED STEATOTIC LIVER DISEASE
survival in HCC patients with ICIs. Jing Zhang1, Ying Shang2, Johan Vessby3, Kamal Kant Mangla4, Riku
Table and Figure:Figure 1.Figure 1. Flow chart of the study. Ota5, Marc Pedersen5, Mattias Ekstedt6, Hannes Hagström2,7
Figure 2.Figure 2. Irregular and regular tumor shape on cross-sectional 1
Department of Hepatology, Beijing Youan Hospital, Capital Medical
imaging.
University, 2Department of Medicine, Huddinge, Karolinska Institutet,
3
Department of Medical Sciences, Gastroenterology Research Group,
OP0222 Uppsala University, 4Market Access, Novo Nordisk Service Center
India Pvt Ltd., 5Novo Nordisk A/S, 6Department of Gastroenterology
AKR1B10 as a New Diagnostic and Prognostic Serum Marker for
and Hepatology and Department of Health, Medicine and Caring
Hepatocellular Carcinoma
Sciences, Linköping University, 7Division of Hepatology, Department
Xu Ye1, Qi Yu2, Xi Zeng2, Deliang Cao2 of Upper GI, Karolinska University Hospital
1
The Affiliated Cancer Hospital of Xiangya School of Medicine,
Background: Patients with metabolic dysfunction-associated steatotic
Central South University, Hunan Cancer Hospital, Changsha 410031,
liver disease (MASLD) may progress at different rates toward cirrhosis
China, 2Hunan Engineering Research Center for Early Diagnosis and
Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor and major adverse liver outcomes (MALO). We aimed to identify
Cellular & Molecular Pathology, Cancer Research Institute, Hengyang factors associated with rapid progression to MALO.
Medical School, University of South China, Hengyang, Hunan Method: We used data from 959 patients in Sweden with biopsy-
421001, China. proven MASLD. Over a median follow-up of 17 years, 103 patients
(10.7%) experienced MALO events and 52 (5.4%) had a repeat liver
Background: Aldo-keto reductase 1B10 (AKR1B10) is a secretory
biopsy. Rapid progressors were defined as patients experiencing
protein mediated via the functional domain of α-helix 10. AKR1B10 is
MALO events earlier than the median time to MALO, stratified by
highly expressed in hepatocellular carcinoma (HCC) and secreted into
baseline fibrosis stage. MALO events were compensated cirrhosis,
circulation blood. This study examined the serum levels of AKR1B10 in
decompensated cirrhosis, liver failure, hepatocellular carcinoma,
HCC patients and evaluated the diagnostic and prognostic values for
liver transplant, and death due to other liver diseases, identified from
HCC in comparison with the serum marker α-fetoprotein (AFP).
national registers and by chart review. Factors associated with rapid
Method: A multicenter study was conducted via enrolment of 1,244
progressors were analyzed with Cox regression models.
participants from three independent hospitals, including HCC patients,
Result: For the 103 patients who experienced MALO events, the
healthy controls, and individuals with benign liver tumors, chronic
median times to event, stratified by fibrosis stage, were 20.0 years in
hepatitis B, or liver cirrhosis. Serum AKR1B10 levels were measured
F0, 15.1 years in F1, 8.8 years in F2, 5.5 years in F3, and 3.0 years in
using time-resolved fluorescence assays, and receiver operating
F4. Compared with non-rapid progressors (n=51), rapid progressors
characteristic (ROC) curve analysis was performed to determine an
(n=52) were older at baseline (59 vs 55 years, p=0.050), had a higher
optimal diagnostic cutoff value and diagnostic performance. AFP data
prevalence of type 2 diabetes (T2D; 50% vs 29%, p=0.033), and
of the same cohort of subjects were collected for analysis in parallel.
had less severe hepatic steatosis (grade 3 steatosis, 15% vs 41%,
A sub-cohort of 273 surgical patients were followed up for 2 years
p=0.034 for overall comparison); no other major differences in patient
and their survival was analyzed using the Kaplan–Meier method and
characteristics were observed. Baseline T2D (hazard ratio [HR]: 3.90,
Cox regression. A cohort of 33 cirrhosis samples were subjected
95% CI 1.15–13.20; p=0.029) was associated with rapid progression,
to immunohistochemical (IHC) analysis to evaluated AKR1B10
but not when considering the development of T2D over time (HR: 2.52,
expression.
95% CI 0.75–8.42; p=0.134) (Table). Similar findings were observed in
patients with repeat liver biopsies, of whom 24 (46%) progressed by at correlation between CAP values and the severity of steatosis as
least one fibrosis stage. determined by MRI-PDFF. Normal patients (MRI-PDFF ≤ 5.1%)
Conclusion: No strong predictors were identified for rapid progression had CAP values of 259.8 dB/m. Mild steatosis (5.1% < MRI-PDFF ≤
of fibrosis at the time of MASLD diagnosis, apart from the presence 14.1%) had CAP values of 293.9 dB/m. Moderate steatosis (14.1% <
of T2D. Although T2D may affect incidence rates, the association MRI-PDFF ≤ 28%) had CAP values of 332.2 dB/m. Severe steatosis
was stronger at baseline, suggesting that duration of T2D may be a (MRI-PDFF > 28%) had CAP values of 344.9 dB/m. CAP’s diagnostic
stronger predictor of MALO events than the diagnosis itself. (Zhang efficacy, benchmarked against MRI-PDFF, was over 80% across all
Jing (Chinese speaker) is not part of the original author team and categories, with clear cutoff points at 286.5, 306.5 and 308.5 dB/m.
will only report on behalf of Ying Shang, Johan Vessby, Kamal Kant However, CAP’s ability to discern between moderate and severe
Mangla, Riku Ota, Marc Künkel Pedersen, Mattias Ekstedt, Hannes steatosis was less distinct, indicating a need for refinement in its
Hagström.) diagnostic application.
Table and Figure:Figure 1.Factors associated with rapid progression to In the analysis of 187 MASLD cases, the study found clear links
MALO in patients with MASLD between non-invasive markers and steatosis severity. Grade 0
steatosis patients (22 cases) had low qSteatosis (6.3%) and MRI-
PDFF (4.3%), with CAP at 270.5 dB/m and ALT at 21.8 U/L. Grade 1
OP0224
(82 cases) showed mild steatosis with higher qSteatosis (24.9%) and
Prevalence and Associated Risk Factors of Metabolic dysfunction- MRI-PDFF (7.9%), and increased CAP (286.5 dB/m) and ALT (37.2
associated fatty Liver Disease in the Elderly People with type 2 U/L). Grade 2 (54 cases) indicated moderate steatosis with qSteatosis
diabetes (44.1%) and MRI-PDFF (16.3%), and further rises in CAP (326.8 dB/m)
Jing Zhang1, Xiaodie Wei1, Yaning Li1, Lixia Qiu1 and ALT (56.6 U/L). Grade 3 (29 cases) presented severe steatosis
1
Capital Medical University Beijing Youan Hospital with the highest qSteatosis (64%) and MRI-PDFF (27.9%), and peak
Background: Metabolic dysfunction-associated fatty liver disease CAP (335.1 dB/m) and ALT (76.3 U/L).
(MASLD) and type 2 diabetes mellitus (T2DM) synergistically increases As steatosis progresses, qSteatosis, MRI-PDFF, CAP, and ALT values
the risk of morbidity and mortality. This study aimed to investigate the increase, making them reliable for liver fat assessment in MASLD.
prevalence of MASLD and advanced fibrosis in elderly T2DM patients QSteatosis and MRI-PDFF had over 94% diagnostic efficacy at all
in a community setting and to analyze the associated risk factors. levels. CAP was good at distinguishing mild from moderate steatosis
Method: The cross-sectional study recruited elderly T2DM patients but less so for moderate to severe, with cutoff values higher than
from two community centers in Beijing between 2023 and 2024. guidelines.
Liver steatosis was diagnosed by ultrasound. Demographic, clinical, Conclusion: Among the 1215 MASLD patients in Jilin Province,
and biochemical data were collected. Independent risk factors were qSteatosis and MRI-PDFF emerged as highly effective in determining
identified using multivariate logistic regression analysis. and differentiating steatosis. CAP values were relatively effective in
Result: Among 1,671 diabetic patients, the prevalence of MASLD and distinguishing mild to moderate steatosis, albeit with higher values
advanced fibrosis was 55.4% and 14.0%, respectively. Multivariate than the current guideline cutoffs.
regression analysis identified obesity (OR = 3.10 [2.41–3.99], P < Table and Figure:Figure 1.
0.001), ALT (OR = 1.03 [1.02–1.05], P < 0.001), platelet count (PLT; OR Figure 2.
= 1.01 [1.01–1.01], P = 0.031), and triglycerides (TG; OR = 1.85 [1.54–
2.22], P < 0.001) as independent risk factors for MASLD. Furthermore, OP0226
elevated ALT (OR = 1.04 [1.01–1.06], P = 0.002) and reduced PLT
Dietary change affects steatosis patterns in hepatocellular
(OR = 0.95 [0.94–0.96], P < 0.001) were identified as risk factors for
carcinoma with Metabolic Dysfunction-Associated Steatotic Liver
advanced fibrosis.
Disease analyzing by SHG/TPE microscopy imaging combined
Conclusion: The prevalence of MASLD and advanced fibrosis
with scRNA-seq
were highly among elderly T2DM patients. Comprehensive
management strategies emphasizing weight control, lipid regulation, Yuyun Song1, Ke Yin1, Xu Cong1, Ran Fei1, Baiyi Liu1, Zilong Wang1,
and liver enzyme optimization are essential for this population. Xin Ai1, Minjun Liao1, Yayun Ren2, Kutbuddin Akbary2, Qiang Yang3,
Table and Figure:Figure 1.Prevalence of MASLD and advanced Xiao Teng3, Huiying Rao1, Xiaoxiao Wang1, Feng Liu1
fibrosis in the elderly patients with type 2 diabetes. MASLD, Metabolic
1
Peking University People’s Hospital, Peking University Hepatology
dysfunction-associated fatty liver disease. Institute, Infectious Disease and Hepatology Center of Peking
Figure 2.Factors assocaited with MASLD and Advanced fibrosis on University People‘s Hospital,Beijing Key Laboratory of Hepatitis C and
Immunotherapy for Liver Diseases, Beijing International Cooperation
logistic regression.
Base for Science and Technology on NAFLD Diagnosis, Beijing
100044, People’s Republic of China, 2HistoIndex Pte Ltd, Singapore.,
OP0225 3
Hangzhou Choutu Technology Co., Ltd, Hangzhou.
Diagnostic Efficacy of Non-invasive Test Results for Liver Background: The incidence of hepatocellular carcinoma (HCC) with
Steatosis Determination in MASLD Patients Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Jia Xu1, Xiaoxue Zhu1, Hong Zhang1, Ruhan A1, Mengdi Lu1, Yanhua is increasing. Several animal models of MASLD-HCC have been
Ding1 developed to facilitate research in its pathogenesis; however, few
1
Phase I Clinical Trials Unit, First Hospital, the First Hospital of Jilin studies have focused on the changes of steatosis in the development
University, Jilin, 130021, China and regression of HCC. This research aims to analyze the characteristics
of steatosis in HCC and adjacent tissues in mice with MASLD-HCC
Background: Rising obesity is fueling a global increase in MASLD,
using Second Harmonic Generation/Two Photon Excitation (SHG/TPE)
emphasizing the need for accurate, non-invasive diagnostics. This
microscopy and Artificial Intelligence (AI) analysis.
study aims to evaluate the accuracy of various methods, including
Method: Two models (DEN-WDF and WD-CCl4) for MASLD derived
traditional pathology, qSteatosis, MRI-PDFF, and FibroScan, for
HCC were established. The dietary modification study was performed
measuring liver fat in MASLD patients in Jilin Province, China.
on mice in DEN-WDF at 38 weeks that were switched to normal diet for
Method: From September 2020 to April 2024, the study enrolled 1215
12 weeks, and mice in WD-CCl4 group at 28 weeks that were switched
MASLD patients from Jilin Province. 1215 MASLD patients in Jilin
to normal diet for 12 weeks. Seven normal mice were also included
underwent MRI-PDFF, FibroScan, and blood tests, with 1761 results.
in the analysis as controls. The characteristics of hepatic steatosis in
122 patients also had liver biopsies, with 187 results. Diagnostic
tumor nodules and adjacent non-tumor tissue were evaluated using
metrics like AUROC, cutoff values, sensitivity, and specificity were
SHG/TPE microscopy with AI analysis on their unstained liver biopsy
analyzed.
sections. The percentages of steatosis regions (comprising of macro-
Result: The analysis of 1761 MASLD cases revealed a significant
and microsteatosis) and associated morphological features were
quantified based on these SHG/TPE images. Also, single-cell RNA Conclusion: Ferroptosis, a mode of regulatory cell death driven
sequencing was performed on liver tissue. by accumulated lipid peroxidation in an ferrous iron manner, and is
Result: 100% of mice had tumors in WDF-CCl4 treated groups and considered to be an important factor in the pathogenesis .For example,
DEN-WDF treated groups at 28 weeks and 38 weeks, respectively. ferroptosis causes hepatic steatosis and abnormal accumulation of
Compared to the control group liver biopsy, steatosis area in both hepatic lipids at different stages of the disease, and accelerates the
tumor nodules and adjacent non-tumor tissue analyzed by AI showed progression from simple steatosis to nonalcoholic fatty liver disease by
an increasing trend for both WDF-CCl4 and DEN-WDF groups. After inducing an inflammatory response in the liver that a. Destroying normal
diet was switched to normal diet, overall steatosis in tumor nodules and liver cells, thereby aggravating liver injury b. Activating liver cell death,
adjacent non-tumor tissue along with macro- and microsteatosis ameliorating fibrosis, thereby improving the liver microenvironment
markedly decreased in both the MASLD-HCC mice groups (Fig 1). .This creates a mutually antagonistic situation.
scRNA seq analysis also revealed molecular alterations associated Table and Figure:Figure 1.The molecular mechanisms of ferroptosis
with lipid metabolism at 28 weeks during WDF CCl4 model were
partially reversed after diet change to normal diet (Fig 2).
OP0228
Conclusion: AI analysis was able to fully-quantify changes in overall
steatosis area, micro- and macrosteatosis, providing more opportunities PD-1 Inhibitor-Induced Ca2+ Overload Triggering T Cell Apoptosis
for its application in preclinical MASLD research. Consequently, The in MASLD-HCC
study also found that in the mouse model studied, dietary changes Hao Shen1, Tao Yuan1, Jun Li1
(by switching to a normal diet) may influence liver steatosis through 1
Department of Hepatobiliary and Pancreatic Surgery, Tenth People’s
regulation of genes associated with lipid metabolism, which in turn Hospital of Tongji University
plays a role in MASLD-HCC related resolution. Background: PD-1 monoclonal antibodies have poor efficacy in treating
Table and Figure:Figure 1.Figure 1A. Parameters in tumor nodules. NAFLD-HCC, but the exact mechanism remains controversial.Current
Figure 1B. Parameters on normal non-tumor adjacent tissue. research has only explored the effects ofPD-1/PD-L1monotherapy,
Figure 2.Figure 2A. ND (normal diet), HCC (WDF-CCl4 for 28w), HCC- how about the efficacy of the most widely used and effectivetreatment
PND (post-normal diet for 12 weeks) group differential expression for HCC-VEGFA/VEGFR2-targeted therapy combined withPD-1/PD-Ll
genes that are up-regulated in HCC and down-regulated in HCC-PND ICB in treating NAFLD-HCC?
(left), down-regulated in HCC and up-regulated in HCC-PND (right). Method: We developed an in vitro immune microenvironment system
Figure 2B. The two differential expression gene sets have statistically simulating a NAFLD background using liver/tumor organoids and
different lipid metabolity-related pathways in GO and KEGG. immune cells to overcome the limitations of in vivo models. Ca2+
homeostasis in immune cells was assessed using a layered strategy,
OP0227 including intracellular Ca2+ quantification using Fluo4 and Fura Red
probes, along with blocking key Ca2+ channels (e.g., ORAI1 and
Reconsider: Ferroptosis in NAFLD, molecular mechanisms of its
TRPC1). Channel function and quantity were further analyzed using
regulation, and therapeutic implications
patch-clamp and Western blotting. Additionally, molecular interactions
Zhen Yuan1, Junhua Ma2 influencing Ca2+ signaling were studied through molecular docking,
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia immunoprecipitation, and FRET, providing dynamic, spatially resolved
medical university , 2Department of Endocrinology, Gongli Hospital of evidence of molecular interactions. This system and strategy offer a
Shanghai Pudong New Area powerful tool to study immune responses in a NAFLD context with
Background: Non-alcoholic fatty liver disease is a chronic metabolic improved precision and efficiency.
liver disease,,Ferroptosis is one of the new ways to regulate cell Result: Animal models and organoid microenvironment systems have
death, which is characterized by excessive accumulation of iron and confirmedthat a-PD-1 monotherapy accelerates the progression of
cumulative lipid peroxidation, and plays an important role in a variety MASLD-HCCwhile a-VEGFA combined with a-PD-1 therapy exhibits
of pathological processes.Given the liver’s critical role in iron and lipid a tumor-promotingefect initially, followed by a tumor-suppressing
metabolism and its susceptibility to oxidative damage, many studies therapeutic effect.In the background of MASLD, a-PD-1 induced
have found varying degrees of association between ferroptosis a reduction of CD8’T cells.accelerating tumor progression, while
and various liver diseases. we summarize the complex molecular hepatocyte-specific VEGFA knockoutcan reverse this process.
mechanism and regulatory network system of ferroptosis, illustrate the KEGG analysis highlighted significant enrichment in the calcium
different roles of ferroptosis in different stages of NAFLD. In addition, signalingpathway, suggesting that calcium-induced apoptosis might
some potential effective therapies targeting ferroptosis are discussed contribute to thereduction in intratumoral CD8’T cell.VEGFA promotes
to point out new directions for the treatment calcium influx by altering the structure of the TRPC1 channel, leading
. to intracellular calcium accumulation.
Method: 1To summarize the molecular mechanism of ferroptosis Conclusion: In NAFLD, VEGFA upregulates TRPC1 channels,
in NAFLD by collecting more than 10 literatures on ferroptosis related increasing extracellular calcium influx and accumulating calcium in
NAFLD, summarize the research, and conduct a systematic review the endoplasmic reticulum. High fat also induces IP3R expression
analysis 2.To study the functions of key ferroptosis genes such as through SREBP, but without increased IP3, most IP3Rs remain closed,
FSP1 and GPX4 by bioinformatics and animal models.3To verify the preventing calcium overload. When PD-1 monoclonal antibody is
potential effectiveness of novel ferroptosis inhibitors (such as Ferl) and used, IP3 levels rise, opening IP3Rs and allowing a large Ca2+ influx,
physiological regulators (such as Tβ4 and Quercetin) in the treatment triggering calcium overload and T cell apoptosis. Sequential immune
of NAFLD by high-throughput screening and experimental validation therapy that blocks VEGFA followed by PD-1 monoclonal antibody can
Result: Through a literature review, we found that the normal reduce Ca2+ accumulation in the endoplasmic reticulum, reversing
metabolic pathways of iron in humans are crucial for key metabolic the negative effects of immunotherapy.
activities such as cell signaling, DNA replication. Excessive iron, Table and Figure:Figure 1.Research model diagram
especially Fe2+, can trigger the Fenton reaction and produce a large Figure 2.Key findings
of reactive oxygen species, which in turn leads to lipid peroxidation
and subsequent ferroptosis. Lipid peroxidation disrupts the integrity
OP0229
of the cell membrane by altering the fluidity and permeability of the
cell membrane, thereby affecting cell function. Lipid peroxidation is Neuropilin-1 promotes liver fibrosis by reprogramming M2
considered to be a key marker of ferroptosis, and its accumulation polarization of macrophages and crosstalk with hepatic stellate
can lead to membrane destruction and ferroptosis. Free iron and ROS cells
play central function.The main regulatory mechanisms of ferroptosis Chenxi Liu1, Yingchun Wang1, Miaomiao Tian1, Songbo Zhao1, Jianni
include: a) system Xc-/GSH/GPX4 axis; b) FSP1/CoQ axis; c) GCH1/ Qi1, Wanhua Ren1, Qiang Zhu1
BH4 axis 1
SHANDONG PROVINCIAL HOSPITAL
Background: We have confirmed that neuropilin-1 (NRP-1) plays a receiver operating characteristic (AUROC) curve for IPVD prediction
critical role in liver fibrosis. However, the effect of NRP-1 in modulating was 0.792 (95% confidence interval [CI]: 0.737 – 0.847), and for HPS
macrophage during liver fibrosis has not been documented. Herein, prediction, it was 0.891 (95% confidence interval [CI]: 0.848–0.934).
we aimed to characterize the roles of macrophage NRP-1 in the Conclusion: This study systematically compared the clinical
development of liver fibrosis. characteristics of patients with cirrhosis, IPVD, and HPS, and
Method: Macrophage-specific NRP-1-deficient (Lyz2Cre/Nrp-1loxP) constructed predictive models for IPVD and HPS based on clinical
mice were constructed to explore the function and mechanism of parameters and laboratory indicators. These models have shown
macrophage NRP-1 in CCl4-induced liver fibrosis mouse models. good predictive value for IPVD and HPS in cirrhotic patients. They can
Meanwhile, the role and mechanism of NRP-1 in regulating the assist clinicians in early prognosis assessment of cirrhotic patients,
profibrotic of M2-type macrophages were found in THP-1 cells in vitro. ultimately benefiting the patients.
Furthermore, effects and mechanisms of the activation of hepatic Table and Figure:Figure 1.Figure 1. Predictive model for IPVD
stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) combining clinical parameters and biomarkers.
induced by macrophages were investigated by real-time quantitative Figure 2.Figure 2. Predictive model for HPS combining clinical
PCR, western blotting, tube formation and CCK-8 assay. Finally, parameters and biomarkers.
macrophage NRP-1 expression analysis was conducted with human
liver samples obtained from patients with liver fibrosis and individuals OP0231
without fibrosis serving as controls.
Result: NRP-1 expression was significantly elevated in macrophages Safety and immunogenicity of hepatitis E vaccine in compensated
from fibrotic livers of mice. In Lyz2Cre/Nrp-1loxP mice, the progression liver cirrhosis with chronic hepatitis B
of liver fibrosis was effectively attenuated. Macrophage-specific NRP- Xuejiao Liao1, Dapeng Li1, Yingying Su2, Xinwu Wang3, Shuting Wu1,
1 deficiency macrophages exhibited suppressed M2 polarisation and Yanling Chen2, Zhiyu Li1, Qiyuan Tang1, Zhenghua Ma1, Xiaobin Wan1,
autophagy pathway activation in vivo and in vitro. Mechanistically, Jingke Dong1, Liping Zhang1, Changxiang Lai1, Haiyan Wang1, Qing
NRP-1 enhanced autophagy through p38, ERK, and JNK MAPK He1, Jun Zhang2, Fang Wang1, Zheng Zhang1
pathways to promote M2 macrophage polarization. Furthermore, 1
Shenzhen Third People’s Hospital; The Second Affiliated Hospital,
this study showed that NRP-1 promotes the production of pro-fibrotic School of Medicine, Southern University of Science and Technology.,
factors by M2 macrophages in the microenvironment leading to the
2
School of Public Health, Xiamen University, 3Shenzhen Luohu adult
activation of HSCs. Consistently, clinical investigations confirmed vaccination clinic, Shenzhen
that the upregulation of NRP-1 in M2 macrophages is consistent with Background: Hepatitis E virus (HEV) is a global health concern, causing
enhanced intrahepatic fibrosis in cirrhotic patients. acute hepatitis with severe consequences, especially in patients with
Conclusion: NRP-1 promoted M2 polarization by activating chronic liver disease. Despite the availability of a recombinant hepatitis
macrophage autophagy via the MAPK signaling pathway, and further E vaccine (Hecolin), its safety and immunogenicity in patients with pre-
exacerbated hepatic fibrosis by increasing the production of pro- existing liver cirrhosis remain uncertain. This study aimed to assess the
fibrotic cytokines in macrophages to promote the activation of HSCs safety and immunogenicity of Hecolin in compensated liver cirrhotic
and LSECs. individuals with chronic hepatitis B (CHB).
Table and Figure:Figure 1.Schematic diagram of NRP-1 mediated M2 Method: This study was conducted in Shenzhen City, China, from
polarization of macrophages via autophagy contributing to hepatic November 2019 to June 2022. Adult participants were stratified into
fibrosis through stellate cell and sinus endothelial cell activation. CHB untreated group, CHB treatment group, CHB cirrhosis group,
and control group based on their disease status. Safety assessments
OP0230 included adverse events and liver function tests. Serology samples
were collected before vaccination and post-vaccination to assess anti-
Comparison of Clinical Characteristics and Prediction of HEV IgG antibodies.
intrapulmonary vascular dilatation and Hepatopulmonary Result: A total of 162 eligible participants, including 43 with CHB
Syndrome in Patients with Cirrhosis cirrhosis, 50 with treated CHB, 50 with untreated CHB and 19 controls
Yingfei Wang1, Zhipeng Wu1, Fengwei Shi1, Hongbo Shi1, Yingmin were included in the study. A total of 157 (96.9%) participants received
Ma1 three doses of vaccine. Safety analysis showed a comparable
1
Beijing Institute of Hepatology, Beijing Youan Hospital, Capital incidence of adverse events across all groups and all reported
Medical University, Beijing, 100069, People’s Republic of China. adverse reactions were mild. There were no serious adverse events
Background: Cirrhotic patients with hepatopulmonary syndrome deemed causally related to vaccination. After vaccination, there was
(HPS) have a poorer prognosis. The pathogenesis of HPS remains no significant worsen observed in clinical liver function indexes. In
unclear, and predictive models are lacking. The purpose of the study the per-protocol set for immunogenicity, all of the vaccinated cirrhotic
is to compare the clinical characteristics of patients with cirrhosis, participants were seroconverted and 82.8% (24/29) of them had anti-
cirrhosis combined with intrapulmonary vascular dilatation (IPVD), and HEV IgG levels higher than 1.0 WU/ml at one month after the final dose
HPS, and to establish predictive models for IPVD and HPS. (median, 36 days).
Method: Cirrhotic patients were prospectively screened at a liver- Conclusion: This study suggested that Hecolin was safe and highly
specialized university teaching hospital. Clinical information and blood immunogenic in CHB individuals with compensated liver cirrhosis,
samples were collected, and biomarker levels in blood samples were supporting its use to prevent HEV superinfection in this high-risk
measured. The cirrhotic patients were divided into three groups: those population.
with pure cirrhosis, those with combined IPVD, and those with HPS Table and Figure:Figure 1.Proportion of participants who experienced
based on contrast-enhanced transthoracic echocardiography (CE- change of liver function: (A) One month after the first dose versus
TTE) results and the Pulmonary Alveolar-Arterial Oxygen Gradient Before; (B) One month after the third dose versus Before. (C) Before
(P(A-a) O2) values. Univariate logistic regression and LASSO the first dose and at one month after the third dose.
regression methods were utilized to identify risk factors for IPVD and Figure 2.Dynamic change of anti-HEV IgG during vaccination.
HPS, and nomograms were constructed to predict IPVD and HPS. Comparison of (A) seropositive rates and (B) geometric mean
Result: A total of 320 patients were analyzed, with 101 diagnosed with concentrations of IgG antibodies against hepatitis E among four
IPVD, of which 54 were diagnosed with HPS. There were statistically groups.
significant differences in clinical parameters among these three groups
of patients. Among the tested biomarkers, Sphingosine 1 Phosphate OP0232
(S1P), Angiopoietin-2, and Platelet-Derived Growth Factor BB (PDGF-
BB) were significantly associated with IPVD and HPS in cirrhotic
patients.Following LASSO logistic regression screening, prediction
models for IPVD and HPS were established. The area under the
DIABETES MELLITUS AS A KEY INDEPENDENT PREDICTOR CHB liver fibrosis patients into CClow and CChigh groups, with the
OF SIGNIFICANT LIVER FIBROSIS IN PATIENTS WITH CHRONIC latter predictive of fibrosis regression during AVT in two independent
HEPATITIS B AND CONCURRENT HEPATIC STEATOSIS cohorts. Single-cell RNA sequencing (scRNA-seq), deconvolution
Jie Li1, Fajuan Rui1, Xue Bai1, Wenjing Ni1, Liang Xu2, Youwen Tan3, analyses, and multiplex immunofluorescence identified a novel subset
Chuanwu Zhu4, QingLei Zeng5, Nan Geng1, Jiacheng Liu1, Chao Wu1, of CD8+ T cells —Tpro cells—as the main cellular source of the
Junping Shi6, Mindie Nguyen7 changes in CC gene expression. Tpro cells were characterized by
1
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, enhanced proliferative capacity, tissue-resident memory features, and
Nanjing University, 2Tianjin Second People‘s Hospital, 3The Third cytotoxic functions. Patients with more Tpro cells at baseline exhibited
Hospital of Zheniiang Affliated Jiangsu University, 4The Affiliated reduced low-level viremia and a greater likelihood of fibrosis regression
Infectious Diseases Hospital of Soochow University, 5The First during long-term AVT.
Affiliated Hospital of Zhengzhou University, 6The Affiliated Hospital Conclusion: This study revealed that fibrosis regressors among CHB
and Institute of Hepatology and Metabolic Disease of Hangzhou patients undergo rapid transcriptomic and functional reprogramming
Normal University, 7Stanford University School of Medicine following AVT. CHB liver fibrosis patients at baseline with higher
Background: Chronic hepatitis B (CHB) patients and hepatic steatosis expression of CC genes and greater infiltration of Tpro cells in the
(HS) frequently co-exist, but the association of diabetes mellitus (DM) liver are more likely to experience reversal after AVT. These findings
with fibrosis and inflammation is not well characterized. The study offer valuable insights for the screening, monitoring, and managing of
aims to investigate the relationship between DM and fibrosis and patients whose fibrosis does not regress in response to AVT.
inflammation in CHB patients concurrent with HS. Table and Figure:Figure 1.Figure 1. Characteristics of fibrosis
Method: We enrolled CHB patients with HS who underwent liver regressors.
biopsy from 8 medical centers from March 1996 to December 2022.
Univariable and multivariable logistic regression analyses were OP0234
conducted to the association of DM with moderate-to-severe steatosis, YB-1 contributes to liver fibrosis by mediating the capillarization
significant fibrosis and inflammation. Propensity score matching (PSM) of liver sinusoidal endothelial cells through the Twist1/EndMT
was performed to adjust the confounders between patients with and pathway
without DM.
Zhenyang Shen1, Xiaobo Cai1, Lungen Lu1
Result: A total of 1,019 CHB patients with HS (mean age 40.3±10.4
years, 75.4% male) were included in the study, with 107 (10.5%)
1
Department of Gastroenterology, Shanghai General Hospital,
Shanghai Jiao Tong University School of Medicine, Shanghai, China
having DM. Multivariable logistic regression analysis identified DM
as a significant risk factor for significant fibrosis in CHB patients with Background: Liver fibrosis is characterized by excessive deposition of
HS, both before and after propensity score matching (PSM) (before extracellular matrix, accompanied by capillarization of liver sinusoidal
PSM: OR 1.85, 95% CI: 1.19-2.88, p = 0.01; after PSM: OR 1.84, 95% endothelial cells (LSECs). Our previous studies have shown that Y-box
CI: 1.13-3.00, p = 0.01). Significant inflammation was associated binding protein-1 (YB-1) played a crucial role in liver fibrosis mediated
with HBeAg positivity and BMI, but not DM. After PSM, BMI was no by hepatic progenitor cells. In this study, we aimed to investigate the
longer associated with significant inflammation, while HBeAg positivity role of YB-1 in capillarization of LSECs and the progression of liver
remained a key risk factor. fibrosis.
Conclusion: In CHB patients with concurrent HS, DM is the primary risk Method: The expression of YB-1 was detected in LSECs of human
factor for significant fibrosis, while hepatic inflammation is associated cirrhosis and mouse liver fibrosis models. We generated YB-1flox/flox
with HBeAg positivity. Management should focus on controlling both Cdh5-Cre conditional knockout mice and induced chronic liver injury
DM and weight, along with aggressive antiviral therapy. using CCl4 and DDC in mice. Liver injury and fibrosis were assessed
Table and Figure:Figure 1.Multivariable logistic regression for fibrosis using H&E and Sirius Red staining, as well as immunohistochemical
stage > 2 and inflammation grade > 2 before and after propensity staining for F4/80 and α-SMA. Liver sinusoidal capillarization was
score matching. examined by scanning electron microscopy. Primary mouse LSECs
were isolated and cultured. YB-1 in LSECs was intervened using
small interfering RNA and overexpression plasmids. Transcriptional
OP0233
regulation between YB-1 and Twist1 probed by dual luciferase
Transcriptomic and Cellular Traits of Liver Fibrosis Regression in reporter gene assay. AAV9-Tie1-sh-Twist1 and AAV9-Tie1-OE-Twist1
Chronic Hepatitis B Patients on Treatment were constructed and intravenously injected into mice. The expression
Wei Chen1, Shuyan Chen1, Yameng Sun1, Wen Zhang1, Hong Li1, and distribution of genes related to capillarization and EndMT were
Wenyue Wu1, Xiaoning Wu1, Natalia Nieto2, Hong You1 detected by RT-PCR, immunofluorescence, and Western blot.
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical Capillarization and vascular formation ability of LSECs were assessed
University, Beijing 100050, China., 2Department of Pathology, by Matrigel tube formation assay and Transwell migration assay.
University of Illinois Chicago, Chicago, IL 60612, USA Result: YB-1 expression was increased in liver fibrotic tissues from
Background: Suppressing the hepatitis B virus (HBV) does not cirrhotic patients and CCl4-induced mice, and was especially
consistently lead to liver fibrosis remission, posing challenges for the significantly increased in LSECs. Deletion of YB-1 significantly
long-term management of patients undergoing antiviral treatment alleviated CCl4 and DDC-induced liver injury and fibrosis in mice.
(AVT). This study aimed to investigate the transcriptomic and cellular YB-1 deletion mitigated liver sinusoidal capillarization, validated in
characteristics associated with fibrosis regression in chronic hepatitis primary LSECs cultured in vitro. YB-1 deletion alleviated CCl4/DDC-
B (CHB) patients undergoing treatment. induced LSECs EndMT and liver fibrosis. Twist1 was identified as a key
Method: A total of 68 liver biopsies (LBx) from 42 CHB patients with regulator of EndMT mediated by YB-1, impacting the capillarization
liver fibrosis following AVT were included in the study. Bulk RNA of LSECs. Knockdown of Twist1 in LSECs reduced capillarization,
sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq) partially reversing the effects of YB-1 deletion. In liver fibrosis, EndMT
analysis, deconvolution analysis, and multiplex immunofluorescent in LSECs preceded capillarization, and the YB-1-Twist1 axis regulated
staining were performed. capillarization of LSECs. Validation through AAV9-mediated Twist1
Result: Transcriptomic analyses of three consecutive LBx, collected knockdown and overexpression confirmed Twist1’s role in LSECs
longitudinally at baseline, 78 weeks, and 260 weeks of AVT, revealed capillarization, partially reversing the effects of YB-1 deletion. YB-1
that regressors undergo rapid transcriptomic and functional inhibitor SU056 exhibited anti-inflammatory and anti-fibrotic effects
reprogramming throughout the course of treatment. At baseline, these in CCl4/DDC-induced mouse models of liver fibrosis, associated with
patients exhibited an activated immune environment, suppressed capillarization and EndMT in LSECs.
metabolic signaling, and elevated expression of cell cycle (CC) Conclusion: During chronic liver injury, there was an increase in YB-1
genes. Baseline CC gene expression levels enabled us to subclassify within LSECs. YB-1 binds to the Twist1 promoter region and promoted
its transcription, inducing EndMT in LSECs. This process further
facilitated liver sinusoidal capillarization, exacerbating the progression Research in South China (Southern Medical University),, 2Department
of liver fibrosis. of Infectious Diseases, Nanfang Hospital, Southern Medical
Table and Figure:Figure 1.Graphic Abstract University, Guangzhou, China; State Key Laboratory of Organ Failure
Figure 2.YB-1 contributes to liver fibrosis by mediating the capillarization Research; Key Laboratory of Infectious Diseases Research in South
of liver sinusoidal endothelial cells through the Twist1/EndMT pathway China (Southern Medical University)
Background: Liver abscesses, as pus-filled cavities in the liver, are
OP0235 life-threatening infections linked to biliary diseases, diabetes, and
immunocompromise. Despite diagnostic and therapeutic advances,
A novel model for identifying infections in patients with acute-
incidence has risen, especially in specific populations, increasing
on-chronic liver diseases (AoCLD) : a nationwide, multicentre,
healthcare burden. Management is challenging, often resulting
prospective cohort study
in prolonged hospitalization and complications like sepsis or liver
Hui Zhou1, Hai Li2,3,4, Guo Hong Deng5,4, Xian Bo Wang6,4, Xin failure. Understanding clinical features, epidemiology, etiologies, and
Zheng7,4, Jin Jun Chen8,4, Yan Huang1,4, Ruo Chan Chen1,4 prognostic markers is essential for improving outcomes and reducing
1
Department of Infectious Diseases, Hunan Key Laboratory of Viral costs.
Hepatitis, Xiangya Hospital, Central South University, Changsha, Method: A retrospective study of 138 liver abscess patients at Southern
China, 2Department of Gastroenterology, School of Medicine, Ren Hospital (2021-2023) included cases with fever, confirmed abscesses,
Ji Hospital, Shanghai Jiao Tong University, Shanghai, China, 3Key positive bacteriology, post-antibiotic improvement, and percutaneous/
Laboratory of Gastroenterology and Hepatology, Shanghai Institute surgical verification, excluding amoebic and tuberculous abscesses.
of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong Data collected covered demographics, comorbidities, lab results,
University), Shanghai, China, 4Chinese Chronic Liver Failure (CLIF)
and etiology via blood/abscess cultures and NGS. CRP, fibrinogen,
Consortium, Shanghai, China, 5Department of Infectious Diseases,
and lipids were monitored. Linear regression analyzed hospital stay
Southwest Hospital, Third Military Medical University (Army Medical
factors; Kaplan-Meier curves assessed clinical impacts. Analyses
University), Chongqing, China, 6Center of Integrative Medicine, Beijing
were conducted in RStudio (P < 0.05).
Ditan Hospital, Capital Medical University, Beijing, China, 7Department
of Infectious Diseases, Institute of Infection and Immunology, Tongji Result: Among these 138 patients with pyogenic liver abscess,
Medical College, Union Hospital, Huazhong University of Science the average age was 55.16 years, with males accounting for 72%.
and Technology, Wuhan, China, 8Hepatology Unit, Department of Diabetes was common (62%), followed by gallbladder and biliary tract
Infectious diseases, Nanfang Hospital, Southern Medical University, issues (35%). At admission, the most common symptoms were fever
Guangzhou, China (85%) and abdominal pain (47%). Most abscesses were located in the
right liver lobe (68%) and were multiloculated (55%).
Background: This study aims to establish an early and quick diagnostic
Etiological analysis identified Klebsiella pneumoniae as the main
model for infections in patients with AoCLD, assisting clinicians in early
pathogen, with high detection rates across various tests: blood culture
intervention, reducing antibiotic abuse and resistance, and lowering
(29%), abscess culture (89%), blood NGS (86%), and pus/tissue NGS
the occurrence of adverse clinical outcomes.
(95%). Polymicrobial infections were less common but still observed in
Method: This study analyzed 3,949 patients from two multicenter
pus/tissue NGS (26%).
prospective cohorts of the Chinese Acute-on-Chronic Liver Failure
Diabetic patients had a higher incidence of complications compared to
(CATCH-LIFE) study. The dataset was randomly divided into training
non-diabetic patients (63% vs. 45%, P=0.03), although there were no
and validation cohorts in a 7:3 ratio. In the training cohort, logistic
significant differences in specific complications. Inflammation-related
regression and least absolute shrinkage and selection operator
biochemical markers, fibrinogen, and lipid levels showed dynamic
regression analyses were used to identify predictive risk factors
changes, increasing during treatment and decreasing within one year
for infection in patients with AoCLD, and a simple nomogram was
after discharge (P<0.05).
established. Two different cutoff values were determined to stratify
Conclusion: In conclusion, our study of 138 liver abscess patients
infection risk in AoCLD patients.
revealed key findings: male predominance, mean age 55.2 years, high
Result: The developed diagnostic model included six variables:
diabetes comorbidity increasing complications, main symptoms of
cirrhosis, ascites, neutrophil count (N), and total bilirubin, C-reactive
fever and abdominal pain, Klebsiella pneumoniae as the predominant
protein (CRP), and blood sodium levels. The area under the receiver
pathogen affecting the right liver lobe, persistent lipid metabolism
operating characteristic curve for the training and validation cohorts
disorders post-treatment, and shorter hospital stays associated with
were 0.818 and 0.809, respectively, significantly higher than using
higher HDL levels indicating anti-inflammatory effects. Further research
CRP, procalcitonin, or N alone. Validation through calibration and
is needed on long-term effects and interventions.
decision curves demonstrated that our diagnostic model exhibits good
Table and Figure:Figure 1.table
calibration and clinical utility. Additionally, in the training cohort, we
Figure 2.figure
set a low cutoff value of 0.2028, resulting in a sensitivity of 80.15%,
specificity of 68.25%, and a negative predictive value of 92.7% for rule-
out diagnosis. A high cutoff value of 0.4045 resulting in a specificity of OP0237
90.1%, sensitivity of 52.7%, and a positive predictive value of 64% for Risk factors for poor 90-day outcomes of 816 acute hepatitis E
rule-in diagnosis. These cutoff values were validated in the validation inpatients in Shanghai, China: a retrospective analysis
cohort. XUE MEI1, YING ZOU1, YU LIU1, HUI ZHU1, HONGYING GUO1, WEI
Conclusion: We established a nomogram model to assist clinicians in YUAN1, ZHIGANG YI2, YUYI ZHANG1, ZHIPING QIAN1
diagnosing infections in patients with AoCLD, effectively improving the 1
Department of Liver Intensive Care Unit, Shanghai Public Health
accuracy and timeliness of diagnosis. Clinical Center, Fudan University, 2Research Unit, Shanghai Public
Table and Figure:Figure 1.Evaluation of Model Diagnostic Performance Health Clinical Center, Fudan University
and Calibration.
Background: The annual number of cases of hepatitis E infection in
China has recently increased, ranking first among the causes of acute
OP0236 viral hepatitis. It is necessary to understand the distribution and clinical
Underlying Conditions, Etiology, Clinical Characteristics, and characteristics of patients with severe illness of acute hepatitis E,
Long-term Prognosis in Patients with Pyogenic Liver Abscess A especially those with a poor 90-day prognosis.
Retrospective Cohort Study Method: We retrospectively analyzed the clinical data of 816 patients
Mingzhu Tao1, Xuwen Xu2 with hepatitis E between January 2019 and June 2024, including
1
Department of Infectious Diseases, Nanfang Hospital, Southern demographic data, clinical findings, laboratory examination results,
Medical University, Guangzhou, China; State Key Laboratory of and 90-day outcomes. We aimed to determine the risk factors and
Organ Failure Research; Key Laboratory of Infectious Diseases construct a simple and reliable model to predict a 90-day poor
prognosis.
Result: The 816 hospitalized patients with acute hepatitis E were faecium among Gram-positive organisms (9/32) and Escherichia
included in our study, aged 17 to 92 years, and 69.6% (568/816) coli (18/35) among Gram-negative organisms. Ascites was identified
were male. The high-incidence seasons for hepatitis E are winter to be an independent risk factor for bacterial infections across all
and spring. Among all the patients, chronic liver diseases, chronic ESLD phenotypes (SDC&UDC, Pre-ACLF, and ACLF). SBP shows
underlying diseases (non-liver disease), immunocompromised a moderate positive correlation with ascites (r=0.675; P<0.001),
patients, pregnant women, and the elderly accounted for 28.4% and pneumonia exhibits a moderate positive correlation with ACLF-
(232/816), 46.5% (380/816), 10.3% (84/816), (46/ 816), and 51.6% 2 (r=0.730; P=0.007). The 90-day mortality rates for patients with
(421/816), respectively. The median number of days of onset was bacterial infections at admission in the SDC&UDC (10.4% vs 5.0%;
10 and the median number of days of hospitalization was 17. The P=0.002) and ACLF-1 (38.6% vs 15.2%; P=0.028) groups were
incidence of severe disease (high jaundice, hepatic failure, and early significantly higher than those without infections. Fungal infections
liver failure) was 50.3% (411/816), the progression of organ failure were identified in 7 SDC&UDC patients (0.7%), 6 Pre-ACLF patients
within 28 days was 6.6% (54/816), and the 90-day adverse outcome (5.0%), and 5 ACLF patients (1.8%), with corresponding 90-day
was 4.5% (37/816). In the univariate analysis, chronic liver diseases, mortality rates of 14.3%, 66.7%, and 80%, respectively.
age, MELD score, NLR, PLT, CRP, ALB, blood sodium, lactate, Conclusion: Bacterial infections are highly prevalent in ESLD patients
ammonia, and renal failure were associated with a poor prognosis of and are associated with significant mortality. Early identification of
90 days. Multivariate analysis showed that chronic liver diseases (odds risk factors and prompt initiation of targeted antimicrobial therapy are
ratio [OR] 5.06), MELD score at admission (OR 1.396), and NLR (OR crucial for improving outcomes in this vulnerable patient population.
1.159) were independent risk factors for poor prognosis within 90 days
in patients with acute hepatitis E; a prognostic model was constructed OP0239
using these three predictive factors. The area under the curve for
this prediction model was 0.935 (P<0.000). Among patients with Hepatitis E virus X domain critically supports viral replication
acute hepatitis E complicated with cirrhosis, the disease severity rate through its intricate interdomain interaction with the RNA-
increased by 3.83 times (OR 3.827, 95% CI [1.987-7.371], P=0.000), dependent RNA polymerase
the risk of liver failure increased by 4.79 times (OR 4.789, 95% CI Xiao Hui Ding1, Dou Zeng1, Dan Liu1, Qiu Di Li1, Ji Kai Zhang1, Jia Qi
[2.724-8.419], P=0.000), and the risk of adverse outcomes at 90 days Xu1, Hong Bo Guo1, Wen Shi Wang1
increased by 6.04 times (OR 6.041, 95% CI [2.754-13.251], P=0.000). 1
Xuzhou Medical University
Conclusion: Combined chronic liver diseases, MELD score (>20 Background: Hepatitis E virus (HEV) is the most common cause of
points), and NLR (>3.2) were independent risk factors for a poor 90- acute viral hepatitis and has emerged as a worldwide health challenge.
day prognosis of patients with acute hepatitis E. Elderly and patients Currently, there are no proven medications specifically for treating HEV,
with chronic liver diseases(especially liver cirrhosis) need to be alert to besides supportive care and off-label use of ribavirin or pegylated
the worsening of acute hepatitis E. Chronic underlying diseases (non- interferon-alpha. It is imperative to perform in-depth exploration of HEV
liver disease), autoimmune diseases, pregnancy status, and AIDS do replication machinery to identify virus-specific antiviral targets and
not seem to increase the risk of disease aggravation and short-term develop highly potent and specific antivirals against HEV.
poor prognosis in patients with acute hepatitis E. Method: In this study, we conducted detailed research on the
Table and Figure:Figure 1.Clinical characteristics of all enrolled yet unexplored X domain in the HEV life cycle using site-directed
participants mutagenesis based on HEV reverse genetic systems. We
Figure 2.Epidemiological characteristics of hospitalized patients with systematically examined the interactions of the X domain with other
acute hepatitis E functional domains of ORF1 using co-immunoprecipitation, Swiss
Model, and GRAMM (Global Range Molecular Matching) server-based
OP0238 protein docking analysis.
Result: Our findings revealed that the X domain plays a critical role
Prevalence and Characteristics of Bacterial and Fungal Infections
in HEV replication machinery. Rather than its classical ADP-ribose
in End-Stage Liver Disease: A Multi-Center, Cross-Sectional Study
hydrolase activity, the X domain supports HEV replication through
from Central China
intricate interdomain interaction with the RNA-dependent RNA
Wei Liu1, Lanyue Huang1, Yuxin Niu1, Yunhui Liu1, Tingting Liu1, Qiuyu polymerase (RdRp) domain. The interaction between the X and RdRp
Cheng1, Tao Chen1, Qin Ning1 domains creates a “pocket-like” cavity (PC) on their interdomain
1
Tongji Hospital, Tongji Medical College and State Key Laboratory interface. Mutation of specific amino acid residue of the X domain
for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, significantly enhanced their interdomain interaction, but disrupted the
Huazhong University of Science and Technology PC and hindered HEV replication. This highlights the essential role
Background: Patients with end-stage liver disease (ESLD) are at an of the PC in HEV replication and suggests its potential as a specific
elevated risk of bacterial and fungal infections due to their weakened target for anti-HEV treatments. As a result, we screened over 10,000
immune systems and compromised liver function. This cross-sectional commercially available drugs using a PC-targeted virtual screening
study aims to assess the prevalence, types, and risk factors associated and further identified saikosaponin D and liriopesides B as potent anti-
with infections in ESLD patients, providing insights into the clinical HEV compounds.
characteristics and outcomes of these infections. Conclusion: In conclusion, this study emphasizes the crucial role of
Method: A cross-sectional study was conducted, encompassing the X domain in HEV replication machinery. Understanding the intricate
patients with stable decompensated cirrhosis (SDC), unstable interdomain interactions within the HEV ORF1 polyprotein not only
decompensated cirrhosis (UDC), acute on chronic liver failure enhances our knowledge of HEV replication but also helps to identify
(ACLF) and Pre-ACLF from multiple tertiary hospitals in central new virus-specific targets for treating HEV.
China, spanning from January 2012 to December 2023. Data on
demographics, laboratory results, complications, types of infections,
OP0240
identified pathogens, organ failure incidences and mortality were
collected at admission and subsequently analyzed. Mechanisms Underlying Cyclosporine A-Mediated Promotion of
Result: Out of the 1328 patients enrolled, 935 were classified as HEV Replication
SDC&UDC, 121 as Pre-ACLF, and 272 as ACLF, with bacterial Disen Yuan1, Fengmin Lu1, Lin Wang1
infection rates of 38.3%, 52.1%, and 62.1% at admission, respectively. 1
Department of Microbiology and Infectious Disease Centre, School
Within the ACLF group, bacterial infection rates for ACLF-1, ACLF- of Basic Medical Sciences, Peking University Health Science Center,
2, and ACLF-3 were 57.5%, 64.8%, and 56.3%, respectively. In Beijing, China
each ESLD phenotype, spontaneous bacterial peritonitis (SBP) and Background: Hepatitis E virus (HEV) infection is an acute, self-limiting
pneumonia were the most common types of bacterial infections. Out disease. In recent years, HEV has been reported with chronic infection
of 67 identified bacteria, the most prevalent strains were Enterococcus
in organ transplant recipients who are treated with immunosuppressive grouping analysis.Select specific subpopulations of B lymphocytes
agents. In our preliminary study using a rabbit model of HEV infection, for further segmentation, and perform differential gene analysis. The
we investigated the effects of various immunosuppressive agents key differentially expressed genes of B cell subsets in two groups of
on HEV chronicity and found that calcineurin inhibitors, such as children were obtained through differential gene analysis et al. The
cyclosporine A (CsA), were more effective at inducing HEV chronicity differentiation characteristics of B lymphocyte subsets in two groups
compared to other immunosuppressive drugs. Previous studies of pediatric patients were determined through pseudo temporal
also demonstrated that CsA and its intracellular binding proteins, analysis.Differential genes that play a key role in the differentiation of B
cyclophilin A (CypA) and cyclophilin B (CypB), can directly influence lymphocytes have also been identified.
HEV replication in vitro. In this study, we further explored the molecular Result: Analysis of differentially expressed genes in B lymphocyte
mechanisms by which CsA and its derivative, NIM811, directly affect subsets showed that the top significantly upregulated differentially
HEV replication. expressed genes in B lymphocyte subsets in the HBsAg loss group
Method: HEV transfection, infection, and replicon models are used, were interferon stimulating genes (IFITM1, IFI6, IFI27, MX1, ISG15)
combined with Co-immunoprecipitation (Co-IP) and Western blotting, and antigen of presentation related genes (HLA-DRB1, HLA-
to investigate the interactions between CsA, NIM811, cyclophilin DRA1, HLA-DPA1, and IGLV2-14). Functional enrichment analysis
and HEV. Additionally, RNA pull-down assays coupled with mass also showed that significantly upregulated differentially expressed
spectrometry are used to identify potential host factors that may affect genes in B lymphocyte subsets were significantly enriched in virus
HEV RNA stability. related diseases and antigen processing and presentation signaling
Result: First, we validated in HEV transfection, infection, and pathways.The expression scores of Janus kinase (JAK) and JAK-STAT
replicon models that both CsA and NIM811 promote HEV replication signaling pathways in B lymphocyte subsets of HBsAg loss group were
in a concentration-dependent manner. Through knockdown or significantly higher than those in non HBsAg loss group.Upregulation
overexpression of CypA and CypB, we found that CypA and CypB of the key differentially expressed gene IFITM1 contributes to the
directly inhibit HEV replication. Subsequent Co-IP and Western blot differentiation and development of immature B cells and plasma cells
analyses indicated that viral proteins did not directly interact with in the HBsAg loss group.
CypA and CypB, and neither CsA nor NIM811 affected the expression Conclusion: The B lymphocyte subpopulation is closely related to
of viral proteins. Therefore, we hypothesize that this effect may be the activation of interferon related signaling pathways.Upregulation of
related to HEV RNA. The results of RNA pull-down assays and RNA IFITM1 gene contributes to HBsAg loss.
turnover showed that CypA and CypB did not bind to HEV RNA.
However, treatment with CsA and NIM811 or knockdown of CypA and
OP0242
CypB enhanced the stability of HEV RNA.To further identify potential
molecules influencing HEV RNA stability, we conducted RNA pull- HBsAg Declines and Immune Responses Following a Single Dose
down assays combined with mass spectrometry, and revealed two of VRON-0200: Interim Results from a Phase1B Study for HBV
factors—RACK1 and SAMHD1. Both of them showed reduced binding Functional Cure in Chronic HBV-Infected Patients
to HEV RNA after CsA and NIM811 treatment. Previous studies have Grace LH Wong1, Sue L Currie2, Andrew D Luber2, Tien Huey Lim3,
reported that SAMHD1 has RNase domain. By RNA turnover with Marie E Bonhomme4, Edward J Gane5
overexpressing or knocking down SAMHD1, we demonstrated that 1
Medical Data Analytics Centre, Department of Medicine and
SAMHD1 can bind and degrade HEV RNA. Therapeutics, and Institute of Digestive Disease, The Chinese
Conclusion: Our study demonstrates that CsA and its derivative University of Hong Kong, 2Virion Therapeutics LLC, 3Middlemore
NIM811 promote HEV replication by inhibiting the expression of their Hospital, 4Laboratory Services, Vaccine Sciences Department, PPD,
intracellular targets, CypA and CypB. Furthermore, we elucidate that Part of Thermo Fisher Scientific, 5New Zealand Liver Transplant Unit,
this process is associated with increased HEV RNA stability. SAMHD1 Auckland City Hospital, University of Auckland
plays a critical role in RNA degradation. Reduced binding of SAMHD1 Background: VRON-0200 is a therapeutic vaccine for CHB functional
to HEV RNA following drug treatment significantly enhances RNA cure that expresses a genetically encoded checkpoint modifier, fused
stability, thereby promoting HEV replication. with HBV core and pol (but not S) antigens, designed to enhance,
broaden, and prolong CD8+ T cell responses. Here we report
OP0241 immunogenicity, HBsAg and safety data, in pts who received a single
dose of VRON-0200.
Transcriptional features of peripheral blood B lymphocyte in Method: CHB, virally suppressed pts, with HBsAg <500IU/mL,
children with chronic hepatitis B (CHB) treated with the Interferon are randomized to receive i.m. VRON-0200 1x1010vp(Cohort 1)
α or 5x1010vp(Cohort 2). Cohort 1a/2a receives a prime, followed by
Yanwei Zhong1, Min Zhang1, Ce Shi1, Xiuchang Zhang2, Wenling a boost, on D91; Cohort 1b/2b receives prime only. Assessments
Wang1, Jia Liu1, Yanbo Yu1, Fang Chu1 include safety, virologic, and immunologic. T cell frequencies are
1
the Fifth Medical Center of chinesePLA General Hospital, 2Hebei assessed pre-tx (2 timepts) and at multiple post-tx timepts, via IFN-Ɣ
North University ELISpot(LLOD<30 SFU/1e6) from PBMCs using 3 peptide pools (core
Background: An effective HBV specific immune response is crucial & pol representing the vaccine peptides, and S antigen peptides). Pts
for the clearance of HBV. Recent study has shown that HBsAg loss is who received a VRON-0200 dose with D28 PBMC results are included.
closely related to functional improvement of B cell subsets.Conducting Responders are defined as 2 consecutive core plus pol ELISpot values
research on B cells is not only beneficial for finding new effective at D28 above the avg of the 2 pre-tx values. A one-sided paired t-test
therapeutic targets, but also helps to discover early immune predictive assessed if there was a difference between pre-tx and D28 values.
indicators and further improve clinical cure rates.However,the D91 response was defined as pts with a core plus pol ELISpot value
transcriptional differences and related molecular mechanisms of above the avg of the 2 pre-tx values. HBsAg levels were assessed in
B cells between individuals with and without HBsAg loss Still unclear. pts with results at their most recent study visit; > D91 for prime only
This study aims to explore the changes in the transcriptional profiles of and Day 91 for prime-boost pts (censored before boost, and after
peripheral blood B lymphocyte subpopulations in children with chronic prime only); declines > 0.4 log10IU/mL are reported.
hepatitis B (CHB) treated with the Interferon α (IFNα). Result: 25 pts are included(13-Cohort 1;12-Cohort 2): 80% male, 85%
Method: A total of 100 children with chronic hepatitis B (CHB)treated Asian, mean age, 46yrs, median BL HBsAg, 179 IU/mL(range:10–623).
with interferon α were enrolled in this study. Among of them,peripheral As of October 18, 2024, there are 4,952 pt safety days, with 29 AEs(24-
blood B lymphocyte of 8 children were detected by single-cell Grade 1;5-Grade 2) in 14 pts reported, and no SAEs, and no study
sequencing. According to the outcome of antiviral treatment at week discontinuations. 22 and 16 pts have ELISpot results through D28
48, single-cell sequencing samples were divided into HBsAg loss and 91, respectively. At BL, the majority of pts(n=12;55%) had both
group and non HBsAg loss group.Then,the sequencing results of B pre-tx ELISpot values to both core and pol below LLOD. At D28,
lymphocyte were subjected to dimensionality reduction, clustering, and responses to core and pol significantly increased 2.2-fold (p=0.02);
among responders(n=7;32%), responses were 5.5-fold higher(Fig). safety of combination therapy with a PD-1 inhibitor in patients who did
10/16(63%) pts were determined to have a D91 response, with 5 of 6 not achieve HBsAg loss after 48 weeks of pegylated interferon α (Peg-
(83%) D28 immunologic responders having a D91 response. Of the 22 IFNα) treatment.
pts with HBsAg evaluable at their last study visit, 4 pts had a -2.3, -0.6, Method: This non-randomized controlled trial was conducted
-0.4 and -0.4log10IU/mL declines(Fig). at the Second Affiliated Hospital of Xi’an Jiaotong University
Conclusion: A single i.m. dose of VRON-0200 was safe, well tolerated, (ChiCTR2400091948) from April 2024. Inclusion criteria were HBsAg <
and significantly increased T cell responses. At D91, HBsAg declines 1500 IU/ml, HBeAg negative, HBV DNA < 5 IU/ml, and ongoing Peg-
occurred in several pts even though VRON-0200 does not target S. IFNα therapy for >48 weeks without achieving HBsAg loss. Exclusion
VRON-0200 is a potential simple, easy-to administer, IFN-sparing criteria included contraindications to interferon or PD-1 inhibitors,
immunotherapy, alone or in combination, for HBV functional cure. liver cirrhosis, and hepatocellular carcinoma. Patients were allocated
Immunologic, clinical, and safety analyses are ongoing. into two groups based on treatment preference: the treatment group
Table and Figure:Figure 1. received combination therapy with a PD-1 inhibitor (Sintilimab, 1 mg/
kg every 12 weeks) and Peg-IFNα (180 μg/week), while the control
group continued Peg-IFNα monotherapy. All patients also received
OP0243
nucleos(t)ide analog therapy. Follow-up assessments were conducted
Prevalence of metabolic dysfunction-associated steatotic liver at weeks 4, 12, and 24 to evaluate HBsAg clearance and the safety of
disease and its impact on liver fibrosis in patients with chronic PD-1 inhibitor combined with Peg-IFNα. The primary endpoint was the
hepatitis B HBsAg clearance rate at week 24.
Jian Wang1,2, Shaoqiu Zhang1, Ye Xiong3, Tao Fan3, Li Zhu4, Xiaomin Result: A total of 64 patients completed a 24-week follow-up.
Yan1, Jie Li1,2,3, Chuanwu Zhu4, Rui Huang1,2,3, Chao Wu1,2,3 Treatment group included 33 patients (42.79 ± 10.13 years) with
1
Department of Infectious Diseases, Nanjing Drum Tower Hospital, a baseline median HBsAg level of 0.95 (0.28–1.92) log10 IU/ml,
Affiliated Hospital of Medical School, Nanjing University, Nanjing, and the control group included 31 patients (45.78 ± 10.51 years)
Jiangsu, China, 2Institute of Viruses and Infectious Diseases, Nanjing with a baseline median HBsAg level of 0.25 (-0.06–1.89) log10 IU/
University, Nanjing, Jiangsu, China, 3Department of Infectious ml. At week 12, HBsAg loss was observed in 4 patients (12.1%) in the
Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing treatment group and 3 patients (9.7%) in the control group. By week
University of Chinese Medicine, Nanjing, Jiangsu, China, 4Department 24, the treatment group showed a HBsAg clearance rate of 30.3%
of Infectious Diseases, The Affiliated Infectious Diseases Hospital of (10 patients) compared to 9.7% (3 patients) in the control group (P =
Soochow University, Suzhou, Jiangsu, China 0.047). HBsAg levels in the treatment group decreased significantly
Background: It is unclear for the prevalence and clinical characteristics from baseline at week 24 [0.03 (-1.60–1.75) log10 IU/ml vs. 0.95
of metabolic dysfunction-associated steatotic liver disease (MASLD) (0.28–1.92) log10 IU/ml, P = 0.023], while the control group showed
in patients with chronic hepatitis B (CHB). We aimed to investigate no significant change [0.49 (-0.29–1.86) log10 IU/ml vs. 0.25 (-0.06–
the virological and metabolic features, as well as liver fibrosis in CHB 1.89) log10 IU/ml, P = 0.970]. AEs were more frequent in the treatment
patients with MASLD. group, with higher incidences of oral mucositis (12.1% vs. 0.0%, P =
Method: This study included 3,114 untreated patients with CHB. 0.045) and fever (36.4% vs. 16.1%, P = 0.043). However, other AEs
Transient elastography was used to evaluate the presence of liver showed no statistically significant differences. No severe AEs were
steatosis and fibrosis. reported in either group.
Result: The prevalence of MASLD was 38.9% in patients with CHB. Conclusion: This study shows PD-1 inhibitor combined with Peg-IFNα
Patients with MASLD had lower HBsAg (3.0 Log10IU/mL vs. 3.2 therapy has good safety and achieves an approximately 30% HBsAg
Log10IU/mL, P<0.001) and HBV DNA (2.8 Log10IU/mL vs. 3.2 clearance rate at 24 weeks in CHB patients who failed prior interferon
Log10IU/mL, P<0.001) levels but had higher liver stiffness values (6.9 therapy, which is more effective than extended Peg-IFNα monotherapy.
kPa vs. 6.1 kPa, P<0.001) and higher proportions of significant fibrosis Adding PD-1 inhibitors to Peg-IFNα therapy may represent a potential
(34.9% vs. 22.2%, P<0.001) and cirrhosis (15.0% vs. 7.6%, P<0.001) strategy to enhance the clinical cure rate for CHB.
than those without MASLD. Concomitant MASLD was an independent Table and Figure:Figure 1.Overall study design diagram
risk factors of significant fibrosis (OR 1.772, P<0.001) and cirrhosis Figure 2.Changes in HBsAg levels between treatment group and
(OR 2.304, P<0.001). After propensity score matching for background control group
characteristics, MASLD was also independently associated with
more severe liver fibrosis. MASLD patients with ≥3 cardiometabolic
OP0245
factors (OR 1.592, P=0.007) and 2 cardiometabolic factors (OR
1.363, P=0.048) had higher risk of significant fibrosis compared to 1 The Impact of Hepatitis D Virus Infection on the Clinical Efficacy
cardiometabolic factor. Similar higher risk of significant fibrosis was of Antiretroviral Therapy in Patients Coinfected with Hepatitis B
also found in patients with severe steatosis (OR 3.399, P<0.001) and and HIV
moderate steatosis (OR 1.536, P=0.006) compared to those with mild Yaozu He1, Weiyin Lin1, Xianglong Lan1, Fei Gu1, Weiping Cai1,
steatosis. Xiaoping Tang1, Linghua Li1
Conclusion: About 40% of CHB patients had MASLD. Concurrent 1
Guangzhou Eighth People’s Hospital, Guangzhou Medical University
MASLD was associated with low HBV replication, but higher risk of Background: Previous studies have shown that co-infection with
significant liver fibrosis and cirrhosis, especially for those with more hepatitis D virus (HDV) in patients with hepatitis B virus (HBV) infection
cardiometabolic factors and more severe steatosis. can significantly accelerate the progression of liver fibrosis, leading
to an increased mortality rate due to end-stage liver disease. While
OP0244 the prevalence of HDV infection in HIV/HBV coinfected individuals has
been studied internationally, there is limited research in China. The
Evaluation of the Efficacy and Safety of a PD-1 Inhibitor Combined
impact of HDV infection on the clinical efficacy of antiretroviral therapy
with Peg-IFNα in Patients with Chronic Hepatitis B: A Prospective
(ART) and liver disease progression in HIV/HBV coinfected patients
Nonrandomized Controlled Trial
remains unclear.
Chenrui Liu1, Yaping Li1, Liu Yang1, Guoe Gou1, Dandan Feng1, Mei
Method: This study is a retrospective cohort study that included
Li1, Meng Zhang1, Shuangsuo Dang1
patients with HBV/HIV-1 co-infection who visited the Eighth Affiliated
1
Department of Infectious Diseases, Second Affiliated Hospital of Hospital of Guangzhou Medical University between January 1, 2009,
Xi‘an Jiaotong University and August 31, 2022. Baseline plasma and longitudinal samples
Background: HBsAg clearance treatment options are limited for were collected for the determination of HDV antibody IgM and IgG.
patients who fail interferon therapy. Programmed death receptor 1 For patients who tested positive for HDV antibodies, HDV RNA was
(PD-1) inhibitors have the potential to become therapeutic agents for measured. The study aimed to analyze the impact of HDV infection on
CHB. This non-randomized controlled trial evaluates the efficacy and the clinical efficacy of ART in HBV/HIV-1 co-infected patients.
Result: A total of 1,130 patients with HBV/HIV-1 co-infection were fibrosis at baseline, and 0.72 for delicate fibrosis regression in all 103
included in the study, among which 84 patients (7.4%) tested positive patients. The proteins within these pathways were primarily involved
for HDV antibodies. Of the HDV antibody-positive patients, 19 in extracellular matrix receptor interaction and blood coagulation,
(22.6%) were HDV RNA-positive. The HIV transmission routes in the showing significant interactions with each other.
HDV/HBV/HIV-1 triple-infected patients were heterosexual (44.0%), Conclusion: We developed a novel strategy using serum proteomics
intravenous drug use (28.6%), and homosexual transmission (22.6%). based on ssGSEA to differentiate liver fibrosis regression in on-
Approximately 41.7% of the HDV/HBV/HIV-1 co-infected patients also treatment CHB patients. Further external validations are necessary in
had HCV co-infection. The median duration of ART in the 1,130 HBV/ future studies to confirm these findings.
HIV-1 co-infected patients was 7.35 years (IQR: 4.50, 10.02). After
adjusting for the impact of HCV co-infection, there were no significant OP0247
differences in HIV and HBV virological suppression rates, HBsAg
clearance rates, or CD4+ count increases between the HDV/HBV/HIV- Circular RNA-based neoantigen vaccine for hepatocellular
1 triple-infected patients and the HBV/HIV-1 co-infected patients after carcinoma immunotherapy
ART (P values all > 0.05). The incidence rates of new liver cirrhosis Bixing Zhao1
and hepatocellular carcinoma were also similar between the two 1
Mengchao Hepatobiliary Hospital of Fujian Medical University
groups (P values all > 0.05). In HDV RNA-positive patients, the HDV Background: mRNA vaccines are regarded as a highly promising
RNA levels rapidly declined after ART, and by the last follow-up, 92.8% avenue for next-generation cancer therapy. Nevertheless, the intricacy
had become negative. There were no significant differences in the of production, inherent instability, and low expression persistence of
aforementioned indicators between HDV RNA-positive and HDV RNA- linear mRNA significantly restrict their extensive utilization. Circular
negative patients (P values all > 0.05). RNAs (circRNAs) offer a novel solution to these limitations due to their
Conclusion: Approximately 7.4% of HBV/HIV-1 co-infected patients efficient protein expression ability, which can be rapidly generated in
also had co-infection with HDV. HDV infection did not affect the efficacy vitro without the need for extra modifications.
of HIV and HBV treatments in these patients. HDV RNA rapidly became Method: circRNA-based neoantigen vaccine system has been
undetectable after ART, which may be related to the suppression of developed through the rational design of a self-splicing Group I intron
HBV virus. and auxiliary sequences that facilitate splicing, enabling the in vitro
cyclization of linear RNA molecules. The immunogenicity of the circular
OP0246 RNA neoantigen vaccine was validated in vitro by simulating the
antigen presentation process within the body and inducing tumor cell
A Novel Strategy for Identifying Liver Fibrosis Regression in On-
killing. Lipid nanoparticle (LNP)-formulated circRNA was characterized
Treatment Chronic Hepatitis B Patients Using Serum Proteomics
in terms of particle size, charge distribution, encapsulation efficiency,
Mengyang Zhang1, Wen Zhang1, Wenyue Wu1, Hong Li2, Shuyan and targeting specificity to assess the physicochemical properties
Chen3, Xiaoning Wu1, Jialing Zhou2, Bingqiong Wang1, Tongtong of LNP-circRNA. The in vivo antitumor efficacy of the neoantigen
Meng1, Yameng Sun1, Wei Chen1, Hong You1 vaccine was evaluated using orthotopic and subcutaneous HCC
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical mouse models. The induction of antitumor immune responses by the
University, Beijing Key Laboratory of Translational, Medicine on Liver circRNA neoantigen vaccine was assessed by analyzing immune
Cirrhosis, National Clinical Research Center of Digestive Diseases, markers in HCC mice. Additionally, a preventive mouse model of
Beijing, China., 2Beijing Friendship Hospital, Capital Medical HCC was constructed to evaluate the induction of specific immune
University, 3Liver Research Center, Beijing Friendship Hospital, Capital
memory by the circRNA neoantigen vaccine. The biosafety of the
Medical University, Beijing, China
circRNA neoantigen vaccine was characterized by monitoring serum
Background: Exploring serological biomarkers for assessing liver biochemistry and tissue pathology in mice after treatment.
fibrosis regression in on-treatment chronic hepatitis B (CHB) patients Result: Here, we present a novel neoantigen vaccine based on
is critical. However, mass-spectrometric-based proteomics faces circRNA that induces a potent antitumor immune response by
challenges in robustly detecting and validating low-abundance expressing hepatocellular carcinoma-specific tumor neoantigens. By
proteins, limiting its clinical translation. Novel strategies are required cyclizing linearRNA molecules, we were able to enhance the stability
to address these issues. of RNA vaccines and form highly stable circRNA molecules
Method: We analyzed paired serum samples from CHB patients who with the capacity for sustained protein expression. We confirmed
received 78 weeks of antiviral treatment. Serum proteomic profiles were that neoantigenencoded circRNA can promote dendritic cell (DC)
generated through four-dimensional data-independent acquisition- activation and enhance DC-induced T-cell activation in vitro, thereby
based proteomics. The normalized enrichment scores (NES) for enhancing T-cell killing of tumor cells. Encapsulating neoantigen-
Reactome pathways were calculated through single-sample gene set encoded circRNA within lipid nanoparticles for in vivo expression
enrichment analysis (ssGSEA), based on the protein abundance ratios has enabled the creation of a novel circRNA vaccine platform. This
(post-treatment/pre-treatment). Key pathways associated with liver platform demonstrates superior tumor treatment and prevention in
fibrosis regression were validated in an additional nine CHB patients various murine tumor models, eliciting a robust T-cell immune response.
using paired serum proteomics and liver transcriptomics. A support Conclusion: Our circRNA neoantigen vaccine offers new options and
vector machine (SVM) was used to develop a diagnostic model for application prospects for neoantigen immunotherapy in solid tumors.
fibrosis regression.
Result: After data cleaning, 298 qualified proteins were included in the
analysis of paired proteomics from 103 CHB patients. Serum proteins
OP0248
alone may not fully reflect histological fibrosis regression. We further Gut microbial metabolite butyrate suppresses hepatocellular
examined serum proteomic changes in 18 of 67 patients with baseline carcinoma growth via CXCL11-dependent enhancement of natural
Ishak fibrosis stage ≥3, showing either at least a 2-stage decrease killer cell infiltration
in the Ishak fibrosis score or a 1-stage decrease with Progression to Menghan Zhang1,2, Huichun Xing2
Regression in the P-I-R classification. Using NES from ssGSEA, we 1
Department of Gastroenterology, Shandong Provincial Hospital
identified and validated seven Reactome pathways in nine additional Affiliated to Shandong First Medical University, Jinan, 250021, China.
patients with paired serum proteomics and liver transcriptomics. , 2Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital
Notably, three Reactome pathways—Integrin cell surface interaction, Medical University, 8 Jingshundong Street, Chaoyang District, Beijing
Disease of hemostasis, and Defects of the contact activation system 100015, China.
(CAS) and kallikrein/kinin system (KKS)—demonstrated stable change Background: Gut microbiota-derived butyrate, plays a pivotal role
profiles associated with fibrosis regression. An SVM-based diagnostic in ameliorating hepatocellular carcinoma (HCC) in a mouse model.
model incorporating the NES of these pathways achieved an AUC Nevertheless, the underlying mechanisms still remain largely unknown.
of 0.76 for obvious fibrosis regression in patients with advanced
Method: Using gas chromatography-mass spectrometry (GC-MS), we with a PC diet may offer a novel therapeutic strategy to enhance anti-
assessed the association between plasma SCFAs and the prognosis tumor immunity in HCC.
of HCC patients. Tumor-infiltrating immune cells were comprehensively Table and Figure:Figure 1.Abstract
profiled using flow cytometry analysis. The interactions between
butyrate and NK cells have been explored through in vitro OP0250
investigations, including migration assays, cytotoxic degranulation
assays, and coculture assays. These findings was confirmed through Bridging the Gap Between Imaging and Molecular Characterization:
in vivo neutralization assays. To elucidate the underlying molecular Current Understanding of Radiomics and Radiogenomics in
pathways of butyrate at a more detailed level, RNA-seq, ChIP-seq, Hepatocellular Carcinoma
and ATAC-seq have been conducted. Liying Ren1, Dongbo Chen1, Shaoping She1, Yao Yang1, Xue Zhang1,
Result: Our investigation has uncovered a positive correlation between Hongsong Chen1
elevated levels of butyrate and a more favorable prognosis in patients 1
Peking University People’s Hospital, Peking University Hepatology
with HCC. Notably, butyrate impedes tumor progression by augmenting Institute, Infectious Disease and Hepatology Center of Peking
NK cell infiltration into the tumor tissue. Mechanistically, by stimulating University People’s Hospital, Beijing Key Laboratory of Hepatitis
the release of cytokines, butyrate encouraged the production of the C and Immunotherapy for Liver Diseases, Beijing International
chemokine CXCL11 and facilitated the infiltration of NK cells into tumor Cooperation Base for Science and Technology on NAFLD Diagnosis
tissue. Accordingly, GSEA analysis of hepatic tumor cell lines showed Background: Hepatocellular carcinoma (HCC) is the sixth most
that the chemokine signaling pathway and NK cell mediated cytotoxicity common malignancy worldwide and the third leading cause of cancer-
pathway were up-regulated after butyrate stimulation. Finally, after related deaths. While imaging plays a crucial role in the screening,
exposure to butyrate, epigenomic and transcriptomic analyses of diagnosis, and monitoring of HCC, the potential mechanism regarding
differentially expressed genes in hepatic tumor cells elucidated the phenotypes or molecular subtyping remains underexplored.
induction of de novo chromatin accessibility and enhancer remodeling, Method: This article provides an up-to-date summary of the
orchestrated by signal-responsive transcription factors STATs. advancements in radiomics and radiogenomics throughout the HCC
Conclusion: In summary, our research findings demonstrate that care continuum, focusing on the clinical applications, advantages, and
butyrate enhances the expression of CXCL11 through chromatin limitations of current techniques.
remodeling, thereby facilitating infiltration of NK cells and exerting anti- Result: Radiomics significantly expands the selection of features
tumor effect. available by extracting quantitative features from imaging data.
Table and Figure:Figure 1.Abstract Radiogenomics bridges the gap between imaging and genetic/
transcriptomic information by associating imaging features with critical
OP0249 genes and pathways, thereby providing biological annotations to
these features. However, there are challenges in interpreting these
4-hydroxyhippuric acid drives SLC22A4+ neutrophils to deteriorate connections, assessing their universality, and considering the diversity
CD8+T cell anti-tumor immunity in hepatocellular carcinoma in HCC etiology and genetic information across different populations.
Hanyi Zeng1, Haijian Wang1, Jiaping Yu1, Lishan Ye1, Siyu Wei1, Li Conclusion: Radiomics and radiogenomics offer new perspectives for
Liu2,1 precision treatment in HCC. Future research should aim to overcome
1
Department of Infectious Diseases, Nanfang Hospital, Southern current challenges to improve the prognosis of HCC patients and
Medical University, 2Department of health management , Nanfang leverage imaging information for patient benefit.
Hospital, Southern Medical University Table and Figure:Figure 1.Timeline of advancements in medical
Background: Exhausted CD8+ T cells (Tex) with imaging and sequencing technologies.
reduced function frequently occur in the hepatocellular Figure 2.Applications of Medical Image Optimization, Radiomics, and
carcinoma (HCC) microenvironment and are implicated in tumor Radiogenomics.
immune escape, exploration of the determinants inducing Tex potentially
provides effective strategies for HCC treatment. The gut microbiota OP0251
influences HCC progression, but the specific metabolites driving
Efficacy and Safety of the Combination of Envafolimab and
CD8+ T cell exhaustion are unclear.
Lenvatinib in Unresectable Hepatocellular Carcinoma: a Single-
Method: Fecal matter, blood plasma, and tumor tissues from HCC
arm, Multicentre, Exploratory Phase II Clinical Study
patients were collected to identify gut microbiota metabolites associated
with CD8+ T cell exhaustion. Single-cell RNA sequencing (scRNA- Yunwei Han1, Yi Jiang1
seq), bulk RNA sequencing (RNA-seq), metagenomic sequencing
1
Southwest Medical University
and computational modeling were utilized to elucidate the intricate Background: Currently, therapeutic combinations of immune
mechanisms underlying CD8+ T cell exhaustion and to explore the gut checkpoint inhibitors (ICIs) with anti-angiogenic agents have shown
microbiota involved in metabolite biosynthesis. promising outcomes and have the potential to establish a new
Result: 4-hydroxyhippuric acid (4-HA), a gut microbiota standard of care. The efficacy and safety of the first-line combination of
metabolite, is elevated in HCC patients and induces Tex and poor envafolimab (an ICI) and lenvatinib (an anti-tumor angiogenesis drug)
prognosis. Mechanistically, 4-HA drives neutrophils to elicit CD8+ T for the treatment of patients with inoperable hepatocellular carcinoma
cell exhaustion. 4-HA is primarily transported into neutrophils via (HCC) has not been demonstrated.
the SLC22A4 translocator to regulate the expression of PIM1, Method: Unresectable HCC patients with an Eastern Cooperative
promoting an immunosuppressive phenotype. PIM1 and SLC22A4 Oncology Group (ECOG) physical status score ≤ 1 and a Child-Pugh
are predominantly expressed in neutrophils and exhibit increased score ≤ 7 who had not received systemic therapy were included in
expression in HCC tumor tissues. In addition, 4-HA is mainly produced this single-arm, exploratory, multicentre phase II clinical study. All
by acsA in gut microbiota Pseudomonas fluorescens (P.fluorescens), patients were required to meet the criteria of being at least 18 years
which is increased in HCC patients. Furthermore, procyanidin (PC) of age, having no history of other malignancies, and existing at least
effectively disrupts the cell membranes of P.fluorescens and diminishes one measurable lesion. The patients were treated with envafolimab
its gut levels. By administering a PC diet, the levels of 4-HA in mice are (150 mg, QW, subcutaneous) in combination with lenvatinib (12 mg
significantly downregulated, which corresponds with the restoration of for patients weighing over 60 kg, 8 mg for patients weighing under 60
CD8+ T cell functionality and a reduction in tumor volumes. kg). The co-primary endpoint of the study was overall survival (OS),
Conclusion: Our study reveals a gut microbiota-metabolite-immune while surrogate endpoints included progression-free survival (PFS),
axis in HCC, where 4-HA produced by P. fluorescens drives CD8+ T objective response rate (ORR), disease control rate (DCR), and safety.
cell exhaustion. And we uncover a novel subset of immunosuppressive Result: Between March 2022 and April 2023, 36 patients were
neutrophils expressing SLC22A4 and PIM1 in response to 4-HA, which enrolled, 30 of whom were treated with envafolimab plus lenvatinib.
possess the capacity to induce Tex. Furthermore, modulating this axis
At data cutoff, the median follow-up duration was 20 months (95% Both UCB and PB-NK cells from patients under 55 years showed
CI 18.9–21.1). Among the 30 assessable patients (patients treated superior in vivo activity compared to PB-NK cells from older patients.
according to the trial protocol), the median overall survival (mOS) and MWA combined with NK cell therapy for primary HCC is safe and
median progression-free survival (mPFS) for the therapy comprising reduces early recurrence. UCB and allogeneic PB-NK cells strongly
envafolimab alongside lenvatinib were 18.5 months (95% CI 13.2– activate lymphocytes compared to autologous NK cells.
23.8) and 9.4 months (95% CI 1.6–15.6), respectively. The ORR and Table and Figure:Figure 1.Gate strategy for flow cytometric detection
the DCR (evaluated according to mRECIST) reached 40% and 80%, of NK cells and lymphocyte subsets, along with the NK cell reinfusion
respectively. In terms of safety, 23 patients (76.7%) experienced at flowchart.
least one treatment-related adverse event (TRAE), of which the most Figure 2.Results from in vitro, in vivo experiments and clinical trials.
common was elevated aspartate aminotransferase (AST, 23.3%).
Furthermore, grade 3 and higher TRAEs occurred in 30%.
OP0253
Conclusion: This study demonstrates that envafolimab in combination
with lenvatinib exhibits favourable anti-cancer activity and a Danggui Shaoyao Powder Ameliorates Metabolic Dysfunction-
manageable safety profile for the first-line treatment of patients with Associated Steatohepatitis by Suppressing Hepatic Macrophage
unresectable HCC. NLRP3 inflammasome
Table and Figure:Figure 1.Kaplan–Meier plots: Overall survival in Qian Huang1,2,3, Sheng Lyu1,2,3, Xin Xin1,2,3, Ziming An1,2,3, QinMei
all patients receiving envafolimab in combination with lenvatinib. Sun4,2,3, Siting Gao1,2,3, YiYang Hu1,2,3, XiaoJun Gou5, Qin Feng1,2,3
Kaplan–Meier plots: Progression-free survival in all patients receiving 1
Key Laboratory of Hepatorenal Diseases (Ministry of Education),
envafolimab in combination with lenvatinib. 2
Shuguang Hospital Affiliated to Shanghai University of Traditional
Figure 2. Waterfall plot: optimal percentage change in target lesion Chinese Medicine/Institute of Liver Disease, 3Central Laboratory,
size (dotted line at 20% for boundaries of progressive disease and Shuguang Hospital Affiliated to Shanghai University of Chinese
dotted line at –30% for boundaries of partial response) Traditional Medicine, 4Shanghai University of Traditional Chinese
Medicine, 5 Central Laboratory, Baoshan District Hospital of Integrated
Traditional Chinese and Western Medicine of Shanghai
OP0252
Background: Metabolic dysfunction-associated steatohepatitis
A Pilot Study of Adoptive Natural Killer Cell Therapy Combined (MASH) is the most prevalent liver disease worldwide. The abnormal
with Microwave Ablation for Hepatocellular Carcinoma activation of the NOD-like receptor thermal protein domain associated
Qian Cai1,2, Jie Yu1 protein 3 (NLRP3) inflammasome plays a vital role in the pathogenesis
1
Department of Interventional Ultrasound, Fifth Medical Center of of MASH. Danggui Shaoyao powder (DGSY) has been proven to exhibit
Chinese PLA General Hospital, 2Clinical Medical School, Qinghai good anti-inflammatory properties, yet its potential pharmacological
University, Qinghai, China mechanisms remain inadequately explored. This study aims to
Background: Recent advances in equipment have made microwave elucidate the molecular mechanisms underlying the therapeutic
ablation (MWA) a promising method for hepatocellular carcinoma effects of DGSY on MASH.
(HCC). However, due to HCC’s heterogeneity, recurrence and Method: A MASH model was established in mice using a high-fat
metastasis are frequent. Immune cell exhaustion limits the efficacy of high-carbohydrate (HFHC) diet, followed by treatment with DGSY
ablation alone, making long-term tumor control difficult. Natural killer to assess its efficacy. RNA-sequencing (RNA-seq) analysis was
(NK) cells, innate immune cells capable of directly killing malignant performed to identify the key pathways involved and explored its
cells, show promise in immunotherapy. underlying mechanisms in vivo. To investigate the activation of the
Method: In vitro and in vivo comparisons were made regarding the NLRP3 inflammasome, bone marrow-derived macrophages (BMDMs)
purity, phenotype, and tumor-killing ability of NK cells derived from were stimulated with LPS+ATP and treated with DGSY to explore its
PB and UCB. The relationship between NK cell purity and age was mechanisms in vitro. Additionally, NLRP3 knockdown was achieved
analyzed in the PB-NK group. A clinical trial was conducted from using AAV-9 to validate the functional targets of DGSY. UHPLC-Q-
November 2018 to February 2023, enrolling HCC patients who Orbitrap HRMS analysis was employed to identify the primary active
underwent MWA followed by NK cell reinfusion from Autologous components of DGSY.
Peripheral Blood NK Cells (Auto-PBNK), Allogeneic Peripheral Blood Result: DGSY was effective in treating the HFHC diet-induced
NK Cells (Allo-PBNK), or Umbilical Cord Blood NK Cells (UCB-NK). MASH mouse model, significantly alleviating liver inflammation.
Result: In vitro, 26 UCB-NK and 38 PB-NK cases (median age: 45 Mechanistically, transcriptome sequencing indicated that the
years) were analyzed. UCB-NK cells had a significantly higher median therapeutic efficacy of DGSY was closely associated with the NLRP3
purity (80%, IQR: 55%-91%) than PB-NK cells (48%, IQR: 20%-67%). signaling pathway. DGSY inhibited NLRP3 protein expression in hepatic
A decline in purity was seen in PB-NK cells after age 55 (P<0.001). macrophages and significantly suppressed caspase-1 activation and
UCB-NK cells expressed higher levels of NKp30 (P<0.001), CD158a IL-1β release. These findings were consistent in LPS+ATP-treated
(P=0.002), and TIGIT (P=0.03), while PB-NK cells expressed more BMDMs. Furthermore, NLRP3 knockdown/knockout in vivo and in
CD16 (P=0.01) and NKG2A (P=0.03). UCB-NK cells secreted more vitro alleviated MASH but counteracted the therapeutic effects of
interferon-γ (P<0.001). Tumor killing assays showed no significant DGSY, abolishing its effect on inhibitting caspase-1 activity and IL-1β
differences between UCB-NK and PB-NK cells in K562 or HepG2 cells release. In addition, UHPLC-Q-Orbitrap HRMS analysis identified four
(P>0.05). Both NK cell groups from patients under 55 years showed main active ingredients in DGSY, with atractenolide III and gallic acid
similar in vivo activity, and both were superior to PB-NK cells from notably inhibiting NLRP3 protein expression.
patients ≥55 years (P<0.01). Conclusion: DGSY exerts a protective effect against MASH by
A clinical trial included 21 HCC patients (median age: 66 years). inhibiting hepatic macrophage NLRP3 inflammasome, suppressing
No reinfusion-related adverse events occurred. MWA combined with caspase-1 activity, and reducing IL-1β release. This study provides a
NK cell therapy showed better early recurrence (ER) rate in primary robust theoretical basis for the future clinical application of DGSY in the
HCC than in recurrent HCC (P=0.009). In the primary HCC group, NK treatment of MASH.
cell therapy significantly reduced ER compared to MWA alone (23.1% Table and Figure:Figure 1.Abstract figure of DGSY powder ameliorates
vs. 44.9%, P<0.001). After 3 and 6 infusions, lymphocyte and T cell MASH
counts increased significantly in the Allo-PBNK and UCB-NK groups Figure 2.DGSY powder ameliorates MASH by inhibiting NLRP3-
(P<0.05). UCB-NK cells increased NK cells (P=0.045), and Allo-PBNK mediated caspase-1 activation in hepatic macrophages and
cells increased NKT cells (P=0.028). Both UCB-NK and Allo-PBNK decreasing the secretion of IL-1β inflammatory factors
cells increased helper T cells (Th) and cytotoxic T cells (CTL) (P<0.05).
Conclusion: In vitro, UCB-NK and PB-NK cells showed similar tumor- OP0254
killing effects but differed in receptor expression profiles. UCB-NK cells
secrete more interferon-γ, which may enhance lymphocyte activation.
The relationship between liver iron assessed by magnetic severity
resonance imaging R2* and MASLD: a cross-sectional and Figure 2.Figure 2. R2* is independently associated with MASLD;
longitudinal study reduction in R2*reflects improvement in MASLD
Ru-Tao Lin1, Sui-Dan Chen2, Sheng Lyu1, Zhong-Wei Chen3, Zi-Ming
An1, Cai-Yun Wen3, Jie Yuan4, Li-You Lian5, Qiao-Hong Liu1, Qi-Han OP0255
Zhu6, Xin Xin1, Zhen Tu1, Qin-Mei Sun1, Yu Zhao1, Yi-Yang Hu1, Ming-
The relationship between MAFLD and CVD in a health check-up
Hua Zheng5,7,8, Qin Feng1,9,10
Chinese population: a prospective cohort study
1
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai
University of Traditional Chinese Medicine, Shanghai, China, Yao Dou1, Jiawei Cui1, Qi Gu2, XiweiXiwei Yuan1, Mengmeng Hou1,
2
Department of Pathology, the First Affiliated Hospital of Wenzhou Wenjing Ni2, Chen Dong1, Chudi Chang1, Jinhua Shao3, Qiuling
Medical University, Wenzhou, China, 3Department of Radiology, the Wang3, Jie Li2, Qiao Liang4, Yuemin Nan1
First Affiliated Hospital of Wenzhou Medical University, Wenzhou,
1
Department of Traditional and Western Medical Hepatology, The
China, 4Department of Radiology, Shuguang Hospital Affiliated to Third Hospital of Hebei Medical University, Shijiazhuang, Hebei
Shanghai University of Traditional Chinese Medicine, Shanghai, 050051, China, 2Department of Infectious Diseases, Nanjing Drum
China, 5MAFLD Research Center, Department of Hepatology, the First Tower Hospital, Affiliated Hospital of Medical School, Nanjing
Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, University, Nanjing, Jiangsu 210008, China, 3Wuxi Hisky Medical
6
Department of Endocrinology, the First Affiliated Hospital of Wenzhou Technologies Co., Ltd, Wuxi 214000, China, 4Storr Liver Centre, The
Medical University, Wenzhou, China, 7Institute of Hepatology, Westmead Institute for Medical Research, The University of Sydney at
Wenzhou Medical University, Wenzhou, China, 8Key Laboratory Westmead Hospital, Westmead, NSW 2145, Australia
of Diagnosis and Treatment for the Development of Chronic Liver Background: Cardiovascular disease (CVD) has emerged as the
Disease in Zhejiang Province, Wenzhou, China, 9Central Laboratory, most significant complications and leading cause of death among
Shuguang Hospital Affiliated to Shanghai University of Chinese metabolic-associated fatty liver disease (MAFLD). This study aims to
Traditional Medicine, Shanghai, China, 10Key Laboratory of Liver investigate the CVD risk among MAFLD subgroups.
and Kidney Diseases, Shanghai University of Traditional Chinese Method: Data of participants from June 2017 to January 2023 in the
Medicine, Ministry of Education, Shanghai, China Physical Examination Center of the Third Hospital of Hebei Medical
Background: Magnetic resonance imaging (MRI) R2* is a non- University were collected. MAFLD were divided into four subgroups:
invasive indicator for assessing liver iron. However, its value in metabolic healthy lean MAFLD, metabolic healthy overweight/
metabolic dysfunction-associated steatotic liver disease (MASLD) obese MAFLD, metabolic dysfunctional lean MAFLD, and metabolic
has not been fully investigated. This study aimed to evaluate the dysfunctional overweight/obese MAFLD. The risk assessment for
relationship between R2* and MASLD through both cross-sectional atherosclerotic cardiovascular disease was performed based on the
and longitudinal analyses, and explore its potential for assessment and flowchart for primary prevention risk assessment in Chinese adults.
management of MASLD. Result: The proportions of metabolic healthy lean MAFLD, metabolic
Method: This study included 641 participants from Shanghai and healthy overweight/obese MAFLD, metabolic dysfunctional lean
Wenzhou. In the cross-sectional analysis, there were 281 histologically MAFLD, and metabolic dysfunctional overweight/obese MAFLD were
confirmed MASLD (with 124 undergoing Perls’ Prussian blue staining to 0.77% (n=185), 10.05% (n=2,406), 1.29% (n=310), and 16.86%
assess liver iron overload), 310 patients with MASLD diagnosed using (n=4,038), respectively. After adjustment for gender, age, smoking
MRI-proton density fat fraction (MRI-PDFF), and 50 healthy controls. In history, drinking history and significant liver fibrosis, the subgroups
the longitudinal analysis, 245 patients underwent two measurements of MAFLD was still an independent risk factor for high adverse
24 weeks apart. MRI R2* was assessed using SIMONS MAGNETOM cardiovascular events (HACE). Compared with the metabolic healthy
Prisma 3.0T, GE Discovery MR750 3.0T, or UNITED IMAGING uMR790 lean MAFLD, the metabolic dysfunctional lean MAFLD had the highest
3.0T scanners. Cross-sectional and longitudinal analysis were risk, followed by metabolic dysfunctional overweight/obese MAFLD (all
conducted to investigate association between R2* and MASLD. P < 0.05), and there was no significant difference between metabolic
Result: In the cross-sectional study, the R2* of patients was healthy overweight/obese MAFLD and metabolic healthy lean MAFLD.
significantly higher than that of healthy controls (median [inter-quartile We performed regression analysis according to age (65 years) and
range] 66.0 [18.0] vs. 47.1 [10.1], p < 0.001). R2* demonstrated good gender (male or female), respectively, and the results were similar to
diagnostic accuracy (AUC 0.805) for liver iron overload assessed by those of the total population.
Perls’ Prussian blue staining. R2* was significantly positively correlated Conclusion: MAFLD is associated with a higher risk of CVD, especially
with iron overload grade (Perls’ Prussian blue staining), NAFLD in metabolic dysfunctional overweight/obese MAFLD. Classification of
activity score, steatosis (r = 0.619, p <0.001; r = 0.147, p = 0.014; MAFLD based on BMI and metabolic status helps in risk stratification,
r = 0.250, p < 0.001). Additionally, R2* showed significant positively which will mitigate or prevent the development of CVD.
correlations with MRI-PDFF, magnetic resonance elastography (MRE), Table and Figure:Figure 1.Results
liver stiffness measurement (LSM) by transient elastography, and ALT)
(r = 0.529, r = 0.404, r = 0.155, r = 0.304, all p < 0.001) (Figure 1).
OP0257
R2* shows a rising trend as MRI-PDFF, LSM, and ALT levels increase.
Multivariable-adjusted logistic regression analysis showed that ALG-055009, a Novel Thyroid Hormone Receptor Beta (THR-β)
R2* were independently associated with MASLD prevalence (odds Agonist, was Well-tolerated with Significant Reductions in Liver
ratio [OR] = 1.112, 95% CI: 1.022–1.210), but not MASH and fibrosis. Fat at Week 12 in Non-cirrhotic MASH Patients in the Randomized,
In the longitudinal study, changes in R2* were significantly positively Double-Blind, Placebo-controlled Phase 2a HERALD Study
correlated with changes in MRI-PDFF, MRE, LSM, and ALT (r = 0.556, Rohit Loomba1, Dimple Desai2, Daniel Santillano2, Kathryn Jean
r = 0.388, r = 259, r = 0.424, all p < 0.001). In addition, MASLD Lucas3, Naim Alkhouri4, Guy Neff5, Antonio Bianco6, Eveline
responders (defined as a relative decrease in MRI-PDFF ≥ 30%, or Bruinstroop7, Stanley Wang8, Kha Le8, Megan Fitzgerald8, Min Wu8,
LSM decline ≥ 30 %, or ALT decrease ≥ 17 IU/L) showed significantly Ifong Kan-Eng8, Genevieve Harrington8, Chris Burnett8, Jen Rito8,
greater decreases in R2* versus non-responders (Figure 2). Doug Clark8, Naqvi Mohammed8, Venkat Venkatraman8, TseI Lin8,
Conclusion: MRI R2* is effective in assessing liver iron in MASLD, and Sushmita Chanda8, Hardean Achneck8, Lawrence Blatt8, Christos
is associated with the severity of MASLD. A decrease in R2* generally Mantzoros9
corresponds to the improvement of MASLD. These findings support 1
University of California, San Diego, 2Pinnacle Clinical Research,
R2* as a potential non-invasive indicator for the assessment and 3
Lucas Research – Diabetes & Endocrinology Consultants, 4Arizona
management of MASLD. Liver Health, 5Covenant Metabolic Specialists, LLC , 6University of
Table and Figure:Figure 1.Figure 1. Methods; differences in R2* Texas Medical Branch, 7Amsterdam University Medical Center, 8Aligos
between MASLD and non-MASLD populations; diagnostic efficacy Therapeutics, Inc., 9Harvard Medical School
of R2* for liver iron overload; relationship between R2* and MASLD Background: THR-β agonists reduce atherogenic lipids, decrease
hepatic fat, and improve liver histology in MASH. ALG-055009 is study assessed the efficacy and safety of EPL in patients with MASLD,
a novel next generation THR-β agonist with β selectivity and in vitro in addition to Standard of Care (SoC), utilizing FibroScan and validated
potency exceeding that of first generation THR-β drugs. Ph2a quality-of-life (QoL) questionnaire.
HERALD (NCT06342947) was a randomized, double-blind, placebo- Method: This multicenter, double-blind, phase IV clinical trial enrolled
controlled study evaluating the efficacy, safety, pharmacokinetics patients with non-invasive test confirmed MASLD (steatosis scores
and pharmacodynamics of ALG-055009 in non-cirrhotic adults with S1–S3 and estimated liver fibrosis scores F1–F3) and associated
presumed MASH and F1-F3 fibrosis. Final analysis results for this Ph2a metabolic comorbidities. Patients were randomized (1:1) to receive
study are reported here. 1800 mg/day of Essentiale® plus SoC or a placebo with SoC, taken
Method: In this Ph2a randomized, double-blind, placebo-controlled orally, and followed for 9 months. The primary endpoint was to evaluate
study, 102 subjects (~20/arm) were randomized to receive 0.3, 0.5, the efficacy of EPL in reducing hepatic steatosis over 6 months,
0.7 or 0.9 mg ALG-055009 or placebo, orally once daily for 12 weeks. measured by transient elastography (controlled attenuation parameter
Only subjects with body weight >85 kg were enrolled in the 0.9 mg [CAP] score). The secondary endpoints assessed QoL using the
arm, with no weight restrictions for other arms. The primary endpoint CLDQ (Chronic Liver Disease Questionnaire)-MASLD and symptoms
was relative change from baseline in liver fat by MRI-PDFF at Week of asthenia, depression, abdominal pain, and fatigue using Global
12. Levels of lipid/lipoproteins, sex hormone binding globulin (SHBG), Overall Symptom scale. Exploratory endpoints examined fibrosis, liver
MASH/fibrosis biomarkers and safety/tolerability were assessed. enzymes, and lipid profiles, and safety. Results were analyzed using
Result: Baseline characteristics were generally similar across arms: a mixed-effects model based on the modified intention-to-treat (mITT)
62% female, mean age 50 yrs, mean BMI 39 kg/m2, 46% Type 2 population.
diabetes, 18% stable GLP-1 agonist use (majority [67%] with use for >1 Result: Of 193 enrolled patients (mean age 52.5 years), 82 were
year before randomization). ALG-055009 dose groups met the primary randomized to EPL and 83 to the placebo in the mITT set. EPL reduced
endpoint, with statistically significant placebo-adjusted median relative CAP scores significantly vs placebo at 6 months (Least Square Mean
reductions in liver fat of up to 46.2% at Week 12 with a dose response Difference [LSMD] [95% CI]: -14.81[–27.89 to -1.72]; p=0.0269).
between 0.3-0.7 mg (Figure 1). Among the 18 subjects with baseline Numerical improvement was observed in QoL total score in EPL
stable GLP-1 agonist use, 11/14 treated with ALG-055009 had liver fat group vs placebo (LSMD: 0.17; p=0.2445) at 6 months. Statistically
decreases and 4/4 treated with placebo had liver fat increases (Figure significant improvement was observed in fatigue subscore at 6 months
2). Up to 70% of subjects achieved ≥30% relative reduction in liver (LSMD: 0.31 [0.04, 0.58]; p=0.0229; Figure 1) in the EPL group vs
fat compared to baseline. Significant reductions in atherogenic lipids, placebo. Symptom evaluations showed improvement trends with EPL:
including LDL-C, lipoprotein (a) and apolipoprotein B, regardless of numerical improvements were observed for fatigue (LSMD: -0.24
baseline GLP-1 agonist use, and dose-dependent increases in SHBG [-0.57, 0.1]; p=0.1627) and asthenia symptoms (LSMD: -0.23 [-0.55,
were observed. The majority of treatment emergent adverse events 0.09]; p=0.1583) in the EPL group vs placebo. EPL treatment improved
(TEAEs) were mild to moderate, with no SAEs in subjects receiving liver stiffness measurement (LSMD = -0.06; p=ns) at month 6. LDL
ALG-055009 and one discontinuation due to worsening insomnia in a decreased (LSMD: -0.03 [-0.45to 0.39] and HDL increased slightly
subject with pre-existing insomnia. No clinically meaningful findings in (LSMD: 0.22 [-0.52 to 0.96) with EPL vs placebo at 6 months. An
laboratory tests, ECGs, vital signs, physical exams or clinical evidence overall improvement of patient satisfaction was observed, and safety
of hypo/hyperthyroidism were observed. Incidence of gastrointestinal profiles were comparable to placebo.
(GI)-related TEAEs, including diarrhea, were similar in ALG-055009 Conclusion: Treatment of EPLs with SoC reduced hepatic steatosis
dose groups compared to placebo. and improved fatigue at 6 months in MASLD patients compared to
Conclusion: 12 weeks of once daily ALG-055009 treatment in placebo, with acceptable safety profile making it a promising option for
MASH subjects met the primary endpoint, demonstrating significant early intervention of MASLD.
reductions in liver fat and was well-tolerated, with rates of GI-related Table and Figure:Figure 1.Change in QoL total and fatigue scores
TEAEs similar to placebo. Additional liver fat reduction was observed (Change from baseline)
among subjects with stable GLP-1 agonist use. This data supports
evaluation of longer durations of ALG-055009 and its effects on liver
OP0259
histology.
Table and Figure:Figure 1.Figure 1: Placebo-adjusted Median Relative A Dynamic Model of Liver Fibrosis Regression Based on
Change in Liver Fat at Week 12 Longitudinal Liver Stiffness Measurements in Chronic Hepatitis
Figure 2.Figure 2: Median Relative Change in Liver Fat at Week 12 by B Patients
Stable GLP-1 Agonist Use at Baseline Jiayi Zhang1, Shuyan Chen, Jialing Zhou, Bingqiong Wang, Xiaoning
Wu, Xiaoqian Xu, Xinyu Zhao, Yuanyuan Kong, Xiaojuan Ou, Jidong
Jia, Yameng Sun, Hong You
OP0258 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
Effect of Essential phospholipids on hepatic steatosis and quality University, State Key Lab of Digestive Health, National Clinical
of life in patients with MASLD associated with type 2 diabetes Research Center of Digestive Diseases, Beijing Key Laboratory of
mellitus and/or hyperlipidemia and/or obesity – a Phase IV, Translational Medicine on Liver Cirrhosis
randomized double-blind clinical trial
Background: Liver fibrosis associated with chronic hepatitis B (CHB)
Norbert Stefan1, Marek Hartleb2, Jian Gao Fan3, Branko Popovic4, could be regressive after effective antiviral treatment. The aim of this
Rafael Varona5, Beatrice Bois De Fer5, Guillaume Blanchard6 study was to develop and validate a time-dependent noninvasive
1
Department of Internal Medicine IV, University Hospital Tübingen, model, based on liver stiffness measurement (LSM) to predict liver
Tübingen, Germany, 2Department of Gastroenterology and fibrosis regression within 5 years of antiviral therapy.
Hepatology, Faculty of Medicine, Medical University of Silesia, Method: A total of 386 patients with CHB were enrolled in the study,
Katowice, Poland, 3Department of Gastroenterology, Xinhua Hospital including 175 patients who had at least twice liver biopsies at baseline
Affiliated to Shanghai Jiao Tong University School of Medicine, and either at week 78 or week 260, and 211 patients who had
Shanghai, China, 4Opella, a Sanofi company, Frankfurt am Main, undergone liver biopsy after one year of antiviral treatment. Liver fibrosis
Germany, 5Opella, a Sanofi company, Neuilly-sur-Seine, France,
regression was defined as a decrease of ≥ 1 stage in Ishak score or
6
Opella, a Sanofi company, 6-, Barcelona, Spain
predominantly regressive according to P-I-R classification in patients
Background: Metabolic dysfunction-associated steatotic liver disease with unchanged Ishak stage, or according to P-I-R classification
(MASLD) is a prevalent chronic liver condition generally associated alone. A longitudinal discriminant analysis algorithm, employing Monte
with obesity, diabetes, or dyslipidemia. Essential phospholipids (EPL) Carlo Markov Chain (MCMC) sampling, was designed to track the
are recommended as a supportive treatment for MASLD, cirrhosis, and trajectory of LSM, ALT, ALB and PLT to develop models for predicting
viral hepatitis. Despite substantial evidence on the treatment’s efficacy, liver fibrosis regression.
linking these findings to patient clinical outcomes was essential. This Result: For the whole patients, the mean age of the patients was
42±10 years, with males constituting 47.4% (183/386). The median Shandong First Medical University, Jinan, Shandong, China, 4School
baseline values of LSM and ALT were 14.1 (9.9, 21.3) and 47.5 (31.0, of Chemistry and Pharmaceutical Engineering, Medical Science and
89.9), respectively. A total of 307 CHB patients were included in the Technology Innovation Center, Shandong First Medical University and
training set, and 79 patients were included in the testing set. This Shandong Academy of Medical Sciences, Jinan, Shandong, China,
study resulted in the development of eight models, each comprising a
5
Department of Infectious Diseases, Shandong Provincial Hospital
distinct combination of variables based on LSM. Four models with an Affiliated to Shandong First Medical University, Jinan, Shandong,
area under the receiver operating characteristic curve (AUC) greater China
than 0.950, were subjected to further validated. In the testing set, the Background: Liver fibrosis is a major contributor to the morbidity
AUCs of these four models were more than 0.800, and the model and mortality associated with chronic liver diseases, yet effective
incorporating LSM, ALT and PLT demonstrating the most favourable treatment options remain limited. Hepatic stellate cells (HSCs) are
performance with the AUC of 0.836 (95% CI, 0.768-0.904). a promising target for hepatic fibrogenesis due to their pivotal role
Conclusion: The dynamic liver fibrosis regression model, which in disease progression. The pan-peroxisome proliferator-activated
integrates LSM, ALT and PLT, demonstrated significant potential for receptor (PPAR) agonist lanifibranor has antifibrotic activity in patients
real-time monitoring and prediction of liver fibrosis regression. with nonalcoholic steatohepatitis by favoring a less activated and
more quiescent phenotype of HSC regulation. However, the clinical
OP0260 application of lanifibranor is challenged by its poor aqueous solubility
and lack of specificity for HSCs. Therefore, developing an HSC-specific
A Novel Non-invasive Model to Identify HRV in Patients with HBV- delivery system for lanifibranor is important to ameliorate liver fibrosis.
related Cirrhosis Method: We developed an HSC-specific delivery system
Haiyu Wang1, Peishuang Xu1, Jinlin Hou and Jinjun Chen’s group for lanifibranor by conjugating Ferrous sulfide (FeS) nanosheets
1
Department of Infectious Diseases, Nanfang Hospital, Southern with vitamin A (VA), utilizing PEG2000 as a linker (VA-FeS@LA). VA-
Medical University, Guangzhou, China FeS@LA was therapeutically administered in carbon tetrachloride-
Background: Early diagnosis of high-risk varices (HRV) in individuals induced mouse models to analyze the attenuation of liver fibrosis. The
with HBV-related cirrhosis is important to improve the prognosis and potential mechanisms of VA-FeS@LA were studied by RNA sequencing,
decrease mortality. The aim of this study was to develop a novel non- and we used primary HSCs for additional functional validation.
invasive model, for ruling out and ruling in HRV in patients with HBV- Result: VA exhibits a specific binding affinity to retinol-retinol-binding
related cirrhosis. protein (RBP) receptor located on the membrane of HSCs. This
Method: The clinical data from patients with compensated cirrhosis interaction enables VA to target HSCs specifically. Flow cytometry and
at the hepatology unit of the Nanfang Hospital in China were used to a laser confocal assay indicated that the endocytosis of VA-FeS@LA by
develop a new diagnostic model. Liver stiffness measurement (LSM) primary HSCs increased rapidly upon the addition of RBP, compared
and spleen stiffness measurement (SSM) (FibroScan®630), spleen to FeS. The cellular uptake efficiency of VA-FeS@LA was found to be
size and esophagogastroduodenoscopy (EGD) were performed at time-dependent. Whole-body imaging showed a gradual accumulation
enrollment. of VA-FeS@LA in the liver, confirming the successful hepatic targeting
Result: Overall 616 consecutively enrolled patients between July of the formulation in vivo.Fluorescence imaging of fibrotic liver
2021 and April 2024 used to develop and internally validate the sections stained with α-SMA antibody demonstrated the HSC-specific
performance of PASS for varices screening. They were randomly distribution of VA-FeS@LA. Subsequently, intervention with VA-FeS@LA
assigned into the training (n=432) and validation (n=184) cohorts with has shown a notable reduction in serological indicators of liver injury
a ratio of 7:3. The model consisting of SSM, platelets, spleen diameter, (ALT and AST), collagen accumulation, and inflammatory responses
spleen thickness and sex, named PASS model, performed robustly (serum concentrations of IL-1β, IL-6, and TNF-α). In vitro experiments
(training cohort, AUROC 0.94, AUPRC 0.81; validation cohort, AUROC confirmed that VA-FeS@LA significantly reduced the levels of α-SMA,
0.92, AUPRC 0.78). Cut-off of 4.84 for ruling out and 78.28 for ruling in Col3α1, and Col1α1. These effects may be attributed to the regulation
were best for discriminating HRV. In the training cohort, for ruling out of the PPAR-γ signaling pathway.
HRV, PASS model spared 53.47% (231/432) unnecessary EGDs with Conclusion: In this study, we developed an HSC-specific
a HRV missed rate of 1.11% (1/90), with the corresponding sensitivity, delivery system (VA-FeS@LA) to improve the therapeutic efficacy
negative predictive value, LR-negative were 98.89%, 99.57%, 0.02, of lanifibranor on liver fibrosis. Compared with FeS and lanifibranor,
respectively; the rest patients were to rule in HRV, 92.50% (37/40) of VA-FeS@LA exhibited increased deposition in HSCs and a favorable
positive patients were correctly classified (specificity 97.32%, positive antifibrotic effect. VA-FeS@LA nanocomposite represents a promising
predictive value 92.50%). In the validation cohort, 53.26% (98/184) of therapeutic approach to the treatment of liver fibrosis.
patients were classified as low probability of HRV with a high sensitivity Table and Figure:Figure 1.Ferrous Sulfide Nanosheet as a Novel Drug
of 97.37% and 19.77% (17/86) were classified as HRV with a high Delivery System for Lanifibranor to Ameliorate Liver Fibrosis
specificity of 97.96%.
Conclusion: The PASS model (ranging from 0 to 100) can accurately OP0262
rule out and rule in HRV in patients with HBV-related cirrhosis. PASS
EUS criteria for predicting the occurrence of decompensation or
could avoid unnecessary EGDs and maintain high levels of clinical
death in patients with compensated cirrhosis
accuracy in the identification of HRV in patients with HBV-related
cirrhosis. Li Li Zhao1, Ping Han, Jie Liu, Jia Li
Table and Figure:Figure 1.Diagnostic performance of the PASS model
1
Department of Gastroenterology and Hepatology, Tianjin Second
for HRV in training and validation cohorts. People’s Hospital, Tianjin, China
Figure 2.Accuracy for diagnosis of HRV in the training and validation Background: Prognosis is worse in patients with compensated cirrhosis
cohorts using the PASS Model two cut-off approach. with gastroesophageal varices (GEV) compared to those without
GEV. Endoscopic ultrasonography (EUS) can observe the vascular
OP0261 network around esophagogastric wall. We aimed to investigate the
value of EUS and develop an EUS-based criteria for predicting the
Ferrous Sulfide Nanosheet as a Novel Drug Delivery System for occurrence of decompensation, hepatocellular carcinoma or death
Lanifibranor to Ameliorate Liver Fibrosis (DHD) in compensated cirrhosis.
Yinuo Yang1,2, Wenzhe Li3, Ke Ren4, Hui Liu4, Wanhua Ren5,2, Xiao Method: In this retrospective study, compensated cirrhosis patients
Sun4, Qiang Zhu1,5,2 were enrolled from November 2015 to December 2016 and were
1
Department of Gastroenterology, Shandong Provincial Hospital, divided into training and validation cohorts. Patients were followed
Cheeloo College of Medicine, Shandong University, Jinan, Shandong up unless the occurrence of DHD. An EUS-based nomogram (EUS
province, China, 2National medical center for infectious diseases, criteria) for predicting DHD was developed using the training cohort
3
Central Laboratory, Shandong Provincial Hospital Affiliated to and further tested using bootstrap resampling in the validation cohort.
Result: A total of 389 patients with compensated cirrhosis were Epidemiology and distribution of traditional Chinese medicine
included with 276 and 113 of them were recruited in the training syndrome differentiation of non-alcoholic fatty liver disease
and validation cohorts, respectively. The median follow-up time (NAFLD) in traditional Chinese medicine liver disease clinics
was 41.8 (range, 2.6-50.2) months for the overall cohort. An EUS Jian-bo DING1, LI LI2
score was generated based on two EUS-based parameters (the 1
Beijing Health Vocational College, 2Beijing Hospital of Traditional
maximum diameter of subesophageal vein and paraesophageal vein) Chinese Medicine Affiliated to Capital Medical University
and showed a good predictive accuracy and discriminative ability for
Background: The epidemiological situation of NAFLD in traditional
DHD in both training and validation cohorts. EUS criteria based on
Chinese medicine liver disease clinics is not very clear. This study
EUS score, age, diabetes mellitus, spleen diameter, and liver stiffness
retrospectively analyzed the changes in the epidemiology of non-
were formulated and showed a good performance for predicting
alcoholic fatty liver disease (NAFLD) in the TCM liver disease outpatient
3-year DHD-free survival with a C-index of 0.861 (adjusted C-index,
department of a tertiary hospital in Beijing from 2019 to 2023, as well
0.857) and 0.947 in the training and validation cohorts, respectively.
as the distribution of TCM syndromes in NAFLD, providing objective
Conclusion: The EUS criteria have a good predictive value for
evidence for future clinical and basic research on NAFLD.
occurrence of DHD in compensated cirrhosis.
Method: A retrospective statistical analysis was conducted on the
Table and Figure:Figure 1.A schematic diagram showing esophageal
epidemiology and the distribution of traditional Chinese medicine
varices and vascular structures around the esophageal wall using
syndrome differentiation of NAFLD in traditional Chinese medicine
endoscopic ultrasonography. Long arrow: paraesophageal veins;
liver disease clinics of a 3a grade hospital. Analyze the changes in
short arrow: periesophageal veins; arrow head: subesophageal veins.
the proportion of NAFLD visits to total outpatient visits, as well as the
Figure 2.EUS criteria for predicting DFS. (A) A nomogram for DFS
changes in gender and age in 2019 and 2023.
prediction for compensated cirrhosis patients. To use the nomogram,
Result: The proportion of NAFLD in the total outpatient visits of
find the position of each variable on the corresponding axis, draw a
traditional Chinese medicine liver disease clinics was 19.9% in 2019
line to the points axis for the number of points, add the points from all
and increased to 28.9% in 2023.The male proportion of NAFLD
of the variables, and draw a line from the total points axis to determine
patients was 54.3% in 2019 and 58.4% in 2023.The average age of
the likelihood of 3-year survival. (B, C) Kaplan-Meier curve of DFS for
NAFLD patients was 51.75 ± 13.44 years in 2019 and 46.42 ± 13.76
patients in training (B) and validation (C) cohorts. EUS, endoscopic
years in 2023. The patients with a significant increase are those aged
ultrasonography; DHD, decompensation events, hepatocellular
26-44 years old and aged ≤ 25 years old. The above differences
carcinom or death; DFS, DHD-free survival.
are statistically significant. The top ten traditional Chinese medicine
syndrome differentiation for NAFLD were: damp-heat in liver and
OP0263 gallbladder, the syndrome of liver-depression and spleen-deficiency,
Effects of Nucleoside analogues on liver fibrosis remission in Phlegm-dampness stagnation syndrome, Qi stagnation and blood
patients with HBV-related hepatocellular carcinoma stasis syndrome, Phlegm stasis syndrome. And combination syndrome
JianRong Li1, LeiPo Lin1, JiaYong Su1, BeiBei Long1, ChengPiao Luo1, types account for 51.25%. The main syndrome elements of NAFLD
YiLi Ma1, Liang Ma1, ZhenZhen Li1, JianHong Zhong1 patients are dampness, heat, depression, stasis, phlegm, spleen
deficiency, and Qi deficiency.
1
guangxi medical university cancer hospital
Conclusion: The proportion of NAFLD visits to total outpatient visits has
Background: Recent years have seen an increasing trend in significantly increased, and the average age of NAFLD patients has
recommending expanded antiviral therapy indications in both significantly decreased in traditional Chinese medicine liver disease
domestic and international hepatitis B guidelines. Much of the clinics. The main traditional Chinese medicine syndrome differentiation
previous evidence on antiviral efficacy focused on chronic hepatitis for NAFLD were: damp-heat in liver and gallbladder, the syndrome of
B (CHB) patients, lacking clinical evidence based on patients with liver-depression and spleen-deficiency, Phlegm-dampness stagnation
hepatitis B-related hepatocellular carcinoma (HBV-HCC). Hence, syndrome, Qi stagnation and blood stasis syndrome, Phlegm stasis
this was a retrospective study on liver samples from patients after syndrome. The main syndrome elements of NAFLD patients are
two hepatectomies, comparing the impact of different Nucleoside dampness, heat, depression, stasis, phlegm, spleen deficiency, and
analogues (NAs) therapy durations on fibrosis, to provide additional Qi deficiency. It is necessary and urgent to conduct basic and clinical
clinical support for expanding chronic hepatitis B treatment indications. research on NAFLD.
Method: This was a retrospective cohort study. A total of 131 CHB Table and Figure:Figure 1.Changes in the percentage of NAFLD visits
patients who received two hepatectomies were admitted to the Guangxi to outpatient visits per month in Traditional Chinese Medicine Liver
Medical University Cancer Hospital from July 2015 to March 2024, and Disease Clinic from 2019 to 2023
were divided into three groups for different NAs therapy durations: Figure 2.Distribution of Traditional Chinese Medicine Syndrome Types
less than 12 months therapy group (n=34), 12 to 24 months therapy in NAFLD Patients
group (n=40) and more than 24 months therapy group (n=57). The
differences in liver fibrosis between two liver samples before and after
treatment were analyzed and compared to evaluating the efficacy of OP0265
NAs therapy by using Ishak and Scheuer score system. A specialist liver home-based nursing program following inpatient
Result: The scores of liver fibrosis were decreased after NAs admission facilitates alcohol abstinence in patients with cirrhosis.
therapy, and 12 to 24 months can achieve more remission. In terms Leya Nedumannil1, Catherine Yu1, Kristen Peake1, Kendall
of decreasing the Ishak score, NAs therapy of 12 to 24 months Fitzpatrick1, Vanessa Lowen1, Mustafa Mohamedrashed1, Mayur
remitted than NAs therapy of more than 24 months (52.5% vs 28.0%, Garg1, Diana Lewis1, Siddharth Sood1
P=0.019), and slightly remitted than NAs therapy of less than 12 1
Department of Gastroenterology, Northern Health, Epping, Victoria,
months (52.5% vs 44.1%, P=0.494), although no significant difference Australia
was showed (Figure 1A). The decrease of Scheuer score also shown
Background: Liver at Home (L@H) is a 3-month home-based program
similar result (Figure 1B).
at a tertiary metropolitan health service designed for the community-
Conclusion: NAs therapy for 12 to 24 months may achieve more
based management of recently hospitalised patients with cirrhosis.
fibrosis remission in patients with HBV-HCC. This study provides a new
L@H provides continued care for such patients, a large proportion of
basis for antiviral therapy to prevent the progression of fibrosis in CHB
whom have alcohol-related cirrhosis, through regular home visits and
patients.
telehealth reviews by hepatology nurses. We aimed to evaluate alcohol
Table and Figure:Figure 1.Figure 1 Changes in liver fibrosis in the three
use in patients enrolled to L@H with alcohol-related cirrhosis.
groups
Method: Patients with cirrhosis who were discharged from the
Gastroenterology service were prospectively enrolled to L@H
OP0264 between 01/03/2023 and 01/09/2024. Exclusion criteria from L@H
included patient preference not to participate, residence outside the induced liver injuries.   
hospital catchment, and high-risk score on home safety screening. Table and Figure:Figure 1.
Whilst trained in the management of liver-related complications, the
hepatology nurses were not specifically trained in alcohol use disorder
OP0267
management. Disengagement was classified as failure to participate
in reviews on > 3 occasions. Harmful alcohol consumption amongst Mas1 deficiency protects against acute liver failure by suppressing
enrolled patients who were actively drinking prior to admission was the FXR/S1P/Raf-dependent NETosis in mice
analysed before and after their time with L@H. Patients who Bo Yang1, Qing Chang Yang1
disengaged from the program were assumed to have resumed alcohol 1
Tongji Hospital Affiliated to Tongji University
consumption. Background: Mas is a newly discovered G protein-coupled receptor
Result: Of 61 patients enrolled to L@H in the study period, 75% that plays a critical role in inflammatory responses. The gut-liver axis
(n=46) had alcohol-related cirrhosis, of whom 65% (n=30) reported regulated neutrophilic inflammation is crucial in acute liver failure
harmful alcohol consumption up until hospital admission [median (ALF); however, the underlying mechanisms remain poorly understood.
age 45 years (IQR 41-58), 26.6% (n=8) female, median MELD-Na The aim of this study is to investigate Mas signaling and neutrophilic
score 20 (IQR 17-23)]. Only 6.7% (n=2/30) actively drinking patients inflammation in ALF, and to elucidate its underlying mechanisms.
were prescribed anti-craving therapy (acamprosate) at the time of Method: The 8-10 week-old male Mas1-/-, Vil1creMas1f/f, and wild-
hospital discharge. Overall, 67% (n=20/30) of those enrolled to L@H type control mice were subjected to intraperitoneal challenge with
who were actively drinking prior to hospitalisation achieved alcohol D-galactosamine/lipopolysacchari de(D/L) for in vivo analysis of the
abstinence during L@H, all of whom engaged well with the program. gut-liver axis-dependent formation of neutrophil extracellular traps
95% (n=20/21) of patients who engaged with L@H achieved alcohol (NET), utilizing pharmacological compounds and genetic tools. Age-
abstinence. At 3-month follow-up, 5% (n=1/20) of those who achieved matched mice received injections of phosphate-buffered saline as
alcohol abstinence had a liver-related hospital readmission, compared vehicle controls.
to 20% (n=2/10) of those who did not, p= 0.252. All 3 cases of all- Result: The hepatic expression of Mas was significantly upregulated
cause mortality to date (censor date 01/12/2024) were patients who in ALF patients and mice models. The knockout of the Mas1 gene in
disengaged from L@H. both systemic and intestinal epithelial cells significantly alleviated D/L-
Conclusion: In this single-centre study, we have identified a large induced NETosis and hepatotoxicity in mice. The involvement of gut
proportion of patients with alcohol-related cirrhosis and ongoing microbiota in the attenuated hepatotoxicity of Mas1-/--D/L mice was
harmful alcohol consumption prior to hospitalisation achieving alcohol confirmed through antibiotic experiments. The co-housed experiments
abstinence through good engagement with L@H. This was in the between Mas1-/- and WT mice have demonstrated that Mas1-/- may
absence of hepatology nurses having any formal training in the domain confer protection by reducing the intestinal abundance of Eubacterium
of addiction management. These notable results suggest that the sp. and inhibiting deoxycholic acid (DCA) production. This was
support and encouragement that can be imparted through consistent accompanied by hepatic activation of farnesoid X receptor (FXR)
liver-focused home visits for recently hospitalised patients with alcohol- signaling and suppression of downstream sphingosine-1-phosphate
related cirrhosis could significantly increase their chances of achieving (S1P)-dependent NETosis. As revealed by single-cell transcriptomics,
alcohol abstinence, and in turn, likely improve long-term outcomes. the downregulation of NETosis in Mas1-/--D/L mice was found to be
dependent on the senescence of Cldn1+CD177+ neutrophils and the
OP0266 activation of Raf signaling.
Conclusion: Mas1-/- significantly protects mice from D/L-induced
Characteristics of DILI, HILI and alcohol induced liver injury
hepatotoxicity by suppressing the FXR/S1P/Raf-dependent NETosis,
among 4087 patients in Mongolia
thereby suggesting Mas as a promising therapeutic target for ALF.
Erdenebayar Gonchig1,2, Dolgormaa Batsaikhan2,1, Byambatsetseg Table and Figure:Figure 1.Figure 1 The hepatic and ileal expression of
Togtuunbayar2,1, Enkhtuya Damba1,2, Enkhbayar Gonchig2, Enkhtuya Mas1 in D/L induced ALF mice.
Enkhtuvshin2, Ganchimeg Gelenkhuu2, Oidov Baatarkhuu3,2, Figure 2.Figure 2 The knockout of the Mas1 gene in both systemic
Amarsana Jazag2,1,4 and intestinal epithelial cells significantly alleviated D/L-induced ALF
1
Happy Veritas Hospital, 2Mongolian Association for the Study of Liver in mice.
Diseases, 3Department of Infectious Diseases, School of Medicine,
Mongolian National University of Medical Sciences, 4Otoch Manramba
Universty OP0268
Background: Hepatotoxicity is one of the most common causes of Characterization of mucosal-associated invariant T cells in drug
hepatitis and cirrhosis in the population and has become a major public induced liver injury
health problem affecting mortality. Therefore, we aimed to determine Zherui Liu1, Zhuoya Deng2, Xingran Zhai3, Ang Huang4,5, Zhengsheng
the causes of liver toxicity in large scale for the first time in Mongolia. Zou5,1
Method: 4087 patients with AST higher than ALT, high AST and GGT, 1
Peking University 302 Clinical Medical School, 2Beijing Key
high AST and ALP, high AST,GGT and ALP, and high AST and T-BIL Laboratory for HIV/AIDS Research, Beijing Youan Hospital, Capital
in their lab reports were selected from 24,488 people who underwent Medical University, Beijing, China, 3Department of Infectious
screening at Happy Veratis Hospital between 2015 and 2023, and Diseases, Shandong Provincial Hospital Affiliated to Shandong First
were analyzed in detail using anamnesis-synthesis method, and the Medical University, Jinan, Shandong, China., 4The First Medical
correlation between them was summarized and analyzed Center of PLA General Hospital, Beijing, China, 5The Fifth Medical
Result: Categorized by cause of liver toxicity: Center of PLA General Hospital, Beijing, China
- Alcohol (5 types of alchohol containing drinks) 37.5% Background: DILI is a common adverse drug reaction with potentially
- Herbs (9 types of herbs) 31.7% severe consequences, which can be classified as acute or chronic
- Supplements (7 types) 17.3% based on its course. While chronic DILI is characterized by persistent
- Medications ( 9 types) 9.3% or recurrent liver damage and the mechanisms underlying DILI
- Other 2% chronicity remain poorly understood. Mucosal-associated invariant
Conclusion: According to our study alcohol induced liver injury was T (MAIT) cells, a subset of innate-like T cells abundantly present in
the most common cause of liver injury, among them mixed alcoholic the human liver, influence the local immune environment and are
beverages cause the most severe liver injury. Among herbal causes implicated in various liver diseases. However, MAIT cells’ role in DILI
three herbs were causing most of the liver injuries namely: Roots of and its chronicity remains unclear. This study aims to explore and
Rheum Undulatum, flowers of Chelidonium majus, Thymus Gobicus. characterize the quantitative and phenotypic alterations of MAIT cells
Top DILI causes were antibiotics, Milk Thistle and pain relievers. Weight in peripheral blood and liver tissue during DILI chronicity to elucidate
losing supplements were the most common type of supplement their potential role in this process.
Method: We collected Peripheral blood mononuclear cells cancer (ALC), and CPT2 expression levels were evaluated. HepG2
(PBMCs) from individuals and DILI patients (including acute and cells were treated with 200 mM ethanol, followed by the detection of
chronic DILI cases). Flow cytometry was used to analyze the proportion, mRNA and protein levels, as well as transcriptome sequencing.
phenotype, and functional changes of MAIT cells in PBMCs across the Result: Analysis of the TCGA database reveals a significant reduction
three groups. Additionally, liver biopsy samples were obtained from in CPT2 expression in liver cancer patients. Immunofluorescence
both acute and chronic DILI patients. Multicolor immunofluorescence staining demonstrates that the progression of alcoholic liver disease is
was employed to localize and quantify MAIT cells in liver tissue. associated with a marked decrease in CPT2 expression. In comparison
Result: A significant decline in peripheral blood MAIT cell frequency to adjacent normal tissues, both mRNA and protein levels of CPT2
was obsevered in chronic DILI patients. Multicolor immunofluorescence are considerably lower in alcoholic liver cancer tissues. At the cellular
also showed decreased hepatic MAIT cell numbers in chronic DILI level, ethanol exposure significantly diminishes CPT2 expression.
patients. Furthermore, caspase-1+ MAIT cells in peripheral blood from Transcriptome sequencing indicates that post-ethanol treatment,
chronic DILI group showed the highest frequencies. Spearman genes are predominantly enriched in the Hippo pathway and cancer
correlation analysis revealed a significant negative correlation between stem cell regulatory pathways.
Caspase-1+ MAIT cells and the proportion of MAIT cells. Furthermore, Conclusion: The high incidence and low cure rate of alcoholic liver
phenotypic analysis showed significant upregulation of activation cancer present a substantial challenge to global public health. This
markers CD69 and HLA-DR on MAIT cells in both DILI groups study reveals that ethanol reduces CPT2 expression and subsequently
compared to healthy controls. Interestingly, chronic DILI patients decreases CPT2-mediated carnitine catabolism, thereby promoting
exhibited significantly lower expression of the early activation marker stemness in alcoholic hepatocellular carcinoma. These findings offer a
CD69 but higher expression of the late activation marker HLA-DR crucial theoretical basis for strategies aimed at reducing the incidence
compared to acute DILI patients. and mortality of alcoholic liver cancer.
Functional analysis revealed significantly increased CD107a Table and Figure:Figure 1.Ethanol decreases CPT2-mediated Carnitine
degranulation in MAIT cells from chronic DILI patients. The proportion catabolism to promote stemness in alcoholic hepatocellular carcinoma
of granzyme B+ MAIT cells was significantly higher in chronic DILI
patients. The percentage of IL-22+ MAIT cells was significantly OP0270
elevated in DILI patients compared to healthy individuals, with a trend
towards decrease in chronic DILI patients compared to acute cases. IL-8 Expression in Drug-Induced Liver Injury (DILI) and Its
Conclusion: This study demonstrates a significant reduction in MAIT Correlation with Pathological Inflammation
cell numbers in both peripheral blood and liver tissue of chronic DILI Diandian Hao1, Linlin Zhang2, JiaLin Du1, Limei Qu2, Xiaoyu Wen1
patients, potentially associated with pyroptosis. The persistent liver 1
Center for Infectious Diseases and Pathogenic Biology / Department
injury in chronic DILI may be linked to sustained chronic activation of Hepatology, The First Hospital of Jilin University, Changchun
of MAIT cells, elevated tissue damage, and reduced tissue repair 130021, China., 2Department of Pathology, the First Hospital of Jilin
capacity. University, Changchun 130021, China.
Table and Figure:Figure 1.Frequency and distribution of peripheral and Background: To assess the clinical and pathological characteristics
liver MAIT cells and Caspase-1+ cells of DILI patients and the expression of interleukin-8 (IL-8) in liver tissue,
Figure 2.Phenotype and functional alteration of MAIT cells in peripheral evaluating its relationship with the severity of liver damage.
blood Method: 40 patients with drug-induced liver injury with a clear history
of drug use or exposure to environmental toxicants and diagnosed by
OP0269 liver puncture biopsy who attended the Department of Hepatobiliary
Medicine of the First Hospital of Jilin University from January 2023
Ethanol decreases CPT2-mediated Carnitine catabolism to to August 2024 were enrolled. Patients were categorized into G1 to
promote stemness in alcoholic hepatocellular carcinoma G4 groups based on the grade of pathological inflammation, with
Xiaoxue Yuan1,2,3, Wenqian Geng1,2,3, Yang Wang1,2,3, Xi Wang1,2,3, 10 patients per group. A control group of 10 healthy individuals with
Song Yang4,3,2 normal liver function was also selected. Demographics, biochemical
1
National Key Laboratory of Intelligent Tracking and Forecasting for indices, and pathological reports were analyzed using SPSS 27.0. IL-8
Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, expression was assessed by immunohistochemical staining (IHC) and
Beijing,100015, China, 2Beijing Key Laboratory of Emerging Infectious compared between groups. Spearman’s rank correlation was used
Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, to examine the correlation between IL-8 expression and the grade of
Capital Medical University, Beijing 100015, China, 3National Center for pathological inflammation.
Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Result: The study cohort included 40 DILI patients aged 49 to
Beijing 100015, China, 4Center of Liver Diseases Division 3, Beijing 70 years, with a female predominance. Traditional Chinese medicine
Ditan Hospital, Capital Medical University, Beijing 100015, China
was implicated in 47.5% of cases. Jaundice was the main clinical feature
Background: Alcoholic Liver Cancer (ALC) is a liver disease resulting (62.50%), followed by fatigue (37.50%). Based on the R values, DILI
from prolonged excessive alcohol consumption. Chronic alcohol abuse patients were classified as cholestasis (43%), hepatocellular injury
can lead to pathological changes such as fatty liver, alcoholic hepatitis, (40%), and mixed types (17%), with significant differences in liver
and cirrhosis, which may eventually progress to Hepatocellular function tests (P<0.01). All patients received hepatoprotective
Carcinoma (HCC). Globally, liver cancer is one of the leading causes treatment, with 27.5% also receiving steroids. After treatment, 10
of cancer-related deaths, and alcoholic liver cancer, as a specific type, (25%) patients were cured, 21 (52.5%) patients improved, 9 (22.5%)
is particularly prevalent in regions with high alcohol consumption. did not recover and became chronic, no death or liver transplantation
The incidence of alcoholic liver disease is notably high in certain occurred.Pathologically, the cholestasis type is characterized by
Asia-Pacific countries (such as China, Japan, and South Korea) and cholestasis in hepatocytes and capillary bile ducts, the hepatocellular
Eastern Europe, where the burden of liver cancer is also significant. injury type by interfacial inflammation and focal necrosis, and the
Early diagnosis of alcoholic liver cancer remains challenging, and mixed type shows both features. Compared to the control group,
effective treatment methods are still lacking. Therefore, early diagnosis IL-8 expression in DILI patients is significantly elevated (P<0.001),
and further research into the molecular mechanisms of alcoholic liver increasing with the severity of inflammation (Fig.1). Specifically, G1
cancer are crucial for improving survival rates. This not only helps shows a modest increase (P = 0.0025), while G2, G3, and G4 exhibit
to elucidate the pathogenesis of liver cancer but also provides a substantial rises (P < 0.0001)(Fig.2). Spearman’s analysis reveals a
theoretical foundation for developing new treatment strategies. positive correlation (r=0.53, P<0.01), suggesting IL-8 as a potential
Method: CPT2 expression levels were analyzed using the TCGA biomarker for DILI inflammation.
database. Immunofluorescence staining was conducted on liver tissue Conclusion: IL-8 expression in the liver tissue of DILI patients’
sections from patients with alcoholic liver disease. RNA and protein correlates positively with the degree of pathological inflammation,
were extracted from the liver tissues of patients with alcoholic liver suggesting its potential as a biomarker for DILI inflammatory activity.
Table and Figure:Figure 1.Fig.1 behaviors, perceptions, and expectations for CHB functional cure.
Figure 2.Fig.2 Hypothetical regimen attributes were presented to HCPs and patients
to assess preferences. Data were analyzed using a content analysis
framework, and descriptive analysis was applied where proper.
OP0271
Result: Patients acknowledged the challenges of curing CHB but
Clinical Characteristics and Risk Factors for HBsAg Clearance in maintained high expectations for achieving a cure for a normal,
Patients with Acute Hepatitis B Virus Infection: A Retrospective stigma-free, and infection-free life. However, their understanding of
Study in China “functional cure” was limited. HCPs had incorporated HBsAg loss
Lu Zhang1,2, Xiaohao Wang1,2, Shan Zhong1,2, Dachuan Cai1,2, Zhi into their treatment goals and emphasized the importance of anti-HBs
Zhou1,2, Hong Ren1,2, Peng Hu3,2, Hu Li1,2 as a key indicator of relapse risk. While pegylated interferon alpha
1
Department of Infectious Diseases, The Second Affiliated Hospital of (Peg-IFNα) was widely recognized as a potential option for achieving
Chongqing Medical University, China., 2Institute for Viral Hepatitis, The functional cure, low efficacy and significant side effects were identified
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry as major limitations. For future curative regimens, both patients and
of Education), Chongqing Medical University, China., 3Department HCPs prioritized higher treatment efficacy over shorter treatment
of Infectious Diseases, The First Affiliated Hospital of Chongqing duration (e.g., 24 weeks). Both groups strongly preferred a regimen
Medical University, China. option offering early identification of responsive patients with a higher
Background: Acute hepatitis B virus (aHBV) infection is typically self- likelihood of achieving functional cure and sparing costly or not well
limiting, with HBsAg clearance expected within six months. However, tolerated regimens to optimize the risk, benefit and cost of care.
recent data from the Hepatitis B Research Network reveal that the Conclusion: This study provides valuable insights into the
clearance rate is only 36% at six months. This study aims to describe perspectives of Chinese patients and HCPs on HBV functional cure.
the clinical characteristics of aHBV patients in China and identify It highlights patients’ limited awareness of functional cure concepts
associated risk factors for HBsAg clearance. and underscores the need for targeted education and communication
Method: A retrospective study was conducted on hospitalized patients efforts. Furthermore, it identifies a strong demand for predictive
diagnosed with aHBV from January 1, 2010, to December 30, 2023. approaches to identify high-response patient groups early in the
Demographic characteristics, clinical data, and outcomes (including treatment cascade. These preferences should guide future drug
HBsAg loss and anti-HBs development) were collected. Univariate development to improve patient outcomes and acceptance while
and Cox regression analyses were performed to identify risk factors addressing both clinical and patient-centered priorities.
associated with HBsAg clearance.
Result: A total of 171 consecutive eligible aHBV patients (43.3% male, OP0273
median age 29.0 years) were included in the study. After a median
follow-up of 128.1 weeks, HBsAg loss occurred in 82.5% of patients, Comparison of Antiviral Efficacy of Nucleos(t)ide Analogs
and anti-HBs developed in 53.1%. The median times to HBsAg Monotherapy or Combined with Interferon-α in Children with
loss and anti-HBs development were 9.00 weeks and 23.86 weeks, HBeAg-positive Chronic Hepatitis B Aged 1-6 Years
respectively. Cox regression analyses revealed that a longer symptom Ziwei Wang1, Yi Dong1, Jianguo Yan1, Lili Cao1, Wenxian Ouyang2, Lin
onset to first medical contact (SO-to-FMC) time (>5 days) (hazard Pang3, Hongmei Xu4, Yi Xu5, Yu Zhu6, Junliang Fu1, Fusheng Wang1,
ratio [HR]: 0.67; 95% confidence interval [CI]: 0.46-0.97), along with Min Zhang1
baseline ALT (HR: 1.03; 95% CI: 1.02-1.04) and AST levels (HR: 0.97; 1
The Fifth Medical Center of the Chinese PLA General Hospital ,
95% CI: 0.96-0.99), HBV-DNA load (≥5 log10 IU/mL) (HR: 0.54; 95% 2
Hunan Chidlren‘s Hospital, 3Beijing Ditan Hospital, Capital Medical
CI: 0.35-0.82), and HBeAg positivity (HR: 0.39; 95% CI: 0.26-0.59), University, 4Children‘s Hospital of Chongqing Medical University,
was significantly correlated with HBsAg loss. Additionally, baseline
5
Guangzhou Women and Children‘s Medical Center, 6West China
ALT level (HR: 1.01; 95% CI: 1.01-1.02), viral load (HR: 0.49; 95% CI: Second University Hospital, Sichuan University
0.28-0.84), and HBeAg status (HR: 0.48; 95% CI: 0.30-0.77) were also Background: Functional cure marked by hepatitis B surface antigen
significantly associated with the development of anti-HBs. (HBsAg) loss is the ideal therapeutic endpoint for children with chronic
Conclusion: Only about half of patients with aHBV achieve HBsAg hepatitis B (CHB). Current studies have shown that the younger the
seroconversion within six months. Assessing liver function, viral load, CHB children, the better the antiviral effect. After 24-36 months of
and HBeAg status helps physicians effectively identify and manage antiviral therapy based mainly on Interferon-α (IFN-α), the functional
patients with aHBV. cure rate of children aged 1-7 years can reach more than 40%,
Table and Figure:Figure 1.Graphical abstract and even as high as 60% in the group aged 1-3 years. However,
the incidence of IFN-α adverse events is relatively high. Jonas et al.
OP0272 found that the HBsAg clearance rate of nucleos(t)ide analogs (NAs)
monotherapy in children under 6 years old was 23.2%, suggesting that
Patients and healthcare providers’ perspectives for functional children with NAs monotherapy can also obtain a higher cure rate than
cure of HBV: a qualitative interview study in China adults. The aim of this study was to compare the antiviral efficacy of
Yao Zhang1, Cindy Tang1, Xiaofei Chen1, David Margolis 1, Qing Zhu1 NAs monotherapy and combination therapy with IFN-α in circulating
1
Brii Biosciences hepatitis B e antigen (HBeAg)-positive CHB children aged 1-6 years.
Background: The field of HBV cure has advanced significantly in Method: Seventy-eight children aged 1-6 years old with HBeAg-
recent years, with multiple regimens entering late-stage development, positive CHB were included in the multicenter study from November
requiring a careful balance between safety, efficacy and affordability. 2020 to August 2023. According to the antiviral treatment regimen,
Understanding the perspectives and preferences of patients and they were divided into NAs+IFN group (n=54) and NAs group (n=24).
healthcare providers (HCPs) on HBV functional cure is critical to The NAs group was given lamivudine or entecavir. The NAs+IFN
guide drug development and ensure alignment with stakeholder group was combined with IFN-α (≤3 years) or pegylated interferon-α
expectations. For this study, “functional cure” is defined as the (>3 years) on the basis of NAs. After 48 weeks, the HBV DNA loss
sustained loss of HBsAg with undetectable HBV DNA. rate, HBeAg loss/seroconversion rate, HBsAg loss rate and functional
Method: Between August and December 2023, individual interviews cure rate of the two groups were compared. In addition, according to
were conducted with six national opinion leaders (KOLs), 18 HCPs the age of initial antiviral treatment, the patients were divided into 1-3
(clinical directors or vice directors specializing in infectious diseases group (>1-≤3 years) and 4-6 group (>3-≤6 years), and the rate of HBV
and hepatology), and 16 Chinese patients diagnosed with chronic DNA loss, HBeAg loss/seroconversion, HBsAg loss and functional
hepatitis B (CHB) living in tier I cities (Beijing, Shanghai, Guangzhou) cure were compared between the two groups. Comparisons between
or tier II cities (Chengdu, Wuhan, Zhengzhou, Hefei, Jinan, Fuzhou, the groups were conducted using either chi-squared or Fisher’s
Hangzhou, Nanjing, Changsha). A semi-structured interview approach exact tests for categorical variables, and Mann-Whitney U tests for
was used, guided by open-ended questions on current treatment continuous variables.
Result: Compared with the NAs group, the NAs+IFN group significantly CHB and that Tfh17 may play an important role in regulating the
increased the rate of HBsAg loss (29.63% vs 8.33%, P=0.039) and immune response to chronic HBV infection.
functional cure (22.22% vs 4.17%, P=0.048). There were no significant Table and Figure:Figure 1.Figure legend: (A)PD-1, ICOS expression in
differences in HBV DNA loss rate, HBeAg loss/seroconversion rate, Tfh17 cell subsets of CHB patients and HC group. The analysis of Tfh17
HBsAg loss rate and functional cure rate between NAs+IFN group and frequencies and ALT (B) Frequencies of Tfh cell subsets in patients
NAs group in the 1-3 group (P>0.05). However, for children aged 4-6 with CHB in different ALT levels (C) Correlation analysis of Tfh17 cells
years, the HBV DNA loss rate (80.65% vs 41.18%, P=0.006), HBsAg and their subsets with ALT in CHB patients. Tfh, follicular T helper cell;
loss rate (35.48% vs 5.88%, P=0.035) and functional cure rate (22.58% CHB, chronic hepatitis B; ALT, alanine aminotransferase; MFI, mean
vs 0%, P=0.041) of the NAs+IFN group were significantly higher than fluorescence intensity; HBV, Hepatitis B virus; ; HC, healthy control;
those in NAs group. PD-1, programmed cell death-1; ICOS, inducible T-cell costimulator.
Conclusion: The antiviral efficacy of combination therapy of NAs and
IFN-α was better than that of NAs monotherapy. However, the antiviral OP0275
efficacy of NAs monotherapy was comparable to that of combination
therapy of NAs and IFN-α in CHB children aged 1-3 years. Sustained functional cure in chronic hepatitis B patients treated
Table and Figure:Figure 1.Comparison of antiviral efficacy of different with peginterferon alpha-2b combined with TDF: Reports at 52
treatment for HBeAg-positive CHB children aged 1-3 years at the end weeks extended follow-up after a phase 3 trial
of the 48-week follow-up period Fengqin Hou1, Jia Shang2, Qing Xie3, Chunliang Lei4, Jianmei Lin5,
Figure 2.Comparison of antiviral efficacy of different treatment for Guoxin Hu6, Zhiliang Gao7, Yilan Zeng8, Jiabin Li9, Qianguo Mao10,
HBeAg-positive CHB children aged 4-6 years at the end of the 48- Liying Zhu11, Jun Chen12, Xiaozhong Wang13, Zuxiong Huang14, Jiming
week follow-up period Zhang15, Ping An16, Xiulan Xue17, Yan Huang18, Tianyan Chen19, Jianqi
Lian20, Yueyong Zhu21, Huiling Xiang22, Xinyue Chen23, Hui Guo24,
Ruoyi He25, Yalin Yin25, Li Sun25, Guiqiang Wang1,26
OP0274 1
Peking University First Hospital, Beijing, 100034, China, 2Henan
Less circulating T follicular helper 17 cells defected the anti-HBV Provincial People‘s Hospital, Zhengzhou, 450000, China, 3Ruijin
humoral immunity in CHB patients Hospital, Shanghai Jiaotong University School of Medicine, Shanghai,
Shengxia Yin1, Tong Xin1, Yuxin Chen2, Chao Wu1, Jie Li1 2
00000, China, 4Guangzhou Eighth People‘s Hospital, Guangzhou
1
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Medical University, Guangzhou, 510000, China, 5Sichuan Provincial
The Affiliated Hospital of Nanjing University Medical School, Nanjing, People‘s Hospital·Sichuan Academy of Medical Sciences, Chengdu,
Jiangsu, China;, 2Department of Laboratory Medicine, Nanjing Drum
6
10000, China, 6Peking University Shenzhen Hospital, Shenzhen,
Tower Hospital, The Affiliated Hospital of Nanjing University Medical
5
18000, China, 7The Third Affiliated Hospital, Sum Yat-Sen University,
School, Nanjing, Jiangsu, China; Guangzhou, 510000, China, 8Public Health Clinical Center of
Chengdu, Chengdu, 610000, China, 9The First Affiliated Hospital of
Background: Dysfunction of Hepatitis B virus (HBV)-specific B
Anhui Medical University, Hefei, 230000, China, 10Xiamen Hospital of
cell and lacking of antibody against hepatitis B surface antigen
Traditional Chinese Medicine, Xiamen, 361000, China, 11The Fourth
(HBsAg) is associated with failure of functional cure in chronic hepatitis Affiliated Hospital of Harbin Medical University, Harbin, 150001, China,
B (CHB). Since follicular helper T (Tfh) cells are essential for B cell 1
2Shenzhen Third People‘s Hospital, Shenzhen, 518000, China,
differentiation into plasma cells, previous studies have suggested that 1
3Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese
dysregulated Tfh responses among CHB patients. Blood Tfh cells Medicine, Urumqi, 830000, China, 14Mengchao Hepatobiliary Hospital
comprised three subsets with distinct capability to help B cells.: T of Fujian Medical University, Fuzhou, 350000, China, 15Huashan
helper 1 (Tfh1), Tfh2, and Tfh17 cells, with distinct capability to help Hospital, Fudan University, Shanghai, 200040, China, 16The Sixth
B cells via IL-21, ICOS and many other ways. However, the function of People‘s Hospital of Shenyang, Shenyang, 110000, China, 17The
Tfh cells, especially its subsets, among CHB patients have not been First Affiliated Hospital of Xiamen University, Xiamen, 361000, China,
carefully dissected. Here, we characterized the phenotype of Tfh 1
8Xiangya Hospital Central South University, Changsha, 410000,
cells to explore the potential mechanisms responsible for the aberrant China, 19The First Affiliated Hospital of Xi‘an Jiaotong University,
immune response to HBV. Xi‘an, 710061, China, 20The Second Affiliated Hospital of the Air Force
Method: Samples of peripheral blood mononuclear cells Military Medical University of CPLA, Xi‘an, 710038, China, 21The First
(PBMCs) from CHB patients treated naive, treated with untreated Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, China,
nucleoside analogues and/or Peg-IFN-α were colected. And
2
2Tianjin Third Central Hospital, Tianjin, 300170, China, 23Beijing
healthy individuals who completed the standard HBV vaccine Youan Hospital, Capital Medical University, Beijing, 100000, China,
immunization were also included. The frequencies of peripheral Tfh
2
4First Teaching Hospital of Tianjin University of Traditional Chinese
cells (CD4+CXCR5+), Tfh1 cells (CD4+CXCR5+CXCR3+CCR6-), Medicine, Tianjin, 300170, China, 25Xiamen Amoytop Biotech Co. Ltd,
Tfh2 cells (CD4+CXCR5+CXCR3-CCR6-) and Tfh17 cells Xiamen, 361028, China, 26Peking University International Hospital,
(CD4+CXCR5+CXCR3-CCR6+) and their activated status Beijing, 102206, China
(ICSO+PD-1+) were characterized by flow cytometry. We Background: Functional cure can be achieved through the treatment
further analysed frequencies of the subgroups and surface protein based on peginterferon alpha (PegIFNα) in patients with chronic
features of Tfh and HBsAg-specific B cells by flow cytometry. HBsAg- hepatitis B (CHB). Multiple studies have demonstrated good durability
specific Tfh cells were identified by IL-21 secreting Tfh cells from of HBsAg loss obtained by PegIFNα therapy. This study evaluated
PBMC co-cultured with HBsAg pooled peptides for 48 hours. the long-term durability of functional cure in patients who achieved by
Result: Compared to healthy individuals, patients with chronic hepatitis PegIFNα-2b from a phase 3 clinical trial.
B had significantly more Tfh cells (P <0.0001), significantly less Tfh17 Method: Patients who achieved functional cure (maintain HBsAg loss
cells (P=0.0283), and significantly more PD-1 expression in Tfh17 and HBV DNA undetectable for 24 weeks follow-up after all drugs
(P<0.0001). Further analysis revealed a increase in the frequency of discontinuation) at the end of a phase 3 trial (NCT04846491) were
IL-21+ Tfh17 cells and a decrease in the frequency of quiescent Tfh17 enrolled in cohort 1 of this long-term follow up study (NCT06707922),
cells during the HBeAg-negative chronic hepatitis (ENH) phase (all observing for 5 years to evaluate the persistence and long-term
P<0.05). The frequencies of quiescent Tfh17 cells had a negatived outcomes in different groups. In the preliminary phase 3 trial,
correlation with HBsAg+ B cells (P=0.0002, r=-0.4481). The frequency nucleos(t)ide analogue (NA)-experienced patients were randomized
of quiescent Tfh17 cells was positively correlated with total IgG to receive tenofovir disoproxil fumarate (TDF) monotherapy (group 1),
(P =0.0285, r=0.3873). Further analysis revealed that the frequency of TDF combined with PegIFNα-2b 180 μg/week (group 2) or 90 μg/week
quiescent Tfh17 cells was positively correlated with IgG1 (P=0.0128, (group 3); after 48 weeks of TDF treatment, patients in group 1 either
r =0.4353) and IgG3 (P =0.0083, r =0.4583). continue TDF monotherapy (group 1a) or switch to adding PegIFNα-2b
Conclusion: Our study suggested that Tfh17 frequency and HBsAg- 180 μg/week (group 1b). Treatment-naïve patients were also included
specific Tfh cell differed in varied immune stages of patients with to receive TDF combined with PegIFNα-2b 180 μg/week (group 4).
The treatment period was 144 weeks and the follow-up was 24 weeks. patients (Figure 3 a-c).
PegIFNα-2b were given intermittently in cycles. The results of cohort 1 Conclusion: In the clinical management of CHB patients, HBV RNA
of this extended long-term follow-up study at 52 weeks were analyzed can reflect the transcriptional activity of intrahepatic cccDNA. It
here. is necessary to monitor the changes in HBV RNA so as to achieve
Result: A total of 88 patients achieved functional cure were enrolled in personalized diagnosis and treatment for CHB patients.
cohort 1 of the follow-up study, including 32, 23, 29, and 4 patients from Table and Figure:Figure 1.Figure1&Figure2&Table1
PegIFNα-2b treatment groups 2, 1b, 3, and 4 of the preliminary phase Figure 2.Figure3
3 trial, respectively, and no patients from the TDF monotherapy group
(group 1a). All patients were functionally cured at enrollment, with both
OP0277
HBsAg and HBV DNA negative. The mean age of NA-experienced
patients in groups 2, 1b, and 3 ranged from 36.1 to 41.5 years, with Contrast-enhanced ultrasound based intelligent model for multi
58.6% to 82.6% being male. For treatment-naïve patients in group classification diagnosis of focal liver lesion
4, the mean age was 30.5 years and 25% were male. By 52 weeks Wenzhen Ding1, Jie Yu, Kun Wang, Ping Liang
of follow-up, 100% (32/32), 91.3% (21/23), 89.7% (26/29) and 100% 1
Chinese PLA General Hospital
(4/4) of patients maintained functional cure in groups 2, 1b, 3 and 4, Background: Accurate multi-classification diagnosis is the prerequisite
respectively, (Figure 1). Only 2 patients in group 1b and 3 patients in for reasonable management of focal liver lesions (FLLs). Ultrasound
group 3 relapsed, of which one patient in group 3 experienced HBV is the common image examination, but lacks accuracy for multi-
DNA reactivation (≥ 20 IU/mL) but remained HBsAg negative, and the classification. Contrast enhanced ultrasound (CEUS) offers better
other 4 patients had HBsAg relapse only. performance, but highly relies on experience. Therefore, we aimed to
Conclusion: The functional cure induced by PegIFNα-2b combination develop a CEUS-based artificial intelligence (AI) model for FLL multi-
therapy was durable, with a maintenance rate of 100% at 52 weeks classification and evaluate its performance in multicenter clinical tests.
of extended follow-up both in NA-experienced and treatment-naïve Method: CEUS videos, immunohistochemical biomarkers and clinical
patients receiving PegIFNα-2b 180 μg/week. Only one case of HBV information of solid FLLs larger than 1cm were collected to build
DNA recurrence was observed in the low-dose PegIFNα-2b group. model. Model was set to classify FLLs into six types: hepatocellular
PegIFNα-based therapy enables sustained functional cure for patients carcinoma, hepatic metastasis, intrahepatic cholangiocarcinoma,
with CHB, allowing for safe discontinuation of all drugs. hepatic hemangioma, hepatic abscess and others. Model building
Table and Figure:Figure 1.Figure 1. 52 weeks maintenance rate of was divided into two stages. Module-Disease, Module-Biomarker and
functional cure in each group Module-Clinic were built in training set A and validation set, and three
modules were aggregated as Model-DCB in training set B and internal
OP0276 test set. Model-DCB performance was compared with CEUS and MRI
radiologists in three external test sets.
Serum HBV RNA Distribution in Patients with Chronic Hepatitis B
Result: Since January 2017 to December 2023, 3725 FLLs from
Jiaojiao Wang1, Dachuan Cai1 52 centers were divided into training set A (n=2088), validation set
1
the Second Affiliated Hospital of Chongqing Medical University (n=592), training set B (n=234), internal test set (n=110), external
Background: Serum HBV RNA is a downstream transcription product test set A (n=113), B (n=276) and C (n=312). In external test sets A,
of cccDNA and is not directly inhibited by nucleos(t)ide analogues B and C, Model-DCB all achieved significantly better performance
(NAs). This study investigates the distribution of serum HBV RNA in (Accuracy from 0.85 to 0.86) than junior CEUS- radiologists (0.59-
chronic hepatitis B virus-infected patients and in patients with chronic 0.73), and comparable to senior CEUS- radiologists (0.79-0.85) and
hepatitis B(CHB) after long-term and regular NAs antiviral therapy. senior MRI- radiologists (0.82-0.86). In multiple subgroup analyses on
Method: This study analyzed 196 untreated chronic hepatitis B virus- demographic characteristics, tumor characteristics and ultrasound
infected(UN) patients and 804 CHB patients who had received regular devices, accuracy of Model-DCB ranged from 0.79 to 0.92.
NAs therapy for more than 48 weeks. The NAs-treated CHB patients Conclusion: CEUS-based Model-DCB provides accurate multi-
were divided into two groups:664 patients with maintained virological classification of FLLs. It holds promise to benefit a wide range of
response (MVR), whose HBV DNA was less than 20 IU/mL, and 140 population, especially for patients in remote suburban areas who have
patients with low-level viremia (LLV), whose HBV DNA was between difficulty accessing MRI.
20IU/mL and 2000 IU/mL. We evaluated the HBV RNA levels and Table and Figure:Figure 1.
distribution across these groups.
Result: The median HBV RNA levels in UN, LLV, and MVR patients
OP0278
were 2.76 (IQR 2.00 - 4.31), 3.27 (IQR 2.15 - 6.53), and 2.24 (IQR 2.00
- 3.21) log10 copies/mL, respectively. Overall, HBV RNA levels were Proteomics-Based Identification of Promising Serum Biomarkers
highest in LLV patients(Figure 1 a). Among HBeAg-positive patients, for Early Diagnosis of HBV-Related HCC in a Longitudinal Follow-
the level of HBV RNA was higher than HBeAg-negative patients.The Up Cohort
HBV RNA detection rates were 100% (UN), 99.3% (LLV), and 100% Junjie Chen1, Xiaoqi Yu1, Yongjun Chen2, Di Ma2, Xinxin Zhang1
(MVR) in HBeAg-positive patients,respectively. In HBeAg-positive and 1
Department of Infectious Diseases, Research Laboratory of Clinical
HBeAg-negative patients, there was no significant difference in HBV Virology, Ruijin Hospital, Shanghai Jiao Tong University School of
RNA levels between UN and LLV patients, but the levels were higher in Medicine, Shanghai 200025, China, 2Department of General Surgery,
UN and LLV patients compared to MVR patients (Figure 1 b). Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,
In UN patients, there was no significant difference in HBV RNA levels Shanghai, China
between HBeAg-positive infection and HBeAg-positive hepatitis, or Background: It is widely believed that antiviral therapy can reduce
between HBeAg-negative infection and HBeAg-negative hepatitis the occurrence of hepatocellular carcinoma (HCC) related to chronic
(Figure 2). hepatitis B (CHB). However, there are still some CHB patients
Among MVR patients, the HBV RNA detection rates did not change developing HCC during or after antiviral treatment. HCC is a leading
with prolonged treatment, and there was no significant differences in cause of cancer-related mortality, and its early diagnosis is critical
HBV RNA levels between different treatment times. In HBeAg-negative for improving survival rates. Identifying reliable biomarkers is key to
patients, those treated for more than 5 years had the lowest HBV RNA developing non-invasive diagnostic approaches. This study aims to
detection rates and levels(Table 1). investigate potential diagnostic biomarkers in the serum of patients
Correlation analysis showed that in UN patients, HBV RNA was with hepatitis B virus (HBV)-related HCC.
correlated with both HBV DNA and HBsAg (Figure 3 a,d). However, Method: We performed a comprehensive serum proteomics analysis
in LLV patients, there was no significant differences between HBV using Astral-Data Independent Acquisition (DIA) mass spectrometry to
RNA and HBV DNA (Figure 3 e). In both LLV and MVR patients, the identify potential biomarkers for HCC. A total of 352 serum samples from
correlation between HBV RNA and HBsAg was weaker than in UN
111 individuals collected between June 2008 and September 2024 worse survival. ESTIMATE analysis showed higher immune scores in
were analyzed. The samples included 13 healthy controls, 13 CHB the low-risk group (p=0.003). CIBERSORT revealed greater infiltration
patients, 11 HBV-related liver cirrhosis (LC) patients, 37 HCC patients of CD4+ T cells, CD8+ T cells, B cells, NK cells, and DC cells in the
of the experimental cohort, and 37 HCC patients of the validation low-risk group, while M2 macrophages were more prevalent in the
cohort. The HCC experimental cohort included 278 longitudinal serum high-risk group. The signature also predicted better outcomes for anti-
samples spanning up to 11 years before tumor occurrence and 5 PD-1/PD-L1 therapy in the low-risk group (p<0.0001).
years after tumor resection. HCC diagnosis was confirmed through Conclusion: The prognostic signature based on phagocytosis
postoperative pathology or enhanced MRI diagnosed by at least two regulators related genes demonstrates robust predictive performance
experienced radiologists. CHB and LC diagnoses were based on liver for HCC outcomes. Risk scores derived from our PRRGs-based
biopsy, while healthy controls were confirmed through serological signature reveal significant differences in immune cells, serving as
tests. potential indicators for treatment response in HCC.
Result: Proteomics analysis identified 6,514 proteins. Mfuzz time- Table and Figure:Figure 1. PRRGs enrichment in liver Kupffer cells by
series analysis of longitudinal HCC serum samples revealed clusters of scRNA sequencing
proteins with expression patterns changing during tumor progression, Figure 2.Validation of predictive efficacy of the PRRGs signature
including 402 proteins. Differential expression analysis showed that
CHI3L1, IQGAP3, SLC22A10, PRKG1, and C1orf124 were significantly
OP0280
elevated in HCC patients compared to healthy controls, CHB, and
LC patients (p < 0.05), while SCCPDH was significantly reduced (p Impact of Splenic CD101+ Neutrophils and Mechanism of Their
< 0.05). In the validation cohort, PRKG1 also effectively distinguished Phenotypic Transformation during Hepatocellular Carcinoma
HCC from non-HCC groups (p < 0.05). Progression
Conclusion: This study highlights the potential of PRKG1 as a non- Gaixia He1, Ying Zhou1, Wenjuan Li1, Yingxue Liang1, Jun Feng1,
invasive biomarker for early diagnosis of HCC in patients with chronic Chen Zhang1, Xi Liu1, Qi Shang1, Fanpu Ji1, Guangyao Kong1,
HBV infection. These findings support further validation of PRKG1 in Zongfang Li1
larger cohorts to improve early detection and monitoring of HCC. 1
National & Local Joint Engineering Research Center of Biodiagnosis
and Biotherapy, The Second Affiliated Hospital, Xi‘an Jiaotong
University, Shaanxi Province, Xi‘an, P.R. China.
OP0279
Background: The immune microenvironment of hepatocellular
A Prognostic Signature of Phagocytosis Regulators Predicts
carcinoma (HCC) is highly complex, leading to tumor immune evasion.
Outcomes and Immune Landscape in Hepatocellular Carcinoma
Given the abundant neutrophils in the spleen, an in-depth exploration
Hao Cui1, Tao Han2, Baoxin Qian1, Yintang Gao3 of the relationship between splenic neutrophils and HCC progression
1
Department of Gastroenterology and Hepatology, The Third Central may provide a basis for developing novel immunotherapy strategies
Hospital of Tianjin, 2Department of Hepatology and Gastroenterology, for HCC.
Tianjin Union Medical Center affiliated to Nankai University, 3Tianjin Method: The present study established an orthotopic HCC mouse
Key Laboratory of Extracorporeal Life Support for Critical Diseases, model to comprehensively analyze frequency and phenotype changes
Tianjin Institute of Hepatobiliary Disease, Nankai University Afnity the of splenic neutrophil. Through tissue immunofluorescence staining,
Third Central Hospital, Tianjin, China
we visually observed the infiltration of neutrophils in both the spleen
Background: Hepatocellular carcinoma (HCC) is one of the most and HCC tissues. Additionally, using in vivo co-injection experiments,
common malignant tumors globally.Tumor-associated macrophages we analyzed the role of splenic neutrophils in HCC progression.
(TAMs) are integral to the tumor microenvironment and play a Furthermore, RNA sequencing technology was employed to dissect
crucial role in HCC progression, immune evasion, and treatment the gene expression profiles of different neutrophil phenotypes within
resistance. However, the regulatory mechanisms of macrophage- the spleen.
mediated phagocytosis remain poorly understood.In this study we Result: Compared with the control group, a significant increase in the
constracted a predictive signature based on phagocytosis regulator- number of splenic neutrophils was observed in the HCC orthotopic
related genes (PRRGs) ,and assess its role in infiltration,patient mouse model, accompanied by phenotypic changes. Notably,
outcomes,and treatment responses in HCC. under the tumor burden, the number of CD101+ neutrophils in the
Method: PRRGs were identified through literature mining.GO and spleen increased markedly, aligning with the trend observed in HCC
KEGG pathway analyses highlighted their functions. Single-cell RNA tissues. It is worth mentioning that the expression level of PD-L1 on
sequencing (GSE149614) revealed PRRGs enrichment in liver Kupffer the surface of neutrophils in tumor-bearing mice was significantly
cells. A prognostic signature based on PRRGs was constructed elevated, suggesting that neutrophils may be involved in the tumor
using univariate Cox and LASSO regression with TCGA-LIHC as the immune regulatory process. In vivo co-injection experiments further
training cohort and GSE14520 and GSE76427 as validation cohorts. confirmed that CD11b+Ly6G+CD101+ neutrophils isolated from the
Survival analysis and ROC curves assessed the predictive accuracy. spleen could inhibit HCC tumor growth to a certain extent. However, an
Quantitative RT-PCR validated gene expression in 84 paired tumor and in-depth analysis of the gene expression characteristics of the splenic
adjacent normal tissues. Immune cell infiltration was analyzed using CD11b+Ly6G+CD101+ neutrophil subset revealed that, compared to
CIBERSORT and ESTIMATE algorithms. Immune checkpoint blockade the CD101- neutrophil subset, the CD101+ neutrophil subset exhibited
(ICB) responses were evaluated using GSE135222. significantly higher expression levels of genes related to angiogenesis,
Result: Among 271 phagocytosis regulators, GO and KEGG analyses neutrophil activation, myeloid cell chemotaxis, extracellular matrix
showed enrichment in immune activation and phagocytosis-related remodeling, tumor cell proliferation, cytotoxicity, and immune
pathways. Forty-five regulators, including SIRPA, FCGR2A, ICAM1, suppression. These findings rationalized the above results of their
and AXL, were highly expressed in Kupffer cells. A prognostic signature promoting HCC growth.
of 13 genes (ALAD, BCOR, CADM1, CIT, EMC1, GRSF1, LCK, Conclusion: Our study showed that splenic CD101+ neutrophils
MUC12, NDUFC1, PODXL, RNF122, SIRPA, TM2D1) demonstrated increased significantly under tumor burden, thus promoted HCC
robust prognostic value. The AUC for 1-, 3-, and 5-year survival was progression. It provides evidence for the critical role of neutrophil
0.758, 0.736, and 0.692 in the training cohort, and 0.702, 0.734, in hepatic-splenic immune interaction, paving the way for new HCC
0.656 (GSE14520) and 0.781, 0.767, 0.905 (GSE76427). Multivariate immunotherapy strategies.
Cox analysis confirmed the risk score as an independent prognostic Funding: This work was supported by the National Natural Science
factor. PCR validation identified seven signature genes with differential Foundation of China (81802455); Basic-Clinical Fusion Project
expression between tumor and adjacent tissues. ALAD, MUC12, and of Xi’an Jiaotong University (YXJLRH2022098); Free Exploration
NDUFC1 were higher in adjacent tissues, while BCOR, EMC1, PODXL, Project of the Second Affiliated Hospital of Xi’an Jiaotong University
and TM2D1 were upregulated in HCC. Low ALAD and CADM1 [2020YJ(ZYTS)546-03]
expression correlated with poor differentiation, elevated AFP, and
 OP0281 yr OS: ALBI 1=  83.3%, 41.7%, 2.61% vs. ALBI 2= 71.6%, 19.8%,
Early Diagnosis of HBV-related HCC: Application of Liquid Biopsy 0%  vs. ALBI 3= 10.6% . Other predictors of OS on univariate analysis
Technology Based on DNA Methylation were target tumor number (P = 0.009), INR (P = 0.009), platelet
(p=0.006), CPC (p= 0.000), and complete ablation (p=0.002). Only
Xueying Huang1, Yu Chen1, Mei Liu2, Zhongping Duan1
ALBI grade (OR=0.661 ;95% CI=0.089-1.18;p=0.007) and complete
1
Fourth Department of Liver Disease (Difficult & Complicated Liver ablation (OR=0.418;95% CI=0.122-0.626;p=0.002) remained as
Diseases and Artificial Liver Center), Beijing You’an Hospital,
independent predictors of OS on multivariate analysis.
2
Department of Oncology, Beijing You’an Hospital
Conclusion: Our study highlights the importance of both complete
Background: Hepatocellular carcinoma (HCC) is a leading cause of ablation of all tumors and baseline liver function in the prognosis of
cancer-related deaths, with hepatitis B virus (HBV) infection being a HCC patients undergoing thermal ablative therapies.
major risk factor. Early detection in high-risk HBV-positive populations Table and Figure:Figure 1.Table 1: Baseline and Demographic
is crucial for improving survival but is hampered by the limitations characteristics pf the Cohort according to ALBI Grade
of conventional tools such as alpha-fetoprotein (AFP) testing and Figure 2.Cox regression table summarizing the effects of different
ultrasound. This study evaluates the performance of the Hepatocellular predictors
Carcinoma Monitor (HCC Monitor), a liquid biopsy test utilizing cell-
free DNA (cfDNA), for predicting HCC development in HBV-infected
individuals.
OP0283
Method: We conducted a prospective study of high-risk HBV- The stages of liver fibrosis and steatosis in patients with metabolic
positive patients from Beijing You’an Hospital between 2020 and dysfunction-associated steatotic liver disease (MASLD) are
2022. Patients with prior malignancies, recent blood transfusions, associated with specific fatty acid metabolic pathways
autoimmune diseases, or HIV were excluded. Participants were Alexey Goncharov1, Vladimir Zotov1, Vladimir Bessonov1, Vasily
categorized into positive, warning, or negative groups based on HCC Isakov1
Monitor scores, with follow-ups conducted over 24 months to monitor 1
Federal Research Centre of Nutrition, Biotechnology and Food safety
HCC development. The predictive accuracy of the HCC Monitor was Background: Lipidomic analysis has demonstrated that fatty acid
assessed using the area under the receiver operating characteristic metabolism is impaired in MASLD patients; however, there are no
curve (AUC), sensitivity, and specificity, with logistic regression specific lipidomic markers of liver fibrosis or steatosis. This study
analysis to evaluate its independence as a risk predictor. aimed to reveal any associations between lipidomic markers and the
Result: Among the 393 patients included in the study, 47 (11.96%) stages of liver steatosis and fibrosis.
were diagnosed with HCC during the 24-month follow-up period. The Method: Pairs (n=40) of patients with MASLD and control groups
HCC Monitor exhibited strong predictive performance, achieving an matched for sex, age, and BMI were selected from the database.
area under the receiver operating characteristic curve (AUC) of 0.89 The stages of liver steatosis and fibrosis were assessed by vibration-
(95% CI: 0.84–0.94, p<0.001). With a defined cutoff score of 69.5, the controlled transient elastography with a controlled attenuation
test demonstrated a sensitivity of 91.7% and a specificity of 70.4%. parameter. Lipidomic analysis of plasma and red blood cells was
In contrast, the combined use of AFP and ultrasound yielded a lower performed using high-performance gas chromatography with mass
predictive accuracy, with an AUC of 0.73 (p<0.001). Multivariate spectrometry on an Agilent Triple Quadrupole 7000 system. The study
analysis further identified the HCC Monitor as an independent predictor was funded by the Russian Science Foundation (Project No. 19-76-
of HCC risk (OR=1.32, p<0.001). 30014).
Conclusion: The HCC Monitor offers a significant advancement in Result: Differences were found in the levels of palmitic acid (1877.4
early HCC detection for HBV-positive high-risk populations, surpassing [1130.6 - 2558.3] vs. 1343.1 [686.5 - 1735.2] nmol/g) and oleic acid
the diagnostic capabilities of AFP and ultrasound. Its integration into (1145.5 [628.0 - 1777.1] vs. 742.7 [311.1 - 950.9] nmol/g) in erythrocyte
clinical practice could facilitate earlier interventions and improve membranes, as well as behenic acid levels (2.63 [1.66 - 3.17] vs. 3.17
patient outcomes. [1.79 - 12.94] μg/g) in plasma between the MASLD and control groups.
Table and Figure:Figure 1.ROC curve of HCC monitor score, AFP and A positive correlation was identified between several fatty acid levels in
AFP + US erythrocyte membranes and liver fibrosis stages, positive correlations
Figure 2.The HCC monitor scores and contributions of the ctDNA and were observed for tridecanoic, myristic, and palmitoleic acids in
protein biomarkers erythrocyte membranes, and negative correlations were observed for
cis-11,14-eicosadienoic acid in the plasma with liver steatosis stages
OP0282 (Table).
Albumin-Bilirubin Grade As Predictor of Survival in Hepatocellular Conclusion: The stages of liver steatosis and fibrosis in patients with
Carcinoma Patients treated with Thermal Ablation MASLD are associated with different fatty acid metabolic pathways.
Further studies are needed to identify lipidomic markers of the
ERIKA JOHANNA PANADERO TANADA-ESCANLAR1, STEPHEN N
progressive course of the disease.
WONG1
Table and Figure:Figure 1.Table. Founded correlations of specific fatty
1
University of Santo Tomas Hospital
acids, liver steatosis, and fibrosis stages in patients with MASLD
Background: The Albumin–Bilirubin (ALBI) grade has been shown to
predict survival in hepatocellular carcinoma (HCC) undergoing various
treatments. We aimed to determine independent predictors of overall
OP0284
survival (OS) by analyzing liver reserve using ALBI and Child-Pugh Central obesity further increases the risk of adverse liver
classification (CPC) in HCC patients treated with either Radiofrequency outcomes in patients with high BMI
Ablation (RFA) or Microwave Ablation (MWA). Sherlot Juan Song1,2, Terry CheukFung Yip1,2, Grace LaiHung Wong1,2,
Method: Consecutive HCC patients treated with RFA and MWA from Dae Won Jun3,4, Vincent WaiSun Wong1,2
March 2007-August 2023 were included. Log rank and cox regression 1
Medical Data Analytics Centre, Department of Medicine and
analysis were used to compare the OS between different variables Therapeutics, The Chinese University of Hong Kong, Hong Kong,
while cox regression was used to determine independent predictors China, 2State Key Laboratory of Digestive Disease, Institute of
of OS.   Digestive Disease, The Chinese University of Hong Kong, Hong
Result: A total of 242 patients underwent RFA (N= 185) and Kong, China, 3Hanyang Institute of Bioscience and Biotechnology,
MWA  (N=57). Patients with higher ALBI grade were more likely to be Hanyang University, Seoul, Republic of Korea, 4Department of Internal
incompletely ablated (p=0.002). There was incongruence between Medicine, Hanyang University, College of Medicine, Seoul, Republic
ALBI and CPC in that while majority (95.7%) of ALBI grade 1 were CPC of Korea
A, only 71.4% of CPC A patients were classified as ALBI grade 1. A Background: Both overweight/obesity [BMI≥23 (25 Caucasian) kg/
lower ALBI grade was predictive of OS on univariate analysis (1,2,3- m2] and central obesity [waist circumstance (WC) ≥90 cm (M)/80
cm (F) (102/88 Caucasian)] were included in the diagnosis criteria models and restricted cubic spline (RCS) curves were employed to
of metabolic dysfunction-associated fatty liver disease (MAFLD). We measure the relevance of METS-VF to MASLD. Then, we predicted the
aimed to examine any heterogeneity among patients meeting either correlation between the main variables involved in this study via the
obesity-related definition and the impact of these two factors on the “tidyverse” R package. Subgroup analyses were performed to evaluate
liver-related outcomes. the stability of these associations across different subgroups. Finally,
Method: We examined all individuals with MAFLD diagnosis and receiver operating characteristic (ROC) analyses were performed to
BMI≥23 kg/m2 and/or central obesity from Clinical Data Analysis assess and compare the predictive abilities of METS-VF, other central
and Reporting System (CDARS) in Hong Kong SAR of China from obesity indicators, and common clinical indicators for MASLD.
2000-2021 and the National Health and Nutrition Examination Survey Result: After adjusting for potential confounders, the model results
(NHANES) in United States from 2017-2020. Cumulative incidence revealed that the odds ratios (95% confidence intervals) between
function of liver-related events (LRE) in CDARS cohort was evaluated METS-VF and MASLD was 13.00 (7.42, 22.70). A positive correlation
using Aalen-Johansen method, stratified by three groups: overweight/ was observed between the METS-VF score and the prevalence of
obesity alone, central obesity alone, and both overweight/obesity and MASLD in both the unadjusted Model I (Model I: OR = 12.3, 95% CI:
central obesity. Two Fine-Gray regression models were used to estimate 8.2–18.3) and the adjusted Model II for age, gender, race and PIR
subdistribution hazard ratios (SHR) and 95% confidence interval (CI) (Model II: OR = 17.7, 95% CI: 10.7–29.1). Even after adjusting for all
for the mentioned three-grouping variable on LREs, adjusting for factors in Model III, the positive correlation between the METS-VF
other important covariates. Single imputation was performed for any score and the prevalence of MASLD remained significant (Model
missing parameters. Two multivariable logistic regression models were III: OR = 13.0, 95% CI: 7.4–22.7). Moreover, the correlation between
estimated to calculate odds ratios (OR) of LSM measurement ≥ 8/12 METS-VF and MASLD stayed consistent regardless of stratification. In
kPa in NHANES cohort, including the same covariates (with a BMI cut- correlation analyses of indicators, METS-VF was significantly positively
off of 25 kg/m²). correlated with age, weight, waist circumference, BMI, CAP, WHtR and
Result: 13,908 patients and 4,633 patients were included from METS-IR. The results from the RCS showed a significant non-linear and
CDARS cohort and NHANES cohort. A significant difference in the monotonically increasing association between METS-VF and MASLD,
cumulative risk of developing LREs was observed among patients with with no segmental effects observed. The area under the curve (AUC) of
overweight/obesity alone, central obesity alone, and both overweight/ METS-VF was greater than that of other indices for predicting MASLD.
obesity and central obesity (log-rank test p = 0.03, Figure 1), with 10- Conclusion: Among adults in the United States, METS-VF is positively
year cumulative incidence of 1.76%, 3.00%, 3.17%, respectively. Fine- correlated with an increased risk of MASLD. Furthermore, METS-VF
Gray regression model indicated that patients with both high BMI and may function as a more precise diagnostic indicator for MASLD, and
high WC were associated with the highest LRE risk (SHR: 2.04, 95% CI offer a new approach for further evaluating the relationship between
1.17-3.57, p = 0.01, Figure 1). Patients with central obesity alone did visceral fat and MASLD.
not have a significantly different risk of LRE (SHR:1.43, 95% CI 0.58- Table and Figure:Figure 1.The results of logistic regression analysis.
3.55, p = 0.44) compared to those with overweight/obesity alone. In Figure 2.The ROC curve.
the NHANES cohort, using patients with overweight/obesity alone as
a reference, those with both overweight/obesity and central obesity
OP0286
had a significantly increased odds of having significant or advanced
fibrosis measured by LSM (OR for LSM≥8 kPa: 1.09, 95%CI 1.03-1. Sarcopenic obesity Increased the Risk of Metabolic Associated
09, p=0.002; OR for LSM≥12 kPa: 1.05, 95%CI 1.02-1.09, p=0.005, Steatotic Liver Disease and Fibrosis in Elderly Residents
Figure 2). Xiaohui Liu1, Xiaodie Wei1, Haiqing Guo1, Jing Zhang1
Conclusion: Central obesity is an additional key risk factor to non-lean 1
Fatty Liver Disease Treatment Center, Beijing Youan Hospital, Capital
MAFLD for the increased adverse liver outcome based on data in both Medical University, Beijing, 100069, China
Asian and US population. Lean patients with central obesity warrant Background: Sarcopenia and obesity are two major public health
the same clinical attention as overweight patients without central issues associated with metabolic associated steatotic liver disease
obesity, given the similar outcomes observed in both groups. (MASLD) respectively. Their coexistence—referred to as sarcopenic
Table and Figure:Figure 1.Time-to-event analysis and fine-gray obesity (SO) —further exacerbates the health challenges particularly
regression analysis on LRE in HK CDARS cohort in the elderly population. However, the relationship of SO and MASLD
Figure 2.Logistic regression analyses for significant/advanced fibrosis were not clear.
in NHANES cohort Method: The research recruited 1160 elderly residents in a Beijing
community. Demographic data, medical history, physical examination
OP0285 and laboratory results were collected. Fatty liver was detected by B
type ultrasound. Liver fat content and fibrosis was examined by Fibro
Association of metabolic score for visceral fat with metabolic
Scan. Body composition was detected by bioelectrical impedance
dysfunction-associated steatotic liver disease: A cross-sectional
analysis. Advanced liver fibrosis was defined as NAFLD fibrosis score
study of NHANES 2017-2020.
(NFS)≥ 0.676.
Zhihong Zhao1, Zhili Wen1 Result: The mean age was 69.00 (66.25,73.00) years old and 33.80%
1
Department of Gastroenterology Department, The Second Affiliated were male. A total of 664 patients (57.2%) were MASLD. The prevalence
Hospital of Nanchang University, 1 Minde Road, Donghu District, of sarcopenia in the MASLD group (20.03%) was significantly higher
Nanchang, Jiangxi, China. than in the non-MASLD group (13.10%, p=0.002). Both obesity and
Background: Metabolic dysfunction-associated steatotic liver disease SO showed a significant correlation with MASLD compared to the
(MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), normal group, regardless the obesity was defined by body mass index
refers to fatty liver disease with at least one cardiometabolic risk (BMI) or central obesity. SO had a higher odds ratio than sarcopenia
factor in the absence of excessive alcohol consumption. MASLD is and obesity (BMI: OR 8.21, 95% CI 5.09-13.24, p <0.001; WC: OR
characterized by extra fat accumulation in the liver, closely relating to a 9.00,95%CI 5.44-14.91, p <0.001). After adjusting for age, gender,
panoply of metabolic disorders such as overweight, insulin resistance, smoking, total cholesterol, hypertension and type 2 diabetes mellitus,
and dyslipidemia. The metabolic score for visceral fat (METS-VF), SO was also associated with advanced fibrosis by NFS (BMI: OR
as acknowledged by its term, is a metabolism-related measure that 11.28, 95% CI 4.13-30.87, p <0.001; WC: OR 11.04,95%CI 2.47-49.29,
reflects visceral adiposity levels. In order to investigate the association p =0.002) among MASLD patients.
between the METS-VF and MASLD, an observational cross-sectional Conclusion: In elderly MASLD patients, SO significantly increased the
study was launched based on the data from the 2017–2020 National risk of MASLD and fibrosis. The results indicated that elderly MASLD
Health and Nutrition Survey (NHANES). patients should be screened for sarcopenia. SO MASLD patients
Method: This cross-sectional study, which data from the NHANES 2017- should be more actively monitored and treatment.
2020, extracted 1728 participants. Firstly, weighted logistic regression Table and Figure:Figure 1.Figure 1. Prevalence of MASLD according to
sarcopenia and obesity status. E2F2 reprograms macrophage function by modulating material and
Figure 2.Table 1 ORs and 95% CIs of obesity only, sarcopenia only and energy metabolism in the progression of metabolic dysfunction-
sarcopenic obesity for MASLD development associated steatohepatitis
Zheng Liu1, Ling Lu2
OP0287 1
Department of General Surgery, the First Affiliated Hospital of
Nanjing Medical University, 2Affiliated Hospital of Xuzhou Medical
Insufficient Control of Cholestatic Pruritus in Primary Biliary
University
Cholangitis (PBC) With Current Therapies: Baseline Data From the
East Asian Population Enrolled in the Phase 3 GLISTEN (Global Background: Macrophages are essential for the development of
Linerixibat Itch STudy of Efficacy and safety iN PBC) Study steatosis, hepatic inflammation, and fibrosis in MASH. However, the
Xiong Ma1, Jidong Jia2, Qinglong Jin3, Kazuhito Kawata4, Atsumasa roles of macrophage E2F2 in the progression of MASH have not been
Komori5, Weiwei Mu6, Akari Suyama7, Jennifer Shannon8, Megan M elucidated.
McLaughlin8, Atsushi Tanaka9 Method: Human liver tissues obtained from patients with MASH and
controls were used to assess macrophage E2F2 expression. MASH
1
Shanghai Renji Hospital, Shanghai Jiao Tong University, Shanghai,
models were developed in myeloid-specific Nrf2 knockout (Nrf2M-
China, 2Beijing Friendship Hospital, Capital Medical University, Beijing,
China, 3The First Hospital of Jilin University, Changchun, China, KO), myeloid-specific E2F2 knockout (E2F2M-KO), and wild-type
4
Hamamatsu University School of Medicine, Shizuoka, Japan, 5NHO (Nrf2FL/FL or E2F2FL/FL) mice fed with a high-fat diet (HFD) for 26
Nagasaki Medical Center, Nagasaki, Japan, 6GSK, Beijing, China, weeks or a methionine/choline-deficient diet (MCD) for 6 weeks.
7
GSK K.K., Tokyo, Japan, 8GSK, Collegeville, PA, USA, 9Department of Result: This study revealed that the expression of macrophage E2F2
Medicine, Teikyo University School of Medicine, Tokyo, Japan is dramatically downregulated in MASH livers from mice and humans,
and that this expression is adversely correlated with the severity of
Background: Cholestatic pruritus is common in PBC and negatively
the disease. Myeloid-specific E2F2 depletion aggravates intrahepatic
impacts quality of life. Guideline-recommended therapies show limited
inflammation, hepatic stellate cell activation, and hepatocyte lipid
efficacy for treating pruritus in PBC and few PBC clinical trials include
accumulation during MASH progression. Mechanistically, E2F2 can
itch as the primary outcome. Linerixibat, a minimally absorbed ileal bile
inhibit the SLC7A5 transcription directly. E2F2 deficiency upregulates
acid transporter inhibitor, is a twice-daily oral tablet in development
the expression of SLC7A5 to mediate amino acids flux, resulting in
for the treatment of pruritus in PBC. Understanding pruritus severity
enhanced glycolysis, impaired mitochondrial function, and increased
and treatment is important to identify patient needs. Here, we report
macrophage proinflammatory response in a Leu-mTORC1-dependent
baseline characteristics and pruritus treatment history of East Asian
manner. Moreover, bioinformatics analysis and CUT &Tag assay identify
participants (from China and Japan) as well as for all participants in
the direct binding of Nrf2 to E2F2 promoter to promote its transcription
GLISTEN.
and nuclear translocation. Genetic or pharmacological activation of
Method: GLISTEN (NCT04950127) is an ongoing Phase 3, placebo-
Nrf2 effectively activates E2F2 to attenuate the MASH progression.
controlled study in adults with PBC and moderate–severe pruritus.
Finally, patients treated with CDK4/6 inhibitors demonstrate reduced
Pruritus severity is assessed using a worst itch 0–10 numerical rating
E2F2 activity but increased SLC7A5 activity in PBMCs.
scale (moderate: ≥4–<7; severe: ≥7). Participants are either pruritus
Conclusion: These findings indicated macrophage E2F2 suppresses
treatment-naïve, have received prior pruritus therapy or continue stable
MASH progression by reprogramming amino acid metabolism via
concomitant therapies commonly used for PBC and/or pruritus, except
SLC7A5-Leu-mTORC1 signaling pathway. Activating E2F2 holds
for obeticholic acid. A preliminary analysis of baseline characteristics is
promise as a therapeutic strategy for MASH.
summarised for all participants and the East Asian subgroup, blinded
Table and Figure:Figure 1.Graphic abstract
to treatment status, using descriptive statistics.
Result: Data were included from 71 (East Asia) and 238 (all)
participants (Table). At baseline in the East Asian population, 44% OP0289
had moderate pruritus, 56% severe; 10% had compensated cirrhosis, Baohuoside I inhibits Hepatocellular carcinoma through the
11% had total bilirubin >1x ULN. Fewer participants from East Asia UBE2C/P53 Pathway
had ALP levels ≥1.67x ULN compared with the overall population (37% Xin Zhang1
vs 48%). All East Asian participants were treated with UDCA for PBC. 1
Laboratory of Cellular Immunity, Shanghai Key Laboratory of
Antihistamines were the most common type of prior medication taken Traditional Chinese Clinical, Shuguang Hospital Affiliated to Shanghai
for pruritus among East Asian participants (20%), while prior use of bile University of Traditional Chinese Medicine
acid binding resins was low (3%; 2 participants from China) and none
had received opioid antagonists, selective serotonin reuptake inhibitors Background: The effective clinical prescription Qiling Xiaoji
or rifampicin. Fibrates were the most common concomitant therapy prescription can effectively reduce the postoperative recurrence
that may affect pruritus among East Asian and all participants (24% rate of primary liver cancer, and its subject drug Herba Epimedii
and 22%, respectively). Only Japanese participants received prior has anti-tumor activity, and the important active ingredient of Herba
(8%) and concomitant (7%) nalfurafine. Fewer East Asian participants Epimedii, Baohuoside I (BHS), has the effects of anti-inflammation,
(32%) were taking concomitant medications that may affect pruritus promoting apoptosis and inhibiting tumor. However, the specific
than in the overall population (48%). mechanism remains to be determined. The purpose of this study is to
Conclusion: Prior use of bile acid binding resins was low in the GLISTEN clarify the pharmacological effects of Baohuoside I on liver cancer and
population, despite its first-line position in treatment guidelines in many the molecular mechanism of inhibiting tumor cell proliferation.
countries, including China. Similarly, use of nalfurafine was low among Method: The in vitro effects of BHS on the proliferation of hepatocellular
Japanese participants, despite being approved in Japan for treating carcinoma cells were evaluated using the CCK8 assay and colony
pruritus in chronic liver diseases. Regardless of the use of multiple off- formation assay. Flow cytometry was employed to determine its
label therapies that may impact pruritus, including fibrates, participants influence on cell cycle progression and apoptosis. RNA sequencing
showed evidence of ongoing moderate–severe pruritus, underscoring was utilized to identify differentially expressed genes between the
the unmet need for an approved treatment for pruritus in PBC. normal hepatocellular carcinoma cell group and the BHS intervention
Funding: GSK (study 212620) group. Lentiviral transduction, plasmid transfection, and ubiquitination
Table and Figure:Figure 1.Baseline demographics and clinical experiments elucidated the mechanism by which BHS inhibits
characteristics of East Asian and all participants in GLISTEN hepatocellular carcinoma cell proliferation through the UBE2C/P53
pathway. Additionally, a subcutaneous tumor model was established
in nude mice to investigate the in vivo anti-tumor efficacy of BHS.
OP0288 Result: Our data showed that BHS suppressed HCC cell proliferation
in vitro and in vivo. Colony formation indicated that BHS inhibited cell
proliferation. Cell cycle analysis showed that BHS arrested the cell
cycle in G2/M phase. The RNA-seq analysis revealed a significant in AIC rats by adjusting the proportions of bacterial communities,
enrichment of the P53 signaling pathway in the BHS-treated group. including Bacteroidetes, Firmicutes, Clostridium, Prevotellaceae, and
Notably, differentially expressed genes intimately associated with Lactobacillales.
cell cycle progression and proliferative capacity, including UBE2C, Table and Figure:Figure 1.UPGMA clustering tree based on weighted
exhibited marked downregulation in the presence of BHS. Western Unifrac distance
blot confirmed that BHS increased the protein expression of P53 in Figure 2.Evolutionary Branch Diagram and LDA Value Distribution Bar
nucleus of Huh7 and PLC/PRF/5 cells. The antiproliferative effect of Chart
BHS was intercepted in UBE2C overexpressing and knockdown HCC
cells. After overexpression of UBE2C, P53 ubiquitination increased,
OP0291
while Baohuoside I could reduce UBE2C induced P53 ubiquitination
degradation.Finally, BHS showed an anti-proliferative effect in tumor- Qingchangligan formula plays a protective role in mice with acute
bearing mice with no hepatotoxicity. liver injury by regulating autophagy
Conclusion: Baohuoside I exerts its anti-hepatoma effect by down- Xiangying Zhang1, Xiuhui Li1
regulating the expression of UBE2C, inhibiting the ubiquitin degradation 1
Beijing You‘an Hospital
of P53, increasing the nuclear accumulation of p53, inducing G2/M Background: Liver failure is a critical condition characterized by the
phase arrest and inhibiting cell proliferation. We suggested that BHS rapid deterioration of liver function, often leading to high mortality rates.
might be a potential natural medicine in HCC treatment. The Qingchangligan formula, an institutional prescription from Beijing
Table and Figure:Figure 1.Anti-tumor function of BHS on HCC in vivo You’an Hospital, has shown significant efficacy in protecting liver
Figure 2.BHS inhibits the ubiquitin of P53 by UBE2C function and reducing mortality when used in conjunction with Western
medicine. Recent studies have highlighted the role of autophagy, a
OP0290 cellular degradation process, in mitigating inflammation and apoptosis
in liver cells. This research aims to investigate the therapeutic effects
Analysis of the effect of Compound Yindan Decoction on intestinal
of Qingchangligan formula, a traditional Chinese medicine formula,
microbiota in rats with acute intrahepatic cholestasis based on
on liver failure. We employed a combination of in vitro and in vivo
16S rRNA gene sequencing technology
experiments to assess the impact of Qingchangligan on autophagy
Xiaoling Li1, Fengxia Sun1, Chunjun Xu activation, inflammatory response, and hepatocyte apoptosis in a liver
1
Hepatic Department,Beijing Hospital of Traditional Chinese Medicine, failure model.
Capital Medical University Method: High-performance liquid chromatography was used to
Background: The occurrence of cholestasis is associated with analyze the main components of the Qingchangligan formula; an
reduced microbial diversity. Compound Yindan Decoction (CYD) acute liver injury mouse model was established D-galactose and
exhibits good clinical efficacy in treating AIC. It is unknown whether lipopolysaccharide, and the Qingchangligan was given for intervention,
CYD can protect and repair bile stasis by regulating the intestinal and the survival rate, liver function pathological changes of liver tissue,
microbiota homeostasis in AIC rats. levels of inflammation-related and autophagy-related levels were
Method: Forty SD rats were randomly divided into a normal group, detected in each group; autophagy inhibitors were given to block the
a model group, and high, medium, and low dose groups of CYD, Qingchangligan to protect mice with liver injury, and the inflammatory
with 8 rats in each group. Rats in the high, medium, and low dose response of mice was observed.
groups of CYD were orally administered with 24.48, 12.24, and 6.12 g/ Result: Our results demonstrated that Qingchangligan intervention
kg/day, respectively. The normal group and model group were orally significantly alleviated inflammation and reduced hepatocyte
administered with 1 ml/kg/day of physiological saline once a day for 5 apoptosis, thereby preserving liver function. Notably, the protective
consecutive days. On the third day of administration and 4 hours after effects of Qingchangligan were abolished upon inhibition of autophagy,
administration to each group, the model group and traditional Chinese leading to increased inflammatory responses. Furthermore, cellular
medicine group rats were given 2% ANIT 60 mg/kg by gavage, assays revealed that Qingchangligan markedly decreased cytokine
while the normal group was given equal volume corn oil by gavage. levels associated with the mitogen-activated protein kinase (MAPK)
Comparative analysis of gut microbiota in different groups of rats was pathway, correlating with reduced inflammation and enhanced
conducted using high-throughput sequencing of 16S rRNA. autophagy levels.
Result: (1) The analysis of species differences across various Conclusion: In conclusion, Qingchangligan exerts protective effects
taxonomic levels of the microbiota revealed that, at the phylum level, against acute liver injury through the modulation of autophagy and
compared to the model group, the high-dose group of traditional inflammatory responses, highlighting its potential as a complementary
Chinese medicine exhibited an increased relative abundance of therapeutic strategy in liver failure management.
Bacteroidetes and a decreased relative abundance of Firmicutes. Table and Figure:Figure 1.graphical abstract
Meanwhile, the low-dose group of traditional Chinese medicine
showed a decrease in the abundance of Firmicutes. At the family
OP0292
level, the high- and low-dose groups of traditional Chinese medicine
demonstrated a higher abundance of Prevotellaceae compared to the Restoring energy metabolism by herbal medicine prevents
model group. Conversely, the low-dose group of traditional Chinese alcohol-induced liver injury
medicine exhibited reduced abundances of Lactobacillaceae, Yao Liu1, Chu-jun Xu1, Jiabo Wang2
Helicobacteraceae, Tremendospiraceae, and Ruminococcaceae 1
Beijing Hospital of Traditional Chinese Medicine, Capital Medical
compared to the model group. At the genus level, compared to the University, 2School of traditional Chinese medicine, Capital Medical
model group, the high-dose group of traditional Chinese medicine Univerisity
showed increased relative abundances of Prevotellaceae_UCG-001 Background: Alcoholic Liver Disease (ALD) is one of the most common
and Prevotellaceae_NK3B31_group in rats, while the abundances of liver diseases worldwide, with high prevalence, complex disease
Lactobacillus and Ruminococcus were significantly reduced. In the stages, and a lack of targeted therapeutic drugs. Consequently,
low-dose group of traditional Chinese medicine, the abundances of providing effective intervention and treatment for ALD is crucial in the
Lactobacillus, Mucilaginibacter, Ruminococcus, HT002, Helicobacter, management of ALD.
and Eubacterium xylosum were decreased. (2) LEfSe analysis Method: The NIAAA mouse model was applied for this study, to
indicated that Proteobacteria, Prevotellaceae, and Proteobacteria play evaluate the intervention effects of the three selected Chinese herbal
significant roles in the specificity of gut microbiota in the low-dose medicines, Cangzhu, Zexie, and Dan Douchi at different doses on ALD
Chinese medicine group, while Bacteroidetes, Bacteroidetes, and Result: CangZhu (CZ), ZeXie (ZX), and Dan Douchi (DD) improved
Bacteroidetes play important roles in the specificity of gut microbiota hepatocyte edema, reduced fat droplets in liver tissues, improved
in the medium-dose Chinese medicine group. hepatocyte morphology and reduced liver lipid deposition in ALD
Conclusion: CYD enhances the intestinal microbiota imbalance
mice, serum and tissue test results suggest the protective effects of cohort. In the whole data set, the median OS and PFS in the TCM group
the drugs against alcoholic liver injury, they could ethanol metabolism, are significantly longer than that in the Control group (609 vs. 500 days,
and also inhibit the level of liver pro-inflammatory factor and promote [95%, 0.48, CI 0.33-0.72], p=0.0003; 609 vs. 507 days, [95%, 0.41, CI
the serum and liver levels of anti-inflammatory factor , meanwhile all 0.25-0.68], p=0.0005). However, after 2:1 PSM matching, there is no
three herbs could regulate the oxidative stress, promote the gene significant difference in the median OS between the two groups (558.5
and protein expression of hepatic PPAR-α and down-regulated vs. 474.5 days, [95%, 0.62, CI 0.38-1.01], p=0.0561). The median PFS
the gene expression of UCP2 (P<0.05), and CZ, DD promoted the in the TCM group remains significantly longer than in the control group
protein expression of hepatic CPT1A, ZX, DD could improve the (551 vs. 449.5 days, [95%, 0.43, CI 0.21-0.86], p=0.0171) after 2:1
gene expression of PGC-1α (both P<0.05) and promote the protein PSM matching. There was no significant difference in adverse events
expression of AMPKα1, suggesting that the three herbs can protect and serious adverse events. In the subgroup analysis, the advantage
the liver from alcoholic injury by improving the oxidative stress; CZ, ZX, patients group taking the HSXJ pill was observed with the following
DD promoted the gene and protein expression of hepatic SIRT1 and characteristics: a history of cirrhosis, prior surgical resection, prior
NMNAT1 in NIAAA mice; CZ and low-dose ZX up-regulated the gene local therapy, Child-Pugh A stage, HBV-DNA ≥ 2000, and AFP ≤ 200,
and protein expression of hepatic NAMPT, and ZX promoted the gene respectively.
expression of hepatic MCART1. By regulating the gene and protein Conclusion: The HSXJ pill combined with the standard treatment
expression of SIRT1, NAMPT and NMNAT1, the key enzymes of NAD+ strategy for HBV-related HCC patients showed significantly better PFS
synthesis salvage pathway in the liver of NIAAA mice, the above drugs compared to those who received only the standard treatment strategy.
effectively elevated the liver NAD+ level, up-regulated the NAD+/
NADH ratio (all P<0.05), and regulated the liver tricarboxylic acid cycle
OP0294
in ICDHm , PDH (high-dose DD ), α-KGDH (DD, high-dose ZX) activity
(all P<0.05), improved mitochondrial structure, boosted hepatic ATP Anti-cancer Effects of Yiqi Rougan Jiedu Formula Combined with
level (P<0.05), improved ethanol metabolism-induced dysregulation of PD-1 Inhibitor on Hepatocellular Carcinoma in Mice with Loaded
hepatic NAD+/NADH homeostasis and energy metabolism disorders, Tumors and Its Effects on The Balance of Treg/Th17 and Th1/Th2
and protected alcoholic liver injury in NIAAA mice. Xuan Wu1
Conclusion: This study addresses the imbalance of NAD+/NADH 1
Beijing Hospital of Traditional Chinese Medicine, Capital Medical
homeostasis and disturbance of energy metabolism in the pathological University
mechanism of ALD, evaluated the protective effects of Chinese herbal Background: Primary liver cancer (mainly referred to as hepatocellular
medicine Cangzhu, Zexie, and Dan Douchi against alcoholic liver carcinoma (HCC)) is one of the most common malignant tumors. China
injury through the methods of animal experiments, and a exploration of is a high incidence area of HCC, with new cases accounting for 55% of
the protective effect mechanism revealed that the tested drugs were the total cases in the world. Various existing therapeutic means for liver
capable of improving with hepatic NAD+/NADH homeostasis, improve cancer have limitations, and ICIs-based combination therapies have
hepatic energy metabolism disorders and protect against alcoholic significantly improved the survival benefit of liver cancer patients, but
liver injury, which provides a new perspective and a new approach for the overall efficacy is still unsatisfactory. Traditional Chinese medicine
the prevention and treatment of ALD. (TCM) plays an important role in the comprehensive treatment of
hepatocellular carcinoma, Yiqi Rougan Jiedu Formula(YRJ) is a self-
OP0293 proposed formula for HCC treatment developed by Prof. Xu Chunjun
based on the academic theories of Prof. Guan Youbo. To investigate
Efficacy and Safety of He-Shu-Xiao-Ji Pill Combined with Standard
the anticancer effects of YRJ combined with PD-1 inhibitor on tumor
Treatment Strategy in HBV-related Hepatocellular Carcinoma: A
mice, and its effects on Th1/Th2 and Th17/Treg balance.
Single-center, Prospective Control, Real-world Cohort Study
Method: Eighty 6-8 weeks old SPF mice were randomly divided into:
Xiaoning Zhu 1, Jing Wang 1, Sichuan Clinical Research Center for (1) model control group (CONTROL), (2) PD-1 inhibitor group (PD-1),
TCM of Liver Diseases Group (3) YRJ low-dose group (YRJL), (4) YRJ medium-dose group (YRJM),
1
Hepatobiliary Department, The Affiliated Traditional Chinese (5) YRJ high-dose group (YRJH), (6) YRJL + PD-1 inhibitor group (
Medicine Hospital, Southwest Medical University, Luzhou, China YRJL + PD-1), (7) YRJM + PD-1 inhibitor group (YRJM + PD-1), 10
Background: The low five-year overall survival rate and high animals in each group. YRJM + PD-1 was administered by gavage
recurrence after standard treatment remain significant clinical once a day for a total of 15 times, and PD-1 inhibitor was administered
challenges for patients at every stage of HCC. As a vital and widely by intraperitoneal injection once every 3 days for a total of 5 times.
used adjunct therapy in China, Traditional Chinese Medicine (TCM) The animals were observed daily for feeding and activity, and their
has shown some efficacy in treating HCC. However, high-quality, well- body weight and tumor volume were measured every 2 ~ 3 days. And
designed, long-term clinical trials on TCM for treating HCC are still the proportion of Treg, Th17, Thl and Th2 cells were observed by flow
lacking. This study aimed to investigate the real-world efficacy and cytometry.
safety of the He-Shu-Xiao-Ji (HSXJ) Pill plus the standard treatment Result: The tumor inhibition rates of YRJL, YRJM, and YRJH groups
strategy for HBV-related HCC patients in a single-center, prospective were 38.24%, 59.39%, and 66.2%, respectively, whereas better
control, long-term, real-world cohort. inhibition could be achieved by combining with PD-1 inhibitors, with
Method: In this study, 201 patients enrolled from May 2020 to February inhibition rates of 67.48% in the PD-1 group, 75.74% in the YRJL +
2022 received either the HXSJ pill plus the standard treatment strategy PD-1 group, and 84.17% in the YRJM + PD-1 group . The results of
(TCM group, n=136) or the standard treatment strategy (Control flow cytometry showed that compared with the PD-1 group, the Th1/
group, n=65). The last follow-up time point of these patients was cut Th2 ratio was elevated in the YRJM + PD-1 group, and the differences
off in February 2023. Propensity score matching (PSM) analysis was were statistically significant (P < 0.05). Compared with the PD-1 group,
utilized to adjust for grouping bias. After PSM matching, 61 patients in there was a tendency for the ratio of Th17/Treg to increase in the YRJL
the TCM group and 39 patients in the Control group were matched to + PD-1 group and YRJM + PD-1 group.
run the second stage analysis. The overall survival (OS), progression- Conclusion: With the increase of the dose of YRJL, the tumor growth
free survival (PFS), and safety in the TCM group were compared with was inhibited to different degrees, the tumor volume was reduced,
the Control group. The univariate and multivariate COX proportional and the tumor inhibition rate of each subject drug group showed a
hazard regression analysis was utilized to determine the interactions of good quantitative effect relationship, and the combination with PD-1
TCM and other variables linked to PFS and OS. inhibitor could achieve better inhibition, which could better inhibit the
Result: In the whole data set, more patients in the TCM group had Th2 dominance of the tumor immune microenvironment as well as the
undergone local therapy and neo-adjunctive therapy, and the patients immunosuppressive state of Treg, and correct the drift of Th1/Th2 in
with lower levels of BLCL, Child-Pugh score, HBV-DNA, and AFP were the loaded tumor-bearing mice and the Th17/Treg immune imbalance
more than the control group. After 2:1 propensity score matching, there in tumor-bearing mice, and provide a theoretical basis for the next
was no significant difference in the basic characteristics of the matched clinical application.
 OP0295 Five machine learning methods [random forest (RF), Extreme Gradient
Comparison of Clinical Characteristics between Raw Polygonum Boosting (XGB), gaussian naive bayes (GNB), logistic regression
Multiflorum and Polygonum Multiflorum Praeparata Induced Liver (LR), support vector machines (SVM)] were performed to construct
Injury predictive models for chronic and death/LT outcomes. Furthermore,
the performance of Hy’s Law, nHy’s Law, Robles-Diaz Model, DrILTox
Ligai Liu1, Wanna Yang1, Hong Zhao1, Ting Zhang1, Ying Fan1,
ALF Score, MELD Score, Ghabril Model and constructed machine
Jingjing Wang1, Cheng Cheng1, Qi Wang1, Wen Xie1
learning models were evaluated and compared for predicting death/
1
Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical LT outcome.
University, Beijing, China
Result: Among 331 DILI patients, FABP4 presented higher levels
Background: Polygonum multiflorum (PM) is a widely used traditional in chronic patients than recovery patients (Figure 1A, P<0.0001), as
Chinese medicine. Polygonum multiflorum-induced liver injury (PM- well as in death/LT patients than Non-death/LT patients (Figure 1B,
DILI) is a growing concern. Its prepared form, Polygonum multiflorum P<0.001). Comparing recovery and chronic patients, six features
praeparata (PMP), has been reported to exhibit reduced hepatotoxicity (FABP4, ALT, AFP, total bilirubin, albumin and immunoglobulin G) were
in both in vivo and in vitro experiments. The aim of our study was to identified for constructing models to predict chronic outcome. The XGB
compare the clinical characteristics between raw Polygonum model presented the best predictive performance for chronic DILI, with
multiflorum-induced liver injury (RPM-DILI) and Polygonum multiflorum the AUROC of 0.87 (95%CI=0.80-0.91, Figure 1C) in training cohort
praeparata-induced liver injury (PMP-DILI). and AUROC of 0.91 (Figure 1D, 95%CI=0.85-0.95) in validation cohort,
Method: Adult PM-DILI patients were recruited at Beijing Ditan Hospital. ae well as the great clinical utility (Figure 1E-F). Comparing Non-death/
Patients who used ther drugs with PM and had viral hepatitis, alcoholic LT and death/LT patients, eight features (FABP4, INR, AFP, PLT, WBC,
liver disease, non-alcoholic fatty liver disease and autoimmune liver albumin, direct bilirubin and Ghabril Model Score) were identified
disease were excluded. According to the different processing methods for constructing models to predict death/LT outcome. The RF model
of PM, the patients were divided into RPM-DILI group and PMP-DILI presented the best predictive performance for death/LT outcome, with
group. Clinical information was collected at the onset of the disease, the AUROC of 0.92 (Figure 1G, 95%CI=0.86-0.94) in training cohort
on days 7, 30, 180, and 360. The clinical characteristics in patients and AUROC of 0.91 (Figure 1H, 95%CI=0.79-0.99) in validation cohort,
in the 2 groups were compared by Student’s t test, Mann-Whitney ae well as the great clinical utility (Figure 1I-J). Furthermore, RF model
U test, chi-square and Fisher’s exact test. Results were considered presented satisfying performance for predicting death/LT outcome
statistically significant at P <0.05 (2-tailed). than previous models (Figure 1K-L).
Result: There were 43 cases in RPM-DILI group and 45 cases in PMP- Conclusion: We constructed the XGB and RF models for predicting the
DILI group. Our study comprised 29 (32.9%) men and 59 (67.1%) chronic and lethal outcomes of DILI patients with sufficient accuracy,
women. The average age in the RPM-DILI group was 41.7±14.9, which could be the practical and non-invasive tools for managing DILI
which was lower than that in the PMP-DILI group at 49.4±14.9, with patients.
a statistically significant difference (P=0.018). The median number Table and Figure:Figure 1.Figure 1. Machine learning models based
of days from medication to onset was 30 (IQR 60) days. 83 (94.3%) on fatty acid binding protein 4 help predict the chronic and lethal
patients were hepatocellular injury type. The most common symptom outcomes of patients with drug-induced liver injury
was jaundice. The incidence of jaundice in the RPM-DILI group was
higher than that in the PMP-DILI group (83.7% vs 64.4%, P=0.039).
OP0297
At onset, the AST level in the RPM-DILI group was significantly higher
than that in the PMP-DILI group(842.0 (IQR 444.3) vs 629.2 (IQR IGF2 as a Potential Biomarker for Alcohol-Related Liver Disease
565.2)U/L, P=0.027). On day 7 and day 30, the TBil level in the RPM- and Its Mechanism of Regulating Alcohol-Induced Hepatocyte
DILI group was significantly higher than that in the PMP-DILI group Injury through the Mitochondrial Quality Control System
(day 7: 88.3 (IQR 118.0) vs 54.4 (IQR 88.4) μmol/L, P=0.048; day 30: Tian Xia1, Jia Huang1, Jiachi Yu1, Ruibing Li1, Chengbin Wang1
32.4 (IQR 38.5) vs 19.8 (IQR 30.9) μmol/L, P=0.012). There were no 1
Department of Laboratory Medicine, The First Medical Center of
statistically significant differences in ALT, AST, and ALP levels between Chinese PLA General Hospital, Beijing, 100853, China
the two groups at days 7, 30, 180, and 360. Background: Alcohol-related liver disease (ALD) is a leading cause
Conclusion: PM-DILI is mainly hepatocellular injury type. The of liver morbidity and mortality, with 75% of patients diagnosed at a
hepatotoxicity of PMP is lower than that of RPM. Despite similar long- decompensated stage, missing the optimal treatment window. Early
term prognoses, the short-term prognosis for RPM-DILI is poorer. diagnosis is essential, but current methods lack sensitive biomarkers.
Oxidative stress and mitochondrial dysfunction from excessive alcohol
OP0296 consumption are key mechanisms in ALD progression. This study aims
Machine learning models based on fatty acid binding protein 4 to identify the novel serum biomarker for early diagnosis and explore
help predict the chronic and lethal outcomes of patients with its role in ALD development with a focus on mitochondrial quality
drug-induced liver injury control (MQC).
Method: We established a serum screening cohort for ALD patients
Haoshuang Fu1, Shuying Song1, Rongtao Lai1, Ruidong Mo1, Bingyin
and utilized LC-MS/MS to identify key proteins and their functional
Du1, Yaoxing Chen1, Yuelin Xiao1, Tianhui Zhou1, Qing Xie1
and biological characteristics. Subsequently, we developed ALD
1
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao cell models and applied LC-MS/MS to decipher ALD pathogenesis.
Tong University School of Medicine, Shanghai, China
The expression of key proteins was validated by ELISA, and their
Background: Drug-induced liver injury (DILI) is the most common diagnostic potential was evaluated through ROC curve analysis.
cause of acute liver failure in western countries. Moreover, about 20% Next, we generated IGF2KO and WT cell lines using CRISPR/Cas9
of DILI patients would progress into chronicity, which could result in technology and assessed the effect of IGF2 knockout on cell viability
cirrhosis and death. The fatty acid-binding protein 4 (FABP4) was under alcohol induction by CCK8 assays. We then performed LC-MS/
reported as the essential role in liver diseases. However, the evidence MS to analyze the proteomics of both cell lines under alcohol induction.
on the association between DILI and FABP4 was limited. Therefore, we Finally, we evaluated changes in mitochondrial fission, mitophagy,
investigated their association and constructed predictive models for and necroptosis in both cell lines through immunofluorescence and
chronic/lethal DILI using machine learning. Western Blot analyses.
Method: Three hundred thirty-one DILI patients were enrolled with the Result: A total of 180 differential proteins were identified in the serum
RUCAM score exceeding 6, which were categorized into recovery, of ALD patients, with the key protein IGF2 being down-regulated,
chronicity, or death/liver transplantation (LT) group based on 6-month showing a fold change of 0.6. GO and KEGG analyses indicated
follow-up. ELISA was used to determine serum FABP4 levels. Features that these differential proteins are associated with oxidative stress
for model construction were identified using LASSO. Patients were and autophagy. In the ALD cell model, 385 differential proteins were
randomly divided into training (50%) and validation (50%) cohorts. identified in the whole-cell proteome, and 505 differential proteins were
identified in the mitochondrial proteome. Enriched pathways primarily OP0299
focused on MQC and hepatocellular necroptosis. The expression of LncRNA NEAT1 In PBMCs Can Predict Liver Injury In Patients With
IGF2 was found to increase in the early stage of ALD and decrease Anti-tuberculosis Treatment
in the later stage (p < 0.05), effectively distinguishing early-stage ALD
Xi Zhao1,2, Shujun Ma3,2, Huiling Cao3,2, Ping Yao1,2, Wanhua Ren3,2,
patients from healthy controls (AUROC = 0.8338). Compared to WT
Qiang Zhu3,2, Hongfei Du4,2
cells, IGF2KO cells significantly enhanced cell survival under alcohol
induction (p <0.05). Additionally, IGF2KO cells mitigated the alcohol-
1
The First Hospital of Xinjiang Medical University, 2National medical
center for infectious diseases, 3Provincial Hospital of Shandong First
induced upregulation of inflammation and necroptosis, improved
Medical University, 4The First Affiliated Hospital of Chengdu Medical
mitochondrial dysfunction, reduced mitochondrial fission, and
College
promoted mitophagy, all of which were observed in WT cells(p <0.05).
Conclusion: IGF2 is a potential diagnostic marker for early-stage Background: Tuberculosis (TB) is treated primarily with drugs. Drug-
ALD. Differential proteins and major pathways in ALD patient serum and induced liver injury (DILI) is the most serious adverse reaction during
vitro models are linked to MQC and hepatocellular necroptosis. IGF2 treatment, patients are often forced to stop treatment because of liver
knockout preserves mitochondrial homeostasis, thereby reducing damage. Finding blood indicators that correlate with the degree of DILI
alcohol-induced hepatocyte injury. is a critical issue that needs to be addressed in the course of anti-
Table and Figure:Figure 1. tuberculosis treatment with drugs. In recent years, it has been noticed
Figure 2. that lncRNA NEAT1 plays a role in the occurrence and development of
various liver diseases, while its role in DILI is still unclear.
Method: We collected patients with TB according to the inclusion
OP0298 and exclusion criteria. Liver function indices were monitored for
Establishment and evaluation of ACR prediction model for normalization during regular anti-tuberculosis treatment (2 months
assessing the severity of drug-induced liver injury ± 10 days) in patients and were divided into hepatic injury and non-
Chengjie Cui1, Shuxian Zang1, Jing Cui1, Na Fu1, Yuemin Nan1 hepatic injury groups. RNA was collected from peripheral blood of
1
Hebei Medical University Third Hospital the patients and subjected to qRT-PCR. Data processed by the 2
-ΔΔct algorithm were statistically analyzed using SPSS26.0 software.
Background: Drug-induced liver injury (DILI) is caused by drugs or
Measurement data conforming to normal distribution were tested by
their metabolites, which is one of the common causes in liver injury. In
T-test and expressed as mean ± standard deviation (X̅̅ ± s); non-
severe cases, it can lead to acute liver failure or even death. Due to
normally distributed data were tested by rank-sum test and expressed
low acceptance of liver biopsy, DILI faces challenges such as difficulty
as median M (Q25, Q75). Spearman’s correlation analysis was used
in identification and diagnosis, predicting severity and prognosis, and
to assess whether there was a correlation between the expression of
clinical management.
lncRNA NEAT1 in peripheral blood mononuclear cells (PBMCs) and
Method: A retrospective study method was used to enroll 125 patients
liver function in the DILI population, and logistic regression analysis
diagnosed with DILI in Hebei Medical University Third Hospital from
was performed to screen for independent risk factors of DILI. The ROC
June 2021 to October 2024. According to the severity assessment
curve was plotted to calculate the AUC assessment of lncRNA NEAT1
criteria of the 2023 DILI guideline, 39 cases were classified as mild
in the diagnosis of DILI. Specificity, sensitivity and diagnostic value of
(grade 1) and 86 as moderate to severe (≥grade 2) (Figure 1).
lncRNA NEAT1 in the diagnosis of DILI.
SPSS 27.0.1 was used to analyze clinical data, make univariate and
Result: A total of 100 patients with TB were included in this study,
multivariater logistic regression (backward stepwise method) and
including 41 patients in the liver injury group and 59 patients in the
generate the ROC curve (CHE is negatively correlated with severity,
non-liver injury group. Statistical analysis showed that the median and
so the ROC for 1/CHE was used). The calibration curve, DCA curve
quartile of lncRNA NEAT1 expression in the liver injury group was 1.65
and nomogram were created using the CNSknowall platform (https://
(1.05,2.18) and in the non-hepatic injury group was 0.62 (0.27,1.00).
cnsknowall.com), a comprehensive web service for data analysis and
The expression of lncRNA NEAT1 in the PBMCs of people with DILI
visualization.
was higher than that of people without liver injury, z=5.856 (P=0.001).
Result: The general information of the two groups was shown in
Spearman’s correlation analysis showed a positive correlation between
Table 1. The primary symptoms in both groups were fatigue and
the expression of lncRNA NEAT1 and liver function indexes ALT and
decreased appetite. Laboratory indicators with P<0.1 were induced
AST (r=0.484, 0.532, both P<0.05). After multifactorial adjustment,
in univariate logistic regression analysis, which identified ALB, ALT,
lncRNA NEAT1 was an independent correlate of anti-tuberculosis
AST, ALP, CHE, red cell volume distribution width (RDW) and INR as
DILI (OR=9.98, 95%CI: 3.83-26.00, P<0.01), whereas there was no
factors affecting the severity assessment of DILI (Table 2). Multivariate
statistically significant association with the factors such as gender,
logistic regression analysis revealed that AST, CHE and RDW were
age, smoking and alcohol consumption. The AUC was 0.845 (95%CI:
independent predictors of severity (Table 3). The Hosmer-Lemeshaw
0.766~0.924, P<0.05), sensitivity was 0.78 and specificity was 0.814.
test indicated P<0.05, which represented a good fit. The variance
Conclusion: LncRNA NEAT1 levels in PBMCs have a certain
inflation factor (VIF) of the prediction factors (AST, CHE, RDW) were
diagnostic value of DILI, and are expected to be used as a biomarker
all less than 5, indicating no multicollinearity. The prediction model
for the diagnosis of DILI in the future.
ACR= 0.004AST+ 0.715RDW- 0.3CHE- 8.779 was established. The
Table and Figure:Figure 1.Flowchart
AUCs of ACR model, RDW, AST and CHE were 0.882, 0.822, 0.754
and 0.722 respectively (Figure 2). There were significant differences
between ACR and the other indicators (P=0.045, P<0.001, P<0.001). OP0300
The sensitivities were 0.895, 0.930, 0.895 and 0.465, respectively, Investigating the Mechanism of Scutellaria (Huangqin)-induced
and the specificities were 0.744, 0.590, 0.513 and 0.897 (Table 4). Liver Injury through Network Pharmacology and In Vitro Studies
The calibration curve demonstrated that the ACR had good predictive
Tiantian Guo1, Jiahao Yuan1, Yu Wang1, Lei Wan2, Xinyan Zhao1
value, with the prediction curve closely matching the ideal curve (mean 1
Beijing Friendship Hospital, Capital Medical University, 2Kunming
absolute error = 0.015, Figure 3). The DCA curve showed a threshold
Medical University
probability range of 11% to 95%, and the net benefit of the model
was higher than the two extreme cases, indicating high clinical value Background: Scutellaria (Huangqin, HQ), categorized
(Figure 4). The nomogram visualizes the ACR model (Figure 5). as LiverTox class B, has been increasingly reported as a cause of
Conclusion: The predictive performance of ACR model is significantly drug-induced liver injury (HQ-ILI) worldwide. Our multicenter cohort
better than that of AST, CHE and RDW. It is expected to serve as a new study observed that HQ-ILI clinically manifests as hepatocellular injury
prediction model for evaluating the severity of DILI. However, these of mild to moderate severity and is histopathologically characterized
results need to be validated in larger, multi-center studies. by acute hepatitis and acute cholestatic hepatitis, which may progress
Table and Figure:Figure 1.Figure to chronicity, liver transplantation, or even death. However, the specific
Figure 2.Table components and mechanisms underlying HQ-induced liver injury
remain unclear. This study aims to investigate the mechanisms of HQ- inflammation.
ILI using a combination of network pharmacology and in vitro tests. Conclusion: Serum qanti-HBc may be a reliable indicator for assessing
Method: Compounds from HQ were screened in TCMSP database. significant liver inflammationin in children with HBeAg-positive chronic
Targets of HQ and drug induced liver injury (DILI) were predicted hepatitis B.
through the PubChem, Swiss Target Prediction, and GeneCards
databases. In vitro tests were performed on the human HepG2
OP0302
hepatocarcinoma cell line, exposed to various concentrations of active
compounds up to 24h. Protein-protein interaction (PPI) analysis of The occurrence of low-level viremia in patients with chronic
hepatotoxic compounds was performed using the STRING database hepatitis B virus infection is related to gut microbiota and
and Cytoscape’s Cytohubba plug-in. Functional enrichment analysis, metabolites
including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Tianquan Huang1,2, Hongyan Xiang3,2, Yongdong Huang1,2, Jing
Gene Ontology (GO), was conducted via the DAVID database. Xiao1,2, Huan Liu1,2, Qiao Tang1,2, Pingping Yu4,2, Xiaoqing Liu1,2, Yi
Result: A total of 36 active compounds were identified from HQ with Zeng1,2, Mingli Peng1,2, Hong Ren1,2, Wei Shen1,2, Peng Hu5,2
drug-like properties (≥0.18) and oral bioavailability (≥30%), including 1
Department of Infectious Diseases, The Second Affiliated Hospital
flavonoids, phenolics, esters, and steroids, associated with 254 targets. of Chongqing Medical University, 2Institute for Viral Hepatitis, The Key
Additionally, 2831 targets related to DILI were retrieved. Literature Laboratory of Molecular Biology for Infectious Diseases, Chinese
review identified the most likely hepatotoxic compound from each Ministry of Education, Chongqing Medical University, 3Department
category: hispidulin, dihydrooroxylin A, Di-(2-ethylhexyl) phthalate, of Geriatrics, Chongqing General Hospital, Chongqing University,
and β-sitosterol, which were subsequently tested in vitro. Among these,
4
Department of Health Management, The Second Affiliated Hospital
hispidulin demonstrated concentration-dependent toxicity in HepG2 of Chongqing Medical University, 5Department of Infectious Diseases,
cells (IC50 = 293.9 μmol/L, CI 267.0–326.6). Further analysis revealed The First Affiliated Hospital of Chongqing Medical University
168 shared targets between HQ and DILI, with 41 targets specific to Background: The occurrence of low-level viremia (LLV) during antiviral
hispidulin. PPI network analysis identified core targets such as ESR1, therapy (AVT) will affect the benefit of patients with chronic hepatitis
KDR, and APP. GO and KEGG enrichment analysis suggested that B virus (HBV) infection (CHB). Gut microbiota and metabolites may
hispidulin may contribute to liver injury by modulating the sphingolipid affect the clearance of HBV, but the gut characteristics of patients with
signaling pathway and enzyme binding molecular functions. MAPK14 different virological response remain unclear. The aim of this study was
emerged as a core target in the Hispidulin-DILI-Enzyme binding- to systematically compare the gut microbiota and metabolites between
Sphingolipid signaling pathway. patients who developed LLV and those who achieved complete
Conclusion: This study identified hispidulin as a potential toxic virological response (CVR) during AVT, and provide new ideas for
compound responsible for HQ-ILI and provided insights into its achieving better results in AVT for CHB patients.
possible mechanisms of hepatotoxicity. Method: The gut microbiome and metabolome of 42 CHB patients
Table and Figure:Figure 1.In vitro experiments with hispidulin, who received continuous AVT for 48-72 weeks were examined
dihydrooroxylin A, Di-(2-ethylhexyl) phthalate, and β-sitosterol in HpG2 using shotgun metagenomic sequencing and non-targeted liquid
Figure 2.Network Topology of Hispidulin-Induced Hepatotoxicity: chromatography-tandem mass spectrometry, respectively. The
Insights from GO, KEGG, and PPI Pathway Analyses patients’ virological response was determined according to the high-
precision HBV DNA quantification. The lower detection limit is 10 IU/
mL. LLV was defined as a patient’s serum HBV DNA ≥ 10 IU/mL and <
OP0301
2000 IU/mL, and CVR as serum HBV DNA < 10 IU/mL.
Correlation between serum hepatitis B core antibody and Result: A total of 22 patients with CVR and 20 patients with LLV were
significant liver inflammation in children with HBeAg-positive eventually enrolled. In the comparison of gut microbial alpha diversity,
chronic hepatitis B Chao1 and Shannon indexes of patients with CVR were significantly
Yuxi Ning1,2, Yanwei Zhong2, Min Zhang2, Xiuchang Zhang1, Ce Shi2, higher than those of patients with LLV (Chao1: P = 0.003, Shannon:
Ruiyang Yuan1,2 P = 0.039, Mann-Whitney U test) (Figure 1A), indicating that the gut
1
Hebei North University , 2the Fifth Medical Center of chinesePLA microbiota of CVR patients were more abundant than those of LLV
General Hospital patients. Comparing the beta diversity of the gut microbiota between
Background: Hepatitis B core antibodies (anti-HBc) are specific the two groups was statistically significant (P = 0.012, adonis test)
antibodies produced by the body stimulated by the core antigen (Figure 1B), indicating a significant difference in the gut microbial
(HBcAg) after hepatitis B virus (HBV) infection. Recently study has composition between patients with CVR and those with LLV. The linear
shown that quantitative anti-HBc as a novel immune marker reflecting discriminant analysis (LDA) effect size was used to screen differential
the host’s antiviral immune response is receiving increasing attention microbes between the two groups, and a total of 1 phylum, 3 classes,
in evaluating the degree of adult liver inflammation and the efficacy 4 orders, 7 families, 11 genera and 15 species were screened (LDA >
of antiviral therapy. However, there are few reports in children with 3) (Figure 1C). Meanwhile, the result of adonis test further confirmed
chronic hepatitis B. This study aims to investigate the correlation that the difference in metabolite composition between LLV patients
between serum quantitative hepatitis B core antibody (qanti-HBc) and and CVR patients was statistically significant (P = 0.029) (Figure 2A).
significant liver inflammation in children with HBeAg-positive chronic The orthogonal partial least squares discriminant analysis showed
hepatitis B. that a total of 83 metabolites were significantly different between the
Method: Baseline serum qanti-HBc levels of 70 HBeAg-positive two groups (variable importance in the projection > 1) (Figure 2B).
children with chronic hepatitis B were measured using a double- Finally, The Spearman correlation between differential microbes
antigen immunosandwich assay, and liver biopsy were performed for and metabolites showed that significant positive correlations were
inflammation and fibrosis. Patients were categorized into a non- observed roughly between microbes and metabolites enriched in the
significant liver inflammation group (G0-1) and a significant liver same group of patients, and the differentials in different groups were
inflammation group (G2-4) based on liver inflammation grade. The significantly separated in clustering. (Figure 2C).
correlation between serum quantitative hepatitis B core antibody Conclusion: Collectively, the occurrence of LLV are related to gut
(qanti-HBc) and liver inflammation degree. microbiota and metabolites, which provides new ideas for optimizing
Result: Baseline qanti-HBc was significantly correlated with liver the treatment of HBV.
tissue inflammation grade(r=0.51, p<0.001) and fibrosis stage(r=0.29, *Corresponding author: Peng Hu and Wei Shen
p=0.019). Multifactorial regression analysis showed that baseline Table and Figure:Figure 1.Figure 1
qanti-HBc (OR=10.910, p=0.013) was the only influencing factor for Figure 2.Figure 2
significant liver inflammation in children with CHB, with AUROC=0.815,
95%CI 0.708-0.921. Baseline qanti-HBc > 4 log10IU/ml had a OP0303
positive predictive value of 90.9% for the diagnosis of significant liver
Optimized Strategies in Hepatitis B Screening and Linkage to Care treatment, 12-week and 24-week periods .
in Community Settings Result: The rates of clinical cure were 15.98% and 28.27% at
Qiran Zhang1, Hongrang Zhou2, Zhe Zhou2, Guifu Li2, Ruirui You1, Yiqi 24-week and 48-week of PEG-IFN treatment, respectively. At
Yu1, Wenhong Zhang1 24 weeks of PEG-IFN treatment, the number of PD-1+ total B
1
Department of Infectious Diseases, National MedicalCenter for lymphocytes was significantly lower in those who obtained HBsAg
Infectious Diseases, Huashan Hospital, 2Center for Disease Control clearance (0.63%[0.43%, 1.54%]) than in those who did not
and Prevention of Qingpu District (1.61%[0.70%, 17.25%]) ,p=0.037.
Conclusion: It is suggested that interferon treatment may be able
Background: Although health economic models and previous
to reduce PD-1 expression in B-lymphocytes and contribute to
investigation suggest that universal hepatitis B screening for the entire
the restoration of B-lymphocytes function, thus promoting HBsAg
population is beneficial, the feasibility was limited by the the huge
clearance.
population and relatively low carriage rate in general population. A
Table and Figure:Figure 1.Figure 1. Clinical cure rate at 12W, 24W, 36W
considerable proportion of patients with hepatitis B not receiving
and 48W of PEG-IFN treatment
further diagnosis and treatment actually had HBsAg tested in medical
Figure 2.Figure 2. Comparison of the number of PD-1+ total
institutions in the past, but they lack the awareness that the situation
B-lymphocytes (A), PD-1+ naive B-lymphocytes (B), PD-1+
needs to be further managed.
plasmablasts (C), and PD-1+ memory B-lymphocytes (D) between
Method: We conducted a pilot study to explore the strategy of
group R and NR at baseline and 12 and 24 week of PEG-IFN treatment
combining big data identification, HBsAg screening and liver disease
status evaluation in Community Settings. The data was from the
electronic medical history information system, and the desensitized OP0305
information was then exported. Only the staff member of centers Independent Predictive Factors for Rapid HBsAg Seroclearance
for disease control (CDC) within the project could obtain the list at 24 Weeks in Chronic Hepatitis B Patients Undergoing Interferon
of candidates, while other team members of the project could only Treatment
access the desensitized data. After obtaining the informed consent Jianxia Dong1, Shan Ren1, Jing Zhao1, Pengxuan Wu1, Haitian Yu1,
of the candidates, the examinations were conducted in the primary Zhongjie Hu1, Xinyue Chen1, Sujun Zheng1
medical institutions, including hepatitis B serological markers, HBV 1
The First Unit, Department of Hepatology, Beijing YouAn Hospital,
DNA, complete blood count (CBC), liver function, alpha-fetoprotein
Capital Medical University
(AFP), and liver ultrasound were carried out.
Result: Among 1883 candidates identified by big data, 1186 (63.2%) Background: This study aims to identify factors associated with rapid
was confirmed chronic HBV infection. A total of 495 (41.7%) met the Hepatitis B surface antigen (HBsAg) seroclearance within 24 weeks
treatment initiation indications in the Chinese guideline (2022) but have in chronic hepatitis B (CHB) patients who have successfully achieved
not yet started treatment, 125 (10.5%) had the results suggesting HBsAg loss. The goal is to provide effective clinical references for
possible cirrhosis, 91(7.7%) had elevated AFP or abnormal density antiviral therapy.
lesion in ultrasound. Method: This single-center, retrospective case-control study included
Conclusion: Combination of big data identification, HBsAg screening CHB patients who achieved HBsAg seroclearance during treatment
and liver disease status evaluation in community settings is efficient at You an Hospital, Beijing, from March 2008 to May 2024. The
and feasible, for finding and managing the patients with chronic HBV baseline time point of interferon treatment was defined as the start
infection who need further intervention. of sustained interferon therapy leading to HBsAg loss. Patients were
grouped according to whether they achieved HBsAg seroclearance
at 24 weeks. Clinical data from baseline and throughout the treatment
OP0304 course were collected. Univariate and multivariate logistic regression
Study on the efficacy of peginterferon therapy for inactive HBsAg analyses were performed to assess independent factors associated
carriers and the role of B lymphocytes in the clinical cure of with rapid HBsAg seroclearance at 24 weeks.
chronic hepatitis B Result: A total of 444 patients were included, of whom 190 (43%)
Jiangyu Liu1, Daqiong Zhou1, Zichen Zhang1, Feng Zhao2, Jianru Jia2, achieved HBsAg seroclearance (seroclearance group), and 254
Zhenhuan Cao1 (57%) did not (non-seroclearance group). Univariate analysis
1
Beijing Youan Hospital,Capital Medical University, 2Baoding People‘s showed that baseline HBsAg≤100 IU/mL(OR=5.41,95%CI:3.51-
Hospital 8.32,P<0.001), Hepatitis B e antigen (HBeAg) negative (OR=0.43,
95%CI: 0.27-0.69, P=0.001), Hepatitis B Virus DNA (HBV-DNA) <20
Background: Previous studies by our team and others have found
IU/mL (OR=1.71, 95%CI: 1.16-2.50, P=0.006), HBsAg reduction
that the occurrence of clinical cure in inactive hepatitis B surface
>1 log IU/mL at 12 weeks (OR=4.85, 95%CI: 3.22-7.31, P<0.001),
antigen carriers (IHC) treated with peginterferon (PEG-IFN) is very
and alanine aminotransferase (ALT) elevation >1 upper limit of
high, and that the B-lymphocytes may play an important role in the
normal(ULN) at 12 weeks (OR=1.93, 95%CI: 1.25-2.97, P=0.003)
process of HBsAg clearance. This study will evaluate the efficacy of
were significantly associated with HBsAg seroclearance at 24 weeks.
PEG-IFN in the treatment of IHC and further investigate the correlation
Multivariate analysis revealed that baseline HBsAg ≤100 IU/mL
between changes in the frequency of B-lymphocytes subsets and
(OR=3.91,95%CI:2.14-7.29,P<0.001),HBsAg reduction >1logIU/mL
HBsAg clearance and obtain the immunological characterization
at 12 weeks (OR=4.49,95%CI:2.69-7.64,P<0.001),baseline HBV-DNA
of B-lymphocytes from patients with chronic hepatitis B who have
<20IU/mL(OR=1.67, 95%CI: 1.02-2.76,P=0.042), and ALT elevation
achieved clinical cure.
>1 ULN at 12 weeks (OR=2.86,95%CI:1.63-5.18,P<0.001) were
Method: A total of 458 IHC who attended Beijing You’an Hospital of
independent predictors of HBsAg seroclearance at 24 weeks.
Capital Medical University between January 2008 and February 2023
Conclusion: Baseline HBsAg ≤100 IU/mL, baseline HBV-DNA
were included in this study. They received subcutaneous injection of
<20 IU/mL, HBsAg reduction >1logIU/mL at 12 weeks and ALT
PEG-IFN α-2β 135μg or 180ug (weight ≥65kg dose 180ug, weight
elevation>1ULN at 12 weeks are independent predictors of HBsAg
<65kg dose 135ug) once a week. Based on the established PEG-IFN
seroclearance at 24 weeks in CHB patients undergoing interferon
treatment cohort, 36 gender- and age-matched IHC with 96 weeks
treatment. Early changes in HBsAg and ALT provide good predictive
of treatment were selected to detect the number of B lymphocytes,
value for treatment outcomes and can serve as clinical decision-
of which 21 patients were clinical cure (Group R) and 15 patients
making references.
were not (Group NR). The number of PD-1+ B-lymphocyte and IgG+
Table and Figure:Figure 1.Predictors of 24-week HBsAg seroclearance
B-lymphocyte subpopulations, including total B-lymphocytes (CD19+),
by univariate logistic regression
plasmablasts (IgD-CD38+), unconverted B-lymphocytes (CD19+IgD-
Figure 2.Predictors of 24-week HBsAg seroclearance by multivariate
CD38+), initial B-lymphocytes (CD38-IgD+CD27-), and memory
logistic regression
B-lymphocytes (IgD-CD38-), were measured by flow cytometry at pre-
 OP0306 the gut microbial metagenome of patients with CCA through large
Multimodal characterization of the responsiveness of eight cohort data from three different regions in China. The gut microbiome
hepatitis D virus genotype isolates to interferon-alpha treatment biomarkers contribute to non-invasive, robust and specific diagnosis
for CCA.
Yibo Ding1, Qiudi Li1, Zhanghao Feng1, Chengqian Feng2, Mei Liu1,
Table and Figure:Figure 1.Gut microbial diagnostic model for CCA by
Yunlu Sha1, Xutong Ding1, Ying Li1, Ruilin Si1, Huiyuan Fu1, Zhenfeng
random forest model.
Zhang3, Feng Li2, Stephan Urban4, Hongbo Guo1, Wenshi Wang1
1
Xuzhou medical unversity, 2Guangzhou medical unversity, 3Southern
University of Science and Technology, 4University Hospital Heidelberg OP0309
Background: Background: Chronic hepatitis delta virus (HDV) Decade-Long Survival Insights: Upfront Ablation Outperforms
infection causes the most severe form of viral hepatitis. Although Delayed Ablation in Colorectal Liver Oligometastases: A
humans produce 12 subtypes of Interferon-α (IFN-α), IFN-α2a has Comprehensive Nationwide Study
been the only commonly used treatment against HDV. Previously, we Jianming Li1, Jie Yu1, Ping Liang1
characterized eight HDV genotype isolates with varying replication 1
5th Medical Center of Chinese PLA General Hospital
kinetics. Herein, we aimed to thoroughly investigate the antiviral Background: The optimal timing of ablation treatment for colorectal
efficacy of IFN-α2a and other subtypes against HDV 1-8 isolates in liver oligo-metastases (CLOM) remains uncertain, despite the evolution
multimodal conditions. of management from systemic chemotherapy to localized disease
Method: Methods: The anti-HDV potencies of IFN-α subtypes were control. To compare the long-term survival outcomes of upfront versus
evaluated during de novo infection, cell mitosis, or in quiescent cells. delayed ablation strategies in patients with CLOM.
Result: Results: IFN-α2a exhibits potent but varied efficiency against Method: We conducted a nationwide, multicenter, retrospective cohort
HDV 1-8 isolates upon de novo infection and cell mitosis. Conversely, study including 1047 patients from 21 Chinese hospitals diagnosed
HDVs in resting cells are resistant to IFN-α2a and the IFN-containing with CLOM between October 2009 and August 2024. Patients were
cytokine cocktail collected from peripheral blood mononuclear cells categorized into upfront ablation (UA) and delayed ablation (DA)
stimulated with TLR7/8 agonist. Mechanistically, HDV resistance groups. Treatment strategies, determined by a multidisciplinary team,
to IFN-α in resting cells is independent of the permeability of the included UA with adjuvant systemic treatment or DA with peri-ablation
nuclear membrane. Interestingly, although both ADAR1 p110 and systemic treatment. The primary outcome was progression-free
p150 promote L-HDAg production and inhibit HDV replication, the survival (PFS), and the secondary outcome was overall survival (OS),
ADAR1 p150, rather than p110, enhances the anti-HDV efficacy of both assessed using multivariable-adjusted Cox regression analysis
IFN-α during de novo infection and cell mitosis, but not in resting cells. and Kaplan-Meier survival curves. Sensitivity analyses, including
Moreover, different subtypes of IFN-α exhibit varying anti-HDV activities propensity-score matching (PSM), inverse probability treatment
in both de novo infection and cell mitosis settings, due to their disparity weighting (IPTW), and overlap weighting (OW), were performed to
in activating interferon responses. Among these, IFN-α2a, IFN-α10, adjust for confounding factors.
and IFN-α14 exhibit the strongest anti-HDV activity and pronounced Result: Over a 15-year period, UA demonstrated significantly better
synergistic effects with bulevirtide in suppressing HDV replication. PFS (median 1.48 years vs. 0.98 years for DA, P<0.0001) and OS
Conclusion: Conclusions: The anti-HDV efficacy of IFN-α depends on (median 6.94 years vs. 4.74 years for DA, P=0.0014). Sensitivity
multiple factors, including HDV genotypes, ADAR1p150 level, IFN-α analyses and subgroup analyses confirmed these findings, with
subtypes, and HDV’s different survival strategies. These findings adjusted hazard ratios favoring UA for both PFS and OS. There was
provide valuable implications for the development and optimization of no significant difference in the frequency of grade III or IV ablation
IFN-based therapies. complications (5.0% vs 5.9%, P=0.552) or grade III or IV systemic
therapy adverse events (28.9% vs 25.1%, P=0.159) between DA and
OP0308 UA groups.
Multicohort fecal metagenomes analysis contributes to non- Conclusion: For patients with CLOM, upfront ablation combined with
invasive diagnosis for cholangiocarcinoma adjuvant systemic treatment was associated with improved PFS and
OS compared to delayed ablation. These findings provide robust
Zhigang Ren1, Benchen Rao1, Zujiang Yu1
evidence to guide treatment sequencing in CLOM patients.
1
The First Affiliated Hospital of Zhengzhou University
Table and Figure:Figure 1.Study flowchart.
Background: Recent evidence suggested a role for the microbiome Figure 2.Kaplan–Meier curves of progression-free survival in all
in tumorigenesis of cholangiocarcinoma (CCA). We aimed to evaluate patients (A), Kaplan–Meier curves of overall survival in all patients (B),
the potential of gut microbiome as non-invasive diagnostic biomarkers comparing patients who underwent delayed and upfront ablation in
for CCA. crude analysis. Shaded regions around curves represent 95% CIs.
Method: We conducted metagenomic sequencing, identified microbial
species and pathway biomarkers and constructed CCA classifiers
OP0310
based on the discovery cohort from East China (72 CCA and 150
Controls). Two independent cross-regional cohorts from Central China Targeted therapy and Deb-Tace: cardiovascular aspects of HCC
(70 CCA and 84 Controls) and Northwestern China (30 CCA and 37 Saule Kubekova1, Niyaz Malayev2, Yelena Rib1, Natalya Zagorulya1,
Controls) verified the model, respectively. Publicly datasets were used Assel Meiramova1
to further validate disease specificity of the model. 1
Astana Medical University, 2National Scientific Medical Centre
Result: Compared with controls, reduced α diversity and increased Background: Hepatocellular carcinoma (HCC) is the most common
β diversity were found in the CCA group. In addition, Bifidobacterium liver
Adolescentis, Lactobacillus Rogosae were depleted, and Akkermansia cancer with poor prognosis. Although Asia bears the highest
Muciniphila, Parabacteroides distasonis, Prevotella Copri, Clostridium burden of HCC, no studies on cardiotoxicity of the targeted therapy
Citroniae were enriched in the CCA group versus controls. Diagnostic conducted in Central Asia.
models were constructed by 23 species markers and 5 pathway Method: Results are part of a grant project funded by the Ministry
markers, respectively. Better discrimination efficiency was obtained of Education and Science of the Republic of Kazakhstan (Individual
by the species-based model with AUC values of 98.95% and 99.89% registration number AP 19176025). 91 patients with HCC without
in East China cohort. Notably, two independent cross-regional cardiovascular disease divided into two groups: the first group
validation cohort reached 84.32% and 79.37% from Central China and 49 patients on target therapy with sorafenib (800 mg per day)
Northwestern China, respectively. Strikingly, public datasets covering and the second 42 patients on sorafenib 800 mg with Deb-TACE
6847 samples and 31 studies across 11 disease states indicated (doxorubicin 50 mg). All patients underwent 12-channel resting
strong disease specificity of the model to a certain degree. electrocardiography according to AHA/ACC/HRS recommendations
Conclusion: Taken together, this study reported the alterations in
with device calibration of 50 mm/s and 10 mm/mV before the start of OP0312
therapy (4±1 day) and 3 months after the start of treatment. Evaluation of Antiviral and Immunomodulatory Effects of Tenofovir
Result: The mean age of the patients was 59.7±10.2 years. Differences amibufenamide in Chronic HBV-replication Mouse Models
in QRS complex duration in patients in the second group 3 months after
Jia Liu1, Xuesheng Yang1, Xin Zheng1
the start of therapy were significantly higher (82.9±3.5 vs 100.4±10.7,
p=0.022). Differences were also found in resting HR, which was
1
Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology
significantly higher in the target therapy group (88.4±12.8 per minute
versus 74.3±10.8 per minute in the second group, p=0.047).Patients Background: Emtenofovir has been widely used in clinical
with T wave changes was significantly higher in the second group practice for the treatment of chronic hepatitis B infection.In
(40.47% vs. 28.6%, p = 0.046). In addition, low-voltage ECG was this study, the antiviral efficacy and immunomodulatory effects
more frequent in the same group (p=0.032). In 3 months after the of Tenofovir amibufenamide(AMI) in chronic hepatitis B virus (HBV)
start of therapy both in the group there was a significant increase in infection were investigated in two distinct mouse models.
the number of cases of inversion of T wave (in at least two adjacent Method: Two mouse models were employed: (1) the rAAV8-HBV1.3
leads), p<0.001. In the second group the duration of QTc interval also chronic infection model, established by tail vein injection of rAAV8-
increased after 3 months of therapy and reached pathologic values, HBV1.3 recombinant virus; and (2) the BPS HDI chronic replication
moderately exceeding the patients’ sex-age norm (from 419.8±24.9 model, created via hydrodynamic injection of HBV expression
msec to 459.8±22.7 msec, p=0.040). plasmidBPS. Mice were treated with AMI, Entecavir (ETV), or Tenofovir
Conclusion: In patients with HCC without baseline cardiovascular (TAF) orally from 14 to 27 days post HBV challenge. Serum levels of
pathology, comparisons between the target therapy and target HBsAg, HBeAg, HBsAb, HBeAb, and HBV DNA were monitored. At
therapy and Deb-TACE groups, as well as intra-group follow-up at day 28 postHBV challenge, liver-infiltrating lymphocytes were isolated,
3 months after the start of therapy, showed the following: increased and T cell activation, differentiation, and HBV-specific T cell responses
resting HR, increased QRS duration, decreased ECG voltage, QTc were analyzed by flow cytometry.
interval prolongation, and T-tooth inversion. The results emphasize Result: In the rAAV8-HBV1.3 infected mouse model, AMI treatment
the importance of careful monitoring of electrocardiographic significantly reduced serum HBV DNA levels, comparable to ETV
characteristics during target treatment and the use of Deb-TACE in and TAF treatments. AMI also increased the frequency of activated
patients with HCC, especially considering the potential risk of adverse CD69+ CD4+ and CD8+ T cells, precursor effector CD4+ and
cardiovascular events. CD8+ T cells, and IFN-γ-secreting CD4+ T cells. In the BPS HDI
model, AMI treatment similarly reduced serum HBV DNA levels and
increased the frequency of precursor effector CD4+ T cells, IFN-γ
OP0311
and IL-2-secreting CD4+ T cells, and IFN-γ-secreting CD8+ T cells.
Specific gut microbiota contributes to metabolic associated fatty Additionally, AMI treatment showed a trend of increased HBcAg-
liver disease in male mice with DR3 deficiency specific CD8+ T cells in the liver.
Yuefang Ye1, Guangmin Li1, Xiaopeng Wang1, Ruobin Xu1, Hanbo Conclusion: AMI demonstrated significant antiviral activity and
Yang1, Junping Shi2 immunomodulatory effects in both chronic HBV infection and replication
1
Department of Gastroenterology, Affiliated Hospital, School of Clinical mouse models. These findings suggest that AMI has potential as a
Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310015, therapeutic agent for chronic HBV infection by modulating T cell
China, 2Department of Hepatology, Affiliated Hospital of Hangzhou responses and reducing viral load.
Normal University, Hangzhou, Zhejiang 310015, China
Background: Metabolic changes and gut microbiota imbalance are OP0313
critical to the pathogenesis of metabolic dysfunction-associated fatty
Phase I Studies of a Novel Pulsatile FXR Ligand for Treating
liver disease (MAFLD). Over the years, TL1A has been recognized
Cholestatic Liver Diseases
as a key pro-inflammatory regulator in inflammatory bowel diseases
(IBD). Death receptor 3 (DR3) is the only known functional receptor Rong Deng1, Jingjing Shi1, Gaihong Wang1, Guanguan Zhao1, Hualing
of TL1A. Our previous studies demonstrated that enhanced TL1A/ Pan1, Shengsheng Yang1, Zhenwei Zhang1, Eric H Xu1,2
DR3 signaling of T lymphocytes in a mouse model directly results
1
Cascade Pharmaceutic, 2Shanghai Institute of Materia Medica,
in spontaneous ileitis in a microbiota-dependent manner. However, Chinese Academy of Sciences
their association with MAFLD and the effects of TL1A/DR3 signaling Background: Cholestatic liver diseases, including Metabolic
deficiency on intestinal microbiota remain unknown. Dysfunction-Associated Steatohepatitis (MASH), Primary Sclerosing
Method: Female and male WT and DR3 deficiency (Dr3-/-) mice Cholangitis (PSC), and Primary Biliary Cholangitis (PBC), remain areas
were maintained under SPF condition until 7-9 months of age. 16S of significant unmet clinical need. Linafexor (CS0159), a pulse FXR
rRNA sequencing was performed of colon luminal fecal samples ligand with a short half-life, is designed to align with the metabolic
and differential microbial genera were identified by negative binomial cycle of bile acids to maximize efficacy and minimize toxicity. Circadian
models. Body weight and liver histology were used to assess metabolic rhythm and metabolic up-and-down regulation are fundamental
abnormality. aspects of animal physiology, and incorporating these principles into
Result: DR3 knockout male mice were susceptible to obesity or drug design ensures optimal safety and effectiveness. This Phase 1
emaciation with significantly different body weight compared with male study evaluates the pharmacokinetics (PK), pharmacodynamics (PD),
WT mice. There was no difference in body weight between female safety, and tolerability of Linafexor in healthy subjects.
WT and Dr3-/- mice. Liver histology of male mice showed that DR3 Method: The Phase 1 study included six single ascending dose (SAD)
deficiency led to increased hepatocyte steatosis, enlarged portal cohorts (0.2, 0.6, 1.0, 2.0, 4.0, and 8.0 mg) and four multiple ascending
areas, increased fibrous tissue, and obvious chronic inflammatory dose (MAD) cohorts (0.4, 1.0, 2.0, and 4.0 mg). PK assessments
cell infiltration. DR3 deficiency promoted gut microbiota dysbiosis included serum drug concentration profiling and dose-exposure
in both sexes of mice. However, alpha diversity was reduced only relationships. PD markers such as FXR target gene expression
in male Dr3-/- mice. The microbiota composition clustered distinctly were monitored. Safety evaluations included hepatic function tests,
in male mice with decreased Prevotella, and increased Turicibacter, histopathology, and adverse event monitoring.
Alistipe, Ruminococcus, and Desulfovibrio suggesting they might Result: Linafexor exhibited linear pharmacokinetics across all doses,
drive the development of MAFLD. We observed higher abundance of with predictable dose-exposure relationships and rapid clearance
Odoribacter, Desulfovibrio and decreased Bacteroides in female Dr3- consistent with its short half-life. In MAD cohorts, PD markers
/- mice. indicated target saturation at doses ≥2.0 mg, confirming the biological
Conclusion: Our findings firstly identify DR3 as a major regulator of activity of Linafexor. Most notably, there were zero adverse events
specific gut microbiota during the development of MAFLD with male (AEs) associated with Linafexor across all SAD and MAD cohorts,
tendency. highlighting its excellent tolerability and safety profile. The short half-
life and pulsatile FXR activation minimized systemic exposure, further Andreas E Kremer4, John M Vierling5, Kris V Kowdley6, Cynthia Levy7,
supporting its safety advantages. Susheela Carroll8, Ke Yang8, Linda Wu8, Yun Jung Choi9, Daria B
Conclusion: Linafexor (CS0159) demonstrates an exceptional safety Crittenden8, Charles A McWherter9
and tolerability profile in Phase 1 studies, with no adverse events 1
Division of Gastroenterology and Hepatology, Toronto Centre for
reported and clear evidence of pharmacodynamic saturation at higher Liver Disease, University of Toronto, 2Division of Gastroenterology
doses. These findings underscore the advantages of a pulse FXR and Hepatology, University of California Davis School of Medicine,
ligand designed to synchronize with circadian bile acid metabolism, 3
Division of Digestive and Liver Diseases, University of Texas SW
supporting its continued development as a promising therapy for Medical Center, 4University Hospital Zürich, University of Zürich,
cholestatic liver diseases, including MASH, PSC, and PBC. 5
Baylor College of Medicine, 6Liver Institute Northwest, 7Schiff Center
for Liver Diseases, University of Miami, 8Gilead Sciences, Inc.,
9
CymaBay Therapeutics, Inc.
OP0314
Background: Seladelpar, a potent and selective peroxisome
Linerixibat Has Low Potential of Ethnic Differences for the
proliferator-activated receptor-delta (PPAR-δ) agonist, has anti-
Treatment of Cholestatic Pruritus in Primary Biliary Cholangitis
cholestatic, anti-inflammatory and anti-pruritic activity. We report the
Ying Ke1, Mengyuan Zhu2, Romina Nand1, Carwyn Davies1, Janelle results of a 12-month, placebo-controlled trial of seladelpar in patients
Lennie3, Sumanta Mukherjee3, Yuri Shida4, Xuan Zhou2, Weiwei Mu2, with primary biliary cholangitis (PBC) at risk of disease progression
Megan M McLaughlin3, Brandon Swift5 (RESPONSE, NCT04620733).
1
GSK, Sydney, Australia, 2GSK, Shanghai, China, 3GSK, Collegeville, Method: Eligible patients had ursodeoxycholic acid (UDCA) treatment
PA, USA, 4GSK, Tokyo, Japan, 5GSK, Durham, NC, USA for ≥12 months or were intolerant and had alkaline phosphatase (ALP)
Background: Cholestatic pruritus is common in primary biliary ≥1.67 × upper-limit-of-normal (ULN) and total bilirubin (TB) ≤2 × ULN.
cholangitis (PBC), with similar prevalence in Asia, Europe and the Patients were randomized to receive either daily oral seladelpar 10 mg
US, and significantly impairs sleep and health-related quality of life. or placebo. Treatment was stratified by ALP and pruritus numerical
Bile acids (BAs) are key mediators in the pathophysiology of PBC rating scale (NRS; 0–10). The primary endpoint was a composite
pruritus. The ileal bile acid transporter (IBAT) located in the ileum response of ALP <1.67 × ULN, ALP decrease ≥15% and TB ≤ULN at
of the gastrointestinal tract is crucial for enterohepatic recirculation Month 12. Key secondary endpoints were ALP normalization at Month
of BAs. Linerixibat, a selective, minimally absorbed, small-molecule 12 and change in NRS at Month 6.
IBAT inhibitor, reduces circulating BAs and improves PBC pruritus. Result: We enrolled 193 patients (female 94.8%; mean age 56.7 years;
We evaluated the pharmacokinetics (PK), pharmacodynamics (PD) 94% taking UDCA) with mean ALP 314.4 U/L and TB 0.76 mg/dL (13%
and safety of linerixibat in a Japanese versus Western population, for > ULN). Patients had a baseline mean NRS of 3.0; 37.3% of patients
extrapolation to a Chinese population. reported moderate-to-severe itch (baseline NRS ≥4, mean NRS 6.3). At
Method: PK, PD and safety data from a Phase 1 study in Japanese Month 12, 61.7% of patients achieved the primary composite response
patients (pts) were compared with data from two Phase 1 studies in endpoint with seladelpar vs 20% with placebo (P < .0001; Figure 1).
healthy Western pts and data from the Phase 2 GLIMMER trial (Table). The secondary endpoint of ALP normalization occurred in 25% of
The potential ethnic sensitivity of linerixibat in PBC pruritus was those receiving seladelpar vs 0% receiving placebo (P < .0001; Figure
assessed using ICH E5 guidelines. 1). The average decrease in ALP for seladelpar was -133.9 U/L vs.
Result: The Phase 1 studies utilized a less sensitive bioanalytical -16.9 U/L for placebo (P < .0001; Figure 1). Seladelpar, compared to
assay of linerixibat PK (lower limit of quantification [LLQ] = 1 ng/mL) placebo, lowered alanine aminotransferase by 23.5% vs. 6.5% and
which was mostly unmeasurable in both Japanese and Western pts. γ-glutamyl transferase by 39.1% vs. 11.4%. The key secondary pruritus
The Phase 2 GLIMMER study employed a more sensitive assay (LLQ endpoint was met at Month 6 with patients treated with seladelpar with
= 10 pg/mL) with sparse sampling; no clear differences were observed baseline NRS ≥4 reporting decreases of 3.2 vs 1.7 for patients treated
when comparing Japanese and Western pts. The PD response with placebo (P < .005; Figure 1). Improvement of pruritus NRS with
to linerixibat in Japanese pts was generally consistent with that in seladelpar was sustained through Month 12 (P < .005). There were
Western pts. In both populations, total serum BA (TSBA) concentration no treatment-related serious adverse events. Discontinuation from
tended to decrease, whilst serum 7-alpha-hydroxy-4-cholesten-3-one adverse events occurred in 3.1% and 4.6% of patients treated with
(C4) concentration tended to increase following linerixibat treatment. seladelpar and placebo, respectively.
There was interindividual variability in these biomarkers; considering Conclusion: In this placebo-controlled pivotal trial of patients with
the limited sample size, there was no evidence suggesting differences PBC and incomplete response or intolerance to UDCA, seladelpar 10
between Japanese and Western pts. Safety results were consistent mg for 12 months resulted in rapid, statistically significant, and durable
between Japanese and Western pts. The most common adverse event improvements in markers of cholestasis and liver injury, and improved
in linerixibat-treated pts was on-target diarrhoea in both Japanese and pruritus. Seladelpar appeared overall safe and well tolerated through
Western pts. Considering many of the ethnic factors listed in ICH E5, Month 12. The long-term safety and tolerability are being evaluated
there is no evidence suggesting interethnic differences in the PK, PD in an open-label trial (NCT03301506). This abstract was previously
and safety of linerixibat in Asian relative to Western populations. presented at the American Association for the Study of Liver Diseases
Conclusion: The localised target site and limited systemic absorption – The Liver Meeting (TLM 2023).
of linerixibat meant measurable PK was limited. Target engagement Table and Figure:Figure 1.Primary and Secondary Efficacy Endpoints
(measured by proximal biomarkers TSBA and C4), was consistent in the RESPONSE trial
between Japanese and Western pts. The safety profile of linerixibat
was also consistent between both populations. Linerixibat has a low OP0316
potential of ethnic differences across Western and Asian populations
for the treatment of PBC pruritus. The requirement of a Phase 1 PK Prediction of Moderate-to-Severe Interface Hepatitis in Primary
bridging study was waived; China was included in the global Phase 3 Biliary Cholangitis Using Machine Learning and SHAP
GLISTEN study (NCT04950127). Shasha Li1, Yongfeng Yang2
Funding: GSK (studies 205808, BAT114985, BSC116511, 201000). 1
School of Medicine, Nanjing University, Nanjing, China, 2Department
Table and Figure:Figure 1. of infectious disease and liver disease, The Second Hospital of
Nanjing, Clinical Teaching Hospital of Medical School, Nanjing
University, Nanjing, China
OP0315
Background: The evaluation of interface hepatitis is critical for the
Efficacy and Safety of Seladelpar in Patients With Primary Biliary treatment and prognosis of primary biliary cholangitis (PBC). We aimed
Cholangitis in the RESPONSE Trial: A Phase 3 International, to develop and validate a prediction model for identifying of moderate-
Randomized, Placebo-Controlled Study to-severe interface hepatitis in PBC patients (PBC-MTS).
Gideon M Hirschfield1, Christopher L Bowlus2, Marlyn J Mayo3, Method: We retrospectively analyzed the clinical and pathological
data of patients diagnosed with PBC through liver biopsy between Result: Based on preclinical studies and prior clinical data, Linafexor
January 2017 and October 2023. Potential predictors of PBC-MTS is anticipated to demonstrate significant improvements in cholestatic
were screened using univariate analysis, the least absolute shrinkage biomarkers and liver function, with dose-dependent efficacy. Safety
and selection operator (LASSO) regression. Five prediction models, outcomes are expected to align with findings from Phase 1 and MASH
including a nomogram built with logistic regression and four machine Phase 2 studies, where Linafexor showed a favorable safety profile,
learning algorithms (Random Forest, XGBoost, SVM, Decision Tree), minimal adverse events, and circadian-aligned modulation of bile acid
were constructed. Model performance was assessed using the area metabolism.
under the receiver operating characteristic curve (AUROC), accuracy, Conclusion: The Phase 2 study results for Linafexor in PBC and PSC
sensitivity, and precision. Feature importance of individuals was will be reported at the APASL 2025 meeting. Drawing from earlier
interpreted using Shapley Additive Explanations (SHAP). studies, Linafexor is expected to offer a promising therapeutic option
Result: Moderate-to-severe interface hepatitis was found in 53.6% of for these diseases, with efficacy and safety outcomes consistent with
the training cohort and 51.2% of the validation cohort. Key predictors its novel mechanism of action and pharmacological profile.
in the nomogram included IgG, AST, GGT, TBA, IgA, and ALB. The
PBC-MTS nomogram achieved an AUROC of 0.83 in the training set
OP0318
and 0.80 in the validation set. The AUROC of the four machine learning
models was 0.82 (Random Forest), 0.80 (XGBoost), 0.77 (SVM), and The effect of Jianpi Huoxue Tongluo Fang intervention on portal
0.68 (Decision Tree). The sensitivity of the five models ranged from vein recanalization in rats with portal vein thrombosis
66.4% (Decision Tree) to 77.1% (Random Forest), and the accuracy Ruiyuan Tian1, Yong Li2
ranged from 67.6% (Decision Tree) to 76.3% (Logistic Regression). 1
Qilu Gaoxin Hospital of Shandong University, 2Affiliated Hospital of
Conclusion: Logistic regression and four machine learning algorithms Shandong University of Traditional Chinese Medicine
were used to construct five PBC-MTS prediction models. The Background: PVT is present in 10% to 26% of cirrhosis, which can
application of machine learning algorithms can provide convenient risk aggravate portal hypertension, lead to repeated upper gastrointestinal
stratification for patients with primary biliary cholangitis. bleeding, refractory ascites, acute intestinal ischemic necrosis and
Table and Figure:Figure 1.The ROCs and AUCs of PBC-MTS prediction hepatorenal syndrome, and increase the difficulty of liver transplantation
models using the various machine-learning algorithms and mortality after transplantation. Anticoagulation intervention is
Figure 2.The SHAP values of the 6 variables for four patients. Patient mainly suitable for patients with acute symptomatic PVT, waiting for
A and Patient B were histologically confirmed with moderate to severe liver transplantation, and patients with mesenteric vein thrombosis.
interface hepatitis. Patient C and Patient D were without interface For patients with Child-Pugh grade B/ C, anticoagulation intervention
hepatitis. should be carefully considered. The optimal time of anticoagulant
therapy, drug selection and anticoagulant risk avoidance are the
OP0317 problems that need to be studied seriously. Although there have been
reports of successful establishment of PVT models in rats, the animals
Phase II Studies of a Novel Pulsatile FXR Ligand for PBC and PSC
all died within 1 w after modeling. According to the theory of traditional
Eric H Xu1,2, Xiong Ma3, Gai Hong Wang1, Jing Jing Shi1, Guan Guan Chinese medicine, the pathogenesis of cirrhosis is Qi deficiency and
Zhao1, Hua Ling Pan1, Sheng Sheng Yang1, Rong Deng1, Zhen Wei blood stasis. Traditional Chinese medicine promoting blood circulation
Zhang1, Xiu Hong Jiang1, Xiao Xiao3, Hong You4, Su Jun Zheng5, Li and removing blood stasis has the effect of anti-liver fibrosis and
Yang6, Kai Wang7, Hong Liang He8, Qian Cao9, Min Zhang10, Rong reversing cirrhosis. The main pathogenesis of PVT formation is blood
Lin11, Bing Liang Lin12, You Wen Tan13, Ai Ming Yang14, Wen Zhang14, stasis blocking collages, and the intervention of promoting blood
Jun Qi Niu15, Tin Bo Liang16, Shi Ouyang17, Jia Shang18 circulation and removing blood stasis may achieve PVT recirculation.
1
Cascade Pharmaceutic, 2Shanghai Institute of Materia Medica, We successfully established a rat model of PVT and the animals
Chinese Academy of Sciences, 3Shanghai JiaoTong University survived for at least 4 weeks. According to the clinical characteristics
School of Medicine, 4Beijing Friendship Hospital, Capital Medical of liver cirrhosis PVT, we put forward the TCM compound intervention
University, 5Beijing Youan Hospital, Capital Medical University, 6 West of supplementing qi and activating blood to Tongluo, and the results of
China Hospital Sichuan University, 7Cheeloo College of Medicine,
preliminary clinical trials proved that PVT could be re-routed.
Shandong University, 8The First Affiliated Hospital of USTC Anhui
Method: The PVT model of rats was established by intermittent portal
Provincial Hospital, 9Shaoyifu Hospital of Zhejiang University Medica,
vein ligation combined with clamp, and the modeling state was judged
1
0The Second Xiangya Hospital of Central South University, 11 Union
by ultrasound. The model animals were randomly divided into 6 model
Hospital, Tongji Medical College, Huazhong University of Science and
Technology, 12The Third Affiliated Hospital, Sun Yat-sen University, group, 6 model control group, 12 rivaroxaban intervention group and
1
3The Third People‘s Hospital of Zhenjiang, 14Peking Union Medical 12 traditional Chinese medicine intervention group.
College Hospital, 15The First Hospital of Jilin University, 16The First Result: After 2w of experiment, the recurrence rate was 44.4% (4/9)
Affiliated Hospital, Zhejiang University school of Medicine, 17The in the rivaroxaban group and 90.9% (10/11, P<0.05) in the TCM
Fifth Affiliated Hospital of Guangzhou Medical University, 18Henan group. Model group, model control group and Rivaroxaban group
Provincial People‘s Hospital showed vascular intima injury, media edema and thickening, and a
large number of collagen fibers were attached to the portal vein. In
Background: Primary Biliary Cholangitis (PBC) and Primary Sclerosing
the Chinese medicine group, the vascular intima was basically intact,
Cholangitis (PSC) are chronic cholestatic liver diseases with limited
the media was slightly thickened, and only a small number of collagen
treatment options. Linafexor (CS0159), a pulse FXR ligand with a short
fibers were attached. The serum D-dimer level in the Chinese medicine
half-life, is designed to align with the metabolic cycle of bile acids
group was (170.7±6.7).
to optimize efficacy and safety. Circadian rhythm and metabolic up-
Conclusion: A stable rat PVT model was successfully established
and-down regulation are fundamental aspects of animal physiology,
using intermittent ligation combined with clamping method; Both
and drug design incorporating these principles ensures superior
rivaroxaban and Yiqi HuoxueTongluo Formula are effective in promoting
therapeutic potential. This Phase 2 study investigates the efficacy and
PVT recanalization. Yiqi Huoxue Tongluo Formula can resist vascular
safety of Linafexor in PBC and PSC patients at doses of 2.0 mg and 4.0
endothelial fibrosis, and the therapeutic effect of PVT recanalization is
mg, with results expected to be unblinded by March 2025.
better than that of rivaroxaban.
Method: A randomized, double-blind, placebo-controlled Phase
Table and Figure:Figure 1.Figure
2 trial was conducted in patients with PBC and PSC. Linafexor was
Figure 2.Table
administered daily at doses of 2.0 mg or 4.0 mg for 12 weeks. Primary
efficacy endpoints include changes in cholestatic biomarkers, such as
alkaline phosphatase and bilirubin levels, and secondary endpoints OP0319
include improvements in liver function tests. Safety evaluations focus
on hepatic function and adverse event monitoring.
Therapeutic mechanism study of He-he San-ji Formula on NASH- Method: We analyzed 145 CHB-related decompensated cirrhosis
HCC through TREM2-mediated polarization of Tumor associated patients from the Ditan study and 33 from the Changgung validation
macrophages study, categorizing them
Huan-Ming Xiao1, Mei-Jie Shi1, Bo-wen Gao2, You-Sheng Mo1, Yu- based on PVT occurrence. Plasma samples were assessed for NET
Bao Xie1, Chao-zhen Zhang1, Ming Lin1, Fo-Lai Zeng1, Xiao-Ling Chi1 markers, including cell-free DNA (cfDNA) and histone DNA complexes,
1
Guangdong Provincial Hospital of Chinese Medicine, 2Guangzhou along with DNase activity.
University of Chinese Medicine Result: PVT patients exhibited elevated levels of cfDNA and histone-
DNA complexes, and reduced DNase activity. This pattern persisted
Background: As living standards have risen, the rate of hepatocellular
regardless of hepatocellular carcinoma (HCC) status. Histone-DNA
carcinoma (HCC) linked to nonalcoholic steatohepatitis (NASH) has
levels, DNase activity, and hemoglobin were identified as independent
increased annually. Professor Chi Xiaoling from Guangdong Province
risk factors for PVT. Receiver operating characteristic curve analysis
developed He-he San-ji Formula (HHSJ) as an effective treatment for
revealed that high histone-DNA levels may serve as a potential
NASH-HCC, though its mechanism remains unclear. This study aims
diagnostic marker for PVT, with an area under the curve of 0.8628 in
to explore the role of TREM2-mediated TAM polarization in NASH-
the Ditan study and 0.7521 in the Changgung study. When combined
HCC development and to further investigate HHSJ’s efficacy and
with cfDNA and DNase activity, the area under the curve improved to
mechanism in treating NASH-HCC.
0.8774 in the Ditan study and 0.7975 in the Changgung study.
Method: We developed a NASH-HCC mouse model using an HFCD
Conclusion: Imbalances in NET homeostasis are associated with PVT
diet and hepatoma cell injection, treating it with HHSJ Formula. In vitro,
in CHB-related decompensated cirrhosis, including cases involving
we created a TAMs model by co-culturing BMDM and Hepa1-6 cells.
HCC. Histone-DNA complexes, a significant risk factor for PVT, show
Using siRNA and adeno-associated virus, we knocked out TREM2
potential as a diagnostic marker for PVT in decompensated cirrhosis,
and conducted related experiments. We assessed tumor growth,
particularly in HBV-related HCC.
TAMs phenotypes, glycolysis, and how HHSJ Formula regulate TAMs
Table and Figure:Figure 1.The Picture of article abstrct
polarization via the LDL-C/TREM2/PKM2 pathway.
Figure 2.Flowchart of the Ditan study (A) and Changgung study (B).
Result: Bioinformatics analysis revealed that TREM2 expression
rises with NASH progression and is notably upregulated in HCC
tissues. TREM2 is positively linked to M2 macrophage polarization OP0321
and is highly expressed in TAMs. SiRNA-mediated TREM2 knockout Exploring the Mechanism of Shuxuening Injection on Liver
reduces TAM infiltration and PKM2 expression. In NASH-HCC model Fibrosis in Mice Based on Gut Microbiota and Non-targeted
mice, adenovirus-mediated TREM2 knockout slows tumor growth and Metabolomics
reduces TAM infiltration, suggesting TREM2 activation by liver LDL-C Xin Sun1, Tingyu Zhang1, Shihao Zheng1, Wenying Qi1, Xiaoke Li1,2,
overexpression is key in NASH-HCC, affecting PKM2 expression and Xiaobin Zao1,2,3
TAM polarization. HHSJ Formulareduces liver fluorescence, liver/ 1
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing
spleen index, tumor pathology, serum ALT levels, and TAM infiltration
100700, China, 2Institute of Liver Diseases, Dongzhimen Hospital,
in NASH-HCC mice, with the highest dose being most effective. HHSJ Beijing University of Chinese Medicine, Beijing 100700, China, 3Key
Formula lowers TREM2 and PKM2 expression, restores LDLR levels, Laboratory of Chinese Internal Medicine of Ministry of Education and
reduces LDL-C accumulation, and highlights the DL-C/TREM2/PKM2 Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine,
pathway as crucial for its therapeutic effect. Beijing 100700, China
Conclusion: This study highlights TREM2’s crucial role in TAM
Background: Liver fibrosis (LF) is a complex fibrogenic inflammatory
polarization during NASH-HCC progression and demonstrates the
response caused by various etiologies and serves as a critical
effectiveness of HHSJ Formula in treating NASH-HCC, likely by
intermediate stage in the progression to cirrhosis. Shuxuening injection
modulating TAM polarization via the LDL-C/TREM2/PKM2 signaling
(SXN), primarily used for treating ischemic cerebrovascular diseases,
pathway.
has shown anti-fibrotic effects. However, the mechanism by which SXN
Table and Figure:Figure 1.Figure1 The Impact of the Hehe Sanji
exerts its anti-fibrotic impact on the liver remains unclear.
Formula on Tumor Progression in TREM2 Knockout Mice with NASH-
Method: The LF mouse model induced by carbon tetrachloride (CCL4)
HCC
was established. Randomly divided 24 mice into Control, Model, and
Figure 2.Figure 2 The Impact of Hehe Sanji Formula on TAM Polarization
SXN groups. After 6 weeks of intervention with SXN by intraperitoneal
and the LDL-C/TREM2/PKM2 Signaling Pathway in TREM2 Knockout
injection, mouse serum was extracted to detect serological
Mice with NASH-HCC
indexes. The therapeutic effect of SXN on LF was investigated using
histological and immunohistochemical analysis methods. Changes
OP0320 in mice’s gut microbiota and liver metabolites were analyzed using 16S
The Imbalance of Homeostasis in Neutrophil Extracellular Traps rRNA sequencing and non-targeted metabolomics.
is Associated with Portal Vein Thrombosis in Patients with Result: SXN treatment significantly improved CCL4-induced liver
Decompensated Cirrhosis fibrosis in mice, with weight recovery, decreased liver index, improved
Ying Cao1, Ming Han2,3,4, Jia Yu Liu2,3,4, Luan Liu Zhu2,3,4, Yuan serum ALT, AST, and HA levels, and reduced liver histological fibrosis
Huang5 and inflammation. Concurrently, SXN induced structural changes
in the gut microbiota, significantly increasing the abundance of
1
Center of Liver Diseases Division 1, Beijing Ditan Hospital, Capital
Medical University, Beijing, China, 2Beijing Key Laboratory of beneficial bacteria such as Akkermansia and Bifidobacterium, while
Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing decreasing the abundance of harmful bacteria like unclassified_o__
Ditan Hospital, Capital Medical University, Beijing, China;, 3Beijing Bacteroidales. In addition, principal component analysis, supervised
Institute of Infectious Diseases, Beijing, China, 4National Center for partial least squares and orthogonal partial least squares discriminant
Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, analysis of samples from SXN and Model groups showed that
Beijing, China, 5Digestive Department, Beijing Tsinghua Changgung samples within the group were relatively clustered, while samples
Hospital, School of Clinical Medicine, Tsinghua University, Beijing, between the groups were relatively independent, showing a significant
China separation trend, suggesting significant differences in liver metabolic
Background: Portal vein thrombosis (PVT) is a challenging profiles between the two groups. A total of 182 different metabolites
complication in liver cirrhosis, with no currently available sensitive were obtained between the SXN and Model group. The enrichment
diagnostic markers. This study aimed analysis results showed that these different metabolites were related
to investigate the potential of neutrophil extracellular traps (NETs) and to the pathways of Bile secretion, Protein digestion and absorption,
Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic Arachidonic acid metabolism, Choline metabolism in cancer, ABC
hepatitis B (CHB)-related decompensated cirrhosis. transporters, and Glycerophospholipid metabolism.
Conclusion: SXN may improve LF in mice by remodeling intestinal
flora, increasing the dominance of beneficial bacteria such as Background: Portal hypertension (PH) is the primary consequence
Akkermansia and Bifidobacterium in the intestine, and regulating Bile of liver cirrhosis, which could lead to severe complications. Growing
secretion, lipid metabolism, and hormone synthesis in the liver. evidences have verified that gut microbiota dysbiosis is the essential
Table and Figure:Figure 1.Shuxuening alleviates liver cirrhosis in mice: aggravator for PH development, which propels high mortality of
route of in vivo experiments (A); body weight, liver index, and spleen cirrhotic PH patients. Carvedilol is the mainstay for PH pharmaceutical
index of mice (B); Serum levels of AST, ALT, Cr, HA, and IL-6 levels in treatment via decreasing cardiac output and providing superior PH
mice (C); Histopathological examination of the liver tissues: H&E (D) alleviation compared to the other non selective β blockers (NSBBs).
Figure 2.Beta diversity analysis, GMHI index, MDI index (A, B, C); Although carvedilol is recognized as the most effective pharmaceutical
Venn analysis on genus level (D);Community barplot analysis on genus treatment for PH, a comprehensive understanding of its specific
level (E); Wilcoxon rank-sum test bar plot on genus level (F); OPLS- impacts on gut microbiota composition and metabolic profiles has yet
DA, PCA, PLS-DA analysis of liver tissue metabolites (G, H, I); SXN to be thoroughly explored.
vs Model volcano (J); KEGG Enrichment Analysis(SXN_vs_Model) (K) Method: We conducted a trans-omics investigation integrating
the fecal metagenomes and metabolomics data from PH patients
OP0322 achieving hepatic venous pressure gradient (HVPG) response with
carvedilol treatment (n=16) and matched healthy controls (HCs) (n=16)
LOXL1 G153D Mutation Impedes Liver Fibrosis Regression After to investigate the regulatory effects of carvedilol on the aberrant gut
Etiology Removal microbiota community and metabolic profiles in PHs and identify the
Wen Zhang1, Hong Li1, Wenyue Wu1, Yameng Sun1, Ning Zhang1, specific bacteria-metabolites-fungi interkingdom networks involved in
Xiaoning Wu1, Xuzhen Yan1, Aiting Yang1, Wei Chen1, Hong YOU1 carvedilol treatment.
1
Beijing Friendship Hospital, Capital Medical University Result: Carvedilol could re-organize the altered overall cross-domain
Background: Lysyl oxidase-like 1 (LOXL1) is crucial for cross- microbial biodiversities and compositions and rebalance the dynamic
linking and stabilizing extracellular matrix (ECM) structural proteins. and competing interplay between beneficial taxa such as bacteria
Previous studies have indicated that single nucleotide polymorphisms species Roseburia_inulinivorans, fungi genus Saccharomyces and
(SNPs) in the LOXL1 gene are closely associated with disorders the detrimental guild including Streptococcus_sp., fungi genus
stemming from abnormal elastin assembly. However, the relationship Aspergillus in PH to maintain the gut and vascular hemostasis, which
between LOXL1 SNPs and liver fibrosis remains unclear. could consequently promote a holistically healthier gut microbiota
Method: Blood genomic DNA was collected from 168 liver profiles to alleviate PH development. Additionally, re-establishment
fibrosis patients with chronic hepatitis B (CHB) at baseline to of the aberrant metabolic profiles and restoration of specific
analyze LOXL1 SNPs using PCR and Sanger sequencing. The clinical metabolites comprising sphingolipid and thiamine involved in PH
relevance of LOXL1 SNPs, including their associations with blood development after carvedilol management were also clarified. More
biochemistry indices, liver stiffness measurement (LSM) values, and importantly, except for exhibiting pleiotropically restorative roles in
histological Ishak scores pre- and post-antiviral treatment (AVT), as modulating microorganism and their metabolites, carvedilol could
well as liver fibrosis regression following AVT. The roles and functions also systemically restore microbiota homeostasis towards a healthier
of clinically significant SNPs were investigated in vivo using gene- status through improving bacterial-metabolites-fungi network, and
edited mice and in vitro using the LX-2 cell line. Liver fibrosis was consequently alleviated cirrhotic PH.
induced via intraperitoneal injection of carbon tetrachloride (CCl4), and Conclusion: In addition to hemodynamic benefits, carvedilol exerted
spontaneous liver fibrosis regression was established by cessation of pleiotropic roles in restoring the equilibrium of the microbial cross-
CCl4 treatment. domain communities and their intricate interkingdom ecosystem to
Result: Patients with the heterozygous LOXL1 G153D mutation systemically facilitated the gut hemostasis re-establishment and foster
exhibited reduced reversibility of liver fibrosis after 78 weeks of AVT a virtuous cycle in PH alleviation via the gut-liver axis. Accordingly,
(non-mutation vs. G153D mutation: 26.3% vs. 52.4%, p=0.025). the promising therapeutic strategies focused on restoring the specific
Subsequent analysis of blood biochemical indices revealed significantly microbial communities homeostasis and rebuilding the delicate balance
elevated levels of serum ALT and GGT, as well as increased LSM values between bacteria-metabolite-fungi interkingdom interaction involved in
and Ishak scores in patients with the heterozygous LOXL1 G153D PH might provide the encouraging insights on pharmacotherapeutic
mutation compared to non-mutant patients post-AVT. We then management in PH.
established gene-edited mice with the heterozygous Loxl1 G153D Table and Figure:Figure 1.The graphic abstract of the article
mutation (Loxl1G153D) and their littermates (Loxl1WT). Following
CCl4 cessation, Loxl1G153D mice exhibited greater liver inflammatory OP0324
infiltration, enhanced activation of the NF-κB signaling pathway,
Hepatic Adverse Events of Novel Immunotherapy-Based Therapies
and elevated liver IL-1β levels compared to Loxl1WT mice. In vitro
in Clinical Trials: A Systematic Review and Meta-Analysis
experiments demonstrated that the LOXL1 protein was notably
translocated to the cell membrane or extracellular space following Minyan Ye1, Yimin Mao2, Sha Huang1
transient transfection of LX-2 cells with the LOXL1 G153D mutant
1
Fujian tumor hospital, 2Renji Hospital Affiliated to Shanghai Jiaotong
plasmid. This suggests that the LOXL1 G153D mutation promotes the University
extracellular secretion of LOXL1 protein, leading to increased cross- Background: The objective of this study is to evaluate whether the
linking and deposition of ECM structural proteins, thereby hindering incorporation of novel immunotherapies that targeting costimulatory
liver fibrosis regression. molecules or coinhibitory pathways, beyond traditional treatments
Conclusion: Our study highlights the role and biological function involving PD-1, PD-L1, and CTLA-4, increases the incidence of
of the heterozygous LOXL1 G153D mutation after successful HBV hepatic adverse events. Additionally, we investigate the occurrence
suppression. The LOXL1 G153D mutation may delay liver fibrosis rates of liver-related adverse events in cancer patients undergoing
regression through stiff ECM and exacerbate inflammation following novel immunotherapies and combination therapies based on these
the removal of the underlying etiology. This finding may also explain treatments.
why effective AVT does not lead to regression of liver fibrosis in some Method: A comprehensive literature search was conducted
CHB patients from the perspective of genetic heterogeneity. across PubMed, Embase, Cochrane Library, and Web of Science
databases for clinical studies involving cancer patients treated with
immunotherapies that targeting LAG-3, TIGIT, TIM-3, PVRIG, CD112R,
OP0323
VISTA, BTNL2, BTN3A1, BTN2A1, BTLA, NKG2A, CD47, 41BB,
Carvedilol restoring gut microbiota homeostasis: a potential CD137, OX40, TNFRSF4, CD134, ICOS, CD278, CD40, D28, CD27,
therapeutic mechanism for portal hypertension management GITR, and B7-H3.
Yarong Hao1, Chenyu Xie1, Yong Lin1 Result: The search yielded 63 studies reporting on treatment-
1
Changzheng Hospital related or immune-related hepatic adverse events up to May 1,
2024, encompassing a total of 7,327 patients. The analyzed studies N-acyltransgerase, which is responsible for catalyzing the amidation of
included agents targeting LAG-3, TIGIT, TIM-3, CD47, NKG2A, 4-1BB, bile acids (BAs) with the amino acids taurine and glycine. Up-regulated
OX40, ICOS, CD27-CD70, GITR, CD40, and B7-H3. Notably, in the expression levels of BAAT with Harmaline mitigated cholestasis and
6 randomized controlled trials assessed, the addition of LAG-3 or enhanced cell viability in HLOs. We further tested the BAs profiles and
TIGIT inhibitors to traditional antitumor therapies did not result in a found glycocholic acids (GCA) levels decreased in HLOs treated with
higher incidence of elevated ALT, AST, ALP, GGT levels, or hepatitis. BVC. Supplementation of GCA to HLOs with BVC treatment led to a
CD27-CD70-targeted antitumor treatments was most frequently significant improvement in cell viability.
associated with elevated transaminase levels in monotherapy. Among Conclusion: Our data suggested that BVC impaired the GCA synthesis
dual immunotherapy combinations, the most common cause of any- by down-regulating the expression of BAAT, therefore inhibiting bile
grade transaminase elevation involved the combination of 4-1BB flow and inducing cholestasis.
agonists with PD-1/PD-L1 inhibitors; in contrast, high-grade elevations Table and Figure:Figure 1.Graphic abstract
were notably seen with the CD40 agonist in conjunction with CTLA-4
inhibitors. Furthermore, the incidence of transaminase elevation when
OP0326
novel agents were used in combination with chemotherapy was greater
than when combined with targeted therapies. The overall incidence of Molecular mechanism of endoplasmic reticulum stress regulating
any-grade transaminase elevation ranged from 7.50% to 36.64%, while DDX3X-TFEB signaling pathway to promote drug-induced liver
high-grade transaminase elevation occurred within the range of 0% to injury
17.83% during dual immunotherapy combined with targeted therapy Yaling Cao1, Yao Gao1, Ling Xu1, Zihao Fan1, Feng Ren1
or chemotherapy. Cholestatic enzymes elevations during monotherapy 1
Beijing Institute of Hepatology, Beijing Youan Hospital, Capital
with immune agents are most commonly linked to anti-CD27-CD70 Medical University
treatments. For new drug combinations with chemotherapy, the Background: The incidence of drug-induced liver injury (DILI) is
incidence of all-grade cholestatic enzyme elevations ranges from high, characterized by rapid progression and poor prognosis. Several
3.33% to 21.93%, and high-grade elevations range from 1.90% to studies have indicated a close association between the occurrence
20.18%. and development of drug-induced liver injury and endoplasmic
Conclusion: This study found that the addition of novel immunotherapy reticulum stress; however, the specific molecular mechanism remains
to traditional antitumor treatment does not increase hepatic toxicity. unclear. This study aimed to investigate the role of DEAD (Asp-Glu-Ala-
We provide a summary of the incidence rates of liver-related adverse Asp) box polypeptide 3 X-linked (DDX3X) and its regulatory molecular
events associated with novel immunotherapies and combination mechanism in the progression of DILI.
therapies, contributing valuable insights for treatment selection in Method: In the mouse model of drug-induced liver injury by
cancer patients. acetaminophen (AILI), endoplasmic reticulum stress was inhibited
Table and Figure:Figure 1.Figure 2. a all grade hepatic adverse events; to observe the changes in liver injury, and the differential genes of
b grade ≥3 hepatic adverse events; c all-grade ALT increase; d grade hepatocytes were analyzed and further verified. The role of DDX3X
≥3 ALT increase; e all-grade AST increase; f grade ≥3 AST increase; g and transcription factor EB (TFEB) in DILI was determined with
all-grade ALP increase; h grade ≥3 ALP increase; i all-grade hepatitis DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control
increase; j grade ≥3 hepatitis increase (DDX3Xfl/fl) mice or TFEB overexpression, respectively.
Figure 2. Figure 3. A Incidence of All-grade and high-grade ALT and Result: Inhibition of endoplasmic reticulum stress in the mouse AILI
AST increase in monotherapy immunotherapy; B Incidence of All- model can alleviate liver injury. Transcriptomic analysis indicates
grade and high-grade ALT and AST increase in dual immunotherapy that endoplasmic reticulum stress can significantly upregulate the
expression of DDX3X, and knockout of DDX3X can exacerbate AILI.
OP0325 The differential genes induced by APAP are significantly enriched in
the lysosomal pathway, and the expression of DDX3X is significantly
Bavachinin caused cholestasis by down-regulating the expression
positively correlated with that of the key regulatory factor of the
of BAAT and disrupting glycocholic acid synthesis in human liver
lysosomal pathway, TFEB. DDX3X positively regulates the expression
organoids
of TFEB, and high expression of TFEB mitigates AILI. The results of the
Yu Su1, Xue Wang1, Xiaomeng Chen2, Lin Liu1, Xinyan Zhao1, Jidong RIP experiment demonstrate that DDX3X regulates the transcription
Jia1 of TFEB. Additionally, the endoplasmic reticulum stress-DDX3X-TFEB
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical axis is significantly correlated with the prognosis of patients with DILI.
University, State Key Lab of Digestive Health, National Clinical Conclusion: This study demonstrates that endoplasmic reticulum
Research Center for Digestive Disease, Beijing, China, 2Clinical stress promotes DILI by regulating DDX3X-TFEB signaling pathway.
laboratory Center, Beijing Friendship Hospital, Capital Medical Table and Figure:Figure 1.A model describing the endoplasmic
University, Beijing, China
reticulum stress-regulated DDX3X-TFEB signaling pathway promoting
Background: Psoraleae Fructus (PF) is extensively utilized for drug-induced liver injury
dermatological and osseous disorders in China. Whereas, PF-induced
liver injury has become a predominant concern, in which cholestasis
OP0328
is a major injury pattern. The related mechanisms of PF induced
cholestasis varied, including bile salt output and bile transportation. The study on the efficacy of menstrual blood-derived mesenchymal
However, studies on hepatotoxic mechanisms of PF have mainly stem cells in the treatment of alcoholic liver fibrosis.
carried out on 2D cells or rodents, which may not fully encapsulate the Ang Li1, Jun Ge2, Chi Yang3,2, Tao Wu1,2
human physiological surroundings. 1
Hainan Provincial Center for Public Health and Clinical Medicine,
Method: Three Human liver organoids (HLOs) was generated and 2
Hainan Provincial People‘s Hospital, 3Hainan Medical University
characterized. Hepatotoxic components screening and cell viabilities Background: Alcoholic liver disease (ALD) is a chronic liver disease
were conducted by MTT/CCK8 assay. The mechanisms of liver injury caused by long-term alcohol consumption, with currently limited
on HLOs were investigated through RNA-sequencing, quantitative treatment options. Menstrual blood-derived mesenchymal stem cells
polymerase chain reaction, Cholyl-lysyl-fluorescein (CLF) tests and (MenSCs) play an anti-inflammatory, anti-fibrotic, and tissue repair
Western Blot. Changes of bile acids profile were analyzed by UPLC- role in liver diseases such as fibrosis. This study aims to explore the
MS/MS analysis. efficacy of MenSCs in alcoholic liver fibrosis.
Result: We identified Bavachinin (BVC) as the most hepatotoxic Method: Eight-week-old healthy male C57BL/6J mice were selected
component among screened ingredients, with the bile secretion as experimental subjects, with three randomly chosen as the blank
pathway involved in. After validation the cholestasis by CLF tests, group. A total of 35 mice were used to establish an alcoholic liver
we screened genes in bile secretion pathway and identified BAAT might fibrosis model , with three mice randomly selected as the model group.
induced cholestasis. BAAT encodes bile acid-CoA: amino acid
The remaining 32 mice were randomly divided into a control group of the three proteins (TGF-β1, α-SMA, and collagen) in model group
and a treatment group, with 16 mice in each group. The blank group 4 were significantly higher than those in model groups 2 and 3, with
and model group were euthanized and sampled before the experiment statistical significance (P < 0.05). The Ishak score indicated that model
began. The control group received tail vein injections of PBS, while the groups 2 and 3 had mild liver fibrosis, while model group 4 had severe
treatment group received tail vein injections of MenSCs cell suspension. liver fibrosis.
One week later, four mice from each group were randomly selected to Conclusion: Induction by either pyrazole or ethanol alone is insufficient
collect blood and liver tissue samples. The remaining mice underwent to establish an alcoholic liver fibrosis model; however, the combination
another week of treatment before sampling, and this process was of both can successfully construct an alcoholic liver fibrosis model.
repeated four times, with a total treatment duration of approximately
four weeks. Liver function was assessed, and pathological changes
OP0330
were observed through staining of liver tissue. Changes in the levels of
TGF-β1, α-SMA, and collagen were detected using Western blot (WB) Long-term safety of tenofovir alafenamide in Chinese chronic
analysis, and the Ishak score was used to evaluate the stages of liver hepatitis B patients treated for up to 8 years in 2 Phase 3 studies
fibrosis. Jinlin HOU1, Qin Ning2, Zhongping DUAN3, Yu Chen3, Qing XIE4, Lunli
Result: The levels of ALT, AST, and TP in the model group were Zhang5, Shanming Wu6, Hong TANG7, Jun LI8, Feng Lin9, Yongfeng
significantly elevated compared to the blank group (P<0.05). In the YANG10, Guozhong Gong11, Yanwen Luo12, Yan Chen12, Hongyuan
treatment group, the levels of ALT, AST, and TP were significantly Wang13, Irina Botros13, Dana Tedesco13, Leland J Yee13, Frida
lower compared to the model group (P<0.05), and the differences Abramov13, Chengwei CHEN14, Yan Huang15, Mingxiang Zhang16,
were statistically significant. There was no significant difference Jidong JIA17
between the model group and the control group. Compared to the 1
Nanfang Hospital, Southern Medical University, Guangzhou,
blank group, the model group and control group exhibited extensive Guangdong, China , 2Tongji Hospital, Tongji Medical College,
collagen fiber formation and discontinuous liver tissue structure. After Huazhong University of Science and Technology, Wuhan, Hubei,
four weeks, the liver tissue in the treatment group showed a markedly China , 3Beijing Youan Hospital, Capital Medical University, Beijing,
organized arrangement of cells, with clear hepatic lobule structure and China, 4Shanghai Ruijin Hospital, Shanghai Jiao Tong University
no significant fibrosis or collagen deposition. Compared to the model School of Medicine, Shanghai, China, 5The First Affiliated Hospital of
group and control group, the levels of TGF-β1, α-SMA, and collagen Nanchang University, Nanchang, Jiangxi, China, 6Shanghai Public
in the treatment group were significantly decreased (P<0.05), showing Health Clinical Center, Shanghai, China, 7West China Hospital,
significant differences. The Ishak score indicated that both the model Sichuan University, Chengdu, Sichuan, China, 8The First Affiliated
Hospital of Nanjing Medical University, Nanjing, Jiangsu, China,
group and control group had severe liver fibrosis, while the treatment 9
Hainan General Hospital, Haikou, Hainan, China, 10Nanjing No.
group exhibited mild liver fibrosis, and there was no fibrosis in the
2 Hospital, Nanjing, Jiangsu, China, 11The 2nd Xiangya Hospital,
blank group.
Central South University, Changsha, Hunan, China, 12Gilead
Conclusion: MenSCs intervention can improve liver function and
Sciences, Shanghai, China, 13Gilead Sciences, Foster City, CA, USA,
the histological structure of mice with alcoholic liver fibrosis to some 1
4The People‘s Liberation Army No. 85 Hospital, Shanghai, China,
extent, reducing the levels of TGF-β1, α-SMA, and collagen, as well 1
5Xiangya Hospital, Central South University, Changsha, Hunan,
as the Ishak score of liver tissue in mice with alcoholic liver disease. China, 16The Sixth People‘s Hospital of Shenyang, Shenyang,
Liaoning, China, 17Beijing Friendship Hospital, Capital Medical
OP0329 University, Beijing, China
Establishment of an alcoholic liver fibrosis model using the Background: In 2 similarly designed phase 3 studies, the three-
combination of ethanol and pyrazole. year (144-week) double-blind (DB) phase demonstrated comparable
Ang Li1, Jun Ge2, Chi Yang3,2, Tao Wu1,2 efficacy of tenofovir alafenamide (TAF) versus tenofovir disoproxil
fumarate (TDF), with improved bone and renal safety observed in
1
Hainan Provincial Center for Public Health and Clinical Medicine,
2
Hainan Provincial People‘s Hospital, 3Hainan Medical University Chinese patients with chronic hepatitis B (CHB). After completing DB
treatment, all patients could receive open-label (OL) TAF up to week
Background: Alcoholic liver disease (ALD) is a chronic liver disease 384 (year 8). Here we present the final safety results at year 8.
caused by long-term alcohol consumption. Currently, the exploration Method: Treatment-emergent (TE) adverse events (AEs), serious AEs
of disease treatment and mechanisms has been relatively slow, one and graded laboratory abnormalities occurring during OL phase are
important reason being the lack of a more perfect model that simulates included in this pooled analysis.. Changes from baseline in estimated
human drinking habits. This study aims to explore the feasibility GFR (by Cockcroft-Gault; eGFRCG) and changes in hip and spine
of establishing an alcoholic liver fibrosis disease model using a bone mineral density (BMD) by dual x-ray absorptiometry (DXA) scans
combination of pyrazole and ethanol. were assessed over the study period.
Method: A total of 40 male C57BL/6J mice, aged 8 weeks, were Result: Of the 334 randomized and treated patients, 311 entered the
randomly divided into four groups of 10 mice each: model group 1, OL phase. Overall, 88% (186/212) of the TAF-TAF group and 95%
model group 2, model group 3, and model group 4. All groups were (94/99) of the TDF-TAF group experienced TEAEs during OL phase, of
fed with liquid diet L10016A and were gavaged once every three days. which 27% (58/212) and 30% (30/99), respectively, were considered
Model group 1 was gavaged with maltose, model group 2 with ethanol, study drug-related. Rates of Grade ≥3 AEs were low, 6% (12/212)
model group 3 with pyrazole, and model group 4 with a combination of and 6% (6/99) in the TAF-TAF and TDF-TAF groups, respectively.
ethanol and pyrazole. After the 20th gavage, blood and liver samples and there were no AEs leading to study drug discontinuation (Table
were collected to assess liver function. Pathological changes in liver 1). Two deaths, one in each group, occurred during the OL phase.
tissues were observed after Masson and Sirius Red (SR) staining. The between-group differences in renal and bone parameters
Western blotting (WB) was used to detect changes in the levels of through the double-blind phase diminished after both groups started
transforming growth factor-β1 (TGF-β1), alpha-smooth muscle actin OL TAF. At Week 384, the median change from BL in eGFRCG was
(α-SMA), and collagen. The Ishak score was used to evaluate the small and comparable between groups (-1.3 mL/min vs. -2.0 mL/min,
stage of liver fibrosis. P=0.9233). The differences in median percent changes in RBP:Cr and
Result: Compared to model group 1, the levels of ALT and AST in β2M:Cr between groups observed during the DB phase narrowed after
model groups 2, 3, and 4 were significantly elevated, with statistical switching to OL TAF. Small decreases in hip and spine BMD observed
significance (P < 0.05). There were no statistically significant differences during DB TDF treatment improved after switching to OL TAF.
in albumin, total protein, and ALP levels among the four groups (P > Conclusion: Long-term TAF treatment was safe and well tolerated.
0.05). Pathological examination of liver tissues in model groups 2 and 3 Favorable renal and bone effects were sustained through 8 years on
showed a small amount of collagen fibers around blood vessels, while TAF treatment with improvement observed following the switch from
model group 4 exhibited a large amount of collagen fiber formation TDF to TAF.
and a discontinuous liver tissue structure. WB indicated that the levels
Table and Figure:Figure 1.Table 1. Treatment-emergent safety of patients with HBV-related HCC who underwent radical surgery.
parameters during OL phase (OL SAS) Patients were given Peg-IFN-α combined with first-line NAs, including
Figure 2.Figure 1. Changes in eGFRCG, hip and spine bone mineral ETV, TDF, TAF, or TMF. The primary efficacy endpoint was the incidence
density through 384 weeks of HCC at 24/48 weeks in the cirrhosis group, and the recurrence rate
of carcinoma in the HCC group. The safety evaluation mainly focused
on the incidence of decompensated cirrhosis.
OP0331
Result: 76 patients in the cirrhosis group and 17 in the HCC group
Higher risk of postpartum phase transition to immune-active completed 24 weeks of treatment. 28 patients in the cirrhosis group
among HBeAg-positive pregnant women with indeterminate phase and 2 in the HCC group completed 48 weeks of treatment. At baseline,
Qiao Tang1, Peng Hu2,3 there were 41 NAs-treated patients (41/76, 53.95%) in the cirrhosis
1
The Second Affiliated Hospital of Chongqing Medical University, group, whose HBV DNA was not detectable. 35 patients (35/76,
Chongqing, China., 2Department of Infectious Diseases, the First 46.05%) were treatment-naive who had an average HBVDNA of
Affiliated Hospital of Chongqing Medical University., 3Institute for 3.77±2.02 log IU/ml. The HBV DNA of all patients in HCC group was
Viral Hepatitis, Chinese Ministry of Education, Chongqing Medical not detectable. The mean HBsAg of the two groups were 2.76±0.99
University. log IU/ml and 1.94±1.38 log IU/ml, respectively. After 24 weeks of
Background: Investigation on natural history of hepatitis B infection treatment, 1 patient (1/76, 1.32%) in the cirrhosis group developed
helps to guide the timing of initiating antiviral therapy, and which was HCC, and 2 (2/17, 11.76%) in the HCC group had carcinoma
primarily performed in non-pregnant patients. The natural history recurrence. All the HBV DNA was not detectable. The mean HBsAg
dynamics in pregnant women with chronic hepatitis B (CHB) remain was 2.21±1.25 log IU/ml in the cirrhosis group, and 1.71±1.48 log
unknown. IU/ml in the HCC group. They were decreased by 0.55±0.86 log IU/
Method: We performed a retrospective-prospective real-world study ml (P=0.000) and 0.23±0.23 log IU/ml (P=0.007) from baseline,
including 352 pregnant women with CHB. Dynamics of natural history respectively. After 48 weeks of treatment, all patients (28/28,100%) in
during pregnancy (including 248 HBeAg-positive and 48 HBeAg- the cirrhosis group did not develop HCC, and the 2 patients in the
negative participants) and the postpartum period (including 108 HCC group did not have carcinoma recurrence. The mean HBsAg of
HBeAg-positive who received short-term antiviral intervention and the 28 patients in cirrhosis group was 1.92±1.42 log IU/ml at 48 weeks,
21 HBeAg-negative participants), and liver disease progression of which decreased by 0.74±1.09 log IU/ml compared with 2.66±1.03
different phases were investigated. log IU/ml, that of baseline (P=0.007). No decompensated cirrhosis
Result: The proportion of immune-tolerance (IT) gradually increased, occurred. The adverse event of Peg-IFN-α treatment was mainly the
whereas the proportion of HBeAg-positive indeterminate phase (IP) thrombocytopenia.
and HBeAg-positive immune-active (IA) gradually decreased during Conclusion: Using Peg-IFN-α combined with NAs treatment, the
pregnancy. In the third trimester of pregnancy, IT was dominant incidence of HCC was low in patients with HBV related cirrhosis and the
(48.7%), followed by HBeAg-positive IP (24.6%), HBeAg-positive recurrence rate was low in patients with HBV related HCC after radical
IA (9.4%), inactive carrier (9.4%), HBeAg-negative IP (7.1%) and surgery. The patients were safe and the incidence of decompensated
HBeAg-negative IA (0.9%). A numerical higher cumulative incidence cirrhosis seldomly occurs.
of postpartum maintenance the phase and a significantly lower
cumulative incidence of transition to HBeAg-positive IA in pregnant OP0333
women with IT compared with pregnant women with HBeAg-negative
IP. The cumulative incidence of postpartum maintenance the phase Long-term efficacy of tenofovir alafenamide in Chinese chronic
and transition to HBeAg-negative IA were comparable between hepatitis B patients treated for up to 8 years in 2 Phase 3 studies
pregnant women with IC and HBeAg-negative IP (p > 0.05). Pregnant Jinlin HOU1, Qin Ning2, Zhongping DUAN3, Yu Chen3, Qing XIE4, Lunli
women with different phases had similar low risk of postpartum liver Zhang5, Shanming Wu6, Hong TANG7, Jun LI8, Feng Lin9, Yongfeng
disease progression. YANG10, Guozhong Gong11, Yanwen Luo12, Yan Chen12, Hongyuan
Conclusion: Pregnancy, short-term antiviral therapy, and delivery may Wang13, Roberto Mateo13, Tahmineh Yazdi13, Dana Tedesco13, Leland
have an impact on natural history of HBV infection in HBeAg-positive J Yee13, Frida Abramov13, Chengwei CHEN14, Yan Huang15, Mingxiang
pregnant women, especially in those with indeterminate phase at 24- Zhang16, Jidong JIA17
28 weeks of gestation. 1
Nanfang Hospital, Southern Medical University, Guangzhou,
Table and Figure:Figure 1.The distribution and dynamic of natural Guangdong, China , 2Tongji Hospital, Tongji Medical College,
history among pregnant women with CHB during pregnancy. Huazhong University of Science and Technology, Wuhan, Hubei,
Figure 2.The cumulative incidences of maitaining the phase and phase China , 3Beijing Youan Hospital, Capital Medical University, Beijing,
transition to IA among participants with different phases. China, 4Shanghai Ruijin Hospital, Shanghai Jiao Tong University
School of Medicine, Shanghai, China, 5The First Affiliated Hospital of
Nanchang University, Nanchang, Jiangxi, China, 6Shanghai Public
OP0332 Health Clinical Center, Shanghai, China, 7West China Hospital,
The Efficacy and Safety of Pegylated Interferon Alpha Treatment Sichuan University, Chengdu, Sichuan, China, 8The First Affiliated
in Patients with HBV Related Cirrhosis and HCC after Radical Hospital of Nanjing Medical University, Nanjing, Jiangsu, China,
Surgery: Preliminary Data From The TERMINATOR Project
9
Hainan General Hospital, Haikou, Hainan, China, 10Nanjing No.
2 Hospital, Nanjing, Jiangsu, China, 11The 2nd Xiangya Hospital,
Qiuju Sheng1, Dawu Zeng2, Yang Ding1, Chao Han1, Chong Zhang1,
Central South University, Changsha, Hunan, China, 12Gilead
Xiaoguang Dou1
Sciences, Shanghai, China, 13Gilead Sciences, Foster City, CA, USA,
1
Shengjing Hospital of China Medical University, 2the First Affiliated 1
4The People‘s Liberation Army No. 85 Hospital, Shanghai, China,
Hospital of Fujian Medical University 1
5Xiangya Hospital, Central South University, Changsha, Hunan,
Background: In China, most primary hepatocellular carcinoma (HCC) China, 16The Sixth People‘s Hospital of Shenyang, Shenyang,
is caused by HBV infection, and the recurrence rate of HBV-related Liaoning, China, 17Beijing Friendship Hospital, Capital Medical
HCC patients after radical surgery is high. We explored the application University, Beijing, China
of pegylated interferon-α (Peg-IFN-α) combined with nucleoside (tide) Background: In 2 similarly designed phase 3 studies of HBeAg
analogues (NAs) to evaluate the efficacy and safety of Peg-IFN-α in negative and HBeAg positive Chinese patients with chronic hepatitis
reducing the incidence of HCC in patients with HBV related cirrhosis B (CHB), the three-year (144-week) double-blind (DB) phase
and reducing the recurrence of HCC in patients after radical surgery. demonstrated comparable efficacy of tenofovir alafenamide (TAF)
Method: The analysis was conducted in the preliminary data from a versus tenofovir disoproxil fumarate (TDF). After completing 3 years of
multi-center, prospective, real-world cohort study (the TERMINATOR DB treatment, all patients were eligible to receive open-label (OL) TAF
Project) from China. The cirrhosis group was consisted of compensated through Year 8 (Week 384). Here we present the final efficacy results
HBV related cirrhosis patients, and the HCC group was consisted
at year 8. patients achieve with baseline HBsAg < 250 IU/ml.
Method: Efficacy endpoints reported as proportions were analyzed Table and Figure:Figure 1.Baseline charateristics before and after PSM
using both the missing-equals-to-failure (M=F) approach and the Figure 2.HBsAg loss rate in two subgroups and different baseline
missing-equals-to-excluded (M=E) approach. Analyses of viral HBsAg levels
suppression (HBV DNA < 29 IU/mL), alanine aminotransferase (ALT)
normalization (ULN=40U/L), serological responses and fibrosis change
OP0335
by serum FibroTest over 384 weeks were conducted. Resistance
analyses, including deep sequencing of HBV pol/RT (at baseline and Responders to Prior BRII-179 Treatment Achieved Faster and
annually), for those with virologic breakthrough/blip, persistent viremia, Higher Rate of HBsAg Seroclearance Following Treatment of
or treatment discontinuation with viremia were performed, as was Elebsiran and PEG-IFNα in Participants with Chronic Hepatitis B
phenotyping of qualifying samples. Virus Infection: Preliminary Data from ENSURE Study
Result: Among 334 participants, 311 entered OL phase including 212 Grace Lai-Hung Wong1, Apinya Leerapun2, Young-Suk Lim3, Pisit
from DB TAF to OL TAF (TAF-TAF) and 99 switched from DB TDF to OL Tangkijvanich4, Mark W Douglas5, Suparat Khemnark6, Witsarut
TAF (TDF-TAF). At Week 384, the proportion of participants with viral Manasirisuk7, Teerha Piratvisuth8, Martin Weltman9, Chong Zhu10, Ke
suppression in the TAF-TAF and TDF-TAF groups was 79.3% (180/227) Cao10, Weihong Liu10, Xiaofei Chen10, David Margolis11, Qing Zhu11,
and 78.5% (84/107) by M=F method (P=0.8517) and 95.2% (180/189) Man Fung Yuen12
and 95.5% (84/88) (P=0.9407) by M=E method, respectively. At Week 1
Medical Data Analytics Centre, The Chinese University of Hong
384, ALT normalization rates were high and comparable between Kong, 2Maharaj Nakorn Chiang Mai Hospital, 3Asan Medical Center,
groups, (TAF-TAF: 87.8% vs. TDF-TAF: 84.9%, P=0.5514 by M=E. A University of Ulsan College of Medicine, 4King Chulalongkorn
similar trend was observed by M=F analysis. A higher proportion of Memorial Hospital, 5The University of Sydney, Westmead Institute
participants in the TAF-TAF group had serological responses (Table 1). for Medical Research and Westmead Hospital, 6Bamrasnaradura
Among participants with FibroTest scores at both baseline and Week Infectious Diseases Institute, 7Sprinagarind Hospital,
384, the proportions of participants with improvement, no change and
8
Songklanagarind Hospital, 9Nepean Hospital, 10Brii Biosciences
worsening of fibrosis stage in the TAF-TAF group were 26.1%, 71.7% (Beijing) Co. Limited, 11Brii Biosciences, Inc., 12Queen Mary Hospital,
and 2.2%, respectively, and 28.9%, 61.4% and 9.6% in the TDF-TAF The University of Hong Kong
group, respectively. Sequence/phenotyping analysis through 8 yr Background: BRII-179 is a recombinant protein-based
showed no resistance to TAF. immunotherapeutic consisting of Pre-S1, Pre-S2, and HBsAg antigens.
Conclusion: After 8-year of treatment with TAF or switch from TDF, It has been demonstrated that BRII-179 induced robust HBV-specific
virologic suppression and biochemical response rates remained high immune responses in a notable proportion of participants with virally
across all groups of Chinese CHB participants. suppressed chronic HBV infection. It is hypothesized that those
Table and Figure:Figure 1.Table 1. Efficacy results at Week 384 (FAS) participants who elicit detectable HBV-specific immune responses
after BRII-179 treatment may have a less impaired intrinsic immune
profile and be more responsive to curative therapies.
OP0334
Method: Participants who completed 9-dose BRII-179 in combination
Comparative Efficacy of IFN and Nuc Therapy regarding HBsAg with elebsiran (BRII-835, an siRNA) in a previous APAC study BRII-179-
loss in Chronic Hepatitis B Patients 835-001 (NCT04749368) at least 1 year ago were enrolled to ENSURE
Ruirui You1, Qiran Zhang1, Yiqi Yu1, Feng Sun1, Yuxian Huang1, study Cohort 4 (NCT05970289). Participants received elebsiran 100
Jiming Zhang1, Chao Qiu1, Wenhong Zhang1 mg every 4 weeks in combination with pegylated interferon alfa-2a
1
Department of Infectious Diseases, National Medical Center for (PEG-IFNα) every week over a 48-week treatment period and continued
Infectious Diseases, Huashan Hospital, Fudan University nucleos(t)ide analogues. Quantitative HBsAg was assessed; the
Background: Several studies have demonstrated that interferon results were analyzed based on anti-HBs responses induced by BRII-
(IFN) based therapy results in higher rates of HBsAg loss in patients 179 in BRII-179-835-001 study. Preliminary 24-week on-treatment data
with chronic hepatitis B, compared to nucleos(t)ide analogue (Nuc) are reported.
monotherapy. This study aimed to evaluate the effect regarding HBsAg Result: A total of 31 participants were enrolled in Cohort 4, 28 of
loss with IFN-based therapy, based on different prior treatment history whom with baseline HBsAg ≥ 100 IU/mL were analyzed. 18 and
and baseline HBsAg levels with real-world cohorts. 10 participants had peak anti-HBs ≥ 10 IU/L induced by BRII-179
Method: This analysis was conducted in the data from a multicenter, treatment (defined as anti-HBs responders) and < 10 IU/L (defined
real-world study (OASIS project) in China. This analysis was conducted as non-responders), respectively. Median (range) serum HBsAg levels
in the prospective cohort of this study. Participants were assigned at the time initiating elebsiran+PEG-IFNα were numerically higher
to receive either IFN-based therapy (including IFN alone and IFN in anti-HBs responders (539.4 [106.7-2165.0] IU/mL) than in non-
combined with Nuc) or Nuc therapy (Nuc alone). According to the responders (219.3 [106.7-671.5] IU/mL). At Week 24, 11/28 (39.3%)
treatment before enrollment, patients were divided into 2 subgroups: participants achieved HBsAg seroclearance. More than half of the
previously treatment-naïve and Nuc-treated. Kaplan-Meier curves anti-HBs responders (10/18 [55.6%]) achieved HBsAg seroclearance,
were utilized to compare the HBsAg loss rate at 96 weeks. Propensity compared to only 1/10 (10.0%) in non-responders. Elebisiran + PEG-
score matching (PSM) was used to balance the differences between IFNα combination therapy was generally safe and tolerated in this
the baseline characteristics (including age, gender, HBsAg, HBeAg, patient population. The majority of AEs were consistent with the known
HBV DNA, liver histological status) of the IFN group and Nuc group in side effects of PEG-IFNα.
treatment-naïve and Nuc-treated patients. PSM was performed using Conclusion: Preliminary data showed that a substantially higher rate
the nearest-neighbor matching at a 1:1 ratio. of HBsAg seroclearance was achieved following elebsiran and PEG-
Result: Either in treatment-naïve or in Nuc-treated patients, the 96- IFNα treatment in participants who previously had BRII-179 induced
week HBsAg loss rate in IFN group was significantly higher than in the anti-HBs response than those who did not. Responders to prior BRII-
Nuc group. (Treatment-naïve patients: 13.10% in the IFN group, 4.55% 179 appeared to achieve a faster HBsAg seroclearance compared
in the Nuc group, p = 0.0002, Fig. A; Nuc-treated patients: 21.90% in to BRII-179 naïve participants receiving elebsiran+PEG-IFNα as
the IFN group , 5.16% in the Nuc group, p < 0.0001, Fig. B). When previously reported (Jia, 2024). Longer treatment up to 48 weeks is
stratified by baseline HBsAg levels, the highest HBsAg loss rates were ongoing. The early data suggest that BRII-179 induced anti-HBs
observed in patients with baseline HBsAg < 250 IU/ml (29.20% vs response may potentiate HBsAg seroclearance and enrich for patients
14.07% at 48 week, 35.26% vs 18.60% at 96 week in treatment-naïve who are more responsive to curative therapies.
patients, p = 0.024, Fig. A1; 38.74% vs 7.96% at 48 week, 50.51% vs Reference:
14.27% at 96 week in Nuc-treated patients, p < 0.0001, Fig. B1). Jidong Jia, Bingling Lin, Peng Hu, et. al. Efficacy and safety of elebsiran
Conclusion: IFN-based therapy showed higher HBsAg loss rates than and PEG-IFNα combination therapy vs PEG-IFNα in participants with
Nuc therapy in treatment-naive and Nuc-treated patients, especially in chronic HBV infection: preliminary EOT results from ENSURE study.
AASLD TLM, Nov 15-19, 2024. Publication # 5008. Background: Owing to the exposure of gut-derived foreign antigens
Table and Figure:Figure 1.Distribution of serum HBsAg levels and metabolites, a default liver immunotolerance substantially limits
current liver cancer treatments. Intestinal factors orchestrate liver-
OP0336 resident immune cells, particularly natural killer T (NKT) cells, and this
could be a promising intervention.
ACSL4 Identified as a Potential Prediction Biomarker for Invasion Method: Here, by integrated clinical-omics analysis, we reveal the
and Metastasis of Hepatocellular Carcinoma via Multi-center Study survival benefit of NKT cells in patients within 10-year follow-up, and
Yusufukadier Maimaitinijiati1,2, Xiong Chen3, Yuan Meng3, Yingcai the elevated secondary bile acids (BAs) is identified as a critical
Zhang3, Shizhong Yang1, Jiahong Dong1 contributor to insufficient NKT cells. Accordingly, we propose a gut-
1
Tsinghua University,Tsinghua Changgung Hospital, 2People’s Hospital liver axis modulation of NKT cell strategy against liver cancer with an
of Xinjiang Uyghur Autonomous region, 3People‘s Hospital of Xinjiang oral delivery system. The rational designed GMS@αCoat comprises a
Uyghur Autonomous region PLGA microsphere encapsulating a microbial bile salt hydrolase (BSH)
Background: Hepatocellular carcinoma (HCC) has an insidious onset, inhibitor, and an outer spore protein shell containing a NKT cell agonist
easy recurrence and metastasis, and often has a poor prognosis. (αGC).
Tumor invasive front (TIF) is the most active site for tumor cells to Result: This strategy involves the sequential delivery of αGC across
invade outwards, and it is also the source of tumor micro-metastasis. small intestinal barrier destined to liver tumour, while BSH inhibitor
Therefore, a comprehensive understanding of the invasive front of release in colon to suppress the microbiome-modified secondary BAs,
HCC and the mining of its key biomarkers may not only deepen the coordinately activating and proliferating NKT cells. With the improved
understanding of the mechanisms of HCC invasion and metastasis, but immune-metabolic response, our strategy exerts potent efficacy in
also pave the way for the development of new therapeutic strategies diverse orthotopic models, including the clinically-relevant, aggressive
for HCC. This study was to explore the key biomarkers are closely Myc-driven liver cancer.
associated with invasion and metastasis of HCC and its clinical value. Conclusion: Our study highlights that modulating gut-organ
Method: Firstly, we based on the spatial transcriptomic sequencing interactome provides both target and route to empower cancer
data of HCC clinical specimens, the biological characteristics of HCC immunotherapy.
invasive front were deeply analyzed, and an innovative algorithm was Table and Figure:Figure 1.Gut-liver axis modulation of NKT cells for
used to mine the key biomarker of TIF-Acyl-CoA Synthetase Long Chain enhanced liver cancer immunotherapy
Family Member 4 (ACSL4), which is closely related to HCC invasion
and metastasis. Then, the clinical value of ACSL4 demonstrated OP0339
through multi-center cohort that recruited 243 HCC patients from
Decoding Extracellular Vesicle-Derived circRNAs in
3 clinical centers in China. Finally, the functional mechanism was
Cholangiocarcinoma: A Multi-Omics Machine Learning Approach
revealed through in vivo, in vitro and multi-omics joint analysis.
to Predict Immunotherapy Resistance
Result: ACSL4 has significant tissue specificity and spatial specificity
in HCC, and was strongly positive in the whole process of HCC invasion Prihantini Prihantini1, Sahnaz Vivinda Putri2, Andi Nursanti Ureng3,
and metastasis, such as circulating tumor cells, microvascular invasion, Rifaldy Fajar4, Karenina Santika5
intrahepatic metastases and distant metastases lesions. Multicenter
1
Machine Learning for BioMedicine Laboratory, Bandung Institute of
study shows that the overall survival rate (p<0.05) and recurrence- Technology, 2Health Management Laboratory, International University
free survival rate (p<0.05) of the high ACSL4 expression patients Semen Indonesia, 3Department of Pharmacy, Andini Persada College
were lower than the low ACSL4 expression patients. Correspondingly, of Health Sciences, 4Computational Biology and Medicine Laboratory,
the MVI occurrence rate of patients with high ACSL4 expression was Yogyakarta State University, 5Cancer Biology Research Unit,
higher than that of patients with low ACSL4 expression (p<0.05). The Bantaeng General Hospital
results of in vivo and in vitro experiments indicate that the ACSL4 gene Background: Cholangiocarcinoma (CCA), a lethal cancer prevalent
is closely related to the invasive and metastatic abilities of HCC cells. in Southeast Asia, shows poor immunotherapy response. Extracellular
Transcriptomics and metabolomics joint analysis observed that after vesicle (EV)-derived circular RNAs (circRNAs) are underexplored
knocking down ACSL4, key enzymes (CPT1A, CPT2, ACOX1) and regulators of the tumor microenvironment (TME), influencing immune
metabolic products (arachidonic acid, Acetyl-CoA) involved in fatty checkpoints and cell recruitment, contributing to therapy resistance.
acid beta-oxidation process underwent significant changes (p<0.01). Using real multi-omics datasets, this study identifies EV-derived
Conclusion: ACSL4 can be used as a potential prediction biomarker circRNAs as predictive biomarkers and therapeutic targets for
for invasion and metastasis of hepatocellular carcinoma . overcoming immunotherapy resistance.
Table and Figure:Figure 1.Study general framework Method: We analyzed data from “Immune cell atlas of
Figure 2.ACSL4 is positively correlated with poor prognosis in HCC cholangiocarcinomas reveals distinct tumor microenvironments
patients. A: Flow chart of multicenter validation for clinical value of and associated prognoses” (Journal of Hematology & Oncology,
ACSL4. B: Representative immunohistochemical images of patients 2022), including scRNA-seq profiles of 104 surgically resected CCA
with high and low ACSL4 expression. C: The expression of ACSL4 in samples. EV transcriptomics data were obtained from ExoCarta and
patients with postoperative recurrence was significantly higher than Vesiclepedia, while proteomics data came from “Liquid biopsy-based
patients without recurrence and the recurrence rate of patients with protein biomarkers for risk prediction, early diagnosis, and prognosis
high ACSL4 was significantly higher than that of patients with low of cholangiocarcinoma” (Journal of Hepatology, 2023). CircRNAs
ACSL4 expression. D: The expression level of ACSL4 is correlated were annotated using circBase, and differentially expressed circRNAs
with the overall survival rate of HCC patients, and patients with high were prioritized with DESeq2. A machine learning framework, EV-
ACSL4 expression had a relatively poor prognosis. E: The expression circOmicsNet, integrated circRNA, transcriptomic, and proteomic data
of ACSL4 was also associated with recurrence free survival in HCC for predicting immunotherapy resistance phenotypes. Multi-modal
patients, and the relationship was consistent with the trend of overall clustering (Louvain and hierarchical clustering) stratified the TME into
survival. immune states. Predictive models (XGBoost, support vector machines)
were validated using GEO datasets. Kaplan-Meier and Cox models
assessed survival and prognostic markers.
OP0337
Result: Three EV-derived circRNA immune states were identified.
Gut-liver axis modulation empowers natural killer T cells for liver The Immune-Suppressive EV State (46.2%; 95% CI: 41.8-50.6%)
cancer immunotherapy featured upregulated circRNAs targeting PD-L1 transcription
Ting Luo1, Jie Yu1, Xing-Jie Liang2, Ping Liang1 regulators, such as circPDCD1 (3.1-fold increase, p < 0.001), linked
1
Fifth Medical Center of Chinese People’s Liberation Army General to T-cell exhaustion and low anti-PD1 therapy response (response
Hospital, 2National Center for Nanoscience and Technology rate: 19.8%; 95% CI: 15.5-24.1%). The Pro-Inflammatory EV State
(32.7%; 95% CI: 28.3-37.1%) showed enrichment of circRNAs like
circSTAT1 (2.7-fold increase, p < 0.001) correlated with improved General Hospital
therapy response (response rate: 70.4%; 95% CI: 63.9-76.9%). Background: There is limited research on the role of pgRNA in the
The Neutral EV State (21.1%; 95% CI: 17.4-24.8%) showed minimal occurrence and development of advanced HCC and the specific
circRNA activity. EV-circOmicsNet achieved an AUROC of 0.81 (95% mechanisms remain unclear. The objective of this study is to investigate
CI: 0.79-0.83) for predicting resistance, reflecting a moderate ability the predictive value of pgRNA status on recurrence in advanced
to classify phenotypes. Key prognostic markers included circPDCD1 HCC patients, and to explore the effects of pgRNA on the biological
(HR: 3.45; 95% CI: 2.78-4.22) and circSTAT1 (HR: 0.46; 95% CI: 0.33- behavior of HCC cells in vivo and in vitro experiments.
0.58). Median survival was 10.1 months (95% CI: 8.1-12.1 months) Method: This study enrolled treatment-naïve patients with advanced
for immune-suppressive states versus 23.4 months (95% CI: 20.4-26.4 HBV-related HCC who were treated at the Fifth Medical Center of
months) for pro-inflammatory states (p < 0.001). Chinese PLA General Hospital. All patients received systemic therapy
Conclusion: EV-derived circRNAs, particularly circPDCD1 and consisting of stereotactic body radiotherapy, lenvatinib, and sintilimab.
circSTAT1, shape the immune landscape of CCA, with their modulation Baseline pgRNA levels of all enrolled patients were measured by
of PD-L1 and IFN-γ signaling identified as key mechanisms driving qPCR. Univariate and multivariate Cox regression analyses were used
immunotherapy resistance and response, offering novel predictive to identify risk factors for HCC recurrence. The effects of pgRNA on the
biomarkers and therapeutic targets. biological behavior of hepatocellular carcinoma cells were investigated
through in vivo and in vitro experiments.
OP0340 Result: This study included 73 patients with advanced HBV-related
HCC (BCLC stage B or C). The baseline characteristics of two
ATG16L1-mediated macrophage metabolic reprogramming
groups were shown in Table 1. Univariate and multivariate Cox
promotes liver regeneration
regression analyses (Table 2) showed that positive status of pgRNA
Xinyu Zhan1,2,3, Qin Zhu4, Yiyun Gao1,2,3, Haoming Zhou1,2,3
at baseline was an independent risk factor for recurrence in advanced
1
Hepatobiliary Center, The First Affiliated Hospital of Nanjing HBV-related liver cancer (P < 0.001, HR = 4.515 [2.048–9.955]). The
Medical University, Nanjing, 210029, China, 2Key Laboratory of survival analysis revealed a higher recurrence rate in the baseline
Liver Transplantation, Chinese Academy of Medical Sciences,
serum pgRNA-positive group (P<0.001, Figure 1). The patients were
Nanjing, 210029, China, 3NHC Key Laboratory of Living Do nor Liver
categorised as double-positive, single-positive, or negative based
Transplantation (Nanjing Medical University), Nanjing, 210029, China,
on their pgRNA test results at baseline and 3 months post-treatment.
4
Department of Anesthesiology, Jiangsu Province People‘s Hospital
The survival analyses revealed that patients in the double-positive
and Nanjing Medical University First Affiliated Hospital, Nanjing,
2
10029, China group had the highest recurrence rate, followed by the single-positive
group, and the double-negative group had the lowest recurrence
Background: Autophagy plays a synergistic role in liver regeneration. rate(P=0.025, Figure 2). The study constructed Huh7 and HepG2
However, most studies are limited to hepatocytes, and the function and cell lines with overexpressed pgRNA through plasmid transfection
mechanism of macrophage autophagy in liver regeneration remain and lentivirus infection, along with their negative controls. The CCK8
unclear. This study investigated the role of the essential autophagy and EdU assays revealed that pgRNA increased the proliferation of
gene, ATG16L1, which regulates the macrophage phenotype in liver hepatocellular carcinoma cells, and the enhanced proliferation may
regeneration. be mainly due to the increased DNA synthesis. The expression of
Method: We generated FloxP-Atg16l1 (Atg16l1FL/FL), Lyz2-Cre pgRNA significantly enhanced the clone formation and tumorigenesis
Atg16l1 knockout (Atg16l1M-KO), and myeloid-specific Atg16l1- of hepatocellular carcinoma cells, as demonstrated by the results
overexpression-knock-in (Atg16l1OE) mice. Mice were subjected of the clone formation and subcutaneous tumorigenesis assay. The
to 70% partial hepatectomy to demonstrate the role of ATG16L1 in Transwell and scratch assays suggest that pgRNA increases the cell
macrophages during liver regeneration. migration rate of hepatocellular carcinoma cells. Additionally, the cell
Result: ATG16L1 expression significantly upregulated in macrophages invasion assay shows a significant increase in the invasive ability of
during the early stages of liver regeneration. ATG16L1 deletion in hepatocellular carcinoma cells after the expression of pgRNA(Figure
macrophages substantially delayed liver regeneration in mice and 3).
caused a marked imbalance in Ly6Chi and Ly6Clo macrophage Conclusion: The baseline serum pgRNA status is an independent risk
proportions in the liver. RNA sequencing analysis revealed that, factor for the recurrence of advanced HBV-related HCC and pgRNA
compared to macrophages isolated from Atg16l1FL/FL mice, those could enhance the proliferation, migration, and invasive ability of HCC
of Atg16l1M-KO mice exhibited significant downregulation of genes cells.
associated with oxidative phosphorylation and upregulation of Table and Figure:Figure 1.Results of clinical data analysis.
pro-inflammatory gene expression. Mechanistically, ATG16L1 loss Figure 2.Results of in vivo and in vitro experiments.
impaired mitophagy in macrophages, leading to the accumulation
of mitochondrial damage and a metabolic shift that promoted pro-
inflammatory macrophage polarization. ATG16L1 deficiency not OP0342
only promoted macrophage mtDNA release and cGAS-STING Deep Learning-Driven Discovery of Extracellular Vesicle-Derived
activation, but also suppressed STING degradation. Sustained STING Circular RNAs as Biomarkers of Immune Checkpoint Inhibitor
hyperactivation and subsequent increased release of downstream Resistance in Hepatocellular Carcinoma
interferons further contributed to the inhibition of liver regeneration. Rifaldy Fajar1, Rini Winarti2, Elfiany Syafruddin3, Andi Nursanti Ureng4,
Notably, Pharmacological activation or genetic overexpression of Prihantini Prihantini5
ATG16L1 significantly enhanced liver regeneration in mice. 1
Computational Biology and Medicine Laboratory, Yogyakarta State
Conclusion: ATG16L1 plays a pivotal role in liver regeneration by University, 2Molecular Biology and Genetics Laboratory, Yogyakarta
affecting macrophage phenotype transformation and reducing the State University, 3Pathology Research Unit, BLK General Hospital,
production of regeneration-inhibiting mediators. Targeting ATG16L1 4
Department of Pharmacy, Andini Persada College of Health
in macrophages may present a novel strategy for promoting liver Sciences, 5Machine Learning for BioMedicine Laboratory, Bandung
regeneration. Institute of Technology
Table and Figure:Figure 1. Background: Immunotherapy has revolutionized the therapeutic
approach to hepatocellular carcinoma (HCC), providing significant
OP0341 survival benefits in advanced cases. However, resistance to immune
Predictive Value of pgRNA for Recurrence in Advanced checkpoint inhibitors (ICIs) remains a major challenge. Extracellular
Hepatocellular Carcinoma and Its Potential Mechanisms vesicle (EV)-derived circular RNAs (circRNAs) are recognized as key
regulators of immune evasion and tumor progression, but their potential
Yifan Han1, Xiaoyuan Xu1, Wengang Li2
as predictive biomarkers of ICI resistance is largely unexplored. This
1
Peking university first hospital, 2Fifth Medical Center of Chinese PLA
study utilized a deep learning model to combine EV-derived circRNA targeting PHGDH’s RBP function in vivo.
profiles, immune infiltration metrics, and clinical data, aiming to identify Result: RNA pull-down suggested PHGDH as a potential RBP. The RBP
predictive biomarkers and reveal resistance mechanisms. function of PHGDH was found to promote HCC proliferation. RIP-seq
Method: This study analyzed datasets, including RNA sequencing analysis revealed an interaction between PHGDH and PRKCD mRNA,
and clinical outcomes from The Cancer Genome Atlas (TCGA-LIHC), which is involved in mitophagy pathways. A motif (AGUGGAA) in
circRNA profiles from the EVAtlas database, and immune-related the 3’UTR of PRKCD mRNA was recognized by PHGDH. PHGDH
transcriptomic data from the Gene Expression Omnibus (GEO). A enhanced PRKCD mRNA stability and protein levels. PHGDH was
total of 5,982 HCC patients were included, with 2,853 receiving ICI confirmed to activate mitophagy via PRKCD. Decoy oligonucleotides
therapy. EVs were isolated from plasma samples, and circRNA blocked PHGDH-PRKCD mRNA binding and suppressed pro-
sequencing quantified differential expression. Immune cell infiltration proliferative effects of PHGDH both in vitro and vivo. PHGDH knockout
metrics, such as cytotoxic T-cell scores, were estimated using in DEN/CCl4-induced models significantly inhibited expression of
computational deconvolution methods. A graph-based deep learning PRKCD mRNA and tumor growth. In hydrodynamic HCC models,
model was developed to integrate circRNA expression, immune the combination of the PRKCD inhibitor sotrastaurin and sorafenib
metrics, and treatment outcomes. Stratified 5-fold cross-validation significantly reduced tumor growth.
ensured robustness, while external validation was conducted using Conclusion: This study identified PHGDH’s interaction with mRNA and
an independent cohort of 1,502 patients from the International Cancer reported that PHGDH enhances PRKCD protein levels by stabilizing
Genome Consortium (ICGC). Differential expression and pathway its mRNA, which facilitates mitophagy and supports HCC progression.
analyses identified key circRNAs and assessed their roles in resistance Our findings reveal a novel function of PHGDH and establish a
mechanisms. mechanistic link between cellular metabolism, RNA regulation and
Result: The model achieved an AUC of 0.89 (95% CI: 0.87–0.91) for mitophagy. Targeting PHGDH’s RNA-binding activity offers a unique
predicting ICI resistance, with sensitivity and specificity of 86.4% (95% therapeutic strategy for HCC treatment. Our studies provide novel
CI: 84.2–88.5) and 85.7% (95% CI: 83.5–87.8). Key circRNAs included insights for further research on the clinical applications of decoy
hsa_circ_0001955 (fold-change: 2.8, p<0.001), hsa_circ_0008287 oligonucleotides targeting cancer metabolism.
(fold-change: 2.5, p=0.002), and hsa_circ_0001649 (fold-change: Table and Figure:Figure 1.PHGDH stabilizes PRKCD mRNA as an
2.1, p=0.003), which were associated with elevated TGF-β signaling RNA-binding protein and promotes mitophagy via PRKCD
and reduced cytotoxic T-cell infiltration. Pathway analysis revealed Figure 2.Targeting PHGDH’s RNA-binding activity is a unique
disruption of immune checkpoint signaling (p=0.008) and metabolic therapeutic strategy for HCC treatment
reprogramming in tumor-associated macrophages (p=0.007). EV-
derived circRNAs accounted for 43.5% of the model’s predictive
OP0344
capacity, with immune metrics contributing 30.8%, emphasizing their
complementary roles. PCK1 deficiency promotes MASH-HCC progression by 12-HETE-
Conclusion: This study applies deep learning to identify EV-derived induced CD8+ T cell dysfunction
circRNAs as biomarkers of ICI resistance in HCC. By integrating multi- Kang Wu1, Luo Li2,3, Yi Liu4, Kai Wang1, Jianghong Zheng1, Huijun
modal datasets, it offers a robust framework for biomarker-driven Liang1, Xiaosong Li5, Aishun Jin3, Ailong Huang1, Tang Ni1
treatment stratification and precision immunotherapy strategies, 1
Department of Infectious Diseases, Key Laboratory of Molecular
showcasing the translational potential of circRNA profiling to improve Biology for Infectious Diseases (Ministry of Education), Institute for
outcomes in HCC patients. Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical
University, Chongqing 400010, China, 2Department of Laboratory
Medicine, Women and Children‘s Hospital of Chongqing Medical
OP0343 University, Chongqing 401147, China, 3Department of Immunology,
PHGDH acts as an RNA-binding protein to stabilize PRKCD mRNA College of Basic Medicine, Chongqing Medical University, Chongqing
and promote hepatocellular carcinoma progression 400010, China, 4Radiation Oncology Center, Chongqing University
Bin Cheng1, Shi Chen2, Rui Liu1, Xiaosong Li2, Ke Wang1, Jing Ma1, Cancer Hospital, Chongqing 400030, China, 5Clinical Molecular
Pai Peng1, Kai Wang1, Ni Tang1, Ailong Huang1 Medicine Testing Center, The First Affiliated Hospital of Chongqing
Medical University, Chongqing 400016, China
1
Department of Infectious Diseases, Key Laboratory of Molecular
Biology for Infectious Diseases (Ministry of Education), Institute for Background: Immune checkpoint inhibitors have led to breakthroughs
Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical in the treatment of hepatocellular carcinoma. However, patients
University, 2Clinical Molecular Medicine Testing Center, The First with metabolic dysfunction-associated steatohepatitis-related
Affiliated Hospital of Chongqing Medical University hepatocellular carcinoma (MASH-HCC) responded poorly to ICIs,
Background: Emerging roles of metabolic enzymes in cancers has which may be associated with metabolic reprogramming of tumor
greatly extended, apart from their canonical activity. Some metabolic cells and abnormal tumor microenvironment. Phosphoenolpyruvate
enzymes can interact with RNAs as RNA binding proteins (RBPs), carboxykinase 1 (PCK1), the first rate-limiting enzyme in hepatic
thus influencing gene expression and contributing to the progression gluconeogenesis, has been implicated in the progression of HCC
of tumors. Currently, the roles of metabolic enzymes that function as and MASH, while its role in MASH-HCC remains unknown. Here, we
RBPs in hepatocellular carcinoma (HCC) progression remain largely investigated the functional role of PCK1 in MASH-HCC and its interplay
unknown. with the tumor microenvironment.
Method: RNA pull-down was employed with biotinylated oligos (dT) Method: The Gene Expression Omnibus database, clinical liver
to identify the poly(A)+ RNA interactome of HCC cells. Potential RNA- samples, and multiple murine models were used to analyze the
binding capabilities of metabolic enzymes were assessed using expression pattern of PCK1 in MASH-HCC tissues. Hepatocyte-
protein truncation tests based on predicted RNA-binding domains. specific Pten knockout mice and hepatocyte-specific Pten and Pck1
RNA immunoprecipitation sequencing (RIP-seq) and RIP assays was biallelic knockout mice were established to induce MASH-HCC.
utilized to identify target genes of PHGDH. Dual-luciferase assays Single-cell RNA sequencing and multiparametric flow cytometry were
and RNA pull-down were conducted to identify the specific binding performed to analyzed the immune landscape alterations of MASH-
motif of the target gene to PHGDH, while fluorescence in situ HCC mediated by PCK1 deficiency. Untargeted metabolomics were
hybridization assays validated the colocalization of the target gene conducted to elucidate the hepatic metabolism dysregulation.
mRNA to PHGDH. Transmission electron microscopy and confocal Result: PCK1 is downregulated in tumors tissues compared with
microscopy were used to assess the effects of PHGDH on mitophagy. adjacent non-cancerous tissues from patients with MASH-HCC.
Decoy oligonucleotides were utilized to block the interaction between Hepatocyte-specific Pck1 knockout mice exhibited markedly
PHGDH and the target gene mRNA and pro-proliferation capability of increased tumorigenesis in dietary models and genetic models of
PHGDH in HCC. The DEN/CCl4-induced mouse and hydrodynamic spontaneous MASH-HCC, together with elevated exhaustion markers
injection mouse models of HCC were used to validate the impact of (PD-1+ and TIM-3+) and decreased effector markers (TNF-α+ and
IFN-γ+) of tumor-infiltrating CD8+ T cells (Figure 1). Conversely, of cells triggered the formation of a YY1-MDM2-P53 ternary complex,
hepatocyte-specific PCK1 overexpression suppressed tumor growth thus leading to P53 ubiquitination and degradation.
with enhanced effector function of CD8+ T cells. Mechanistically, Conclusion: The lncRNA FTX may be a biomarker of metastasis with
PCK1 deficiency induces the accumulation of endogenous metabolite dual and opposing roles in HCC progression. YY1-MDM2-P53 ternary
12-hydroxyeicosatetraenoic acid (12-HETE), which can be taken up complex contributed to explaining the mechanism.
by CD8+ T cells and activate the p38 mitogen-activated protein kinase Table and Figure:Figure 1.Fig. 2. LncRNA FTX promoted malignant
pathway by directly interacting with the BTB and CNC homology 1 behaviours of anoikis-resistant HCC cells.
transcription factor, ultimately leading to CD8+ T cells dysfunction Figure 2.Fig. 5. LncRNA FTX upregulated anoikis-resistance and
(Figure 2). Notably, PCK1 restoration or 12-HETE inhibition combined distant metastasis via P53 ubiquitination degradation induced by the
with anti-PD1 treatment increases the antitumor capability of CD8+ T YY1-MDM2-P53 ternary complex.
cells and suppresses MASH-HCC development.
Conclusion: This study reveals the pivotal role of the hepatic cell-
OP0347
intrinsic enzyme PCK1 in mediating CD8+ T cell dysfunction via
12-HETE-p38 signaling in MASH-HCC. PCK1 could be a metabolic Concomitant dyslipidemia did not affect the long-term outcomes
checkpoint that enhances the efficacy of anti-PD1 immunotherapy in of patients with primary biliary cholangitis
MASH-HCC. Qin Xiao1, Sha Chen1, Shuxiang Li1, Tingting Lv1, Weijia Duan1,
Table and Figure:Figure 1.Figure 1. Hepatic PCK1 deficiency induces Jidong Jia1
CD8+ T cell dysfunction via 12-HETE accumulation in MASH-HCC. 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
Figure 2.Figure 2. 12-HETE-induced suppression of CD8+ T cell University; Beijing Key Laboratory of Translational Medicine on Liver
functions through BACH1-dependent p38 MAPK signaling activation. Cirrhosis; National Clinical Research Center for Digestive Diseases,
Beijing; State Key Laboratory of Digestive Health, Beijing, China
OP0345 Background: Patients with primary biliary cholangitis (PBC) are prone
to dyslipidemia, but the impact of this comorbidity on their long-term
Long Noncoding RNA FTX Exhibits Dual Roles in Hepatocellular
outcomes remains unclear. This study is designed to delineate the
Carcinoma Progression: Implications for Anoikis Resistance and
prevalence of dyslipidemia among PBC patients and to investigate its
Metastasis
potential effects on their long-term prognosis.
Nannan Zhang1, Keqing Zhong2, Linlin Sun3, Ming Liu4, Rui Sun5, Method: We performed a retrospective analysis of the medical records
Wenli Lu6, Qi Zhao7, Wenrui Zhao2, Xiaolin Tang2, Wanhua Ren2, Tao of PBC patients, gathering follow-up data through regular outpatient
Li2,8 consultations and phone interviews. Endpoints were defined as liver-
1
school of Medicine, Shandong University, Jinan, Shandong, 250012, related death or liver transplantation. Dyslipidemia was defined as total
China, 2Department of Infectious Diseases, Shandong Provincial cholesterol (TC) ≥ 5.2 mmol/L or low-density lipoprotein cholesterol
Hospital Affiliated to Shandong First Medical University, Jinan, (LDL-C) ≥ 3.4 mmol/L or high-density lipoprotein cholesterol
Shandong, 250012, China, 3Department of Gastroenterology, Yantai (HDL-C)<1.0 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L.
Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, Result: A total of 484 PBC patients meeting the inclusion and exclusion
2
64100, China, 4Department of Cell Biology and Medical Genetics, criteria were included in the study, comprising 312 non-cirrhotic patients
School of Basic Medical Science, Shanxi Medical University, Taiyuan,
and 172 cirrhotic patients at baseline. Overall, 335 patients (69.2%)
Shanxi, 030001, China, 5Beijing Ditan Hospital, Capital Medical
had concomitant dyslipidemia at baseline, with hypercholesterolemia
University, Beijing 100069, China, 6Department of Infectious Diseases,
being the most common condition at 51.9%. Compared to cirrhotic
Yangpu Hospital, School of Medicine, Tongji University, Shanghai
patients, non-cirrhotic PBC patients had a significantly higher
200090, China, 7Department of Gastroenterology, Shandong
Provincial Hospital Affiliated to Shandong First Medical University, proportion of concomitant dyslipidemia (Table 1). Interestingly, 38.8%
Jinan, Shandong, 250012, China, 8National Medical Center for of patients had an elevated HDL-C level; this proportion was also
Infectious Diseases, Shanghai 200050, China increased in non-cirrhotic patients compared to those with cirrhosis
(p<0.001). Compared to PBC patients without dyslipidemia, those with
Background: Long noncoding RNA (lncRNA) FTX has been dyslipidemia had higher baseline levels of alkaline phosphatase (ALP),
identified as a significant regulator in hepatocellular carcinoma gamma-glutamyl transpeptidase (GGT), and alanine aminotransferase
(HCC) progression. However, its functions and mechanisms of anoikis- (ALT), but a lower proportion of cirrhotic patients and higher levels
resistance-mediated distant metastasis in HCC remain elusive. of platelets and cholinesterase. After a median follow-up of 4.46
Method: The lncRNA FTX was overexpressed and knocked down in (interquartile range 2.08-7.67) years, 60 patients developed the
HCC cells under attached and detached conditions. Malignant primary endpoint. Kaplan-Meier survival analysis indicated that
behaviours of HCC cells induced by lncRNA FTX were observed using dyslipidemia did not significantly affect the transplant-free survival rate
CCK8, colony formation, transwell, wound healing, and apoptosis of PBC patients, regardless of their cirrhosis status (Fig. 1). In line with
assays. Potential upstream transcription factors(TFs) and target genes this, univariate COX regression analysis disclosed that the presence
of lncRNA FTX were identified using the Promo, Human Transcription of dyslipidemia did not affect the long-term outcomes of PBC patients.
Factor Targets(hTFtarget), Transcriptional Regulatory Relationships Conclusion: We found a high prevalence of dyslipidemia among PBC
Unraveled by Sentence-based Text mining(TRRUST) and Gene patients, with a particularly elevated rate observed in those without
Cards databases. Their relationship was further explored using Gene cirrhosis. However, coexisting dyslipidemia was not associated with a
Expression Profiling Interactive Analysis(GEPIA) and RNA-Protein reduced transplant-free survival in PBC patients.
Interaction Prediction(RPISeq) and validated by qRT-PCR in vitro. Table and Figure:Figure 1.Table 1 Prevalence of dyslipidemia among
Result: The expression of lncRNA FTX was significantly increased PBC patients with and without cirrhosis.
in detached HCC cells and partially reverted upon reattachment. Figure 2.Fig 1. Kaplan-Meier survival analysis indicated that
Overexpression of lncRNA FTX reduced proliferation, invasion, and dyslipidemia did not significantly affect the transplant-free survival
migration in attached HCC cells but enhanced these malignancies rate of PBC patients, whether in non-cirrhotic patients (A) or cirrhotic
in detached conditions. Knockdown of lncRNA FTX reversed these patients (B).
effects.YIN and YANG-1(YY1), identified as a binding partner
for lncRNA FTX, was predicted to be a TF in the Promo and
hTFtarget databases. Using the TRRUST database, we explored P53 OP0348
as a downstream and coregulated gene of YY1. P53 ranked first in the Current analysis of fatigue in patients with primary biliary
Gene Cards database for HCC, metastasis, anoikis, and transcription cholangitis
and interacted with lncRNA FTX by RPISeq. The GEPIA database Ying Han1, Ajuan Zeng , Xueying Liang, Yanna Liu, Keke Jin, Huiguo
showed a positive correlation between YY1, lncRNA FTX, and TP53, Ding
as verified by the qRT-PCR results. We propose that the detachment 1
13520809804
Background: Primary biliary cholangitis (PBC) is the most common diagnostic rates, clinical symptoms, laboratory results, and pathology
form of biliary cholangitis in China. cholangitis, PBC), fatigue is its most across these groups.
common symptom and the symptom that has the greatest impact on Result: 53.3% (88/165) of the patients showed cholangitis activity
patients’ quality of life. However, there are very few relevant studies. In diagnosed with PBC. The diagnosis rate of PBC in the three groups
this study, we proposed to analyse the possible correlates of fatigue was respectively 82.1% (23/28), 48.4% (46/95), and 45.2%(19/42).
by observing the condition characteristics of fatigue in PBC patients. Histological features were as follows: typical (n = 13/21/9),
Method: A total of 267 patients diagnosed with PBC as outpatients consistent (n = 8/21/10), and suggestive (n = 2/4/0). Multivariate
and inpatients at Beijing You’an Hospital of Capital Medical University analysis indicated a significant association between baseline serum
from January 2024 to June 2024 were prospectively collected, and immunoglobulin M (IgM) levels exceeding 0.796 times the upper limit
fatigue was assessed using the Fatigue Scale for Chinese Patients of normal (ULN) (P < 0.001) and the diagnosis of PBC as determined
with PBC. The scale was established by our research team to assess by liver biopsy. In the three groups of non-PBC patients, the major
the fatigue of PBC patients, and it was assessed from five aspects, pathological injury patterns were minor nonspecific reactive changes
namely physical strength, sleep, social and daily life competence, (40.0%/28.6%/39.1%), inflammation (40.0%/24.5%/47.8%), and fatty
mental strength, and emotion, using 12 questions, which covered the changes (20%/20.4%/4.3%). The diagnosis included viral hepatitis,
frequency (divided into five levels) and the degree (divided into six autoimmune hepatitis, fatty liver disease, vascular liver disorders,
levels) of assessment, which could reflect the fatigue of the patients drug-induced liver injury, congenital hepatic fibrosis, and porphyria.
better, and the questions were simple, easy to operate, and easy to be Conclusion: Over 50% of patients with positive PBC-specific
understood by the Chinese patients. antibodies and normal ALP levels have PBC. A liver biopsy is
Result: A total of 267 cases were enrolled, 44 males and 223 females, recommended when both AMAs and PBC-specific ANAs are positive,
aged 59.4±11.0 years. Those who chose ‘none’ on the fatigue scale and baseline serum IgM exceeds 0.796×ULN.
were classified as the ‘no fatigue group’, and those who chose any of Table and Figure:Figure 1.Flow chart
the other options were classified as the ‘fatigue group’. There were 183 Figure 2.The distribution of Hepatic Activity (HA), Cholangitis Activity
cases in the fatigue group (68.5% of the population) and 84 cases in (CA) and stages of the 88 patients with PBC-related antibody-positive
the no-fatigue group. Decreased physical strength: frequency ≥3:104, and normal ALP levels
degree ≥3:96; poor sleep quality: frequency ≥3:115; decreased
social and daily life competence: frequency ≥3:96; mental ability: OP0350
frequency ≥3:122, degree ≥3:78; emotional abnormality: frequency
≥3:109, degree ≥3:67. The general conditions are shown in Table IgG4-associated autoimmune hepatitis: a case report and
1, TBA of the fatigue group was higher than that of the no-fatigue systematic review
group, P<0.05. In the fatigue group, IL-6 61.247±132.50 pg/ml, TNF-α Chun Hsun Liao1, Hsu Hua Tseng1, Ting An Shen1, Tzu Chan Hong2,
18.62±11.57 pg/ml, IL-8 442.96±1025.08 pg/ml, IL-4 7.67±11.22 Shih Jer Hsu1, Jia Horng Kao1, Chun Jen Liu1
pg/ml, IL-10 9.45± 10.33pg/ml, IL-17 6.21±13.99pg/ml, which were 1
National Taiwan University Hospital, 2National Taiwan University
higher than 8.76±20.59pg/ml, 12.21±3.69pg/ml, 73.91±182.13pg/ml, Cancer Center
2.84±3.06pg/ml, 4.08±2.18pg/ml, 0.69±1.69 in the no-fatigue group, Background: IgG4-associated autoimmune hepatitis (IgG4-AIH) is
P<0.001 pg/ml, P<0.05, the difference was statistically significant. IL- increasingly recognized as a distinct diagnostic entity, characterized
1β 16.08±55.6pg/ml, IL-2 6.64±20.85pg/ml, IFN-α 5.14±15.31pg/ml by the overlap of classic autoimmune hepatitis (AIH) features with
in fatigue group were higher than 0.35±1.54pg/ml, 0.77±1.30pg/ml, IgG4-related disease (IgG4-RD) manifestations. IgG4-AIH challenges
1.31±5.62pg/ml in no fatigue group P>0.05. In fatigue group, TGF- β traditional diagnostic criteria by presenting unique features, including
148.68±122.13ng/ml was lower than 189.90±137.06ng/ml in the no- elevated serum IgG4 levels and significant infiltration of IgG4-
fatigue group, P>0.05. Specific results are shown in Figure 1. positive plasma cells in the liver. We aim to synthesize existing case
Conclusion: Fatigue symptoms exist in many PBC patients and may reports and series to enhance the understanding of IgG4-AIH and
be related to the body’s immune-inflammatory response. provide clinicians with a concise overview to aid in its diagnosis and
Table and Figure:Figure 1.Table 1 General conditions of PBC patients management.
grouped according to the Chinese PBC fatigue scale Method: We started with a detailed case vignette of a 70-year-old
Figure 2.Figure 1 Comparison of inflammatory factors between the woman with suspected IgG4-AIH, which guided our systematic review
fatigue group and the no-fatigue group in PBC patients in accordance with PRISMA guidelines. We conducted comprehensive
literature searches in PubMed, Embase, and Web of Science up to
OP0349 January 26th, 2024. Studies on irrelevant topics, conference papers
and animal research were excluded. A rigorous selection process was
Clinical Significance of Anti-Mitochondrial Antibodies and PBC-
conducted by paired reviewers, with a third reviewer mediating any
Specific Anti-Nuclear Antibodies in Evaluating Atypical Primary
disagreements via panel discussion. Summary data were extracted
Biliary Cholangitis with Normal Alkaline Phosphatase Levels
from eligble studies.
Shasha Li1, Xing Liu2, Kai Zhang3, Hongli Liu4, Jialuo Wang2, Yuan Result: A total of 1,210 articles were identified, of which 31 studies
Yang2, Yuxiang Gong2, Miaoyang Chen2, Yongfeng Yang5 (18 case reports and 13 case series) met inclusion criteria. Among the
1
Medical School, Nanjing University, 2The Second Hospital of 262 AIH cases reported, 186 patients were diagnosed with IgG4-AIH.
Nanjing, Affiliated to Nanjing University of Chinese Medicine, 3 The The demographic analysis revealed that 60% (156) of patients were
Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese female. The median age ranged from 44-67 years in case series and
Medicine, 4School of Medicine, Southeast University, 5Department of 40-73 years in case reports. Laboratory findings showed consistent
infectious disease and liver disease, The Second Hospital of Nanjing, elevation of serum IgG levels (1,750-6,614 mg/dL) with variable
Clinical Teaching Hospital of Medical School, Nanjing University,
IgG4 levels. IgG4/high power field (HPF) ratios varied significantly,
Nanjing, China
but many studies reported values ≥10. ALT levels were elevated in
Background: Anti-mitochondrial antibodies (AMAs) and/or primary most cases. When documented, IAIHG scores typically ranged from
biliary cholangitis (PBC)-specific anti-nuclear antibodies (ANAs)are 7 to 22, with most cases exceeding 15. Many patients had concurrent
diagnostically valuable for typical PBC patients. However, the clinical IgG4-RD diagnoses either before or after diagnosis, with IgG4-related
implications of positive AMAs and/or ANAs in patients with normal ALP sclerosing cholangitis and autoimmune pancreatitis being the most
levels remain uncertain. common manifestations. Treatment primarily consisted of either
Method: Patients at The Second Hospital of Nanjing with positive glucocorticoid monotherapy or combination therapy with azathioprine.
AMAs/ANAs and normal ALP levels from January 2016 to July 2024 ALT normalization typically occurred within 1-3 months of treatment
were categorized into three groups based on autoantibody profiles: initiation.
[AMA/AMA-M2]+[gp210/sp100]+, [AMA/AMA-M2]+[gp210/sp100]- Conclusion: IgG4-AIH is a distinct disease entity featuring a slight
, and [AMA/AMA-M2]-[gp210/sp100]+. The study compared PBC female predominance and an age range of 40-70 years. Patients
demonstrate greater responsiveness to corticosteroid therapy disease with unclear pathogenesis where viral infections can trigger
compared to traditional AIH, often showing faster biochemical autoimmunity. Hepatitis A virus (HAV)  and Hepatitis E (HEV) unmasking
remission. Importantly, patients may also develop concurrent IgG4- AIH is difficult to recognise and treatment is usually delayed because
RD in other organs. Recognizing this unique condition, primarily of low suspicion.
diagnosed by the presence of ≥10 IgG4/HPF, is crucial for optimizing Method: This is a study of six patients diagnosed with AIH in a
patient management and improving outcomes. background of acute hepatitis A & E infection. AIH was suspected in
Table and Figure:Figure 1.Summary of case series of IgG4-AIH patients with prolonged hepatitic illness with intermittent or persistent
Figure 2.Summary of case reports of IgG4-AIH elevation of AST and ALT or persistent jaundice. AIH was defined
by persistent abnormal liver functions, hyperglobulinemia, positive
autoimmune serologies and a liver biopsy consistent with AIH.  The
OP0351
demographics, clinical presentation, investigations, serologies, liver
Decoding Long Non-Coding RNA-Driven Epigenetic Dysregulation biopsy and treatment details were noted and reviewed.
in Steroid Resistance of Autoimmune Hepatitis: A Multi-Omics Result: Six patients diagnosed with AIH following confirmed acute
Machine Learning Approach viral hepatitis (five with HAV and one with HEV) were included. Mean
Rifaldy Fajar1, Sahnaz Vivinda Putri2, Prihantini Prihantini3, Andi age of patients was 23 ± 5 years (Male 5 and 1 female). Median time to
Nursanti Ureng4 diagnose AIH  after initial symptoms was 77 days. Persistent elevation
1
Computational Biology and Medicine Laboratory, Yogyakarta State of ASL and ALT was seen in 3 patients. Persistent jaundice with elevated
University, 2Health Management Laboratory, International University AST and ALT was seen in 3 patients. ANA was positive in 2 patients and
Semen Indonesia, 3Machine Learning for BioMedicine Laboratory, ASMA was positive in 1 patient. 3 patients had negative autoimmune
Bandung Institute of Technology, 4Department of Pharmacy, Andini markers.  Serum IgG was elevated in all patient with median value
Persada College of Health Sciences of 1706 gm/L. Liver Biopsy was suggestive of AIH in all patients. All
Background: Steroid resistance in autoimmune hepatitis (AIH) leads patients were treated with prednisolone [median duration of 158 days
to poor outcomes and limited treatment options. Regulatory T cells (90- 260)] initially and azathioprine was added once the bilirubin was
(Tregs) are crucial for immune tolerance, yet their dysfunction in steroid- less than 3mg/dl. Complete biochemical remission was achieved in all
resistant AIH remains unclear. Long non-coding RNAs (lncRNAs) patients at six months. A trial of withdrawal of immunosuppression was
regulate immune cell epigenetics, but their role in Treg dysfunction attempted in one patient after 6 months which lead to flare. Presently
and steroid resistance is not fully understood. This study aimed to all patients are on maintenance therapy with low dose prednisolone
investigate lncRNA-driven epigenetic mechanisms underlying Treg and azathioprine.
dysfunction in steroid-resistant AIH using multi-omics and machine Conclusion: Diagnosis of patients with AVH triggering AIH is usually
learning. delayed. Persistent deranged LFTS beyond the natural course of AVH
Method: Liver biopsy data from 62 AIH patients (steroid-resistant: 34; should raise a strong suspicion. Positive autoimmune markers with
steroid-sensitive: 28) and 20 healthy controls were analyzed using raised serum IgG and characteristic liver biopsy can help to make
datasets from Gene Expression Omnibus (GEO), ArrayExpress, and the diagnosis. Steroids alone or combined with immunosuppressants
Human Cell Atlas (HCA), which provide RNA-seq, ATAC-seq, and usually leads to good response. However, the natural history of AIH
methylation data. A total of 13,200 Tregs were analyzed. Differential post AVH remains to be fully characterized to attempt withdrawal
expression identified lncRNAs enriched in steroid-resistant Tregs of  immunosuppression.
(adjusted p < 0.05). Chromatin accessibility and pseudotime analysis Table and Figure:Figure 1.Demographic characteristics of study
modeled epigenetic transitions. A machine learning model was trained population
to predict steroid resistance based on lncRNA expression, chromatin Figure 2.Histopathological characteristics of the study population
states, and methylation patterns. Validation was performed via five-
fold cross-validation, and functional lncRNAs were annotated using OP0353
GENCODE, LNCipedia, and Ensembl.
Result: From a total of 22 dysregulated lncRNAs, 10 key lncRNAs The advantage of Tomoelastography in the accurate diagnosis of
(MALAT1, NEAT1, LINC00473, TUG1, HOTAIR, MEG3, H19, GAS5, chronic hepatitis B and non-alcoholic fatty liver fibrosis stage and
XIST, and PVT1) were identified as major contributors to steroid significant liver fibrosis stage (F2)
resistance. MALAT1 was linked to hypermethylation of glucocorticoid Guangdong Tong1, Huanhuan Zhang2, Zhen Ye3, Yuxin Sun4,1, Junting
receptor elements, reducing steroid sensitivity (R² = 0.76, p < 0.001). Sai5, Jianping Lai6, Zhongxian Pan3, Deti Peng1, Weichao Zhong1,
NEAT1 and HOTAIR reduced chromatin accessibility at the FOXP3 Qinyang Kang7, Hang Xu7, Yuting Li7, Weijun Ouyang1, Hanqing Lyu3
locus, destabilizing Tregs (fold changes: −1.9 and −2.2; 95% CI: −1.7 1
Department of Hepatology, Shenzhen Traditional Chinese Medicine
to −2.5, p < 0.01). H19 drove metabolic dysfunction, with a 22.5% Hospital, 2Department of Traditional Chinese Medicine, Dongguan
reduction in oxidative phosphorylation (95% CI: −20.2% to −25.8%, Songshan Lake Central Hospital, 3Department of Radiology and
p < 0.001). The machine learning model achieved an AUROC of 0.84 Imaging, Shenzhen Traditional Chinese Medicine Hospital, 4Shenzhen
(95% CI: 0.81–0.87) and an AUPRC of 0.79 (95% CI: 0.75–0.83). Traditional Chinese Medicine Hospital Affiliated to Nanjing University
Pseudotime analysis revealed that LINC00473 and MEG3 mediated of Chinese Medicine, 5National Regional Medical Center of TCM
H3K27ac loss at immunoregulatory loci (posterior probabilities: 0.77 (Pulmonary Disease), the First Affiliated Hospital of Henan University
of Chinese Medicine, 6Department of Infectious Diseases, Shenzhen
and 0.74). XIST and PVT1 increased methylation at TNF-α promoters,
Traditional Chinese Medicine Hospital, 7The Fourth Clinical Medical
amplifying pro-inflammatory signaling (R² = 0.78, p < 0.001).
College of Guangzhou University of Traditional Chinese Medicine
Conclusion: This study identifies 10 pivotal lncRNAs involved in
Treg dysfunction and steroid resistance in AIH. It contributes to Background: Non-invasive diagnosis to accurately differentiate the
understanding epigenetic regulation and potential therapeutic targets, stages of liver fibrosis is a critical unmet medical need. Identifying
using multi-omics and machine learning to support precision medicine patients with significant fibrosis (≥F2) is the most crucial, as these
in chronic liver diseases. individuals need prompt initiation of clinical intervention. This study
was conducted on patients with CHB, NAFLD utilizing 3.0 Tesla MRI.
The investigation focused on evaluate whether tomoelastography can
OP0352 accurately distinguish the stages of liver fibrosis of different etiologies,
Acute Viral Hepatitis Unmasking Autoimmune Hepatitis especially the accurate identification of ≥F2.
Sunil Taneja1, Sweta Rose1, Kannu Priya1, Suvradeep Mitra1, Arka Method: A total of 194 subjects were included in the study: 80
De1, NIpun Verma1, Madhumita Premkumar1, Ajay Duseja1 patients with CHB and 94 patients with NAFLD who underwent liver
1
Postgraduate Institute of Medical Education & Research biopsy, and 20 healthy controls. Participants were assessed using
Tomoelastography, transient elastography (TE), and the FIB-4 index. A
Background: Autoimmune hepatitis (AIH) is  a rare and complex
magnetic field strength of 3.0 Tesla was employed along with a driving
frequency range of 30 to 60 Hz. The cutoff value and area under the changes in liver tissue.
receiver operating characteristic curve (AUC) were determined based Result: Following intragastric administration with ajugol at doses of 20
on wave speed measurements in meters per second. and 40 mg/kg, the mice exhibited significantly lower serum levels of
Result: The critical values and corresponding area under the curve alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
(AUC) of liver fibrosis staging were F1, 1.53 (AUC 0.98); F2, 1.57 (AUC compared to untreated fibrotic mice. Ajugol also reduced the mRNA and
0.95); F3, 1.72 (AUC 0.98); and F4, 2.06 (AUC 0.99). No statistically protein expressions of α-smooth muscle actin (α-SMA) and collagen I
significant difference was observed between the chronic hepatitis B (COL I) in liver tissue. RNA sequencing revealed that ajugol significantly
(CHB) group and the non-alcoholic fatty liver disease (NAFLD) group regulated key genes involved in bile acids (BAs) biosynthesis and
(P > 0.05). The drive frequency with diagnostic value is 40hz and arachidonic acid (ARA) metabolism pathways. Treatment with ajugol
above, and the compound frequency (30 ~ 60hz) is the best. Notably, led to a marked decrease in the protein expressions of cholesterol
Tomoelastography demonstrated superior performance compared to 7α-hydroxylase (CYP7A1) and cyclooxygenase 2 (COX2), as well
transient elastography (TE) and Fibrosis-4 index in identifying fibrosis as in the levels of the toxic bile acid deoxycholic acid (DCA) and
at stage F2 (P = 0.00). ARA metabolites including prostaglandin D2 (PGD2) and E2 (PGE2)
Conclusion: 3.0 Tesla MR Tomoelastography can accurately diagnose in the fibrotic liver. In vitro experiments demonstrated that excess
the stage of hepatic fibrosis in CHB and NAFLD. It also accurately DCA induced toxicity in mouse hepatocytes and macrophages,
identifies patients with significant fibrosis(F2), thus compensating for impairing albumin secretion and promoting the release of inflammatory
the lack of accurate recognition of F2 by TE and FIB-4. cytokines. Mechanistically, DCA inhibited farnesoid X receptor (FXR)
signaling, resulting in hepatocellular damage and macrophage
activation, which were reversed by ajugol treatment.
OP0354
Conclusion: These findings suggested that ajugol can modulate BAs
Identification and validation of ferroptosis-related genes for acute- homeostasis, inhibit inflammatory response, and improve HF.Ajugol
on-chronic liver failure by WGCNA and machine learning may represent be a promising therapeutic agent in the treatment of HF.
Xing Zhang1, Zeqiang Qi1, Hua Tong1, Chang Liu1, Yadong Wang1 Table and Figure:Figure 1.Ajugol improves hepatic fibrosis by
1
Department of Infectious Diseases, Hebei Medical University Third modulating bile acid synthesis and arachidonic acid metabolism in
Hospital mice
Background: Acute-on-chronic liver failure (ACLF) is a critical clinical
syndrome characterized by acute exacerbation of chronic liver disease, OP0356
resulting in multiple organ failure and high short-term mortality. This
Probiotics reduce the incidence of hepatic encephalopathy in
study aimed to explore the role of ferroptosis-related genes (FRGs) in
patients with portal hypertension after Transjugular intrahepatic
the pathogenesis and development of ACLF.
portosystemic shunt: A randomized controlled trial
Method: The gene expression data of ACLF patients and healthy
controls from the GEO database were extracted, and the differentially Xiaotong Xu1, Qinghua Meng1, Jianjun Li1
expressed ferroptosis-related genes (DEFGs) were obtained by the
1
Interventional Therapy Center for Oncology, Beijing Youan Hospital,
‘limma’ package in R software. Weighted gene co-expression network Capital Medical University, Beijing, China
analysis (WGCNA) was used to identify ACLF-related module genes Background: Hepatic encephalopathy (HE) is one of the main
and overlap with DEFGs. Machine learning and protein-protein complications after transjugular intrahepatic portal shunt (TIPS), which
interaction (PPI) network analysis helped to finally screen out hub affects the quality of life of patients and their families. There is currently
genes. a lack of research on the use of Clostridium butyricum in preventing HE
Result: DEFGs associated with ACLF were significantly enriched in after TIPS. Therefore, this study aimed to explore the clinical efficacy of
biological processes and signaling pathways related to ferroptosis Clostridium butyricum viable tablets in preventing postoperative HE in
autophagy, and oxidative stress. Based on the PPI network and patients with portal hypertension undergoing TIPS.
machine learning, BECN1, NQO1, HRAS, and SIRT1 were identified Method: 70 patients with portal hypertension who are about to undergo
as the hub genes. We found that the expression of BECN1, NQO1 TIPS were randomly divided into two groups. The experimental
and HRAS genes was significantly up regulated while the SIRT1 was group was given Clostridium butyricum viable tablets (Clostridium
significantly downregulated in the livers of ACLF patients. butyricum viable count 3.5×105-3.5×108 CFU/tablet 2 tablets, 3/day)
Conclusion: WGCNA was combined with machine learning and PPI and lactulose (10ml 3/day), while the control group was only given
analyses to identify four hub genes associated with ferroptosis. The lactulose (10ml 3/day). Prophylactic medication was taken within 24
hub genes have great potential as diagnostic markers for ACLF and hours after surgery until the end of 3 months after surgery. The primary
even predict disease progression. endpoint was the occurrence of HE within 1 and 3 months after TIPS.
Table and Figure:Figure 1.Fig 1 the hub genes associated with Minimal hepatic encephalopathy (MHE) was evaluated using the
ferroptosis identified based on the PPI networks and machine learning number connection test-A (NCT) and digit symbol test (DST), while
overt hepatic encephalopathy (OHE) was evaluated using the West
Haven criteria.
OP0355
Result: The baseline data of two groups of patients are
Ajugol improves hepatic fibrosis by modulating bile acid synthesis comparable.1.There was no significant difference in minimal HE (MHE)
and arachidonic acid metabolism in mice incidence between the two groups within one month and three months
Xia Wei1, Fangyuan Wang2, Dingqi Zhang1, Ping Liu1, Wei Liu1, Ying (n=3,8.6% versus n=6,17.1%) after TIPS, but the incidence of overt HE
Xu1 (OHE) in the experimental group was significantly lower than that in the
1
Shanghai University of Traditional Chinese Medicine, 2Zhejiang control group at one month (n=4,11.4% versus n=11,31.4%, P=0.041)
Chinese Medical University and three months (n=5,14.3% versus n=15,42.9% ,P=0.008) after
Background: Ajugol is an iridoid glycoside isolated from the TIPS. 2. There was no significant difference in routine clinical laboratory
root of Rehmannia glutinosa, commonly used for treating various indicators between the two groups, but the skeletal muscle index at
inflammatory and metabolic diseases. Until now, the pharmacological the third lumbar vertebra elevation (L3-SMI) in the experimental group
effects of ajugol in hepatic fibrosis (HF) remain poorly understood. increased over time (P<0.001) and was significantly higher than that
This study aims to investigate the therapeutic efficacy of ajugol in in the control group at 3 months after TIPS (P=0.04). 3.The incidence
reversing HF and elucidate its mechanism of action. of sarcopenia in the experimental group (n=14,40%) was significantly
Method: A mouse model of HF was induced using lower than that in the control group (n=24,68.6%) at 3 months after
carbon tetrachloride (CCl4) injection. We evaluated liver histopathology TIPS. The incidence of OHE within 3 months after TIPS in patients
and fibrosis-related markers. In addition to experimental validation, without sarcopenia (n=5, 15.6%) was significantly lower than that in
RNA sequencing technology was employed to profile transcriptional patients with sarcopenia (n=15, 39.5%). 4.50 patients had lower limb
edema at baseline, including 21 in the experimental group and 29 in
the control group. Among them, 6 cases (28.6%) of new lower limb 1
Peking university first hospital
edema occurred in the experimental group, which was lower than 13 Background: Chronic hepatitis B (CHB) is a chronic liver disease that
cases (44.8%) in the control group. causes liver fibrosis and can lead to cirrhosis and even liver cancer
Conclusion: Probiotics can reduce the incidence of HE in patients in the long term. Early assessment of liver fibrosis is momentous for
after TIPS. Probiotics can improve the nutritional status of chronic liver guiding treatment and predicting disease prognosis. Liver elasticity
disease patients. testing is recommended for non-invasive diagnosis of liver fibrosis, but it
Table and Figure:Figure 1.Kaplan Meier analysis of experimental group is limited by equipment and operators and still needs to be popularized
and control group in some remote areas. We are trying to find new biomarkers to more
Figure 2.Comparison of L3-SMI between experimental group and conveniently and accurately predict the degree of liver fibrosis.
control group at different time points Method: Sequencing datasets of patients with different etiologies
of liver fibrosis were downloaded from the publicly available GEO
OP0357 database and bioinformatics analysis was performed to find differential
genes co-expressed in liver fibrosis, and validated in hepatic stellate
Huangjia Ruangan Granules with Entecavir for Fibrosis Regression
cell lines. Untreated CHB patients were collected and tested, the
in Chronic Hepatitis B: A Multicenter, randomized, double-blind,
histological fibrosis score of liver was eevaluated by Ishak Fibrosis
Phase II Trial
Score (F), noninvasive methods were identified through multiple
Xiaojun Zhu1, Jinghao Zhang1, Zhijia Zhou1, Suthat Liangpunsakul2,
analysis.
Jing Wang3, Guohong Ge4, Shanzhong Tan5, Xuan An6, Kewei Sun7,
Result: Bioinformatics analysis of liver fibrosis of different etiologies: a
Gang Wu8, Liying Zhu9, Jinmo Tang10, Xinwen Song11, Anna Zhang12,
total of six gene datasets from populations with differentially expressed
Hui Lv13, Yongfang Jiang14, Chunyan Gou15, Man Li1, Xuehua Sun1,
genes (DEGs) were analyzed, including 91 DEGs in the HBV-infected
Yueqiu Gao1
fibrosis dataset GSE84044, 753 DEGs in HCV-infected fibrosis dataset
1
Department of Hepatopathy, Shuguang Hospital, Affiliated to GSE114323, 101 DEGs in the alcoholic fibrosis dataset GSE103580,
Shanghai University of Traditional Chinese Medicine, 2Division of and the three NAFLD fibrosis datasets: GSE49541, GSE130970,
Gastroenterology and Hepatology, Department of Medicine, Indiana
and GSE135251, had 70, 297, and 171 DEGs, respectively, and the
University, 3The School of Basic Medical Sciences, Southwest
differentially expressed genes common to the six datasets were THBS2,
Medical University, 4Department of Hepatology, The Third Hospital of
TACSTD2, SOX9, LUM, EPCAM, EFEMP1, and CD24. By using PCR
Zhenjiang Affiliated Jiangsu University, 5Department of Hepatopathy,
and WB methods to detect the gene and protein expression of various
Second Affiliated Hospital of Chongqing Medical University, 6The
Third Affiliated Hospital of Chongqing University, 7Department of indicators in the hepatic stellate cell line LX-2, it was found that the
Hepatology,The First Affiliated Hospital of Hu-Nan University of expression of THBS2 and EFEMP1 significantly increased in activated
Chinese Medicine, 8Affiliated Hospital of Southwest Medical University, LX-2. Evaluating non-invasive indicators to diagnose hepatitis B liver
9
The Fourth Affiliated Hospital of Harbin Medical University, 10Xiamen fibrosis: Based on the National Mega-Project for Infectious Diseases,
Hospital of Traditional Chinese Medicine,Xiamen, 11The First Affiliated a cohort of 758 untreated HBV-infected people was established, and
Hospital Of Xinxiang Medical University, 12Henan Infectious Disease through the detection of relevant indicators, it was found that THBS2
Hospital, 13Shandong Public Health Clinical Center, 14The Second was positively correlated with the degree of F, and through different
Xiangya Hospital, Central South University, 15 You‘an Hospital, Capital statistical methods, five joint predictors were fitted, the results showed
Medical University that the area under the ROC curve (AUROC) of the joint predictor
Background: Huangjia Ruangan Granules (HRG), a traditional Chinese Pre4 (Pre4= −8.446+1.383×Drinking History +7.446×INR+0.002×IL-
medicine (TCM) formula, has shown promising therapeutic effects in 2R+0.024×THBS2), which diagnosed significant fibrosis (F≥3) in the
treating hepatic fibrosis in China. However, its specific efficacy and liver of HBV-infected patients, was 0.780 (0.733-0.828), which was
potential synergistic effects with nucleotide analogues (NAs) remain higher than APRI (0.717), FIB-4 (0.690) and THBS2 (0.705), but lower
uncertain. To address this, a multicenter randomized controlled trial than liver stiffness measurement (LSM).
was conducted. Conclusion: THBS2 is a differentially expressed gene, but co-
Method: This 48-week, multicenter, randomized, double-blind, expressed in fibrosis of different etiologies. The prediction model of
placebo-controlled phase II study was conducted across 14 centers THBS2 combined with other diagnostic indexes can diagnose hepatic
in China (No.ChiCTR240008679). CHB patients with an Ishak fibrosis fibrosis in chronic HBV-infected patients at a certain degree of early
score of 2 to 5 were eligible for inclusion. Patients were randomly stage.
assigned to three groups (1:1:1 ratio): ETV (0.5 mg/day) + HRG-20g
(10 g, twice daily), ETV (0.5 mg/day) + HRG-10g (10 g/day, once OP0359
daily), and ETV (0.5 mg/day) + placebo. The primary outcome was the High Dietary Fiber Promotes Cholangiopathy and Biliary Fibrosis
change in fibrosis stage according to the Ishak scale after 48 weeks. in Mice with Human-like Bile Acids Pool
Safety assessments were conducted throughout the trial.
Wenqiang Shen1, Milaine Hovingh1, Niels Mulder1, Bertien Dethmers
Result: From October 21, 2018, to June 28, 2022, 419 patients
Ausema2, Jan Freark De Boer1,3, Folkert Kuipers1,2
were screened, and 240 were randomly assigned to one of the three 1
Department of Pediatrics, University of Groningen, University Medical
treatment groups: ETV+HRG-20g (n=80), ETV+HRG-10g (n=80),
Center Groningen, Groningen, The Netherlands., 2European Research
or ETV+placebo (n=80). After 48 weeks of treatment, the rate of
Institute for the Biology of Ageing (ERIBA), University of Groningen,
fibrosis regression (≥1 stage improvement in histopathology) was
University Medical Center Groningen, Groningen, the Netherlands,
significantly higher in the ETV+HRG-20g group compared to both the 3
Department of Laboratory Medicine, University of Groningen,
ETV+HRG-10g group (67.09% vs. 36.25%; 95% CI, 15.81-45.6) and University Medical Center Groningen, Groningen, The Netherlands.
the ETV+placebo group (67.09% vs. 26.25%; difference, 40.69%; 95%
CI, 26.55-54.83). The incidence of adverse events was similar across Background: Dietary fibers have been shown to modulate hepatic
all three groups, with no reported deaths. diseases in mice via gut microbiota. Cyp2c70-deficient mice have
Conclusion: Combining a 20g dose of the TCM formula HRG with ETV a human-like, hydrophobic, bile acid (BA) composition, which is
significantly enhances liver fibrosis regression in CHB patients. associated with liver pathology and impaired intestinal barrier function.
Table and Figure:Figure 1.graphical Abstract Here, we evaluated the impact of dietary fiber on BA metabolism, liver
pathology and intestinal barrier function in Cyp2c70-/- mice.
Method: Three diets with different fiber contents and compositions
OP0358 were designed, a low fiber diet (LFi), a high fiber diet with high bile
IL-2R combined with THBS2 can predict the degree of liver fibrosis acid binding capacity BABC (HFi-h) and a high fiber with low BABC
in patients with chronic hepatitis B (HFi-l). We fed male and female Cyp2c70-/- mice (aged 5-6 weeks)
Yiqi Liu1, Chi Zhang1, Hong Zhao1, Guiqiang Wang1 with these for 8 weeks and assessed the impact on BA metabolism
and liver pathology. Integrin α5β1–CD40L axis and promoting cancer cell survival. This
Result: Fecal BA excretion in mice fed the HFi-h diet was about 4 study highlights the critical role of the CD40–CD40L interaction in
times higher than in those fed HFi-l, indicating that the fibers in the HCC progression, suggesting that this pathway may be a promising
HFi-h diet did indeed bind BAs in the intestinal tract more effectively. therapeutic target for poorly differentiated HCC.
Surprisingly, both HFi diets were associated with augmented liver Table and Figure:Figure 1.Interplay between CD40 and CD40L in HCC
pathology compared with LFi-fed animals, as evidenced by elevated
serum transaminase and increased collagen deposition. Moreover,
OP0361
female Cyp2c70-/- mice poorly tolerated the HFi-l diet as 4 out of 10
mice fed this diet reached the humane endpoint during the experiment. Faecalibaculum rodentium is a potential pathobiont in metabolic
Intestinal barrier integrity was impaired in male mice fed HFi-h and HFi-l dysfunction-associated steatohepatitis (MASH) via B cell
as compared to those fed the LFi diet. Interestingly, very high levels of dysregulation
UDCA (~50% of total BAs) were found in the circulating BA pool of Hong Sheng Cheng1, Wei Ling Koo1,2, Zhi Kai Koh2, Si Ying Wong2,
Cyp2c70-/- mice fed the LFi diet, translating into a relatively hydrophilic Sook Teng Chan2, Esha Bharathwaj Vijay2, Damien Chua1, Kuo Chao
BA pool, while in mice on HFi-h and HFi-l, the more hydrophobic CA Yew1,3, Hei Sunny Wong1,3, Nguan Soon Tan1,2
and CDCA were the dominant BAs, respectively. 1
Lee Kong Chian School of Medicine, Nanyang Technological
Conclusion: High fiber, but not low fiber, aggravates liver pathology in University, 308232 Singapore, 2School of Biological Sciences,
mice with a human-like BA composition, which is likely due to increased Nanyang Technological University, 637551 Singapore., 3Department
conversion of hepatotoxic CDCA into hepatoprotective UDCA by the of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 308433
gut microbiota in mice consuming low amounts of fiber. Singapore.
Table and Figure:Figure 1.Both high fiber aggravates liver pathology in Background: Metabolic dysfunction-associated steatohepatitis
male mice with a human-like BA composition (MASH), characterized by liver injury and fibrosis, is a severe form
Figure 2. Hepatoprotective UDCA is the dominant bile acid in mice of metabolic dysfunction-associated steatotic liver disease (MASLD)
treated with LFi that increases the risk of liver failure and hepatocellular carcinoma. Its
growing worldwide prevalence highlights an emerging public health
OP0360 concern. While the adaptive immune system is pivotal in MASLD
progression, the mechanisms remain poorly understood. This study
Immune Checkpoint Protein CD40 and Integrin α5β1 in HCC: aims to investigate the gut-immune-liver axis and its role in humoral
Mechanisms Supporting Tumor Survival and Therapy Potential immune dysregulation during MASLD exacerbation.
Le Thanh Thuy1, Hanh Vinh Ngo2, Hoang Hai2, Norifumi Kawada2 Method: We performed an integrative transcriptomic analysis of over
1
Department of Global Education and Medical Sciences, Graduate 800 livers covering the full MASLD disease spectrum to reveal deep
School of Medicine, Osaka Metropolitan University, 2Department insight into its immunopathologies. The integrative analysis has been
of Hepatology, Graduate School of Medicine, Osaka Metropolitan developed into a publicly accessible online tool – MegaMASLD – that
University is available at https://bioanalytics-hs.shinyapps.io/MegaMASLD/.
Background: Hepatocellular carcinoma (HCC), the most prevalent Preclinical assessment was performed using our MASLD mouse
form of primary liver cancer and a leading cause of cancer-related model induced through a specialized diet, LIver Disease Progression
mortality worldwide, is linked to elevated levels of immune checkpoint Aggravation Diet (LIDPAD) and thermoneutral housing. Fecal
proteins (ICPs) such as CD27, CD28, and CD40. This study focuses on microbiota transplantation (FMT) using healthy- and MASH-associated
elucidating the specific role of CD40 in the progression of liver tumors. microbiomes into naïve mice allowed assessment of their impact on
Method: A cohort of 168 HCV-infected patients, comprising 47 with immune response and liver pathology.
HCC and 121 without HCC, was enrolled in this study. Levels of soluble Result: Transcriptomic analysis of MASLD livers identified a high-risk
(sCD40) and membrane-bound (mCD40) CD40 were quantified in subgroup (~40% of early MASLD patients) predisposed to MASH. This
plasma and human liver tissue samples, respectively. CD40 expression subgroup, often misclassified clinically as having mild disease, exhibits
in five human HCC cell lines was assessed via immunoblotting and marked alterations in gene expression related to humoral immune
quantitative RT-PCR. The methylation status of the CD40 promoter response and antibody repertoire. Using the LIDPAD mouse model with
region was also analyzed. CD4+ T cells, isolated from the peripheral a humanized gut microbiome, we demonstrated that dysregulated of B
blood of healthy donors, were activated to express the CD40 ligand cell responses, characterized by auto-immunogenicity against hepatic
(CD40L). In HCC cells, CD40 expression was induced by treatment antigens, preceded MASH onset. This dysregulation coincided with gut
with human recombinant IFN-γ. Mechanisms of CD40 induction were dysbiosis and the emergence of a MASH-associated bacterial cluster
further investigated through RNA sequencing analysis. featuring Faecalibaculum, Marvinbryantia and Romboutsia. FMT of
Result: Patients with baseline soluble CD40 (sCD40) levels ≥ 688 MASH-associated microbiome accelerated MASLD progression and
pg/mL demonstrated a significantly higher cumulative incidence triggered IgG- and IgM-mediated auto-immunogenicity, confirming a
of HCC. Poorly differentiated HCC tumor tissues exhibited elevated causative role for gut dysbiosis in driving humoral immune dysfunction.
expression of membrane-bound CD40 (mCD40), contrasting with Pull-down assays using circulating antibodies from MASH mice against
adjacent non-tumor tissues. Similarly, poorly differentiated HCC their fecal microbiomes captured a high abundance of Faecalibaculum
cell lines showed high mCD40 expression and low CD40 promoter rodentium, emphasizing its potent immunogenicity and potential role
methylation, in contrast to well-differentiated cell lines. Modulation of as a key pathobiont in MASH.
CD40 expression by deletion or overexpression in HCC cells did not Conclusion: Combining robust bioinformatic analysis and preclinical
directly impact cell growth or morphology. Notably, HLFs co-cultured MASLD model, our work reveals Faecalibaculum rodentium as a
with CD40L-expressing activated CD4+ T cells displayed increased potential pathobiont driving MASH through B cell dysfunction. These
CD40 expression, with a modest 3.2% cell death rate, rising to 10.9% findings highlight a linkage between gut-immune-liver axis that
under conditions of CD40 neutralization. Blocking both CD40 and potentially underpins MASLD exacerbation.
Integrin α5β1 resulted in a marked decrease in cell death (1.9%). RNA
sequencing of HLFs co-cultured with activated CD4+ T cells revealed OP0363
upregulation of interferon (IFN) and immune response pathways.
Elevated IFN-γ levels in the activated T-cell media stimulated the Analysis of histological spectrum and regenerative potential of
JAK1/STAT3 pathway, thereby enhancing CD40 expression in HLFs. hepatocytes as a predictor of outcome in acute-on-chronic liver
Treatment with the JAK1 inhibitor CYT387 (2–16 µM) and the ERK1/2 failure (ACLF)- a large single-centre study
inhibitor U0126 (5–80 µM) reduced CD40 expression in HLFs under Archana Rastogi1, Jayati Sarangi1, Rakhi Maiwall1, Chhagan Bihari1,
IFN-γ stimulation. Shiv K Sarin1
Conclusion: These findings indicate that CD40 on HCC cells interacts 1
Institute of Liver & Biliary Sciences
with CD40L on activated CD4+ T cells, preventing apoptosis via the
Background: Background- Limited data exists on the histological triglycerides levels. Fast protein liquid chromatography showed that
predictors of prognosis in Acute-on-chronic liver failure (ACLF). BD lowered HDL-cholesterol levels, while it increased triglycerides
Aims- (a) To correlate histopathological characteristics and levels in all lipoprotein fractions (VLDL, LDL and HDL). Although BD
regenerative potential of hepatocytes with 90-day mortality in ACLF did not induce any liver lesion, hepatic expression of genes involved in
patients (b) To compare the histopathological and IHC parameters with lipogenesis (ACC, Srebp-1c, SCD1, and DGAT2) were all significantly
prognostic scores (MELD, AARC) increased, while genes involved in alcohol metabolism (Cyp2E1,
Method: Methods- 425 clinically diagnosed (as per APASL ADH1 and ALDH1) showed lower expression.
definition) and histologically confirmed cases of ACLF were selected. In the second set, BD in obese MASH hamsters led to higher plasma
Histological features assessed were fibrosis, necrosis, parenchyma triglycerides levels, hepatic inflammation and ballooning scores
involved by fibrosis/necrosis, ductular proliferation, ductular and greater liver fibrosis, as measured with % Sirius Red labelling
bilirubinostasis, cholangiolitis, cholestasis (severity, location), fatty (all p<0.05 vs. control). BD significantly raised the expression of
change, ballooning degeneration, Mallory denk bodies, neutrophilic genes involved in lipogenesis, inflammation (IL-1b, IL-6, and MCP-
satellitosis, eosinophilic degeneration of hepatocytes and sinusoidal 1), cell death (caspase 3) and fibrosis (a-SMA, Col1a1, Col3a1 and
dilatation/congestion. IHCs for CK7 and ki-67 were performed on 70 TIMP1). Compared to hamsters treated with both BD and vehicle,
cases, whole slide imaging followed by calculation of fraction of biopsy LANI significantly lowered total cholesterol, LDL-cholesterol levels,
area showing CK7 positivity using the Aperio Imagescope software, and triglycerides plasma levels. Liver triglycerides content, hepatic
was performed. Ki67 was interpreted on the IKOSA image analysis inflammation and ballooning scores, as well as liver fibrosis were
platform. all reduced with LANI (all p<0.05 vs. vehicle). Additionally, LANI
Result: Result- Histomorphological features showed statistically significantly reduced the hepatic expression of genes involved in
significant correlation with poor outcome were ductular bilirubinostasis inflammation and fibrosis.
(p<0.001), cholestasis (p<0.001), necrosis (p<0.001), cirrhosis Conclusion: While BD only impaired lipid metabolism in healthy
(p=0.039) and eosinophilic degeneration (p<0.001), while neutrophilic hamsters, it worsened hypertriglyceridemia and liver lesions in obese
satellitosis (p=0.001), and ballooning degeneration (p=0.018), were MASH hamsters. LANI significantly improved dyslipidemia and liver
associated with good outcome. Ductular bilirubinostasis (P=0.026), lesions in obese MASH hamsters. This preclinical model will help to
eosinophilic degeneration (P<0.001), Parenchyma involved by fibrosis/ evaluate drugs targeting MASH in a context of moderate to heavy
necrosis (P=0.043) were associated with higher, and ballooning alcohol use.
degeneration (P=0.017) was associated with lower clinical prognostic
scores. Image based analysis of the CK7 positivity fraction and ki67 OP0365
nuclear positivity count did not yield any significant relation with the
outcome and clinical scores. A highly-stable CRISPR-Cas9 variant antagonizes HSC70-
Conclusion: Conclusion- Histomorphological features can aid mediated degradation and promotes HBV genome destruction
in the prognostication of ACLF patients. Ductular bilirubinostasis, Yarong Song1,2, Zhongqing Li1,2, Jie Li1, Jie Wang1,2
necrosis, parenchymal extinction, eosinophilic degeneration, cirrhosis, 1
Department of Microbiology & Infectious Disease Center, School of
ballooning degeneration and neutrophilic satellitosis, which showed Basic Medical Sciences, Peking University Health Science Center,
correlation with 90-day mortality and the clinical scores, should be Beijing 100191, China, 2NHC Key Laboratory of Medical Immunology,
quantified and included as the minimum dataset in reporting ACLF Peking University, Beijing 100191, China
liver biopsies. Further studies to assess regenerative potential of Background: Chronic hepatitis B virus (HBV) infection persists due to
hepatocytes will strengthen the role of liver biopsy in these cases. the lack of therapies that effectively and stably target the HBV covalently
Table and Figure:Figure 1.Histomorphological features grading and closed circular DNA (cccDNA). As an initial adaptive immune system
IHC quantification by Image analysis against phage and foreign genetic material in prokaryote, CRISPR/
Figure 2.Correlation of Histomorphological features with outcome and Cas9 system has been widely used to combat various viral infections
clinical prognostic scores in humans. However, to eradicate viral infections, a more stable and
efficient CRISPR/Cas9 system is needed to clear the constantly
OP0364 expanding viral genome.
Method: The degradation mechanism of Cas9 was explored in HuH7
The pan-PPAR Agonist Lanifibranor Improves Liver Inflammation, and HeLa cells by treating with inhibitors or activators of protein
Ballooning, and Fibrosis in a Diet-induced Obese MASH Hamster degradation system. Cas9 variants were constructed by site-specific
Model of Binge Drinking mutation. The stability of Cas9 was detected by CHX chase experiment.
FRANCOIS BRIAND1, ESTELLE GRASSET1, NATALIA BREYNER1, HBV surface antigen (HBsAg), e antigen (HBeAg) and core protein
CLAIRE BIGOT1, THIERRY SULPICE1 levels in HuH7, HepG2-NTCP cells and hydrodynamic injection mouse
1
PHYSIOGENEX model were detected to explore the inhibition efficiency of Cas9 on HBV
Background: We aimed to validate an animal model to evaluate the replication. Polymerase chain reaction (PCR) and deep sequencing
efficacy of drugs targeting MASH in a context of moderate to heavy were used to detect the destruction of HBV genome. The cytotoxicity
alcohol use, which may aggravate liver lesions in patients with MASH. and off-target effects were detected by whole genome sequencing.
While mouse and rat are not convenient to study the effects of alcohol Result: Cas9 protein could bind to HSC70 protein through its KFERQ
binge drinking, we previously observed that the golden Syrian hamster (-like) motif and was subsequently degraded by the chaperone-
spontaneously shows a high preference for alcohol and may therefore mediated autophagy (CMA)-lysosomal pathway. HRS could stabilize
represent a better animal model. Cas9 protein by competing with HSC70 protein to bind to Cas9
Here we first compared the effects of alcohol binge drinking (BD) in protein, thereby promoting the CRISPR/Cas9 system to destroy the
lean healthy hamsters and diet-induced obese MASH hamsters. We genome of HBV. On this basis, Cas9 variants with mutant KFERQ (-like)
next evaluated the effects of the pan-PPAR agonist lanifibranor (LANI) motif were constructed, and the highly stable Cas9 protein (HSCas9)
on liver lesions induced by binge drinking in obese MASH hamsters. with mutant KFERQ(-like) motifs located at aa 669-673 and aa 893-897
Method: The effects of BD (40% alcohol at 10mL/kg p.o., 3 times per was achieved by antagonizing the HSC70-mediated CMA-lysosomal
week) for 4 weeks were first evaluated in lean healthy hamsters fed a degradation. Further, HSCas9 promoted CRISPR/Cas9 system to
control chow diet. Hamsters treated with saline were used as control. destroy HBV genome and clear HBV infection without producing
In a second set, diet-induced obese MASH hamsters were gavaged cytotoxicity and increasing off-target effects.
with saline (control) or with alcohol (40% alcohol at 10mL/kg p.o., 3 Conclusion: This study uncovers the degradation mechanism of
times per week), and were simultaneously treated with vehicle or LANI Cas9 protein in human cells, and provides a strategy to obtain the
30mg/kg p.o. QD for 5 weeks. highly stable Cas9 proteins. Using HSCas9 protein can enhance
Result: Compared to control, BD in lean hamsters significantly reduced the destruction efficiency of the constantly expanding HBV genome,
body weight gain and plasma total cholesterol but raised plasma thereby promoting the CRISPR/Cas9 system to clear HBV infections.
Table and Figure:Figure 1.Graphic abstract Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV
(three times daily) plus 0.5 mg ETV (once daily) or 0.5 mg ETV (once
daily) monotherapy for 96 weeks, here, this study reports data from
OP0366
48 weeks
Efficacy and safety of GLS4 with entecavir vs entecavir alone in Result: In Part A (n=122), greater least-squares mean (LSM) changes
chronic hepatitis B patients: a multicenter clinical trial from baseline were observed in the GLS4/RTV plus ETV cohort than
Mingyuan Zhang1, Yanhang Gao1, Fei Kong1, Haibing Gao2, Xiangmei in ETV monotherapy cohort in HBV DNA (-6.28 vs -5.72 log10 IU/
Wang2, Yongxiang Yi3, Weifeng Wu3, Chao Wu4, Yongyang Zhang4, ml, p=0.0005), hepatitis B surface antigen (HBsAg) (-0.87 vs -0.65
Yongning Xin5, Wenwen Jin5, Sujun Zheng6, Ming Kong6, Jiajie Lu7, log10 IU/ml, p=0.0653), HBV pregenomic RNA (pgRNA) (-3.83 vs
Tao HAN8, Jun LI8, Yingren Zhao9, Guoyu Zhang9, Peng Hu10, Min -1.91 log10 copies/ml, p<0.0001), HBeAg (-1.02 vs -0.98 log10 IU/
Luo10, Xiaorong Mao11, Xiaofeng Wang11, Qing XIE12, Lanyi Lin12, ml, p=0.8579), and HBV core-related antigen (HBcrAg) (-1.63 vs -1.27
Jie Zhang13, Dongying Xue13, Zhiliang Gao14, Jinlin HOU15, Xieer log10 U/mL, p=0.0601); The proportions of both HBV DNA and pgRNA
Liang16, Yongyu Mei14, Jianqi Lian17, Ye Zhang17, Liang Chen18, Xun negative patients were 17.3% (13/75) and 0% (0/30) for the GLS4/RTV
Qi18, Jia SHANG19, Kuan Li19, Wen XIE20, Yanbin Wang20, Mao Mu21, plus ETV cohort and the ETV monotherapy cohort, respectively.
Jingzhang Zeng21, Zhenjing Jin22, Qian Zhang22, Maorong Wang23, In Part B (n=123), greater mean LSM reductions
Zhiguo Yang23, Shide Lin24, Yinghua Chen24, Huiying RAO25, Guangjun in HBsAg (-0.17 vs -0.06 log10 IU/ml, p=0.0013), HBV
Song25, Dongliang Yang26, Pian Ye26, Huanyu Gong27, Haoye Zhang27, pgRNA (-1.61 vs -0.28 log10 copies/ml, p<0.0001), HBeAg (-0.28
Jianning Jiang28, Diefei Hu28, Fuchun Zhang29, Keng Chen29, Liying vs -0.21 log10 IU/ml, p=0.2519), and HBcrAg (-0.29 vs. -0.21 log10 IU/
Zhu30, Lihua Zhong30, Feng Lin31, Jian Fu31, Xingxiang Yang32, ml, p=0.2029) were observed in the GLS4/RTV+ETV cohort than
Shuqiang Wang32, Wenxiang Huang33, Shujun Zhang33, Yongping in the ETV monotherapy cohort. The proportions of both HBV DNA
Chen34, Xiaodong Wang34, Qin Ning35, Dong Xu35, Heng Zhang36, Dan and pgRNA-negative patients were 71.6% (48/67) and 18.9%
Zheng36, Lin Luo37, Yunfu Chen37, Yulei Zhuang37, Yingjun Zhang37, (7/37), respectively. GLS4/RTV + ETV was well tolerated. The most
Li Deng37, Kanghua Huang37, Yuan Cao37, Zhangqian Liu37, Robert G common adverse events were elevated alanine aminotransferase
Gish38, Li Chen39, Youwen Tan39, Jie Yu40, Jiming Zhang40, Junqi Niu1 levels (correlated with rapid reductions in HBsAg and HBeAg)
1
First Hospital of Jilin University, 2 Infectious Disease Hospital, and hypertriglyceridemia, which were reversed by temporary GLS4/
Mengchao Hepatobiliary Hospital, Fujian Medical University, RTV discontinuation.
Department of Infectious Diseases and Liver Diseases, 3The Second Conclusion: The primary analysis at week 48 showed that the antiviral
Hospital of Nanjing, Hepatology department, 210003,Nanjing, efficacy of GLS4/RTV with ETV was clearly superior to that of ETV
China;, 4Nanjing Drum Tower Hospital, 210003,Nanjing, 5Qingdao monotherapy. GLS4/RTV with ETV was well tolerated; further studies
Municipal Hospital, 6Beijing YouAn Hospital, Capital Medical evaluating its safety and efficacy are ongoing. (clinical trial identifier:
University,100071, Beijing, China, 7West China hospital Sichuan NCT04147208).
University, 610041,Sichuan, China, 8Tianjin Third Central Hospital , Table and Figure:Figure 1.Mean changes of HBV virological markers
9
The First Affiliated Hospital of Xi’an Jiao Tong University, 710061,Xian, at different time points following GLS4/RTV + ETV combination or ETV
China, 10the Second Affiliated Hospital of Chongqing Medical
monotherapy treatment
University, 11The First Hospital of Lanzhou University, 730030,Lanzhou,
China, 12Ruijin Hospital Affiliated to The Shanghai Jiao Tong
University Medical School,200062,ShangHai,China, 13Shanghai OP0367
Putuo District Central Hospital, 200062,Shanghai, China, 14 The Third Clinical efficacy of antiviral combined with anti-fibrotic Chinese
Affiliated Hospital of Zhongshan University, 15 Nanfang Hospital, patent medicine on recompensation of patients with first
Southern Medical University, Department of Infectious Diseases, decompensated hepatitis B cirrhosis: a real-world evidence
1
6Nanfang Hospital, Southern Medical University, Department of
Xuejie Zhang1, Feixiang Xiong1, Lihua Yu1, Xiaoli Liu1, Huiwen Yan1,
Infectious Diseases, 17The Second Affiliated Hospital of Air Force
Military Medical University, 18Shanghai Public Health Clinical Center, Yixin Hou1, Zhiyun Yang1
1
9Henan Provincial People’s Hospital, 450003, 20Beijing Ditan
1
Center of Integrative Medicine, Beijing Ditan Hospital, Capital
Hospital, 21The Affiliated Hospital of Guizhou Medical University, Medical University
2
2The second hospital of Jilin University, Hepatology department, Background: Hepatitis B virus(HBV) infection is a major global health
2
3Chinese PLA 81 Hospital, 24Affiliated Hospital of Zunyi Medical concern, leading to significant morbidity and mortality due to liver
University, 25Peking University People’s Hospital, 26Union Hospital cirrhosis and hepatocellular carcinoma. The progression of HBV-
College Huazhong University of Science and Technology, 27The Third related liver disease to decompensated cirrhosis poses a critical
Xiangya Hospital of Central South University, 28The First Affiliated challenge,necessitating effective therapeutic strategies to improve
Hospital of Guangxi Medical University, 29Guangzhou Eight People‘ patient outcomes. The primary aim of this study was to evaluate
s Hospital, Guangzhou Medical University, 30The Fourth Affiliated the efficacy of Chinese patent medicine with anti-virus and anti-
Hospital of Harbin Medical University, 31Hainan General Hospital, fibrosis properties on the recompensation of patients with the first
5
70311,Hainan Province, 32Sichuan Provincial People’s Hospital, 33The
decompensated hepatitis B cirrhosis.
First Affiliated Hospital of Chongqing Medical University, 34The First
Method: This prospective cohort study included 912 patients with
Affiliated Hospital of Wenzhou Medical University, 35Tongji medical
hepatitis B-related liver cirrhosis who had experienced their first
college Huazhong university of Science & Technology, 36The Central
decompensated event from August 2017 to August 2022 from Beijing
Hospital of Wuhan, 37The State Key Laboratory of Anti-Infective Drug
Development (NO. 2015DQ780357), Sunshine Lake Pharma Co, Ditan Hospital, and had a follow-up period of at least two years.
3
8Hepatitis B Foundation, Doylestown, PA, USA, 39Zhenjiang Third According to whether recompensation occurs, it is divided into two
People’s Hospital, Hepatology department, 40Huashan Hospital, groups: recompensation group(n=421) and no-recompensation
Fudan University, Department of Infectious Diseases group(n=491). Patients were divided into two groups according to
the mode of treatment, involved antiviral and antibiotical therapy
Background: GLS4 is a first-in-class hepatitis B virus (HBV) capsid
group(n=421), and antiviral but no-antibiotical therapy group(n=491).
assembly modulator that inhibits HBV replication by interfering with
Line-table methods, the Kaplan–Meier estimator, and univariable
assembly and disassembly of the virus nucleocapsid. This study
and multivariable Cox regression models were used to analyse the
evaluated the antiviral activity and safety of GLS4/ritonavir (RTV)
independent risk factors influencing the occurrence of recompensation
combined with entecavir (ETV) versus ETV alone in hepatitis B e
of patients with decompensated hepatitis B cirrhosis. The Kaplan-Meier
antigen (HBeAg)-positive patients with chronic HBV infection (CHB).
was used to analyze the effect of antiviral and antibiotical therapy on
Method: A total of 250 patients with CHB was enrolled, including
the incidence of cumulative recompensation at 1-year and 2-year in
treatment-naïve patients and those who had discontinued anti-HBV
patients with first decompensation of hepatitis B cirrhosis.
drugs for ≥ 6 months (Part A, n=125), and patients who had taken
Result: Antiviral and antifibrotic therapy is an independent predictor
ETV for ≥1 year and had achieved viral suppression (Part B, n=125).
of recompensation during the first decompensated phase of
hepatitis B cirrhosis. The incidence of recompensation with antiviral Petersburg, Russia
and antifibrotic therapy was 53.9%. The cumulative incidence of Background: The burden of parenteral virus hepatitis (HBV, HCV,
1-year(46.3%VS32.5%) and 2-year (75.6%VS50.6%) recompensation HDV) continues to increase worldwide and remains important cause
in the antiviral and antibiotical therapy group was significantly higher for liver-related mortality. It is particularly relevant for Asian countries,
than that in the antiviral but no-antibiotical therapy group, and was including Vietnam, where the highest rates of HBV infection incidence
advantageous for patients with the first 1 complication. Univariate and are observed. In this study, we investigated the prevalence of HBV,
multivariate COX regression analysis showd that antiviral and antifibrotic HCV and HDV among the indigenous people of the rural province Cao
therapy[HR (95%CI): 0.53 (0.44~0.64)] VS [0.74(0.61~0.89)] was a Bang, Vietnam.
protective factor for recompensation, and ALT, AST, Cr, PTA, HBVDNA Method: A total of 500 rural healthy adults aged 19-80 years (320/180
were risk factors for recompensation, multivariate COX regression women/men, mean age 46.8±12.3 years) from two districts of Cao
showed that PLT, PT, AFP, MELD, Child-Pugh B and Child-Pugh C Bang province (Cach Linh, Dai Son) were including in our study. The
grade was a risk factor for recompensation. northern province of Cao Bang, located on the border with China, is
Conclusion: Traditional Chinese medicine treatment with antiviral one of the sparsely populated regions of the country. The most of
combined with antibiotics is helpful for recompensation in patients with participants (82.8%) belonged to the minor ethnic group Nùng. Among
the first decompensated hepatitis B cirrhosis. the surveyed residents were representatives of other ethnic groups: Tay
Table and Figure:Figure 1.Figure1: Flow chart and the cumulative (16.4%), Kinh (0.6%), Dao (0.2%). Serum samples from participants
incidence of recompensation with two therapies. were tested for HBV, HCV, HDV serological markers (HBsAg, anti-HBs,
Figure 2.Figure2: Antiviral and antifibrotic therapy is an independent anti-HBc, anti-HCV and anti-HDV) using ELISA-kits (RPC «Diagnostic
predictor and a protective factor of recompensation of patients with Systems», Russia). HBsAg-positive samples were screened for DNA
first decompensated hepatitis B cirrhosis. HBV by RT-PCR.
Result: The prevalence of HBsAg, anti-HBc, and anti-HBs was 10.8%
OP0368 (54/500; 95%, CI 8.37-13.83), 62.2% (311/500; 95%, CI 57.87-66.34),
30.6% (153/500; 95%, CI 26.72 – 34.77), respectively. HBV markers
Peginterferon alpha-2b enhances HBsAg loss in nucleos(t)ide
were determined regardless of the gender, age, ethnicity and place
analogue-treated patients: Findings from a large real-world study
of residence of the surveyed participants. DNA HBV was detected in
(Everest Project)
9.2% (46/500; 95% CI 6.97-12.05) cases. A total of 46 HBV isolates
Chan Xie1, Bingliang Lin1, Zhiliang Gao1, Hui Zhuang2, The Everest
were genotyped, and HBV genotype C was in 63.0% (29/46), genotype
Project group
B – in 30.4% (14/46). Of 46 HBV isolates, 3 were not typed. No anti-
1
Third Affiliated Hospital of Sun Yat-sen University, 2Department of HDV markers were found in all the investigated blood samples. The
Microbiology and Infectious Disease Center, School of Basic Medical prevalence of HCV antibodies was 1.8% (9/500; 95% CI 0.95-3.39).
Sciences, Peking University Health Science Center
HCV RNA was detected in all anti-HCV positive samples. In this study
Background: Chronic hepatitis B (CHB) patients with suppressed two participants (0.4%; 95%, CI 0.11-1.45) were seropositive for HBsAg
hepatitis B virus (HBV) DNA and low hepatitis B surface antigen and anti-HCV. No serological markers of parenteral viral hepatitis were
(HBsAg) levels on nucleos(t)ide analogues (NAs) may benefit from detected in 30.0% (150/500; 95%CI, 26.15-34.16) participants.
peginterferon alpha (PegIFNα)-based therapy. This study evaluates Conclusion: The results of our study indicate a high HBV
the efficacy, safety, and predictors of HBsAg loss with PegIFNα-2b in seroprevalence and HBV/HCV coinfection among the traditionally-
a large real-world cohort. living ethnic groups of rural Cao Bang province, Vietnam.
Method: The Everest Project, a prospective, multicenter study, enrolled
CHB patients on stable NAs with HBsAg <1500 IU/mL, HBV DNA <100
IU/mL, and negative hepatitis B e antigen (HBeAg). Patients received
OP0371
PegIFNα-2b for 48 weeks, either as monotherapy or in combination SBDS Gene Mutations induce Cholestatic Liver Injury via
with NAs. The primary endpoint was HBsAg loss at week 48. Disturbing FXR/BSEP Signaling-Mediated Bile Acid Excretion
Result: In the modified intention-to-treat (mITT) analysis (n=15,896) Zhang Zhenzhen1, Zhou Yujiao1, Liao Yinglan1
and per-protocol (PP) analysis (n=12,260), HBsAg loss rates at week 1
Department of Infectious Disease, Children’s Hospital of Chongqing
48 after propensity score weighting were 26.4% (mITT) and 33.8% Medical University, National Clinical Research Center for Child
(PP). No significant differences in HBsAg loss rates were observed Health and Disorders, Ministry of Education Key Laboratory of Child
between PegIFNα-2b monotherapy and combination therapy. Key Development and Disorders, Chongqing Key Laboratory of Child
predictors of HBsAg loss included younger age, female gender, lower Rare Diseases in Infection and Immunity,Chongqing, China
baseline HBsAg, alanine aminotransferase (ALT) >80 U/L at week Background: Inherited intrahepatic cholestasis is characterized by
12, and HBsAg decline >63.3% at week 12 and >95.3% at week 24. complex etiologies, diverse and atypical clinical manifestations, and
Among patients who discontinued therapy for over 24 weeks, HBsAg significant individual differences, has gradually become a common
loss rates at week 24 post-discontinuation were 28.68% (mITT) and type of pediatric liver disease, even become an important cause
35.63% (PP). PegIFNα-2b was well tolerated with manageable safety of death or transplantation in children with liver disease. With
profiles. the widespread application of high-throughput next-generation
Conclusion: PegIFNα-2b significantly enhances HBsAg loss in sequencing technologies,  more and more rare new cholestasis-
CHB patients with virological suppression on NAs, achieving rates related pathogenic genes, such as ZFYVE19, SEMA7A, and so on,
exceeding 30% in the PP analysis. Baseline and on-treatment have been successively identified. Recently, based on the analysis
predictors support personalized therapy, emphasizing its potential in of whole-exome sequencing of families from a cohort enrolled 210
achieving a functional cure for CHB. children with high clinical suspicion of hereditary cholestasis, our team
Table and Figure:Figure 1.flow chart filtered and screened a batch of unreported potential pathogenic
Figure 2.HBsAg loss rate after 48 weeks of treatment genes related to cholestasis. Among them, we found SBDS gene,
which had a compound heterozygous mutation of c.184A>T and
OP0370 c.258+2T>C, might correlate to cholestasis.
Method: Clinical liver samples, cell models and mouse models were
Prevalence of hepatitis B, C and D in the ethnic minority
utilized to validate the correlation between SBDS gene mutation and
populations of the rural province Cao Bang, Vietnam
cholestasis. The underlying mechanisms were further explored.
Evgeniia Lichnaia1, Nga Bui Thi Thanh2, Daria Starkova1, Nhai Tran Result: Clinical examination revealed elevated ALT, AST and bile
Thi 2, Cuong Vo Viet 2, Alexander Dmitriev3, Olga Kalinina1 acids (BAs) in the four probands with SBDS mutation. Pathological and
1
Saint-Petersburg Pasteur Institute, Saint-Petersburg, Russia, 2Joint electron microscopy of liver tissue biopsy from one proband indicated
Russian-Vietnamese Tropical Science and Technology Center, Hanoi, small bile duct injury, and abundant deposition of bile pigment granules
Vietnam, 3Saint Petersburg State Institute of Technology, Saint-
within hepatocytes, respectively A significantly reduced expression variant in SLCO1B1. While LINE-1 detection has been validated, the
levels of SBDS proteins in the liver tissue was detected in the proband significance of LINE-1 insertion in clinical manifestations remains
when compared to a child with non-cholestatic liver. SBDS knockdown unclear. The classic splice site variant c.1747+1G > A was not detected.
led to elevated levels of ALT and AST in the cell culture supernatant, VUS detected require further annotation. Therefore, it is recommended
reduced mitochondrial ridges and elevated ROS levels. Reintroduction to conduct Rotor syndrome gene testing, including LINE-1 screening,
of SBDSWT decreased the upregulated transaminases levels caused in individuals with unexplained hyperbilirubinemia. When variants are
by SBDS knockdown, whereas reintroduction of mutant plasmids had monogenic, thorough communication with the clinical team is crucial.
no effect. Liver-specific SBDS deletion mice were constructed via Table and Figure:Figure 1.Scientific Question: Were digenic variants
the tail vein with SBDS-containing adeno-associated virus (AAV8- indispensable for penetrance
SBDSWT). An significantly increased levels of ALT, AST and bile acids
in the peripheral blood was found in SBDS knockout mice compared to
OP0373
control mice. These results indicated that SBDS gene mutation (SBDS
protein deletion) could cause a cholestatic phenotype dominated by A Multimodal Neuroimaging and Hepatic Imaging Analysis of
elevated BAs (Fig.1). Preliminary mechanistic studies revealed that Distinct Clinical Manifestations in Wilson’s Disease
SBDS knockdown markedly downregulated the mRNA and protein Chen Liang1,2, Li Bai1, Hui Jiang1, Haitian Yu3, Dong Ning Su4, Tao
levels of BSEP but did not affect expression levels of CYP7A1, Feng5, Sujun Zheng1
CYP27A1, CYP7B1, CYP8B1 or MDR3. We also found that SBDS 1
Beijing Youan Hospital, Capital Mecical University, 2Beijing Jishuitan
knockdown markedly decreased the protein level of FXR, which is a Hospital, Capital Medical University, 3Beijing Youan Hospital, Capital
critical transcription factor in BSEP (Fig.2). Mecical Universityol, 4Capital medical schoolBeijing Tiantan Hospital,
Conclusion: SBDS mutations might downregulate FXR expression, Capital Medical University, 5Beijing Tiantan Hospital, Capital Medical
reduce BSEP expression at the transcriptional level, thus disrupting BAs University
excretion, ultimately leading to cholestatic liver injury. Background: This study aims to investigate the changes in liver MRI
Table and Figure:Figure 1.Fig.1 SBDS gene mutation (SBDS protein fat content, iron quantification, and brain MRI magnetic susceptibility
deletion) causes a cholestatic phenotype dominated by elevated bile and volume in patients with different clinical presentations of WD,
acids. specifically hepatocentric WD (HWD) and neurocentric WD (NWD).
Figure 2.Fig.2 SBDS knockdown affects bile acids excretion via Additionally, this study seeks to evaluate the diagnostic utility of these
downregulating BSEP expression as well as FXR, a critical transcription MRI-related metrics.
factor in BSEP. Method: This study recruited patients diagnosed with HWD, NWD,
and healthy controls (HC) . 3.0 T multimodal brain MRI was utilized to
OP0372 measure various brain regions for morphometric-volumes analysis and
quantitative susceptibility mapping (QSM). Liver MRI involved placing
Clinical penetrance of monogenic Rotor syndrome variants, LINE- the largest-fit region of interest (ROI) in each of the eight Couinaud
1 insertions, and Variants of Uncertain Significance (VUS) segments to measure proton density fat fraction (PDFF) and R2*
Qi XU1, Bilian YAO1, Xinxin ZHANG1, Yue HAN1 relaxation maps. The QSM values, volumes of different brain regions,
1
Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital fat content and iron quantifications in liver ROIs were compared and
Background: Rotor syndrome is generally considered a digenic analyzed among the WD, HWD, NWD and HC group. The diagnostic
disorder involving the SLCO1B1 and SLCO1B3 genes. This study value of these imaging parameters was evaluated using ROC analysis,
aimed to verify in clinical practice whether the presence of deficiencies and the correlation between MRI-related metrics and the severity of
in both genes is an indispensable prerequisite for penetrance. neurological symptoms was explored through correlation analysis.
Additionally, in East Asian populations, the LINE-1 variant is believed Result: A total of 38 patients included in this study, comprising 17
to be pathogenic, though it is relatively difficult to detect. This study cases of HWD, 10 cases of NWD and 11 cases of HC. No significant
established a detection method that includes LINE-1 to assess differences were observed in demographic characteristics among the
the prevalence of variants in these two genes among patients with groups. Similarly, no significant differences were found in demographic
unexplained hyperbilirubinemia. characteristics, age of onset, disease duration, presence of KF ring,
Method: Patients with unexplained bilirubin abnormalities from August therapeutic drugs and treatment duration, ceruloplasmin levels, liver
2023 to August 2024, along with screening controls, were enrolled function, or blood routine parameters between patients with different
for whole exome sequencing and Sanger validation, and the variants clinical types of WD. However, GAS scores for WD and UWDRS
were classified. A LINE-1 screening and validation platform was also scores were significantly higher in NWD. There was no significant
developed. Bilirubin levels were categorized as normal, elevated, and difference in liver fat content among the groups. Compared to HC,
significantly elevated. the NWD group exhibited significant iron deposition in liver segments
Result: A total of 177 patients were included (107 cases and 70 V, VI, and VII. Additionally, QSM values were significantly increased
controls). Five LINE-1 positive cases were identified, one of which was in bilateral Caudate, Putamen, and Pallidus. The volumes of bilateral
exclusively detected using our platform. The Minor Allele Frequency Cerebellum-Cortex, Thalamus-Proper, Ccaudate, Putamen, Pallidus,
(MAF) of this variant among cases was 0.03271, significantly higher Hippocampus, Accumbens-area, and Brain-Stem were significantly
than the general population’s 0.00038 (GnomAD). The classic splicing reduced. These changes in QSM values and volumes demonstrated
site variant c.1747+1G > A was not detected; however, an insertion/ diagnostic efficacy. In the HWD group, atrophy was observed in the
deletion variant at c.1747+8 was found in 16 cases, with 5 being bilateral Cerebellum-Cortex, Left Hippocampus, and Brain-Stem ,
homozygous. Two cases exhibited a heterozygous variant alongside but no significant differences were noted in liver iron quantification or
other rare variants of unknown significance (VUS), one of which was QSM values of brain regions. The GAS score for WD was positively
in the same gene. Digenic origins were relatively uncommon. Four correlated with liver iron quantification, QSM value of the head, and the
patients were found to carry known pathogenic nonsense mutations. degree of brain atrophy.
Among them, three had the p.R580X mutation: one was homozygous Conclusion: Hepatic and cerebral iron deposition, along with the
for both the p.R580X and LINE-1 mutations, exhibiting markedly extent of regional brain atrophy, represent essential neuroimaging
abnormal bilirubin levels. Two others were heterozygous for p.R580X biomarkers for patients with WD, especially those exhibiting
without LINE-1 or other VUS and displayed abnormal bilirubin levels. neurological symptoms.
Additionally, one patient carried a heterozygous p.R253X without the Table and Figure:Figure 1.Table 1 Demographic characteristics,
LINE-1 mutation but with a heterozygous c.1747+8 variant and had neuroimaging and hepatic imaging analysis of neurocentric Wilson’s
mildly elevated bilirubin levels. Twenty-seven patients had two VUS disease and healthy controls
variants, four of whom did not involve digenic variants. Figure 2.Table 2 Demographic characteristics, neuroimaging and
Conclusion: Clinical penetrance of Rotor syndrome can result from hepatic imaging analysis of hepatocentric Wilson’s disease and
single gene variations, particularly in the presence of a nonsense healthy controls
 OP0374 LVMI (g/m2.7) was significantly higher in children with unsuccessful
Efficacy and safety analysis of interferon in the treatment of KPE (p=0.05 & p=0.024) and unoperated BA (p<0.001 & p=0.002)
patients with HBeAg-negative chronic hepatitis B complicated compared to those with successful KPE and GIC. Children with CCM
with Gilbert syndrome exhibited significantly higher serum bile acid levels (p=0.037). CCM
was associated with a lower native liver survival (NLS) and overall
Dacheng Sheng1, Haitian Yu1, Pengxuan Wu1, Jianxia Dong1, Chen
survival (OS) at 12 months (NLS: CCM: 67.39% vs no CCM: 85.71%;
Liang2, Shan Tang1, Wei Hou1, Sujun Zheng1
Log Rank 4.24, p=0.0039; OS: CCM: 78.26% vs no CCM: 95.24%; Log
1
Beijing Youan Hospital, Capital Mecical University, 2Beijing Jishuitan Rank 7.651, p=0.006). No significant associations were found between
Hospital, Capital Medical University
the presence of CCM and post-LT mortality, time to extubation, duration
Background: As the preferable drug in the treatment guidelines of of inotrope use, or length of ICU stay. Seventy-five percent of children
hepatitis B in various countries, interferon could effectively reduce with CCM showed resolution of the condition within three to six months
the risk of liver cirrhosis and liver cancer. Gilbert syndrome (GS) following liver transplantation.
is a kind of long-term intermittent mild unconjugated hereditary Conclusion: CCM is prevalent in almost half of patients with BA and
hyperbilirubinemia due to the decrease of UGT1A1 enzyme activity. GIC and is associated with decreased NLS and OS. Additioally, serum
The UGT1A1 enzyme with low activity could lead to drug toxicity or bile acid levels were significantly higher in those with CCM.
elevated level of bilirubin. This study evaluates the impact of interferon Table and Figure:Figure 1.Kaplan-Meier survival curve depicting and
on safety and efficacy in patients with CHB and GS. comparing native liver and overall survival among patients with and
Method: A total of 46 patients with HBeAg-negtive CHB(n=23) and without cirrhotic cardiomyopathy
HBeAg-negative CHB(n=23) were analyzed after propensity score
matching (PSM). Both groups were treated with interferon. Clinical
OP0376
outcomes were followed up for a mean of 48 weeks. Toxicity was
assessed at each phase according to Common Toxicity Criteria - Propanolol For Primary Prophylaxis For Variceal Bleed In Infants
Adverse Events (CTCAE) version 5.0. SPSS25.0 software was used for And Children With Biliary Atresia – Results Of A Single Blind
statistical analysis. Randomized Controlled Trial (BABB-Trial)
Result: The incidence of HBsAg-negative conversion was higher in Anmol Anmol1, Rajeev Khanna2, Seema Alam3, Vikrant Sood4, Bikrant
the CHB combined with GS group(7, 30.4%) than in the CHB group(3, Biharilal4
13.0%), with a risk ratio(RR) for HBsAg-negative conversion in the GS 1
senior resident, 2Additional Professor, 3professor, 4Associate Professor
group of 2.33(95% CI: 0.69-7.93, P=0.284). The incidence of HBV Background: Non-selective beta-blockers (BB) decrease portal
DNA-negative conversion was higher in the GS group than in the non- pressure and thus bleeding and non-bleed decompensation in
GS group(0.91 vs 0.81; RR 1.12, 95% CI: 0.83-1.51, P=0.624). cirrhotic adults. Portal hypertension (PHT) is progressive in biliary
In the meantime, there was no significant between GS and non-GS atresia (BA) and is a reason for listing children for Liver transplantation
group (P=0.455) for the adjustment of the interferon dose. Patients with (LT). Usage of BB in infants and children with BA has not been studied
GS were likely to have the milder drug toxicity. They were associated in a controlled manner. In this single blind randomized controlled trial
with a reduced risk of elevated alaine aminotransferase(RR: 0.53, we aimed to study the effect of propranolol in comparison to placebo
95% CI: 0.34-0.81, P=0.002) and decreased neutrophil count(RR: for primary prophylaxis on bleed free survival and overall survival at
0.739, 95% CI: 0.58-0.94, P=0.022). Especially, the change of ratio of 18 months.
total bilirubin(TB) level from baseline did not reach significance in GS Method: Infants and children under-5 years of age with BA were
group(P=0.202). screened for presence of esophageal varices starting at the age of
Conclusion: GS patients with CHB had a lower incidence of drug 6 months. Those with varices (small or large) were randomized in a
toxicity. It’s safe for GS patients to use interferon. There is no statistical 1:1 ratio to receive either propranolol @1-4 mg/kg/day (dose titrated
difference about the result of treatment in two groups. to achieve heart rate reduction to 25%) or placebo in a single blind
Table and Figure:Figure 1.Figure 1 Change of ratio of TB level from manner. Primary outcome was bleed-free survival at 18 months.
baseline Secondary outcome was overall survival at 18 months. Trial was
Figure 2.Table 1 Clinical outcomes of antiviral therapy registered as NCT04494763 following ethical clearance.
Result: Total 50 BA children (19 females and 16 were unoperated)
OP0375 were enrolled at a median age of 8.2 (6.4, 12) months. 26 received
Cirrhotic cardiomyopathy among children with biliary atresia and propranolol while 24 received placebo. Three children had large
genetic intrahepatic cholestasis: prevalence, natural history and varices, while rest had small varices, one-third of whom were high
outcomes risk with presence of red colour signs. At 18 months from the time of
enrolment, 2 lost to follow-up – 8 patients developed variceal bleed
Anmol Anmol, Tamoghna Biswas1, Bikrant Bihari Lal1, Rajeev
in a median interval of 4 (1.5, 12) months from first endoscopy. In
Khanna1, Vikrant Sood1, Vikas Kohli2, Jaswinder Maras1, Viniyendra
propranolol group, ten (40%) survived with their native liver, 20% had
Pamecha1, Seema Alam1
variceal bleeed as compared to placebo group, nine (39%) survived
1
Institute of liver and biliary sciences, 2Delhi Child Heart Center
with their native liver, 13 % had variceal bleeed. Further results were
Background: The present study aimed to investigate the prevalence analysed using intention to treat analysis. There were no differences in
and progression of cirrhotic cardiomyopathy (CCM) in children with proportion of patients with bleed-free survival (80% vs 87%, p=0.704)
biliary atresia (BA) and genetic intrahepatic cholestasis (GIC), as well and overall survival between propranolol and placebo groups (40% vs
as its association with outcomes before and after liver transplantation 39%, p=0.951).The predictors of variceal bleed on univariate analysis
(LT). included success of kasai surgery,HPS, ascites and gastric varices.
Method: This was a prospective observational study. The study However in multivariate analysis albumin, unsuccessful kasai surgery
included all children aged 0-18 years diagnosed with BA or GIC, while and INR were found to be significant predictors of bleed. Applying
excluding those with structural congenital heart diseases. Transthoracic Competitive risk analysis presence of large esophageal varices,
echocardiography, encompassing two-dimensional, color Doppler, and albumin and gastric varices were significant predictors of timing of
motion modes, was performed for cardiac evaluation. Left ventricular bleed on univariate analysis but none were significant on multivariate
mass index (LVMI) ≥95 g/m2.7 and/or relative wall thickness (RWT) of analysis.
left ventricle (LV) ≥0.42 was used for defining CCM. Conclusion: Portal hypertension in BA children show poor response
Result: The prevalence of CCM in children with BA and GIC was 54% to beta-blockers. Heterogeneity due to bilirubin and drop-outs due to
and 48%, respectively. Within the BA group, CCM occurred in 53% death or LT prompted us for this interim analysis. Larger studies with
(n=30) of children with successful Kasai portoenterostomy (KPE), uniform cohorts of BA based on bilirubin levels are required.
69% (n=13) with unsuccessful KPE, and 45% (n=20) with unoperated Table and Figure:Figure 1.Predictors of bleed multivariate analysis
BA, showing no significant difference among these subgroups. Figure 2.Competitive risk analysis vs kaplan meier curve
 OP0377 outpatient clinic (5.57%), and hepatobiliary surgery ward (3.78%). The
Plasma exchange improves survival with native liver by three HCV antibody positive rate was statistically significantly higher in the
folds in wilson disease with New Wilson’s Index ≥ 11 & early ≥40 age group than in the <40 age group (χ2 = 1892.577, P = 0.000).
hepatic encephalopathy The 60-69 and 80-99 age groups exhibit the greatest HCV antibody
positive rates (both 1.88%), while the 50-59 age group has the highest
Anmol Anmol, Snigdha Verma1, Seema Alam1, Bikrant Bihari Lal1,
HCV RNA positive rate (39.30%) . The positive rate was markedly
Tamoghna Biswas1, Vikrant Sood1, Rajeev Khanna1, Meenu Bajpai2
lower in males (15.75%) than in females (18.53%) (χ2 = 8.066, P <
1
Department of Pediatric Hepatology and Liver Transplantation, 0.01). The HCV RNA positive rate exceeded 38.97% when the HCV
2
Department of Transfusion medicine
antibody level exceeded 9 S/CO. The antibody levels between 15 and
Background: Decision about liver transplant is difficult in Wilson’s 17 S/CO exhibited the highest HCV RNA positive rate of 56.17%.
disease (WD) with liver failure, especially with conflicting reports about Conclusion: We have identified critical populations for HCV antibody
New Wilson’s index (NWI). Therapeutic plasma exchange (TPE) can screening, including: (1) patients aged 40 and older, with a particular
provide survival with native liver (SNL) in WD. This study was done to emphasis on females aged 50-69; and (2) patients from the liver disease
see the effect of TPE on outcome and identify factors for SNL. outpatient clinic, gastroenterology outpatient clinic, ophthalmology
Method: All cases of WD with liver failure (INR ≥2.5) from prospectively outpatient clinic, gynaecology outpatient clinic, and hepatobiliary
maintained data were included for propensity score matching (PSM) to surgery ward. Additionally, it is strongly advised that patients with HCV
select TPE (n=48) and no TPE (n=48) groups. Three sessions of TPE antibody levels above 9 S/CO undertake HCV RNA testing.
on three consecutive days were given to TPE group. Preliminary results of non-interventional study to assess virological
Result: 159 cases were included in the PSM with NWI & hepatic effectiveness, safety, and tolerability of NVR/RTV+SOF combination in
encephalopathy (HE) grading as predictors. SNL was comparable (26 HCV infected persons living with HIV
versus 17 cases (OR 1.45, p=0.05), but significantly improved in cases Denis Gusev1, Konstantin Kozlov2,  Svetlana Romanova3,  Svetlana
with no to early HE (OR=1.70, p=0.03). Kaplan Meier survival curves Kizhlo3,  Tatiana Tkachenko4,  Viacheslav Zhukov5,  Stella
were significantly (Log Rank 0.019) improved in the TPE group when Minaeva6,   Natalia Sofronova7,  Margarita Radzikhovskaya8,  Valeriy
analysing in no to early HE. Lower INR (Adjusted OR=0.47, 95%CI 0.28- Shevchenko9,  Yana Ulyanova10,   Julia Ermolaeva11,  Natalia
0.79, p=0.005) and TPE administration (Adjusted OR=3.12, 95%CI Rymarenko12,  Emiliya Krasavina13,  Mikhail Samsonov13
1.10-9.4, p=0.032) at enrollment were independently associated with 1Clinical Infectious Diseases Hospital Named After S.P. Botkin, St.
SNL. Lower NWI (Adjusted OR 0.686, 95%CI 0.53-0.89, p=0.005) at 96 Petersbug, 2Military Medical Academy named after SM Kirov, St.
hours was independently associated with SNL. Petersburg,  3St. Petersburg City Center for AIDS and Infectious
Conclusion: TPE improves SNL by 3 folds in early HE. Advanced HE Diseases Treatment and Prophylaxes,  4Novgorod Regional Center
should be offered immediate LT. Lower INR at enrollment can increase for the Prevention and Control of AIDS and Infectious Diseases
SNL by 50% but 3 sessions of TPE, NWI < 11 increases SNL by 32%, HELPER,   5Sverdlovsk Regional Center for AIDS treatment and
hence should be kept low with further TPE. Prophylaxis,  6Nizhny Novgorod Regional Center for the Prevention and
Table and Figure:Figure 1.Survival with Native Liver in TPE versus No Control of AIDS and Infectious Diseases,   7Perm Regional Center for the
TPE group in those with No to Early HE Prevention and Control of AIDS and Infectious Diseases,  8Chelyabinsk
Figure 2.Algorithmic Approach to Wilson Disease with NWI ≥ 11 Regional Center for the Prevention and Control of AIDS and Infectious
Diseases,  9Altai Regional Center for Prevention and Control of AIDS
OP0378 and Infectious Diseases, Barnaul,  10City Infectiouns Clinical Hospital
No.1, Novosibirsk,  11Sibmed University Clinics, Tomsk,  12Order
Evaluation of the present condition of hepatitis C infection in a
of Labor Red Banner S. Georgievsky Medical Institute, V. Vernadsky
comprehensive tertiary hospital in Beijing
Crimean Federal University, Simferopol,  13 R-Pharm Group, Moscow
Haiying Zhang1, Runling Zhang1, Huiying Rao1 Background
1
Peking University People‘s Hospital, Peking University Hepatology Narlaprevir (NVR) is a NS3 protease inhibitor of HCV used for hepatitis
Institute, Infectious Disease and Hepatology Center of Peking C therapy in combination with ritonavir (RTV) and other direct-acting
University People‘s Hospital, Beijing Key Laboratory of Hepatitis antivirals. In this analysis to date, the effectiveness of NVR/RTV +
C and Immunotherapy for Liver Diseases, Beijing International sofosbuvir (SOF) once‐daily for 12 weeks was assessed in a large
Cooperation Base for Science and Technology on NAFLD Diagnosis, population of Russian people who are infected with HCV (genotype 1)
Beijing 100044, China. and living with HIV (PLHIV).
Background: The World Health Organization (WHO) has set a target Methods
to eliminate hepatitis C by 2030; however, there is still a substantial Adults treated with NVR 200 mg co-administered with RTV 100
lacuna to be filled in order to achieve this objective. Hepatitis C mg + SOF 400 mg for 12 weeks were included in this prospective
screening in healthcare settings is both cost-effective and efficient. observational study. All HCV patients reaching Week 12 post‐treatment
The objective of the study is to assess the distribution of hepatitis C were assessed for SVR12. All PLHIV initiated antiretroviral therapy
virus (HCV) infection among patients at a tertiary hospital in Beijing and before starting therapy with NVR.
its relationship to gender, age, and case sources. Results
Method: A retrospective analysis was performed on 631,424 patients Overall, 909 patients with co-infection HIV/HCV were included in this
who underwent HCV antibody (anti-HCV) testing at a tertiary hospital in analysis: 60.51% male, 68.9% with fibrosis (METAVIR score F0–F1),
Beijing from January 2017 to December 2023. For the detection of anti- 55.67% with HIV-VL < 50 copies/ mL; 71.73% with HIV stage 3 (WHO
HCV, the Abbott i2000 automated chemiluminescent immunoassay clinical staging), 49.4% current/former intravenous drug use. Of the
analyser was employed, while the Roche Cobas AmpliPrep/Cobas 649 patients evaluated for effectiveness, 94.92% (95% CI 92.93 -
TaqMan 96 real-time PCR system was employed for HCV nucleic acid 96.47) achieved SVR12. Only 33 patients did not achieve SVR12 due
testing. Sequencing was used to perform HCV genotyping. to a virological reason.
Result: The positive rate of HCV antibodies in the tertiary hospital in Conclusion
Beijing demonstrated a decreasing trend, decreasing from 1.62% in Genotype-specific treatments for HCV are being actively employed in
2017 to 1.01% in 2023. From 2017 to 2023, the overall anti-HCV positive national plan for eliminating HCV infection in Russia. NVR/RTV + SOF
rate among patients was 1.36% (8,574/631,424). The HCV nucleic in HIV/HCV co-infection was highly effective and tolerable in clinical
acid testing rate was 59.24% (5,079/8,574), and the HCV RNA positive practice, drug use is a potential barrier to reach HCV elimination in
rate was 34.28% (1,741/5,079). We conducted a retrospective analysis PLHIV.
of 8,574 patients from 37 departments. The results showed that the
liver disease outpatient clinic (22.00%) was the primary source of HCV
OP0381
antibody-positive patients, followed by the gastroenterology outpatient
clinic (12.08%), ophthalmology outpatient clinic (6.03%), gynaecology
Improved Survival Outcomes in Cirrhotic Patients with Acute Background: Digital quantification of scarring from either stained
Variceal Bleeding Following Full Adherence to Clinical Practice or stain-free liver sections reduces observer-related variability in the
Guideline (CPG) Quality Metrics: A Retrospective Cohort Study histological assessment of metabolic dysfunction-associated steatotic
Laurence Laurel1, Tonee Ann Abella1, Jovito Balbosa1, Suzette Grace liver disease (MASLD). To date, computational methods have mainly
Kho-Herman1, Ian Homer Cua1 provided ordinal scores analogous to those provided by a pathologist
1
Institute of Digestive and Liver Diseases, St. Luke‘s Medical Center- as disease outcomes are strongly correlated with stage. Direct
Global City prediction of outcomes from tissue, without using fibrosis stage as a
surrogate, has not been possible due to the lack of suitable event-
Background: The Asian Pacific Association for the Study of the Liver
rich cohort data. Using SteatoSITE, an integrated-multimodal data
(APASL) recognizes acute variceal bleeding as a life-threatening
commons for MASLD research, we applied stain-free imaging to
complication of liver cirrhosis, associated with a mortality rate of
develop tools for outcome prediction based on architectural features
approximately 20% within the first six weeks. In May 2024, the American
imperceptible to human observers.
Association for the Study of Liver Diseases (AASLD) released an
Method: Sections from n=452 biopsies were randomized into training
updated clinical practice guideline (CPG), highlighting importance in
(300) or test (152) sets and imaged for fibrosis, steatosis, and
supportive and pharmacologic therapies—specifically Terlipressin,
ballooning parameters using second harmonic generation/two-photon
prophylactic antibiotics and nonselective beta-blockers (NSBB), and
excitation fluorescence (SHG/TPEF) microscopy. 5 of 184 fibrosis
the critical role of timely endoscopy (within 12hrs) and band ligation.
parameters have previously been used to derive separate fibrosis-
These CPGs from international societies have significantly enhanced
based indices for risk of clinical outcome mortality (COMI-F) and
the standard of care in managing acute variceal bleeding. Our study
clinical outcome decompensation (CODI-F). By feature traversing, the
aims to assess whether full adherence to these CPGs correlates with
effect of adding 65 steatosis and 21 ballooning parameters to COMI
improved 6-week survival in cirrhotic patients with acute variceal
and CODI was tested, and improved composite outcome indices (-FS
bleeding in a Philippine tertiary care center.
and -FB) generated. In the testing set, the predictive power of the new
Method: This study employed a retrospective cohort design
composite indices was compared with assigned NASH-CRN fibrosis
conducted at St. Luke’s Medical Center-Global City, encompassing
stage (F0/1/2 v F3/4), stain-free imaging derived qFibrosis stage
cirrhotic patients admitted with acute variceal bleeding between 2018
(qF0/1/2 v qF3/4), and previously derived fibrosis-only indices using
and 2023. The primary predictor was full adherence to all five key
Kaplan–Meier analysis and Cox proportional hazards modelling.
CPG quality metrics for acute variceal bleeding management, which
Result: Composite indices incorporating ballooning parameters
included: (1) prophylactic antibiotics, (2) somatostatin analogues, (3)
(COMI-FB and CODI-FB) demonstrated superior predictive power
timely endoscopy, (4) endoscopic hemostasis, and (5) administration
for all-cause mortality and hepatic decompensation, respectively,
of NSBB following the bleeding event. The 6-week mortality rates
compared to COMI-F, CODI-F, qFibrosis stage, and NASH-CRN
were compared between patients with full adherence to these quality
fibrosis scores. Similarly, composite indices for all-cause mortality
metrics versus those with suboptimal adherence, stratified by CTP and
(COMI-FS) and hepatic decompensation (CODI-FS) generated by
MELD-Na score.
including steatosis parameters also had greater predictive power
Result: A total of 105 patients were included in the study, with 44.76%
than the COMI-F, as well as qFibrosis-derived stage and NASH-CRN
demonstrating full adherence to the CPG quality metrics. Baseline
fibrosis score.
characteristics were comparable between the full adherence and
Conclusion: SHG/TPEF imaging-derived microarchitectural features
suboptimal adherence groups. Full adherence was associated with
of scarring and disease activity improve predictive value for all-cause
a significant reduction in 6-week mortality (10.6% vs. 25.9%; OR =
mortality and liver-related events beyond traditional fibrosis-based
0.34, 95% CI: 0.11–1.0, p = 0.0493). Patients in the full adherence
scores or ordinal staging. These indices may offer enhanced participant
group also experienced lower rates of early infection (23.4% vs.
stratification and endpoint analysis for clinical trials. Prospective
32.8%,) and acute-on-chronic liver failure (6.4% vs. 8.6%). Although
validation is essential to establish the relationship between baseline
a reduction in 1-year mortality (23.4% vs. 36.2%) was observed, it
microarchitectural features, their modification following treatment, and
did not reach statistical significance (OR = 0.65, 95% CI: 0.3–1.5, p
associated clinical outcomes.
= 0.1584). Subgroup analysis revealed that patients with more severe
Table and Figure:Figure 1.Hazard ratios and p-values for prediction
liver disease (Child-Pugh class C or MELD-Na >15) remained at higher
of all-cause mortality and hepatic compensation using composite
risk for all morbidity and mortality outcomes even with full adherence
stain-free fibrosis, ballooning and steatosis parameter-derived indices
to CPGs.
compared with NASH-CRN fibrosis scores, qFibrosis scores, and
Conclusion: Full adherence to CPG quality metrics is associated with
stain-free fibrosis parameter-only indices.
a significant reduction in 6-week mortality following acute variceal
bleeding, underscoring the importance of adherence to evidence-
based CPGs in improving outcomes. Despite these benefits, patients OP0385
with advanced liver disease remain at higher risk, highlighting the need Assessment of the Diagnostic Efficacy of a Novel Liver Cancer
for additional interventions and targeted strategies to improve survival Biomarker: Multigene Methylation
in this population. Xiangsha Kong1, Jing Yu2, Yijun Shi1, Xu Cong1, Juan Liu2, Lizhong
Table and Figure:Figure 1.FIGURE 1. Clinical outcomes among acute Dai2, Huiying Rao1
variceal bleeding patients between full and suboptimal adherence 1
Peking University People‘s Hospital, Peking University Hepatology
groups.
Institute, Infectious Disease and Hepatology Center of Peking
Figure 2.FIGURE 2. Clinical outcomes in patients with full adherence to University People‘s Hospital, Beijing Key Laboratory of Hepatitis
quality indicators of acute variceal bleeding stratified per CTP Class. C and Immunotherapy for Liver Diseases, Beijing International
Cooperation Base for Science and Technology on NAFLD Diagnosis,
OP0383 Beijing, China. , 2Sansure Biotech Incoporation, Changsha, Hunan,
China.
Stain-free digital pathology imaging reveals microarchitectural
insights into disease activity and scar evolution to enable Background: Currently, traditional liver cancer biomarkers are
outcome prediction in metabolic dysfunction-associated steatotic insufficient for early diagnosis of hepatocellular carcinoma (HCC) in
liver disease clinical practice. This study aimed to identify novel biomarkers for
Timothy J Kendall1, Elaine Chng2, Yayun Ren2, JiaoJiao Li2, Dean the early detection of HCC, assess the diagnostic value of multigene
Tai2, Jonathan A Fallowfield1 methylation in early-stage HCC, and compare the clinical diagnostic
performance of this multigene methylation panel with that of other
1
Centre for Inflammation Research, Institute for Regeneration
established HCC diagnostic markers, including seven microRNAs
and Repair, University of Edinburgh, Edinburgh, UK, 2HistoIndex,
Singapore (miRNA7™), alpha-fetoprotein (AFP), and des-gamma-carboxy
prothrombin (DCP).
Method: A total of 54 HCC patients and 77 non-HCC patients, with an AUC of 0.97 in predicting 1-year mortality, significantly higher
all confirmed through pathology or imaging, were enrolled as than those of CLIF-C AD (0.72, p<0.001), Child-Pugh (0.82, p=0.003)
participants in this study conduceted at Peking University People’s and MELD score (0.79, p=0.002). The outperformance of AD-MRI
Hospital from September 2023 to June 2024 Parallel detection was score over traditional scores was well validated in the test cohorts
carried out with multigene methylation markers (OTX1,MTHFD2, and (Figure 3)
FAR1), miRNA7™, AFP and DCP. The diagnostic efficacy of multigene Conclusion: Machine learning models based on MRI demonstrated
methylation was compared with that of miRNA7™, AFP, and DCP to higher accuracy in predicting 1-year mortality of patients with ADC
evaluate its clinical utility in HCC detection. compared to the traditional scores. This imaging technique could be
Result: The sensitivity and specificity of multigene methylation detection a promising way for better risk-stratification of long-term prognosis in
were 96.3% and 64.9%, respectively; the sensitivity and specificity of patients with ADC, complementing the currently available tools at our
miRNA7™ detection were 64.8% and 66.2%, respectively, and the hands.
sensitivity and specificity of AFP and DCP detection were 58.5% and Table and Figure:Figure 1.Figures
71.8%, respectively. The sensitivity of multigene methylation combined
with AFP and DCP detection was as high as 100%, and the negative OP0387
predictive value was 90.9%. The sensitivity of microRNA combined
with AFP and DCP detection was 81.5%, and the negative predictive Evaluation of Hemodynamic Alterations in Patients with
value was 94.5%, which is an improvement over multigene methylation Intestinal Obstruction via Whole-Liver CT Perfusion Imaging and
alone or miRNA7™ alone. Development of a Clinical Prognostic Model.
Conclusion: The detection sensitivity of multigene methylation for Han Lin1,2, Daiquan Fu3, Bo Wang4, Xiaodang Yang4, Mengmeng
HCC is significantly higher than that of miRNA7™and the traditional Liu2, Xue Li2, Zhenghaoyu Huang1,2, Shiwei Chen3, Bingcang Huang4,
liver cancer diagnostic marker, thus avoiding missed diagnoses. Yonghong Guo2
The combined detection of multi-gene methylation and serological 1
School of Gongli hospital Medical Technology,University of Shanghai
markers can significantly improve the diagnostic efficacy for early liver for Science and Techonology, Shanghai 200093, China , 2Department
cancer. This also indicates that the combination of multiomics liquid of Infectious Disease,Shanghai Pudong New Area Gongli
biopsy technology can compensate for the lack of single-dimensional Hospital,219 Miaopu Road, Shanghai,200135,China, 3Department
detection of liver cancer diagnostic markers and opens up a new ofInterventional Surgery Department,Shanghai Pudong New
path for improving the diagnostic efficiency of liver cancer. Detection Area Gongli Hospital,219 Miaopu Road, Shanghai,200135,China,
of multigene methylation has great clinical application value in the
4
Department of Radiology Department,Shanghai Pudong New Area
diagnosis of early liver cancer. Gongli Hospital,219 Miaopu Road, Shanghai,200135,China
Background: To evaluate clinical indicators and prognosis-related
parameters in intestinal obstruction patients, develop a clinical
OP0386
prediction model using whole-liver computed tomography perfusion
Machine Learning of liver magnetic resonance imaging signatures (CTP) imaging data.
outperforms traditional prognostic scores in the prediction of Method: A retrospective study analyzed data from 53 intestinal
1-year mortality in patients with acutely decompensated cirrhosis obstruction patients at Gongli Hospital of Shanghai Pudong Area,
Qingren Cao1, Lan Zhu2, Chenxi Zhang1, Baoyan An1, Dandan Weng3, between January and November 2024.Evaluation of Hemodynamic
Minghao Cai1, Zhuping Qian4, Ziqiang Li1, Ruokun Li2, Haiguang Xin1, Alterations in Patients with Intestinal Obstruction via Whole-Liver CT
Zhujun Cao1, Qing Xie1 Perfusion Imaging.All participants underwent whole-liver perfusion
1
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao scanning utilizing a 64-slice dual-source spiral CT scanner. Based
Tong University School of Medicine, 2Department of Radiology, on clinical outcomes, the cohort was categorized into a conservative
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, treatment group (n=36) and a surgical treatment group (n=17).
3
Department of Infectious Diseases, Yuyao People’s Hospital, Comparative analyses were conducted on clinical data, including
4
Department of Nursing, Ruijin Hospital, Shanghai Jiao Tong complete blood counts, coagulation profiles, biochemical markers, and
University School of Medicine CT perfusion parameters between the two groups. Both univariate and
Background: Mortality of patients admitted with acutely multivariate logistic regression analyses were conducted to investigate
decompensated cirrhosis (ADC) ranges from 20% to 63% at 1-year the determinants affecting the severity of intestinal ischemia in cases
outcome. Population-specific model, i.e., the CLIF-C AD score, or of intestinal obstruction and to identify critical risk factors. A predictive
general score for cirrhosis like Child-Pugh and MELD are all limited model was developed to assess the necessity for surgical intervention
in predicting long-term mortality. This study aimed to evaluate the in patients with intestinal obstruction. The predictive efficacy of these
prognostic value of organ-specific imaging features captured by the parameters for severe intestinal ischemia was evaluated using receiver
magnetic resonance imaging (MRI)-derived radiomics of the liver in the operating characteristic (ROC) curves.
prediction of 1-year mortality in patients with ADC. Result: The surgical treatment group had significantly lower peak
Method: The current study was an imaging investigation of the RJH aortic and splenic values, portal vein perfusion, but higher hepatic
(Ruijin Hospital) cohort of adult patients with cirrhosis non-electively artery perfusion and index, blood volume, and blood flow density
admitted for ADC between 2016 and 2021 (RJH-radiomics). Patients compared to the conservative group (P<0.05). Univariate logistic
underwent contrast-enhanced upper abdominal MRI (Philips) during regression indicated that these parameters, along with cystatin C,
the index admission were included for analysis. In addition to baseline total cholesterol, and cholinesterase, could predict severe intestinal
clinical and lab data, sequences from T1, T2, diffusion weighted outcomes.An imaging prediction model using peak splenic values,
imaging, and portal phases were collected for features extraction. HPI, and BFD showed an AUC of 0.834 for severe intestinal ischemia,
Patients were randomly divided in a ratio of 8:2 to train and test a with 94.1% sensitivity, 61.1% specificity, and a cut-off of -1.060. Adding
machine-learning MRI radiomics model (AD-MRI) for predicting 1-year total cholesterol improved the AUC to 0.913, with 88.2% sensitivity,
mortality (Figure 1). Prognostic performance evaluated by the area 86.1% specificity, and a cut-off of -0.285, demonstrating good
under the receiver operating characteristic curves (AUC) of the AD- discrimination and clinical utility.
MRI model was subsequently compared to the CLIF-C AD, Child-Pugh Conclusion: Whole-liver CT perfusion parameters (peak splenic
and MELD score. values, HPI, BFD) and total cholesterol are effective predictors of
Result: A total of 80 patients were included for this analysis (mean age severe intestinal ischemia in patients with intestinal obstruction. Both
55.4±11.9, 67% male, median CLIF-C AD 45.90 [39.93, 51.09], median the three-factor imaging model and the four-factor model including total
Child-Pugh 9.00 [8.00, 10.00], median MELD 15.46 [10.90, 19.71]). cholesterol show strong predictive accuracy, aiding early identification
By 1-year follow-up, 20 patients died without liver transplant, and the of patients likely to need surgical intervention.
remaining 60 survived or transplanted. AD-MRI score was developed Table and Figure:Figure 1.Figure1: The whole liver CT perfusion
based on the 10 MRI features from liver in 64 ADC patients (Figure 2) images of patients undergoing surgical treatment (below) and those
undergoing conservative treatment (above). The surgical treatment A Novel Mitochondrial Micropeptide HRMM1 Interacts with ATP5B
group exhibited prolonged MTTD, increased BVD, BFD, ALP, and HPI, to Promote Energy Metabolism and Hepatocellular Carcinoma
and decreased PVP compared to the conservative treatment group, Progression
with no significant differences observed in TMAXD and MIP. Wenli Xu1, Lijuan Liao, Zhi Tan, Tingfeng Xu, Pengzhan Deng, Qiuli
Figure 2.Figure 2 : Illustrates the receiver operating characteristic Xie, Songqing He
(ROC) curves for CT imaging models predicting severe intestinal 1
Division of Hepatobiliary Surgery, the First Affiliated Hospital of
ischemia requiring surgical intervention (left). The areas under the Guangxi Medical University
curves (AUCs) for the peak spleen, HPI, BFD, and composite models
Background: Emerging evidence has shown that the small open
were 0.704, 0.779, 0.723, and 0.834, respectively (Left side) , the
reading frames (smORFs) inside long non-coding RNAs (lncRNAs)
curves for the composite model are presented, with AUC values for
could encode functional micropeptides. However, their roles in cellular
total cholesterol, imaging models, and composite models at 0.704,
energy metabolism and hepatocellular carcinoma (HCC) progression
0.834, and 0.913, respectively (Right side).
remain largely unknown. Therefore, the search for functional
micropeptides that target energy metabolism may provide a potential
OP0388 biological target for HCC therapy.
The Role of Cell-Intrinsic Matrisome-Related Molecules in Human Method: We combined ribosome profiles, RNA-seq and mass
Hepatocyte Fate Maintenance spectrometry methods to explore the translational potentials of
Yuji Ishida1,2, Go Sugahara1,2, Masashi Okawa1,2, Chihiro Yamasaki2, lncRNAs in HCC tissues, and confirmed the function of selected
Meng Li3, Karl Hillebrandt4, Hyungjin Eoh1, Chise Tateno2, Takeshi lncRNA-encoded peptides in HCC cell lines.
Saito1 Result: Here, we identified a 94-amino acid micropeptide encoded
by lncRNA-X in HCC. Subsequently, we also characterized its
1
Keck School of Medicine, University of Southern California,
2
PhoenixBio, Co., Ltd, 3University of Southern California, 4Berlin conservation across humans and mice, localization to mitochondria
University of Medicine and the synergistic functions in HCC. This micropeptide was highly
expressed in p53-mutated HCC tissues and cells, which could be
Background: Extracellular matrix (ECM) plays a crucial role in activated by HNF4A, high expression of this micropeptide predicted
shaping an organ-specific microenvironment that determines fate of poor prognosis of HCC patients, and enhanced the ATP synthase
tissue resident cells. In the liver, hepatic stellate cells and periportal activity via interacting with the ATP5B and thereby promoted HCC cell
fibroblasts have long been considered the primary ECM producers. proliferation as well as the production of reactive oxygen species (ROS).
However, the contribution of hepatocyte-derived matrisome-related Hence, this micropeptide was termed HNF4A-regulated micropeptide
molecules remains poorly understood. Our prior study, utilizing a for energy metabolism 1 (HRMM1). Furthermore, knocking out HRMM
refined in vitro culture approach, demonstrated that primary human in HCC cells, we found that HRMM, but not its lncRNA, could suppress
hepatocytes (HH) undergo dynamic morphological changes leading cell proliferation and mitochondrial ATP production.
to the restoration of their bona fide architectural structure. These Conclusion: Taken together, this study reveals that the putative
processes culminate in the reinstatement of proper cellular polarity lncRNA encodes a new functional peptide in HCC cells and provides
and the restoration of hepatocyte marker gene expression and hepatic a novel potential biomarker and target for the diagnosis and treatment
functions. Additionally, we observed abundant production of ECM- of HCC.
related molecules by HH during the fate restoration process. This Table and Figure:Figure 1.The proposed model for the transcriptional
study, therefore, aims to elucidate the role of hepatocyte-intrinsic regulation and function of HRMM1
matrisome factors in determining HH cell fate.
Method: The culture medium used during HH fate restoration
processes, containing HH-derived matrisome-related molecules, was OP0390
pooled as conditioned medium (CM). A comparative assessment Qiling Xiaoji Formula enhances the immunotherapy of anti-
of the CM and its base medium (BM) was conducted to define the PD-L1 antibody through the modulation of gut microbiota in
contribution of matrisome-related factors in supporting HH fate hepatocellular carcinoma
maintenance through transcriptome analysis to identify responsible Wenlan Zheng1, Shihan Yu1, Jia Shi1, Xuemei Zhang1, Wurong Du1,
pathways, and loss of function approaches for the functional Liming Zheng1, Hao Liu1, Hai Feng1, Zhuo Yu1, Yueqiu Gao1
validation. In addition, immunofluorescence and electron microscopy 1
Shuguang Hospital Affiliated to Shanghai University of Traditional
were employed to evaluate the microenvironmental niche established Chinese Medicine
by matrisome-related molecules contained in the CM. Furthermore,
Background: The traditional Chinese formula Qiling Xiaoji Formula
the human relevance of HH-intrinsic matrisome-related molecules was
(QLXJ) has exerted clinical efficacy in treating hepatocellular
assessed by identifying their presence in decellularized human liver
carcinoma (HCC). Anti-PD-L1 (α-PD-L1) therapy, while promising,
tissue. Lastly, the significance of the CM in HH fate maintenance was
faces challenges such as low response rates, resistance, and
evaluated by examining its capacity in establishing humanized liver
adverse effects, limiting its broader clinical application. Notably, oral
chimeric mice (HLCM).
administration of traditional Chinese medicine has been shown to
Result: Transcriptome analysis and loss-of-function studies indicate
modulate the gut microbiota. However, the potential role of QLXJ in
that HH cultured with the CM remain terminally differentiated, in part
enhancing the efficacy of α-PD-L1 therapy against HCC through gut
by repressing TGFβ-YAP/TAZ pathway activation. In contrast, these
microbiota modulation remains to be elucidated.
pathways are upregulated in HH cultured with the BM, leading to
Method: Tumor growths were detected in Hepa1-6 orthotopic
dedifferentiation into hepatic progenitor-like cells. Microscopic analyses
or diethylnitrosamine (DEN) plus carbon tetrachloride (CCL4)-
revealed that matrisome-related molecules in the CM, such as fibrin,
induced HCC mouse models treated with ctrl, QLXJ, α-PD-L1 and
fibronectin, and vitronectin, assemble into macromolecular complexes
combination of both, and the sort and population of immune cells
that form a bioscaffold critical for maintaining HH morphology. HH-
infiltrated in liver tumor samples were assessed by flowcytometry. Gut
derived ECM molecules were also abundantly present in decellularized
microbiota analysis and metabolomics were performed using fecal
healthy human liver tissues. Additionally, HH cultured with the CM
samples to identify bacterial and metabolic components associated
showed efficient proliferation in the livers of HLCM host mice, whereas
with QLXJ treatment compared to ctrl. Gut microbiota depletion by
HH cultured with the BM failed to establish HLCM.
antibiotics was employed in QLXJ-treated HCC mouse models, and
Conclusion: Our work defines the fundamental role of hepatocyte-
replenished gut microbiota using QLXJ-treated fecal transplantation
derived matrisome-related molecules in establishing the
was conducted in antibiotics-treated HCC mouse models. Identified
microenvironmental niche that supports the cell fate of HH.
metabolic components were used to treat HCC mouse models, and
the constitutive alteration of infiltrated immune cells in liver tumor
OP0389 samples were examined.
Result: In this study, we demonstrated that the combination of QLXJ injury. After exposure to the hepatotoxic drug chlorpromazine for 24
and α-PD-L1 suppressed HCC development more efficiently than hours, Calcein-AM/PI double staining and JC-1 staining revealed that
either monotherapy, with the significantly increased infiltration of the GNP-FDOs cultured for 7 days maintained high cell viability and
stimulatory immune cells such as effector CD8+ T cells, suggesting the preserved the stability of biliary trees. The expression of apoptosis-
capacity of QLXJ to enhance the efficacy of α-PD-L1 therapy in HCC and inflammation-related genes in GNP-FDOs were significantly
mouse models. Depletion of gut microbiota by antibiotics abolished suppressed in response to chlorpromazine exposure.
the effect of QLXJ on stimulating anti-tumor immune response, while Conclusion: Such GNP-FDOs with the specific functions of bile
replenishment of QLXJ-treated microbiota-containing feces rescued the secretion and drug metabolism exhibit high resistance to injury,
tumor suppressive effect, indicating QLXJ induced anti-HCC immunity providing promising potential for future clinical therapeutic applications
through the modulation of gut microbiota. Gut microbiota analysis in biliary diseases.
revealed the enrichment of probiotics Lachnospiraceae_NK4A136_ Table and Figure:Figure 1.Generation and Transcriptomic
group in QLXJ-treated group compared to ctrl, in parallel with the Characterization of Injury-Resistant Functional Ductal Organoids
increase of indole-3-pyruvic acid (IPyA) identified by metabolomics,
which has been reported to be produced by Lachnospiraceae through OP0392
tryptophan metabolism. Administration of IPyA could efficiently
suppress tumor growth in both HCC mouse models, with the increase The role and pathogenesis of hydrogen sulfide in angiogenesis of
of effector CD8+ T cells, suggesting QLXJ stimulated anti-HCC HCC vascularized organoid
immune response by upregulating Lachnospiraceae-produced IPyA. Lingna Lyu1, Shanshan Wang1, Huiguo DING2
Conclusion: QLXJ modulated gut microbiota by promoting the 1
Beijing You‘an Hospital, Capital Medical University, 2Beijing Youan
proliferation of Lachnospiraceae, which subsequently increased the Hospital,Capital Medical University
production of IPyA, leading to the stimulation of anti-HCC immune Background: Hepatocellular carcinoma (HCC) is the third leading
response. These findings provide valuable sights into promising cause of cancer-related mortality worldwide, and the associated
strategies to enhance α-PD-L1 therapy in HCC. mortality rates continue to rise annually. As a highly vascularised
Table and Figure:Figure 1.Qiling Xiaoji Formula enhances the malignant tumour, its angiogenesis represents a critical core issues
immunotherapy of anti-PD-L1 antibody through the modulation of gut in liver cancer progression as well as treatment failure. However, the
microbiota in hepatocellular carcinoma molecular mechanisms of angiogenesis in HCC remain incompletely
elucidated.
OP0391 Method: In this study, we established a HCC vascularized organoid
and treated it with H2S donor to examine HCC angiogenesis. Then
Generation and Transcriptomic Characterization of Injury-
human umbilical vein endothelial cell (HUVEC) were used to analyze
Resistant Functional Ductal Organoids Optimized by Genipin
the regulation of NaHS on the tube formation, cell migration and cell
Shiwen Ma1, Jiaxian Chen1, Meiqian Hu1, Jiaojiao Xin1, Jing Jiang1, proliferation. Finally, RNA sequencing and bioinformatics analysis
Dongyan Shi1, Jun Li1 of NaHS treated HUVEC were performed and western blotting and
1
State Key Laboratory for Diagnosis and Treatment of Infectious rescue assay were applied to confirm the expression and effection of
Diseases, National Clinical Research Center for Infectious Diseases, PI3K/Akt signaling pathway in the HUVEC cells under NaHS treatment.
National Medical Center for Infectious Diseases, The First Affiliated Result: We observed the loose vascular structure and reduced
Hospital, Zhejiang University School of Medicine angiogenesis in HCC vascularized organoid after H2S donor
Background: Cholangiocytes may suffer from oxidative stress injury treatment. Further, the tube formation ability, cell motility and viability
and mitochondrial dysfunction during the construction of functional of HUVEC were suppressed by NaHS. Decreased transcription
ductal organoids (FDOs) for liver regenerative medicine, which limits levels of angiogenesis-related factors and significant difference of
the functional performance and application potential of the organoids. cellular ultra-structure was observed. A total of 337 mRNA transcripts
We aimed to construct injury-resistant FDOs with biliary tree networks. were differentially expressed in the HUVEC exposed to NaHS,
Method: We used genipin, a crosslinking agent with anti-inflammatory among which plenty of angiogenesis-related genes were identified
and antioxidant properties, to optimize rat decellularized liver scaffolds and enriched in PI3K/Akt signaling pathway. The p-PI3K and p-Akt were
(DLSs) and reconstructed FDOs with primary cholangiocytes isolated significantly inhibited by NaHS in HUVEC, which could be reversed by
from mouse bile ducts. The genipin-crosslinked FDOs (GNP-FDOs) Y-P 740, a specific antagonist of PI3K. This antagonist also recovered
were characterized through functional assays and transcriptomics. NaHS-inhibited tube formation, cell motility and viability of HUVEC.
Hepatotoxic drug chlorpromazine was used to assess the injury- Conclusion: Conclusively, these results suggest that the exogenous
resistance ability of GNP-FDOs. H2S may inhibit HCC angiogenesis through regulating PI3K/Akt
Result: We observed that genipin-crosslinked DLSs exhibited improved signaling pathway, which serves as a potential treatment target of
resistance to degradation, showing a degradation rate of about 60% HCC. However, validation in animal models of liver cancer is still
after 120 hours of treatment with collagenase, while non-crosslinked necessary.
DLSs were completely degraded. Calcein-AM/PI double staining Table and Figure:Figure 1.graphic abstract
revealed that GNP-FDOs formed a continuous and multibranch biliary
tree network at 7 days. JC-1 staining showed that cholangiocytes in
OP0393
GNP-FDOs had stable mitochondrial potential at day 7 compared
with non-crosslinked FDOs. The primary cilia in biliary lumen of GNP- OTUD5 suppresses interferon antiviral efficacy by targeting STAT1
FDOs was observed at day 7 with scanning electron microscopy for K27-linked ubiquitination
and immunostaining for acetylated α-tubulin. The rhodamine 123 JIN LIU1, Lincong Jin, Feng Qian, Chuanwu Zhu, Ming Li, Li Zhu, Hui
transport assay exhibited the mature functions of bile secretion and Zheng
transportation in GNP-FDOs by day 7. Transcriptomic analysis of 1
Department of Infectious Diseases, The Affiliated Infectious Diseases
GNP-FDOs cultured for 1, 7, and 14 days revealed that anti-apoptotic Hospital of Soochow University; The Fifth People‘s Hospital of
genes were significantly upregulated, while apoptosis-related genes Suzhou, Suzhou, Jiangsu, China.,
were downregulated at days 7 and 14. Enrichment analysis of 1,014 Background: Interferons (IFNs) have broad-spectrum antiviral activity
differentially expressed genes between days 1 and 7 demonstrated to resist virus infection. This study identified a new regulator involved
that GNP-FDOs exhibited enrichment in gene sets related to primary in the antiviral signal of IFN-I and provide a potential drug target for
cilia at 7 days. Pathways related to bile synthesis and secretion, drug clinical improvement of antiviral efficacy of interferon.
metabolism, lipid metabolism, and retinol metabolism were significantly Method: (1) After IFNα stimulation, STAT1 was immunoprecipitated
activated at day 7 and remained activated at day 14. The GNP-FDOs and the changes of K27-linked ubiquitination of STAT1 were detected
upregulated Muc5ac and Lcn2 expression by the IL-17 signaling by Western Blot. The deubiquitinase overexpression library was
pathway, exerting antibacterial effects and protecting cells from
used by to screen the deubiquitinases targeting STATI K27-linked line drugs treatment (P<0.05), lower rate of complete biochemical
ubiquitination, The regulation of K27-linked ubiquitination of STATl by remission after 6 months’ therapy (P<0.05) and a higher rate of relapse
OUTD5 was investigated by immunoprecipitation and Western Blot. compared with AIH or PBC groups (P<0.05).
(2) After knockdown of OTUD5, Western Blot was used to investigate Risk factors to efficacy: At initial diagnosis, lower albumin concentration,
the effect of OTUD5 on the levels of key proteins in the IFN signaling higher IgG, and IgM levels, and concomitant cirrhosis were risk factors
pathway. The dual luciferase reporter gene technology and RT-qPCR for poor therapeutic response, among which, higher IgM level was an
were used to investigate the effects of OTUD5 on ISRE activity and independent risk factor.
ISGs mRNA levels. (3) The database and point mutation methods Prognosis: The incidence of liver related adverse events such as
were used to prepare the STAT1 point mutation plasmids. STAT1 was ascites, esophagogastric varices etc. in the AIH-PBC OS group was
immunoprecipitated, and the K27-linked ubiquitination sites on STAT1 higher than that in the AIH or PBC groups (P<0.05). The cumulative
were determined by Western Blot. Immunoprecipitation and Western incidence of liver related adverse events in the AIH-PBC OS group was
blot were used to determine the regulation of Lys138 and Lys240 of also significantly higher than that in the AIH (P=0.025) or PBC group
STAT1 by OTUD5, Immunoprecipitation and Western Blot were used alone (P=0.013).
to further determine the effects of Lys138 and Lys240 of STAT1 on the Conclusion: AIH-PBC OS often requires immunosuppressive therapy
binding of STAT1 to JAK1. (4) OTUD5 was overexpressed or knocked and second-line drugs, but has a worse response to treatment, and
down, Then the ability of OTUD5 to resist VSV, SeV, H1N1 and other is more prone to relapse. Lower albumin concentrations, higher IgG
viruses was analyzed by RT-qPCR or Western Blot. The effects of and IgM levels, and concomitant cirrhosis at initial diagnosis are risk
OTUD5 on IFN-mediated antiviral function were further analyzed. factors for poor treatment response, while higher IgM levels may be an
Result: (1)IFNα stimulation can up-regulate the K27-linked ubiquitination independent one. The progression is faster, and the overall prognosis
levels of STAT1. OTUD5 regulates K27-linked ubiquitination of is usually worse.
STATl through its deubiquitinase activity, lFNα regulates K27-linked
ubiquitination of STATl through OTUD5. (2) OTUD5 can down-regulate
OP0395
the phosphorylation level of STAT1 induced by lFNα. OTUD5 down-
regulates IFNα-induced ISRE activity and ISG-mRNA levels. (3) Lys138 The multi-center study of functional cure for inactive hepatitis B
and Lys240 of STAT1 undergo K27-linked ubiquitination. OTUD5 can surface antigen carriers in China: interim analysis of E-cure study
regulate K27-linked ubiquitination at Lys138 and Lys240 of STAT1. Zhishuo Mo1, Haifang Cao2, Yu Zhang2, Yawen Luo3, Qingfa Ruan4,
Mutations at Lys138 and Lys240 sites inhibit the interaction of STAT1 Jianqi Lian5, Xiulan Xue6, Xiaobo Lu7, Xiangyang Ye8, Rongxian Qiu8,
and JAK1. (4) OTUD5 promotes VSV, SeV and H1N1 infection. OTUD5 Xiaoping Wu9, Xiaorong Mao10, Qihuan Xu11, Zhiliang Gao11
inhibits IFN-mediated antiviral function. 1
Third Affiliated Hospital of Sun Yat-sen University, 2Qinghai Provincial
Conclusion: OTUD5 is a deubiquitinase targeting K27 Fourth People‘s Hospital, 3Affiliated Hospital of Zunyi Medical
polyubiquitinated STAT1. OTUDs down-regulates the levels of IFN- University, 4Xiamen Hospital of Traditional Chinese Medicine, 5The
induced phosphorylation at Tyr701 of STAT1. OTUD5 down-regulates Second Affiliated Hospital of Air Force Medical University, 6the First
IFN-induced expression of downstream ISGs and antiviral function. Affiliated Hospital of Xiamen University, 7The First Affiliated Hospital of
This project could promote people’s understanding of the antiviral Xinjiang Medical University, 8 Affiliated Hospital of Putian University,
mechanisms of IFN, and also could provide potential ideas for
9
The First Affiliated Hospital of Nanchang University, 10The First
improving the antiviral effect of clinical IFN. Hospital of Lanzhou University, 11The Third Affiliated Hospital of Sun
Table and Figure:Figure 1.IFNα induced K27 poly-ubiquitination of Yat-sen University
STAT1 can be regulated by OTUD5 Background: Approximately 30% to 60% of inactive hepatitis B surface
Figure 2.STAT1 undergoes K27 poly-ubiquitination sites at K138 and antigen carriers (IHCs) exhibit significant liver inflammation (G ≥ 2) or
K240; also inhibits IFN-Ⅰ mediated antiviral function fibrosis (F ≥ 2) on liver biopsy, and the risk of hepatocellular carcinoma
among Asian IHCs is ten times higher than in European IHCs,
underscoring the need for therapeutic intervention. This study aimed
OP0394
to investigate the efficacy of different peginterferon alpha (PegIFNα)-
Clinical Features of Patients with Autoimmune Hepatitis-Primary based treatment strategies for IHCs.
Biliary Cholangitis Overlap Syndrome Method: A multi-center real world study (E-cure) started in January
Yulan Zhu1, Linxi Feng2, Huihong Yu2 2022. The study enrolled IHCs consistent with the definition of inactive
1
The Seventh People‘s Hospital of Chongqing, 2the Second Affiliated CHB in the guideline of AASLD 2018. The patients received one of the
Hospital of Chongqing Medical University following treatments: Nucleos(t)ide analogues (NAs) monotherapy,
Background: AIH-PBC OS is still an unresolved problem, with no PegIFNα monotherapy, Initial combination therapy (PegIFNα-2b
optimal diagnostic criteria and treatment. The purpose of this research with NAs for 12-24w followed by PegIFNα-2b monotherapy), Whole
is to analyze and discuss the clinical features of AIH-PBC OS, to process combination therapy (combination of PegIFNα-2b and NAs for
provide more clinical evidence for the diagnosis and treatment. the entire period) and Sequential combination therapy (NAs for 12-24w
Method: Retrospective analysis was performed to compare the followed by PegIFNα-2b add-on).
differences in clinical features of patients diagnosed with PBC, AIH or Result: As of November 4, 2024, 7899 individuals were screened and
AIH-PBC OS in the Second Affiliated Hospital of Chongqing Medical 5328 eligible IHCs were included. Of these, 1622 patients completed
University from January 2012 to December 2023. Logistic regression 24 weeks of treatment and 1038 completed 48 weeks of treatment.
analysis was used to analyze the risk factors of poor response in AIH- The median (IQR) age of all patients was 41.0 (34.0-48.0) years,
PBC OS. The prognosis of patients with PBC, AIH or AIH-PBC OS was 62.1% (3307/5328) were male, and 73.2% (3900/5328) had a baseline
compared by Kaplan-Meier curve and Breslow test. HBsAg < 1000 IU/mL. The HBsAg clearance and seroconversion
Result: Clinical manifestations: The AIH-PBC OS group had higher rates in patients treated with PegIFNα-2b increased as the duration of
baseline ALP, GGT, IgG, IgM levels compared with the AIH group treatment progressed. By week 48, the cumulative HBsAg clearance
(P<0.05), and ALT, AST, total bilirubin, direct bilirubin, TBA, IgG, IgM, rates for the PegIFNα monotherapy, Initial combination therapy,
IgA levels compared with the PBC group (P<0.05), as well as higher Whole process combination therapy and Sequential combination
percentage of cirrhosis at initial diagnosis compared with the others therapy groups reached 53.3%, 34%, 58% and 65.8%, respectively
(P<0.05). In the AIH-PBC OS group, the concentration of AMA-M2, (P < 0.001) (Figure 1), and the cumulative HBsAg seroconversion
positive rates of AMA and Anti SSA were higher than those in the AIH rates reached 36.8%, 17.6%, 30.1% and 53.3%, respectively (P <
group (P<0.05), while comparing to the PBC group, the positive rates 0.001). The cumulative HBsAg clearance rates at 48 weeks for
of ANA and ASMA were higher (P<0.05). the baseline HBsAg <100 IU/ml, 100-1000 IU/ml, and >1000 IU/
Treatment and response: The AIH-PBC OS group had a higher ml groups were 72.56%, 42.62%, and 8.89%, respectively. HBV DNA
proportion of immunosuppressant treatment than the PBC group was undetectable in more than 90% of patients in the above 4 groups
(P<0.05). AIH-PBC OS group had a higher proportion of second- (92.8%, 95.7%, 97.9% and 95%). Further subgroup analysis revealed
that patients with baseline HBV DNA negative had higher cumulative OP0397
HBsAg clearance rates at each follow-up point compared to those Stratifying the risk of Metabolic dysfunction-associated steatotic
with baseline HBV DNA positive, with rates of 59.4% and 49.1% at 48 liver disease in HIV-Infected patients under antiretroviral therapy
weeks, respectively (P = 0.002) (Figure 2). using transient elastography
Conclusion: PegIFNα-2b based therapy proved effective for IHCs
Fei Ji1, Lifan Zhang2, Wei Lyv2, Yang Gui1, Yang Han2, Qing Zhang2,
to pursue functional cure, with a cumulative HBsAg clearance rate
Yanling Li2, Meng Yang1
of 53% and a cumulative HBsAg seroconversion rate of 34.1% at 48
weeks. Patients with baseline HBV DNA negative achieved HBsAg
1
Department of Ultrasonography, State Key Laboratory of Complex
Severe and Rare Diseases, Peking Union Medical College Hospital,
clearance more frequently than those with baseline HBV DNA positive.
Chinese Academy of Medical Sciences and Peking Union Medical
Table and Figure:Figure 1.Figure 1. Cumulative HBsAg clearance rates
College, No.1, Shuaifuyuan, Dongcheng District, Beijing 100730,
at different time points after initiation of PegIFNα in each group
People’s Republic of China, 2Department of Infectious Diseases,
Figure 2.Figure 2. Cumulative HBsAg clearance rates after initiation of
Peking Union Medical College Hospital, Chinese Academy of Medical
PegIFNα in patients with different baseline HBV DNA status Sciences and Peking Union Medical College, Beijing, China
Background: Metabolic dysfunction-associated steatotic liver disease
OP0396 (MASLD) has become an important health problem affecting the
The efficacy of antiviral therapy for HBV-infected children: A large- quality of life of people with HIV (PWH). The aim of this study was to
scale, multicenter prospective study (Sprout Project) - an interim determine the prevalence of MASLD and its risk factors in PWH.
analysis Method: PWH who had received antiretroviral therapy (ART) for at
Hongfei Zhang1, Qing He2, Wenxian Ouyang3, Shuangjie Li3, Yilan least six months and had been in virological suppressed status were
Zeng4, Hong Zhang4, Jia Shang5, Fang Wang2, Lijuan Ouyang6, Yujing prospectively enrolled in the study. According to different treatment
Tang6, Xiaoguai Liu7, Pengfei Xu7, Chuantiao Zhang8 regimen, HIV patients categorized to INSTIs group (continued to
1
Beijing Huatan Integrative Medicine Hospital, Beijing, China, 2The use integrase inhibitor-based regimen), non-INSTIs group (remained
Third People‘s Hospital of Shenzhen, Shenzhen, China, 3Hunan on NNRTIs or a PI-containing regimen), and switch group (changed to
Children‘s Hospital, Changsha, China, 4Public Health Clinical Center INSTIs from non-INSTIs regime). Clinical evaluation, biochemical
of Chengdu, Chengdu, China, 5Henan Provincial People‘s Hospital, tests and vibration-controlled transient elastography for ultrasound
Zhengzhou, China, 6Xiamen Traditional Chinese Medicine Hospital, attenuation parameter (UAP) and liver stiffness measurement (LSM)
Xiamen, China, 7Xi‘an Children‘s Hospital, Xi‘an, China, 8Shishi General were undergone.
Hospital, Shishi, China Result: Of the 188 patients, the median age was 40 (34,
Background: Nearly two million children in China are HBsAg-positive 48) years, and 4.8% were female. 98 patients had MASLD, among
but data on antiviral treatment for them are limited. We aimed to which 42 cases (42.9%), 37 cases (37.8%) and 19 cases (19.4%)
investigate the efficacy and safety of different antiviral strategies for were mild, moderate and severe, respectively. 24(12.8%) patients
HBV-infected children, and explore the factors associated with HBsAg developed liver fibrosis and 20 (10.6%) PWH with MASLD had
loss. liver fibrosis. High BMI(adjusted OR [aOR], 2.74; 95% confidence
Method: This is a prospective, multicenter real-world study in China, interval [CI], 1.95-3.85) and high ALT (adjusted OR [aOR], 1.06; 95%
three types of HBV-infected children were enrolled, including treatment- confidence interval [CI], 1.02-1.09) were associated with increased
naïve, NA-experienced and normal ALT level population. All patients risk of MASLD. 42.0% of HIV patients were in INSTIs group, 39.4%
were 3-18 years old, HBsAg positive, and received NA monotherapy or in non-INSTIs and 18.6% in switch group. There was no significant
in combination with peginterferon α-2b for 96 weeks according to the difference in BMI, metabolic parameters, UAP and LSM among three
willing of their own or guardian (NCT05792761). groups at 48 weeks.
Result: A total of 297 children who completed 48 weeks of treatment Conclusion: MASLD occurs in about half of virologically suppressed
and had efficacy data were included in this analysis (NA monotherapy HIV-infected patients, and one-fifth of PWH are complicated by
group, n=6; combination therapy group, n=291). The average age liver fibrosis. BMI and ALT during antiviral therapy can indicate
was 7.9 ± 3.77 years, 57.9% were male, 86.8% were HBeAg positive the occurrence of MASLD. Quantitative ultrasound imaging can
and 85.4% were HBV DNA positive. The mean baseline HBsAg, HBV detect the development of MASLD early, even if the lipid profile
DNA and HBeAg were 3.59, 5.85 log10 IU/mL and 2.56 log10 COI, remains normal. Besides, INSTIs seem to exert little influence on the
respectively. 63.6% of patients were treatment-naïve chronic hepatitis development of hepatic steatosis in HIV patients.
B. In the total population and treatment-naïve patients, the HBsAg loss Table and Figure:Figure 1.Multivariable analysis of factors associated
rates at week 48 were 24.7% (72/291) and 26.6% (49/184) and HBeAg with MASLD
loss rates were 19.8% (50/252) and 18.3% (31/169) in the combination Figure 2.Effects of receiving integrase strand transfer inhibitors (INSTIs
therapy group, whereas no patients in the NA monotherapy group group) versus remaining on unchanged NNRTIs or a PI-containing
achieved any of above responses (Figure 1A). Significant HBsAg regimen (non-INSTIs group) and switch to INSTIs from Non-INSTIs
declines were noted in the combination therapy group as the duration regime (switch group) on (a) ultrasound attenuation parameter (UAP),
of treatment progressed, reaching 2.10 and 2.29 log10 IU/mL at week (b) liver stiffness, (c) high density lipoprotein (HDL), (d) low density
48 in the total and treatment-naïve populations, respectively, and lipoprotein (LDL), (e) total cholesterol (TC), and (f) triglycerides (TG).
elevated ALT levels were observed during HBsAg decline. Subgroup
analysis of the combination therapy group showed that higher HBsAg OP0398
loss rates existed in younger children. The HBsAg loss rates at week Alarming rise in Spontaneous Fungal Peritonitis in Cirrhosis:
48 were 30.6% and 19.7% (P = 0.032) for children aged ≥ 3 to < 7 Study of Epidemiology, Clinical Features, Risk Factors and
and ≥ 7 to ≤ 18 years, respectively, in the total population, and 33.7% Development of a Predictive Model for early diagnosis
and 19.6% (P = 0.030), respectively, in the treatment-naïve population
Pratibha Kale1, S M Shasthry2, Vikas Khillan1, Gayatri Ramakrishna3,
(Figure 1B). Both therapies were well-tolerated throughout the study.
Shiv K SARIN2
Conclusion: HBV-infected children can achieve significant higher
HBsAg loss and HBeAg loss rate in peginterferon α-2b combination
1
Department of Clinical Microbiology, Institute of liver and biliary
sciences, 2Department of Hepatology, Institute of liver and biliary
group, especially for those aged < 7 years. Peginterferon α-based
sciences, 3Department of Molecular and Cellular Medicine, Institute of
strategies used at an early age in pediatric patients can better pursue
liver and biliary sciences
functional cure.
Table and Figure:Figure 1.Figure 1. A. Different response rates at week Background: Spontaneous bacterial (SBP) and spontaneous fungal
48. B. HBsAg loss rates over time in children aged ≥3 - <7 and ≥7 - ≤18 peritonitis (SFP) can be a life-threatening infection in patients with
years in the combination therapy group. liver cirrhosis (LC). SFP is underdiagnosed as it lacks typical signs
and symptoms or clinical features. The early differential diagnosis
between SFP and SBP is difficult. The delayed management of SFP domain features included some statistical parameters such as kurtosis,
worsens the prognosis of patients with LC. The aims of this study were coefficient of variation. Envelope statistics features included model
to determine the epidemiology, clinical characteristics, prognosis, and parameters from Nakagami, Weibull, Gamma and K-distribution. The
risk factors of cirrhotic patients with SFP and to develop a predictive power spectrum was used to extract parameters related to acoustic
model to improve early differential diagnosis with SBP. attenuation. With these parameters, the random forest was used to
Method: This was a retrospective study of 11645 patients of cirrhosis perform feature selection and further classification.
with suspected spontaneous peritonitis. We conducted a case–control Result: We used the patienrs’ HVL state as the ground
study of 100 cases of SFP with fungus-positive ascitic culture. 100 SBP truth, and the binary classification results from the classification
cirrhotic patients with bacteria-positive ascitic culture were enrolled as model as the predictive value. The classification performance of
control group. The clinical and laboratory parameters were obtained the proposed method is evaluated by the following metrics, with an
from the hospital records. accuracy of 86.24%, a precision of 83.74%, a sensitivity of 72.56%, a
Result: Although the incidence of SBP was much higher than that of F1-score of 76.59%, a specificity of 92.83%, and an AUC of 90.42%.
SFP (36% vs. 16%), SFP patients exhibited significantly higher 30- Conclusion: The precision of 83.74% and the sensitivity of 72.56%
day, 90-day, and 180-day mortality rates 65.35%, 74%, and 78% vs. indicate that the model minimizes misclassification of VR samples
19.57%, 26.35%, and 40.78%, respectively. Candida albicans was the as VS. However, about one-quarter of VS samples are misclassified,
most common species isolated (54%) followed by C. tropicalis (32%), indicating that the samples classified by our model exhibit some
C. auris (11%), Cryptococcus (5%). 23% of the isolates were resistant false negatives. Overall, the classification performance of our model
to fluconazole. Prolonged hospitalization, prior antibiotic exposure is satisfactory, indicating that our method has the potential to reduce
of more than 7 days, prior antifungal therapy, hospital-acquired the risk of pathogeninfection for clinicians, offering significant clinical
infection (HAI), presence of drains, diabetes, acute kidney injury relevance.
(AKI) and multiorgan failure were significant risk factors. Sepsis, ICU Table and Figure:Figure 1.Pipeline of our proposed model
admission, multiorgan failure, HCC and prolonged hospitalization were
independent predictors of high 30-day mortality in SFP patients. We
developed a predictive nomogram model that included fever,
(1,3)-β-D-glucan, AKI, diabetes and HAI markers for early differential
diagnosis of SFP from SBP, with a reliable diagnostic performance,
AUC of 0.94 (95% CI: 0.882–0.981).
Conclusion: SFP is an emerging concern in LC associated with high
mortality. There is high incidence of non-albicans Candida species
and rise in antifungal resistance. The predictive model is a useful tool
for early identification of SFP from SBP patients. For patients with
suspected SFP, early diagnosis and timely antifungal therapy should
be administered.

OP0399
Non-invasive HIV Viral Load Prediction Based on Quantitative
Ultrasound of Liver
Yuzhan Huang1, Fei Ji2, Xingyue Wei1, Hengrong Lan1, Qiong He1,
Wei Lyu3, Meng Yang2, Jianwen Luo1
1
School of Biomedical Engineering, Tsinghua University, 2Department
of Ultrasonography, State Key Laboratory of Complex Severe and
Rare Diseases, Peking Union Medical College Hospital, Chinese
Academy of Medical Sciences and Peking Union Medical College,
3
Department of Infectious Diseases, Peking Union Medical College
Hospital, Chinese Academy of Medical Sciences and Peking Union
Medical College
Background: Human immune-deficient virus (HIV) remains a major
public health problem facing humanity and affects lots of people
worldwide. Since the advent of highly active antiretroviral therapy, the
survival rate of acquired immune deficiency syndrome (AIDS) patients
has improved, and AIDS prognosis has received more attention.
HIV viral load (HVL) is a key determinant in the assessment of AIDS
prognosis, but traditional assessment methods are invasive, and
related operators have a high risk of iatrogenic infection. Based on the
correlation between the levels of HVL and the degree of liver injury,
this study proposes to use quantitative ultrasound (QUS) to determine
the degree of liver injury and predict the HVL levels non-invasively.
Method: We aimed to extract effective features reflecting liver
microstructure to assess the HVL. We collected ultrasound radio-
frequency (RF) data of the liver from 116 AIDS patients, all of whom
received anti-HIV therapy. They were categorized into two classes based
on 20 copies/mL HVL. The “Viral Suppression (VS)” indicates that HVL
values are less than the threshold, while the “Viral Replication (VR)”
is opposite. The proportion of “VS” and “VR” is 95:21. The original
RF data of the liver were obtained from transient elastography
(TE) examination with an iLivTouch ultrasound imaging system (Wuxi
Hisky Medical Technologies, Wuxi, China). Time gain compensation
recovery was applied to the RF data. Hilbert transformation was used
to obtain the envelope data. Then we extracted 56 features from time
domain, envelope statistics and power spectral, respectively. Time-
POSTER PRESENTATIONS
27 March | WEDNESDAY
 PP0001 Measles-like bacteria (65), Adjacent granular streptococcus (65),
Mass vaccination with community participation as a successful and Minuscule microsporidia (59). On May 10, 2022, the patient was
strategy for Hepatitis B virus Prevention in Kerala, S India admitted to our hospital due to “intermittent fever and abdominal
pain with bloating for more than a year, exacerbated over the past
Shenoy Trivikrama Kotacherry1,2, Leena K B3
four days.” Laboratory tests showed: WBC 18 × 10^9/L , L% 43% ,
1
Sree Gokulam Medical College and Research Foundation ,Dept. N% 92.6% ,CRP 141.28 mg/L ; PCT 0.176 ng/ml ; ESR84 mm/hr.The
of Gastroenterology , 2Executive Director Population Health and
patient was treated symptomatically with piperacillin-tazobactam and
Research Institute Trivandrum, 3Senior Research Scientist Population
ornidazole for infection control.Gastrointestinal Endoscopy Improved:
Health and Research Institute Trivandrum
Multiple protuberant lesions in the duodenum, chronic non-atrophic
Background: Kerala, a state in South India is a prime mover for gastritis, multiple ulcers at the terminal ileum; via anal small intestine
successful implementation of any health promotive and preventive endoscope: multiple ulcers in the ileum.Pathological results report:
activity and has attracted global attention. We, as a Nongovernmental (mid and terminal ileum) severe active chronic enteritis, ulcer formation.
organisation imitated participatory activity for HBV vaccination among After treatment, the patient continued to experience recurrent fever and
children and adolescents and report the success as well as barriers abdominal pain. Considering the patient’s gene sequencing results
in this program from an external hospital, non-tuberculous Mycobacterium infection
Method: Between 1997 July to December 1998, we trained community could not be ruled out. Therefore, on May 20, 2022, a diagnostic
health care workers on HBV disease, transmission and health four-drug antibiotic therapy was initiated: Tigecycline (50mg Q12h),
consequences. These workers initiated participation of the local Clarithromycin (0.5g Q12h), Amikacin (0.75g Qd), and Cefoxitin (2g
population. Using a camp based approach, 65 camps were organised Q4h). On May 24, 2022, the patient’s body temperature returned to
and each such camp catered to approx... 1000 to 2000 subjects. normal and the gastrointestinal endoscopy showed good healing of
Children from age 1 year and adults till 30 years to 19 years were invited intestinal multiple ulcers.
and demographic and social factors of each family was recorded and
consent for vaccination was obtained. Three doses of genetically
engineered HBV vaccine was injected into deltoid/ thigh. Blood PP0003
samples were collected from 400 subjects using a random selection Serum Levels of Oxidative Stress Markers in Patients with Hepatic
process after 6 months of 3rd dose for anti HBs titre estimation at a Steatosis
central reference laboratory in Mumbai. Data were coded and entered Saira Baloch1, Mohsin Shafi2
into data base and analysed for compliance and vaccine efficacy. 1
1Assistant Professor, Bilawal Medical Collage, Liaquat University of
Result: Sample size: 100000 subjects. 80 percent were children 1 to Medical & Health Sciences, Jamshoro, Sindh, Pakistan, 22Assistant
19 years and rest were adults. 94% had received all three doses and Professor (Institute of Health Management & Research Sciences,
6% received one or two doses. Anti HBs titre was > 1000 IU in 95 % Liaquat University of Medical & Health Sciences, Jamshoro, Sindh,
and rest ranged from 300 to 1000 IU/ml. Minor side effects such as Pakistan
pain and redness at injection site was noted in < 15. Major hindrances Background: Background: Previous research suggests that oxidative
encountered during this campaign was negative publicity on vaccine stress may contribute to the development of nonalcoholic fatty liver
efficacy and multinational involvement for profit making and this disease (NAFLD), particularly in the progression from simple fatty liver
did have some impact on the program. Health authorities and local to steatohepatitis.
administration including the collectors and police personnel had a Method: Aim: This study investigates whether circulating oxidative
positive attitude and supported the initiative stress markers are clinically linked to liver steatosis.
Conclusion: Successful mass vaccination campaign with community Materials and methods: Data were collected from a subgroup of 70
participation in Kerala, South India can be replicated in other states of participants with liver steatosis, recruited as part of the nutritional trial.
India .States like Tamil Nadu, Rajasthan have followed our footsteps. Serum oxidative stress markers were measured using ELISA assays.
Table and Figure:Figure 1.Vaccination campaign Liver steatosis was diagnosed and graded based on laboratory tests
and ultrasound results. Statistical analyses included the Kruskal-Wallis
PP0002 test for variance, along with Mann-Whitney tests where applicable.
Categorical variables were analyzed using the χ² test.
A case of peptic ulcer caused by Mycobacterium abscessus
Result: Results: Patients with moderate to severe steatosis had
Zhang Pan1, Liu Yuqin2
significantly elevated serum levels of oxidative stress markers
1
The Third Xiangya Hospital of Central South University, 2Public Health compared to those without steatosis.
Clinical Center of Chengdu Conclusion: Conclusions: Elevated serum oxidative stress markers
Mycobacterium abscessus is widely distributed in natural environments may serve as an indicator of moderate to severe liver steatosis.
such as soil and water and is considered an opportunistic pathogen. Keywords: Oxidative stress markers; Hepatic steatosis
It typically causes infections after trauma, surgery, or cosmetic
injections. In humans, it primarily affects the lungs, followed by
PP0004
the skin, soft tissues, and other areas. Although Mycobacterium
abscessus can colonize gastric epithelial cells, reports of it causing Diagnostic Role of Neutrophil–Lymphocyte Ratio as Marker of
gastrointestinal diseases are relatively rare. This article reports a case Severity in Patients with Acute Cholangitis
of a Mycobacterium abscessus-induced peptic ulcer, highlighting the Uzziel Romar Samoro Alonzo1
issues encountered and lessons learned during the diagnosis and 1
East Avenue Medical Center
treatment process. Background: In a setting where resources are limited, identifying
A 58-year-old female patient presented to the Xiangya Third patients who have severe cholangitis in a fast and economic manner
Hospital of Central South University on September 21, 2022, with a is of advantage. Patients with severe cholangitis is a priority to abrupt
complaint of ‘intermittent fever, abdominal pain, and bloating for biliary drainage, due to its high mortality. We investigated then the
over a year, with a recent exacerbation lasting 5 days’. The patient diagnostic value of neutrophil-lymphocyte ratio (NLR) in identifying
has a history of ‘diabetes’ for over 5 years.Several gastrointestinal patients with non-severe and severe cholangitis. Cut-off level of NLR
endoscopies revealed multiple gastric ulcers, terminal ileal ulcers, which will differentiate the two groups was also determined.
and chronic colitis. In December 2021, tissue was collected during Method: We retrospectively evaluated 108 patients from January
gastroscopy for genetic sequencing, which suggested a suspected 2021 to December 2023 using simple random sampling. Inclusion
positive result, identifying Human Herpesvirus Type 7 (sequence criteria: 1). Patients with Charcot’s Triad, 2). Elevated Bilirubin and
number 5). The microbial list included: Abscess-branching bacillus Alkaline Phosphatase, 3). Presence of ectasia in an imaging. Exclusion
(4), Pneumococcal streptococcus (155), Timonella actinomycetes criteria: 1) Less than 18 years old, 2) Had concurrent inflammatory
(259), Mild streptococcus (220), Oral digestive streptococcus (141),
diseases such as acute pancreatitis, liver abscess, pneumonia, or 0.76-fold, and 1.64-fold higher risk of developing gallstone disease,
acute cholecystitis. Using the formula to estimate the difference of respectively, compared to those in the lowest level group. Additionally,
2 proportions, a minimum of 40 samples per group (non-severe and the diagnostic performance of various lipid-related obesity indicators
severe) were collected. Descriptive statistical analyses were used is ranked as follows: LAP (AUC = 0.636), VAI (AUC = 0.605), and CMI
for the demographic profile of respondents using SPSS version (AUC = 0.597).
23.0. Pearson r Moment of Correlation was used to determine the Conclusion: This study identified a positive association between lipid-
relationship of NLR values and Severity of Cholangitis thru Tokyo related obesity indicators and gallstone disease, showing that LAP
Grading 2018. Receiver Operating Characteristic curve was used to serves as the most reliable predictor of gallstone disease due to its
determine the specificity and sensitivity of NLR in determining Severe simplicity, effectiveness, and cost-efficiency.
Acute Cholangitis. Area Under Curve (AUC) was used to quantify the Table and Figure:Figure 1.RCS plot of the association between CMI,
overall ability of the test to discriminate the severity of the disease. VAI, LAP and NAFLD
Result: The mean NLR of patients classified as non-severe was 8.27 ± Figure 2.ROC curves for different lipid-related parameters to predict
10.23. While the mean NLR of patients categorized as severe was 29.08 NAFLD
± 20.00. A significant relationship (0.004) of NLR values and Tokyo
Severity Grading 2018 of Acute Cholangitis was noted at significance
PP0006
level of 0.01. NLR is a good model of predicting cholangitis given
an AUC of 0.781. Using the cutoff value of 13.7 the sensitivity and Patient Acceptance and Willingness to Pay on Holistic Healthcare
specificity in predicting severe cholangitis using NLR level were 47.5% Management Service Based on Digital Platform: a Quantitative
and 82.4%, respectively. Survey
Conclusion: NLR has an ability to detect severe cases of Cholangitis, Zhuping Qian1, Pingmei Jiang1, Shuhua Zhang1, Jun Ruan1, Lin
comparable to Tokyo Severity Grading of Acute Cholangitis 2018. Wang1, Aina Tu1, Qing Xie1
The higher the NLR is the higher the possibility of having a severe 1
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao
cholangitis. Tong University School of Medicine, Shanghai, China
Table and Figure:Figure 1.ROC Curve of NLR and Severity of Acute Background: Chronic liver diseases (CLDs) represent a higher risk
Cholangitis for hepatocellular carcinoma (HCC). With the disease course of CLDs
Figure 2.Area Under the Curve of NLR and Severity of Acute Cholangitis extended by improved therapeutic interventions and HCC screening,
the importance of holistic healthcare management to further
PP0005 improve patient experience, quality of life, and disease prognosis is
increasingly emphasized. Preliminary data from Ruijin Liver Care study
Correlation between lipid-related obesity indicators and gallstone
has demonstrated the potential of digital platform on increasing early
disease in U.S. adults
HCC screening rate among patients with CLDs (Hong-lian Gui, et al.
Chang Fu1, Xiaocong Li2, Kai Liu1 2024). In order to extrapolating the digital platform to address the
1
Department of Hepatobiliary and Pancreatic Surgery, General unmet needs in healthcare management, we conducted a quantitative
Surgery Center, The First Hospital of Jilin University, 2Department of survey to investigate the patient acceptance and willingness to pay
Pharmacy, China-Japan Friendship Hospital on holistic healthcare management service based on digital platform.
Background: Gallstone disease is a significant global health concern, Method: The survey was conducted from May to July 2024 among
affecting 10-15% of adults in Western countries. Gastrointestinal patients with CLDs visiting Ruijin Hospital using a convenience
symptoms resulting from gallstone disease are a leading cause of sampling method. Pre-specified CLDs included chronic hepatitis B,
hospitalization, with biliary tract disease accounting for $16.9 billion chronic hepatitis C, cirrhosis, MAFLD with fibrosis or abnormal glucose
in U.S. healthcare expenditures in 2018. As a common digestive metabolism, autoimmune liver disease, and a family history of HCC.
system disease, gallstone disease is closely associated with obesity The questionnaire designed by investigators consisted of 12 questions,
and dyslipidemia. Cardiometabolic index (CMI), visceral adiposity covering three sessions of patient characteristics, recognition and
index (VAI), and lipid accumulation product (LAP), as novel lipid- demand on healthcare service package and willingness to pay.
related obesity indicators, can effectively reflect central obesity and Statistical significance was defined as P<0.05.
dyslipidemia. This study seeks to explore the relationship between Result: A total of 209 valid questionnaires were collected. The top 3
lipid-related obesity indicators and gallstone disease while assessing etiologic types were hepatitis B (59.4%), cirrhosis (17.9%) and MAFLD
their predictive abilities. with abnormal glucose metabolism (10.1%). 88% of respondents
Method: The study population was drawn from the National Health and showed high level of recognition (7-10, rating from 1 to10) on
Nutrition Examination Survey (NHANES) 2017-2020 dataset. NHANES holistic healthcare management service, in which the service items
is a national nutritional health survey based on the U.S. population, of outpatient follow-up assistance, personalized CLDs management
providing representative data for public health research. CMI, VAI, and files and online consultation were most commonly mentioned. 60%
LAP were integrated as both continuous and categorical variables within of respondents were willing to pay for service package. Univariable
the multivariate logistic model, respectively to evaluate the connection logistic regression indicated that the willingness to pay was relevant
between various lipid-related obesity indicators and gallstone disease. to age, household income, education level and level of recognition
Additionally, restriction cubic splines and subgroup analysis were on service package (Supplementary Figure), while household income
employed to deepen our understanding of this relationship. The was the only independent factor in multivariable analysis (OR 0.18,
predictive accuracy of CMI, VAI, and LAP for gallstone disease was 95% CI 0.05-0.60, P=0.007).
assessed using the receiver operating characteristics (ROC) curve. Conclusion: The survey results provide preliminary evidence
Result: Out of the 3,738 participants enrolled in the study, 397 supporting the acceptance and demand for holistic healthcare
individuals had gallstone disease, representing a prevalence of management service among CLDs patients. Moreover, the expressed
10.6%. The study population had an average age of 50.7 ± 17.3 willingness of over half of the respondents to pay suggests a market
years, with females comprising 51.5% of the sample. The participants viability and a patient-driven demand that can support the financial
were grouped according to the quartiles of lipid-related obesity sustainability of the service. The findings highlight the importance
indicators. The results showed that, compared to the Q1 group, of patient perceptions in shaping healthcare service delivery and
participants in the Q4 group had a larger waist circumference, higher the potential for a sustainable service model that enhances patient
BMI, higher triglyceride levels, and a higher prevalence of diabetes outcomes.
and hypertension. Importantly, the Q4 group also exhibited a higher Table and Figure:Figure 1.Table and Figure. Characteristics related to
prevalence of gallstone disease. After adjusting for confounding willingness to pay.
variables, a nonlinear positive correlation was observed between
lipid-related obesity indicators and gallstone disease. For CMI,
PP00007
VAI, and LAP, individuals in the highest level group had a 1.48-fold,
Cost-effectiveness of antiviral treatment for chronic hepatitis B Method: CHB patients identified from a prior population-based
virus infection in China under a standard clinical pathway territory-wide HBV screening program conducted in Hong Kong
Mengdie Zhang1, Xin Li1 2015-2016 were proactively called back to our center for assessment
1
Department of Clinical Pharmacy, School of Pharmacy, Nanjing and study recruitment. Enrolled subjects received clinical, virological
Medical University and transient elastography assessment, as well as a questionnaire
assessment of linkage to care status, followed by hepatologist review.
Background: The hepatitis B virus (HBV) epidemic presents a
After assessment, we randomized patients 1:1 to receive an educational
significant global public health challenge, particularly in China. Serious
video via social media on the importance of CHB care retention versus
liver diseases such as cirrhosis and hepatocellular carcinoma caused
standard-of-care information on disease management. Patients without
by the progression of chronic hepatitis B (CHB) are a major contributor
regular clinic follow-up were referred to CHB healthcare providers of
of disease burden. High-barrier-to-resistance nucleos(t)ide analogues
their preference. We contacted patients 1 year post-assessment to
(NAs) have demonstrated significant efficacy in suppressing HBV
evaluate CHB retention-to-care status.
DNA replication and delaying HBV-associated complications and the
Result: Among 803 individuals screened positive for hepatitis B
Chinese Medical Association recommends entecavir (ETV), tenofovir
surface antigen in 2015-2016, 427 CHB patients (53.1%) responded to
disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF),
our retention-to-care program. 143 (33.5%) were male, with a median
and tenofovir amibufenamide (TMF) as the first-line therapeutics for
age of 53 (IQR 44-60) years. 288 (67.4%) patients had regular follow
CHB patients. This study examined the cost-effectiveness of the four
up clinic appointments for CHB prior to study visit. Abnormal alanine
first-line NAs drugs from the perspective of Chinese society, aiming
transaminase level (ALT > 40 IU/L) was detected in 52 patients (12.2%)
to optimize the allocation of health resources and provide a decision-
and advanced liver fibrosis (> 9 kPa by transient elastography)
making basis for international CHB treatment.
was diagnosed in 33 patients (7.7%). 86 patients (20.1%) were
Method: Based on CHB serological characteristics, patients were
on nucleoside analogue therapy. 415 patients (97.2%) agreed for
stratified into HBeAg-positive and HBeAg-negative cohorts. An
educational intervention and randomization. There was no significant
innovative Markov model was developed using Microsoft Excel,
difference in 1-year retention-to-care rates when comparing patients
incorporating annual cycles over a 60-year simulation period. The
receiving educational video (90.8%, 188/207) and standard-of-care
treatment protocol was primarily derived from the Chinese Medical
disease information (89.9%, 187/208) (P=0.75). Factors associated
Association (CMA) guidelines, model parameters were extracted from
with 1-year retention-to-care include increased age (OR 1.08, 95%CI
published literature and preliminary research. The economic evaluation
1.03-1.12, P=0.002), household income (OR 0.61, 95%CI 0.40-
employed incremental cost-effectiveness ratios benchmarked against
0.94, P=0.025) and educational level (OR 0.68, 95%CI 0.493-0.949,
predetermined willingness-to-pay thresholds (1x GDP per capita).
P=0.023). There was no significant difference in post 1-year treatment
Sensitivity analyses were conducted to verify the model robustness.
rates (31.4% vs 26.4%, P= 0.27)
Result: Results showed that TDF (ICER=¥40,299.17/QALY) and TMF
Conclusion: An active call-back program can be effective in
(ICER=¥40,603.18/QALY) were the most cost-effectiveness options for
maintaining subsequent CHB retention-to-care rates. Additional video
HBeAg+ CHB patients, while TMF (ICER=¥95,408.08/QALY) were the
media education did not further increase rates of retention in the CHB
most cost-effectiveness option for HBeAg- CHB. One-way sensitivity
care continuum.
analyses identified the most influential parameters: the transfer
probability from HBeAg+ CHB to HBsAg serological clearance and
the transfer probability from HBeAg- CHB to complete virological PP0009
response. Probabilistic sensitivity analysis indicated 100% probability Treatment cost reduction in Indonesia – through market shaping,
of cost-effectiveness for all four treatments (ETV, TDF, TAF, and TMF) in transparency and stakeholder collaboration – opening momentum
HBeAg+ CHB, whereas none achieved cost-effectiveness in HBeAg- for national scale-up of Hepatitis C elimination
CHB patients. Scenario analyses from a healthcare system perspective Robert Kosasih1, Arief Budiman1, Kushagar Dhall2, Vy Bui2, Yuhui
demonstrated TMF as the sole cost-effective option for HBeAg- CHB Chan2, Caroline Boeke2, Caroline Thomas3, Tri Setyanti4, Oriel
patients. In scenarios incorporating generic medications, TAF and TDF Fernandes2, Ratna Budi Hapsari4, Atiek Anartati1
emerged as the most cost-effective options for HBeAg-positive and 1
Clinton Health Access Initiative - Indonesia, 2Clinton Health Access
HBeAg-negative CHB patients, respectively. The results remained
Initiative - Boston, 3Yayasan Peduli Hati Bangsa, 4Working Team
robust across variations in treatment duration (30 or 40 years) . Hepatitis and Gastrointestinal Infectious Diseases Ministry of Health,
Conclusion: For HBeAg+CHB patients, TDF/TMF>ETV is more cost- Indonesia
effective, whereas for HBeAg-CHB patients, TMF>ETV is more likely
to be cost-effective than other treatment regimens, despite exceeding Background: An estimated 1.4 million people live with chronic hepatitis
WTP. C (HCV) infection in Indonesia (estimated viraemic rate of 0.5% of the
Table and Figure:Figure 1.Markov disease state transfer model total population), requiring treatment of 12 to 24 weeks.[1] Despite
Figure 2.Results the availability of an affordable 12-week cure globally (sofosbuvir
and daclatasvir priced at US$60 ex-works), Indonesia’s national HCV
program was procuring these drugs at a much higher combined cost
PP0008 of US$700 until 2020. This high cost limited annual treatment to just a
Assessing educational video intervention in increasing retention- few thousand courses, impeding progress toward national elimination
to-care rates after population-wide screening for chronic hepatitis goals. This analysis describes the multi-faceted process that
B: a randomized trial successfully drove down HCV treatment costs in Indonesia, unlocking
KwanLung Michael Ko1, LungYi Loey Mak1, WaiKay Seto1, WaiPan the potential for national scale-up.
To1, James Fung1, ManFung Yuen1 Method: The first step was identifying the drivers for higher treatment
1
Department of Medicine, Queen Mary Hospital, The University of costs, which included a supplier monopoly, weak bargaining
Hong Kong power by the public sector, and a lack of market transparency and
information asymmetries. To address these, the Clinton Health Access
Background: Enormous effort has been initiated globally to increase
Initiative (CHAI) leveraged our expertise in market shaping and
diagnosis and treatment coverage of chronic hepatitis B (CHB), with
strong understanding of the local context to employ a multi-pronged
the aim of eliminating hepatitis B virus (HBV) as a public health threat.
approach via engaging with various stakeholders at different stages
Treatment rates remain low, which may be related to inadequate
of the process. First, CHAI fostered a more favorable environment
linkage and retention into the CHB care cascade continuum. Data
for market competition by facilitating engagement between generic
on retention in care after diagnosis and linkage is scarce. Our study
Indian pharmaceutical companies, in-country distributors and local
aimed to assess retention-to-care rates after a population-wide
civil societies to boost in-country drug registration by suppliers. Next,
screening, and whether additional educational videos on the day of
CHAI sought to increase market transparency by widely disseminating
patient assessment can increase retention rates.
the HCV market intelligence covering global and Indonesia landscape.
Finally, CHAI galvanized local civil societies to advocate for treatment for chronic viral hepatitis in Australia, the readability of these resources
price reduction to the government through timely sharing of market is well above the recommended Australian Year 7 level, contain a high
intel. percentage of complex language and lack linguistic diversity. There is
Result: By 2021, these efforts culminated in a 85% cost reduction a need to simply and diversify chronic viral hepatitis patient resources
for a 12-week treatment in the country, from US$700 to approximately to ensure information is accessible to all affected patients.
US$105.6 (cost per bottle, US$150.7 to US$21.9 for sofosbuvir and Table and Figure:Figure 1.
US$82.7 to US$13.3 for daclatasvir). With the same budget, the Figure 2.
national program could procure six times the number of treatment
courses at reduced prices. Furthermore, the private health sector in
PP0011
Indonesia would benefit by procuring treatment drugs at a lower price,
thus helping increase access to HCV treatment in Indonesia. Relationship between hepatocellular tumor size and tumor
Conclusion: Reducing HCV treatment costs enabled the program to markers
concurrently increase procurement volume and redirect savings to Badamsuren Erdene-Ochir1, Byambatsetseg Togtuunbayar2,3,
other key programmatic areas such as improving case finding to scale Baatarkhuu Oidov4,5, Amarsanaa Jazag3,2, Erdenebayar Gonchig2,
up HCV elimination. Cost reductions were possible through strategic Dolgormaa Batsaikhan, Ganchimeg Gelenkhuu
market shaping, enhanced competition, increased transparency, and 1
Happy Veritas Hospital, 2Happy Veritas Hospital Ulaanbaatar
cross-stakeholder collaboration including advocacy by civil society. Mongolia, 3Mongolian National University of Medical Sciences,
With price reductions accomplished, CHAI is now bolstering program
4
Mongolian Association for the Study of Liver Disease, 5Department
management at the central level and program implementation and of Infectious Diseases, Mongolian National University of Medical
service delivery at the provincial level to expand the program’s Sciences
capacity to find and treat more patients. Background: There are two commonly used HCC tumor markers
widely used in Mongolia which are AFP and PIVKA-II, and we
PP0010 investigated the relationship between HCC markers and hepatocellular
carcinoma size.
Readability, Language Diversity and Accessibility of Chronic Viral Method: A random sample of 102 patients with hepatocellular
Hepatitis Patient Resources in Australia carcinoma, the mean HCC size at the time of initial diagnosis and the
Tony Sebastian1,2, Isaac Moh2, Janet Shin2, Danielle Muscat3, Julie mean levels of AFP and PIVKA-II tumor markers were compared.
Ayre3, Karen Waller1,3, Emily He1 Result: Out of a total of 102 patients with hepatocellular carcinoma,
1
Gastroenterology Department, Concord Repatriation General the average marker levels of 65 patients with tumors up to 5 cm in
Hospital. Sydney, Australia, 2Faculty of Medicine, University of Sydney. size were AFP 1440, PIVKA-II 2317, the average marker levels of 25
Sydney, Australia, 3Sydney Health Literacy Lab, School of Public patients with tumors between 5-10 cm in size were AFP 3853, PIVKA-II
Health University of Sydney. Sydney, Australia 16714, the average marker levels of 7 patients with tumors between
Background: Chronic viral hepatitis affects more than 300,000 people 10-15 cm in size were AFP 4915, PIVKA-II 22336, and the average
in Australia with an over-representation of underprivileged populations marker levels of 5 patients with tumors over 15 cm in size were AFP
– including culturally and linguistically diverse (CALD) populations and 80, PIVKA-II 27804.
Aboriginal and Torres Strait Islanders. Underprivileged populations Conclusion: The size of the hepatocellular carcinoma is directly
have lower health literacy levels, contributing to poorer healthcare correlated with tumor markers.
outcomes. The Australian government recommends that public Table and Figure:Figure 1.Table 1. Correlation betweem tumor marker
health resources be written at a Year 7 reading level or below, as and tumor size
approximately half of the Australian population reads at or below a
Year 10 level. The readability and language diversity of resources PP0012
for chronic viral hepatitis can influence patient accessibility and
understanding. However, it is unclear whether existing resources Exploring the Gaps in Disease Knowledge and Surveillance
meet these accessibility standards, potentially posing a barrier to Practices in Cirrhotic Patients: A Prospective Study
effective communication. This study aims to evaluate the readability Yumna Shahid1, Faisal Wasim Ismail1
and language diversity of patient resources for chronic viral hepatitis 1
Aga Khan University Hospital
in Australia. Background: Hepatocellular carcinoma (HCC) is the fifth most
Method: An environmental scan of patient education resources was common tumor in the world. It is also third leading cause of cancer-
conducted, using three search strategies, (a) search of known relevant related deaths worldwide, and the leading cause of death in
websites/organisations, (b) systematic Google searches and (c) patients with cirrhosis. Therefore AASLD and EASL recommend
emails to Australian hepatologists. Gathered resources were screened HCC surveillance every 6 months in individuals who are at high
according to the inclusion and exclusion criteria and exported to risk of developing HCC. Early detection through guidelines-based
a standardised spreadsheet for data extraction. Readability and surveillance in cirrhotic patients is the only way to detect and treat
percentage of complex language of each English language resource HCC at an early stage. It is of high importance to know the disease
was analysed with the Sydney Health Literacy Lab Editor. awareness in our population and their adherence to surveillance for
Result: A total of 136 resources were analysed, 74 were hepatitis B HCC, as there is little data available. Having evidence-based data will
and 62 were hepatitis C resources with only 3% of all resources written lead to targeted interventions to reduce disease burden. The objective
at the recommended level of Year 7 or lower. The mean readability of the study is to evaluate the knowledge, attitudes, and practices of
was 10.3 for hepatitis B resources, with a majority observed to have patients with cirrhosis regarding their disease and to identify barriers
a readability score of between 9.5 – 12.4 (Figure 1A). There were influencing adherence to surveillance practices.
two resources that had the recommended readability score of 7. For Method: This is a prospective study which was conducted in
hepatitis C, the mean readability was 11.2, with a majority determined Gastroenterology department of Aga Khan University Hospital
to have a readability score of between 10.5 - 13.4 (Figure 1A). There from May 2024 to October 2024 after approval from ethical review
was only one resource that had the recommended readability score. committee. Patients with Child A or B cirrhosis above age 18 years
The mean percentage of complex language was between 21-25% for were enrolled to complete an anonymous self-administered survey. A
both hepatitis B and C resources (Figure 1B). The search produced validated questionnaire was used. Surveillance rates and clinical data
140 non-English resources for chronic viral hepatitis with a total of 25 were extracted from the patient electronic medical records.
languages represented. The most common CALD resources were in Result: A total of 150 patients completed the survey. The mean age
Simplified or Traditional Chinese (26%), Vietnamese (11%) and Arabic was 56(±SD 10). Most patients came from an urban and educated
(8%) (Figure 2). background (n=104) (69%). Most common cause of cirrhosis was
Conclusion: Despite the large number of available patient resources
HCV (n=53) (35.3%) followed by Non B Non C (n=51) (34%) and National hepatitis elimination in Niue: a cost-effective model
then HBV (n=46) (30.7%) related. Only 85(56.7%) patients underwent partnering with civil society. Telling the story through film creates
6-12 monthly surveillance. Most patients did not have appropriate an asset for regional elimination, inspiring health care workers
knowledge regarding their disease. More than (n=145) 90% patients and policy makers.
desired more information from their healthcare professional. (Table 2 Hazel Heal1, Alice Lee2,3,4, Sue Huntley5,4, Michael Schultz6,7, Grizelda
and 3) Factors that contributed most as a barrier towards surveillance Mokoia8, Edgar Akau’ola8, Margaret Fraser7
were residing in rural areas, lack of education and employment status 1
GHNZ Limited, 2Sydney University, 3Macquarie University, 4Hep B
(Table 4) (p value <0.001). Free, 5Hepatitis B Free Ltd, Australia, 6Otago University, 7Dunedin
Conclusion: Enhancing patient awareness and addressing barriers Hospital, 8Niue Foou Hospital
to surveillance are essential for effective HCC prevention in cirrhotic
Background: In 2019, civil society group Global Health New Zealand
patients. We need to implement targeted interventions to improve
(GHNZ) contacted the Public Health team in Niue to propose a national
adherence to 6 monthly surveillance to prevent morbidity and mortality
test and treat program. The ambition was for Niue to be the first country
from HCC.
to eliminate viral hepatitis, creating a model that could be applied
Table and Figure:Figure 1.
throughout the Pacific. The proposal was to bring the funding and
Figure 2.
expertise to achieve the aim of total elimination. Niue’s Department of
Social Services, showing leadership, agreed to the proposal.
PP0013 Method: All adults in Niue were invited to screen for HBV and HCV
The mediating effect of health literacy between social support and with point-of-care serological testing (HbsAg, anti-HCV). At the time
self-management ability in patients with chronic liver disease of testing, participants were invited to complete a questionnaire on
Zhuping Qian1,2, Pingmei Jiang1,2, Zhujun Cao2 awareness for hepatitis. Covid-19 pandemic closed borders in2020
necessitating a program redesign, whereby GHNZ provided the rapid
1
Nursing Department, Ruijin Hospital, Shanghai Jiao Tong University
tests, incentives, publicity to Niue’s Public Health team who conducted
School of Medicine, Shanghai, China, 2Department of Infection
Disease, Ruijin Hospital, Shanghai Jiao Tong University School of the community testing for HBV and HCV together with COVID testing.
Medicine, Shanghai, China Clinical support was provided by New Zealand specialists via telehealth
until they were permitted to visit in 2023. Through this they were able
Background: China ranks among the countries with the highest to test 90% of their adult population for HBV and HCV by mid 2021.
prevalence and burden of liver diseases globally, with nearly 300 GHNZ were then joined by Australian project partners Hep B Free.
million individuals affected [1], including 7 million with cirrhosis and In 2022, a visit was made to fibroscan, assess patients and make
approximately 460,000 new cases of liver cancer annually [2]; Chronic treatment plans. In January 2024, Hep B Free and GHNZ returned to
viral hepatitis (infections with hepatitis B and C viruses) impacts nearly Niue; to provide expert staff training, review all patients, and make a
100 million individuals and is a leading cause of liver cancer. Research film to tell the story of the path to elimination validation. The film was
on chronic disease self-management could date back to the mid to privately funded through donations and features interviews with global
late 20th century. The objective has evolved from simply providing leaders in the field.
disease information and enhancing treatment compliance to guiding Result: More than 90% of the resident adult population of Niue
patients in managing their health behaviors. The ultimate objectives underwent testing for HBV and . HCV No cases of HCV were detected.
involve improving their quality of life [3], reducing the disease burden, Eight cases of HBV were detected of whom two have been started on
and decreasing healthcare resource consumption. Current research tenofovir treatment. The prevalence of chronic HBV infection today is
on self-management in chronic liver disease primarily targets patients only 0.5% compared with 12% in 1991 and 9% in 1998.
with cirrhosis and chronic hepatitis B, predominantly within the realm Conclusion: Conclusions: This national screening programme
of health education. identified a much lower rate of HBV infection than previously reported,
Method: A total of 207 chronic liver disease patients were recruited evidence of successful roll-out by Niuean Public Health initiatives to
from the outpatient clinic of a tertiary hospital’s infectious disease prevent mother-to-child transmission, including universal neonatal
department in Shanghai via convenience sampling. Questionnaire vaccination and screening of all pregnant mothers.
surveys were conducted using the General information survey 2. Combining NGO funded staff training on isolated populations with
form, the Partners in Health Scale (PIH) , the Health Literacy Scale expert clinical visits is cost saving and effective.
for Chronic Patients (HLSCP) , the Health Literacy Scale for Chronic 3. Everybody matters. Civil society partnering with clinicians helps
Patients (HLSCP) and the Social Support Rating Scale (SSRS) . elevate key messages for wider impact. Although infection rates in
Result: The overall self-management ability score for chronic liver Niue are low, the power of one human story was captured for the film.
disease patients was (54.22 ± 17.13); Factors influencing self- The film, (40 minutes) Down with Hepatitis was released on WHD,
management ability included residential location, disease type, 28 July 2024. It has inspired policy makers, healthcare workers and
dimensions of willingness to improve health and willingness to support encouraged people to seek treatment around the Pacific. The excerpts
financially in health literacy, and dimensions of subjective support version, Hepatitis B elimination in the Pacific-Niue (15 minutes) is a
and support utilization in social support (all P<0.05); Health literacy valuable and inspiring tool for funders, presentations and conferences.
positively impacted self-management level through social support, with Table and Figure:Figure 1.Butterfly poster
a total effect value of 0.523, comprising both direct effects (β=0.411)
and indirect effects (β=0.112), all at P<0.01.
Conclusion: Chronic liver disease patients exhibit a moderate level PP0015
of self-management ability. Healthcare professionals should enhance Pioneering Endoscopic Sleeve Gastroplasty Services in Rural
patients’ self-management levels by improving health literacy and Pakistan: Initial Outcomes from a Public Sector Program
effectively utilizing social support, taking into account their disease Syed Mujahid Hassan1, Hafiz Hamad Ashraf1, Nadim Bajkani1, Ahsan
and sociodemographic characteristics. Ali Memon1, Asad Ali Kori1, Samreen Rao1
Table and Figure:Figure 1.Table 1. Comparison of self-management 1
Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences
levels in chronic liver disease patients with different characteristics
Background: Endoscopic sleeve gastroplasty (ESG) is an innovative,
(n=207)
minimally invasive procedure for weight loss and the management of
Figure 2.Figure 1. Mediation effect of social support between health
obesity-related comorbidities. This case series evaluates the initial
literacy and self-management behaviors in chronic liver disease
implementation and outcomes of ESG services in Gambat, Pakistan,
patients
within a rural public healthcare setting.
Method: Patients with a body mass index (BMI) greater than 27
PP0014 with comorbidities or a BMI greater than 30 without comorbidities
were included. Those with a very high BMI (greater than 50),
thrombocytopenia, coagulopathy, or advanced cardiopulmonary Nitrogen has an unstandardized beta weight of 0.526, a positive value,
diseases were excluded. A pre-procedural workup included a indicating its positive correlation to mortality rate having p value of
complete blood count (CBC), liver function tests (LFTs), lipid profile, 0.009 which is statistically significant.
thyroid profile, and cardiopulmonary evaluations. Following informed Conclusion: Conclusion: Study showed that elevated blood urea
consent, ESG was performed under general anesthesia using the nitrogen was an informative marker in patients with COVID-19 in
OverStitch™ Sx Endoscopic Suturing System (Apollo Endosurgery, assessing the risk for mortality independent of serum creatinine.
Inc. USA).
Result: From April to November 2024, eight patients underwent ESG.
PP0017
The cohort comprised 2 males (25%) and 6 females (75%), with a
mean age of 31.5 years (range: 24-55). Five patients (62.5%) had Post-endoscopic retrograde cholangiopancreatography
class II obesity, while three (37.5%) had class III obesity. Common pancreatitis independently predicts pancreatic cancer
comorbidities included fatty liver (87.5%), deranged lipid profile development in diabetic patients
(75%), snoring (75%), hypertension (62.5%), osteoarthritis (62.5%), KaShing Cheung1,2, JingTong Tan1, Xianhua Mao1,2, WaiKay Seto1,2
gastroesophageal reflux disease (GERD) (50%), exertional dyspnea 1
Department of Medicine, School of Clinical Medicine, The University
(50%), and type 2 diabetes (37.5%). The average procedure duration of Hong Kong, Hong Kong, China, 2Department of Medicine, The
was 120-150 minutes. An average of 5 sutures and 8-10 stitches with University of Hong Kong-Shenzhen Hospital, Shenzhen, China
each suture were applied, generally following the U-shaped pattern. Background: Both acute pancreatitis (AP) and diabetes mellitus (DM)
Minor bleeding occurred in two patients but resolved quickly after over- are risk factors of pancreatic cancer (PC). We aimed to investigate
suturing. No other intra-procedural complications were reported. Post- whether post-endoscopic retrograde cholangiopancreatography
procedure, minor complaints were noted and managed: epigastric (ERCP) pancreatitis (PEP) was associated with higher risk of long-term
discomfort (62.5%), nausea (50%), and vomiting (25%). Only two pancreatic cancer (PC) among type 2 diabetes (T2D) patients.
patients (25%) required a 48-hour stay; the remaining six (75%) were Method: All newly diagnosed T2D patients aged ≥18 years between
discharged within 24 hours. The mean follow-up duration was 2.6 1993 and 2020 were identified from the territory-wide electronic
months (with individual follow-ups of 8, 3, 3, 3, 1, 1, 1, and 1 month). health registry in Hong Kong. DM was identified by (i) two abnormal
The mean weight loss was 9.3 kg (individual losses: 12, 12, 8, 9, 10, HbA1c ≥6.5% or fasting glucose ≥7 mmol/L test results, (ii) anti-DM
9, 9, and 6 kg). Improvements in comorbidities and quality of life were medications use, or (iii) International Classification of Diseases Ninth
observed as follows: exertional dyspnea and mobility improvement: Revision (ICD-9) code 250. Exclusion criteria included history of PC,
100%; snoring improvement: 83.3%; osteoarthritis improvement: 80%; pancreatic neuroendocrine tumor, pancreatic cysts, and chronic
lipid profile improvement: 66.7%; hypertension reduction: 66.7%; pancreatitis. Index date was defined as three years after T2D diagnosis
diabetes improvement: 66.7%. All patients reported an increased to address reverse causality, in which undiagnosed PC may manifest
sense of well-being. as new onset diabetes (NOD). Primary outcome was PC development.
Conclusion: ESG is a safe, effective, and minimally invasive procedure Primary exposure was PEP, identified by an amylase or lipase level at
for managing obesity and its related comorbidities in rural Pakistan. The least three times upper limit of normal more than 24 hours and within 7
results highlight its potential as an accessible and scalable solution for days after ERCP. We divided the cohort into three groups: (i) absence
obesity treatment in underserved regions. of ERCP before index date [ERCP(-)], (ii) history of ERCP without
Table and Figure:Figure 1.ESG procedure in progress showing tissue PEP [ERCP(+)/PEP(-)], and (iii) history of PEP [ERCP(+)/PEP(+)].
helix pulling the mucosa for stitching Comparison of ERCP(+)/PEP(+)with ERCP(+)/PEP(-) group serves to
Figure 2.Post ESG procedure showing formation of gastric sleeve address indication bias (as those requiring ERCP likely had higher
risk of PC risk due to various hepato-bilio-pancreatic indications).
PP0016 Covariates were age, sex, lifestyle factors, metabolic disorders, time-
weighted mean HbA1c, cardiovascular diseases, other antidiabetic
Role of Blood Urea Nitrogen Level in Predicting Mortality
drugs, aspirin, non-steroidal anti-inflammatory drugs, statins, and
among Patients with COVID-19: A Multicenter Retrospective and
history of AP unrelated to ERCP. Multivariable Cox regression models
Descriptive Cohort Study
were used to drive adjusted hazard ratios (aHRs) of PC with PEP.
Uzziel Romar Samoro Alonzo1 Result: We identified 772,549 T2D patients (mean [SD] age:60.6 [12.4]
1
East Avenue Medical Center years;50.3% male). There were 751,184 (97.2%) patients in ERCP(-),
Background: Background: COVID-19 infections caused by the 20,990 (2.7%) in ERCP(+)/PEP(-), and 375 (0.05%) in ERCP(+)/PEP(+)
SARS-CoV-2 virus posed huge challenges to great global public health groups. During a mean follow-up of 9.1 (+/-5.9) years, there were 2,128
systems and clinical management. Although the majority of COVID-19 (0.3%) newly diagnosed PC cases with a crude incidence rate of 3.0
patients have mild disease, severe and critically ill patients can rapidly per 10,000 person-years. The crude incidence rate of PC was 0.22,
progress to acute respiratory distress syndrome, septic shock, multiple 4.47 and 4.76 per 10,000 person-years among ERCP(-), ERCP(+)/
organ failure and even death. It is therefore imperative to identify PEP(-) and ERCP(+)/PEP(+) groups, respectively. Compared with
prognostic indicators of disease severity, to assist the implementation ERCP(-), ERCP(+)/PEP(-) and ERCP(+)/PEP(+) was associated with
of early measures to prevent the deterioration and death of critically higher risk of PC (aHR:16.8, 95%CI:15.5-18.3; aHR:28.0, 95%CI:15.7-
ill patients. Elevated BUN level has been reported as a predictor of 50.2) (Table 1). Compared with ERCP(+)/PEP(-), aHR of PC was 1.94
worse outcomes in patients with heart failure and BUN level >7mmol/ (95%CI:1.08-3.48) with ERCP(+)/PEP(+).
was one of the criteria of CURB-65 scoring for community acquired Conclusion: PEP was an independent risk factor of PC development
pneumonia. in T2D. Occurrence of PEP should be minimized in order to not just
Objective: We hypothesized that critically ill patients with COVID-19 prevent short-term complications of AP but also PC development.
could have changes in serum blood urea nitrogen during hospitalization, Table and Figure:Figure 1.Table 1. Association between risk of
and that blood urea nitrogen may be considered as a prognostic pancreatic cancer and post-ERCP pancreatitis
marker of severe disease and mortality of COVID-19.
Method: Methods: A total of 58 hospitalized patients with PP0018
COVID-19 were retrospectively studied. Demographic data, clinical
characteristics, BUN level, and mortality rate were assessed and Efficacy of Potassium Competitive Acid Blockers (PCABs) vs
analyzed. Proton Pump Inhibitors (PPIs) for Healing of Duodenal Ulcers: A
Result: Results & Analysis: Present study included 58 confirmed Systematic Review and Meta Analysis
COVID-19 cases of which 14 (24.14%) had elevated blood urea Justine Pua Chua Ching1, Ace Tan Chan1
nitrogen upon admission 24.14% and 44 (76.86%) have normal blood
1
St. Lukes Medical Center
urea nitrogen level upon admission. A total of 12 mortalities were Background: Peptic ulcer disease is a common gastrointestinal tract
recorded from 58 total number of respondents (Table 3). Blood Urea
disorder that affects four million people worldwide with a prevalence of Conclusion: We developed a nomogram based on the results of six
5-10% in the general population. The most commonly used medication multivariable analyses, which has high clinical value for predicting the
to treat peptic ulcer disease include the use of proton pump inhibitors prognosis of EBV-HLH. The concordance index C-index for the training
(PPIs). Proton pump inhibitors are known to be safe and effective. set was 0.846 (0.780-0.913), and for the validation set it was 0.782
Recent studies suggest that proton pump inhibitors have risks such (0.676-0.891). The calibration curve and decision curve showed a
as drug to drug interaction, and long term risks such as increased good fit between the predicted values and the actual values.
risk of fractures and chronic kidney disease. With the advent of
potassium competitive blockers (PCABs), this could be a potential
PP0020
alternative to proton pump inhibitors for acid suppression. PCABs such
as Vonoprazan, Tegoprazan, Soraprazan, Revaprazan, Keverprazan Global, Regional, and National Burdens of Non-alcoholic Fatty
and Linaprazan are reversible, competitive antagonists of the H+/ Liver Disease Attributable to Smoking from 1990 to 2021
K+ ATPase that is seen to have more sustained acid suppression. Pengyue Zhang1, Jie Zhu1, Zhengqi Gao1, Xiaodan Hong1, Zhenhua
Furthermore, PCABs also does not require acid and proton pump Zhang1
activations to achieve the desired effect, thus it has a faster acid- 1
The Second Affiliated Hospital of Anhui Medical University
suppressive effect compared to PPIs. Background: Smoking is a recognized risk factor for non-alcoholic
Method: A comprehensive systematic search of Pubmed, Cochrane, fatty liver disease (NAFLD), yet the associated epidemiological
Clinicaltrials, and Medrvix was performed. Two reviewers independently trends remain unclear. This study aimed to quantify the global burden
screened papers and abstracts. A consensus was done on the studies of NAFLD attributable to smoking from 1990 to 2021, focusing on
included. Critical appraisal studies on the included papers were disability-adjusted life years (DALYs), mortality rates, and trend
done independently. Meta-analysis was done via a random effects analysis.
model using the Revman 5.4 application. The outcome is the healing Method: Data from the Global Burden of Disease Study 2021 were
of duodenal ulcers after using proton pump inhibitors vs potassium extracted and analyzed at global, regional, and national levels. The
competitive acid blockers. analysis encompassed age, sex, region, and socio-demographic
Result: The study included 3 RCTs of 1233 individuals with duodenal index (SDI) for NAFLD attributable to smoking. Key measures included
ulcers. There was a 1.08 mean difference for healing of duodenal age-standardized DALY rates (ASDR), age-standardized mortality
ulcers between the treatment groups crossing the line of no effect rates (ASMR), and average annual percentage changes (AAPCs).
at week 6 (1.08, 95% CI [0.63,1.86], p=0.78, I2 19%). There was a These global trends were further examined across age, sex, and SDI
mean difference of 0.82 between the treatment groups at week 4 categories.
(0.82, 95% CI [0.59, 1.14], p=0.23, I2 49%). There was no substantial Result: Globally, the ASMR of NAFLD attributable to smoking
heterogeneity across the groups and p value >0.05 was obtained on demonstrated a upward trend (AAPCASMR=0.27[95% CI, 0.17-
both week 4 and week 6. 0.37], P < 0.001). The most substantial increases from 1990 to 2021
Conclusion: PCABs such as Vonoprazan 20mg and Keverprazan were observed in Australasia and Southern Latin America. The AAPC
20mg are non inferior to PPIs in the healing of duodenal ulcers. Both for ASDR was 2.89[95%CI, 2.5-3.29] and 2.84[95%CI, 2.16-3.52],
classes of drugs had similar tolerability profiles. respectively. The overall burden of NAFLD attributable to smoking
Table and Figure:Figure 1.Forest plot of PCAB vs PPI on healing of was significantly higher in males compared to females, with DALY
duodenal ulcers at Week 6 rates escalating with age and peaking in the 65-69 years age group
Figure 2.Forest plot of PCAB vs PPI on healing of duodenal ulcers at (8.84/100,000 [95%UI, 2.77-15.69]). In most regions, the SDI exhibited
Week 4 an inverse U-shaped correlation with both ASDR and ASMR. Join-point
analysis indicated a notable increasing trend in disease burden among
PP0019 populations in low-medium SDI regions and among females in high
SDI regions.
Clinical features and prognosis of Epstein-Barr virus-associated
Conclusion: Despite ongoing tobacco control efforts, the global
Hemophagocytic syndrome
burden of NAFLD attributable to smoking has not decreased and
Xiangyang Ye1, Chao Guo1, Rongrong Zhou*1
remains a significant concern. This issue is particularly pronounced
1
Xiangya Hospital of Central South University in low-middle income regions and among female populations in high-
Background: Hemophagocytic lymphohistiocytosis (HLH), also income regions, where rising trends have been observed. To address
known as Hemophagocytic syndrome (HPS), is a rare and fatal this, there is a pressing need to strengthen tobacco control policies
hyperinflammatory response syndrome. HLH is divided into primary and implement targeted prevention initiatives.
HLH and secondary HLH. Secondary HLH (sHLH) is caused by Table and Figure:Figure 1.The burdens of NAFLD attributable to
infections in 15% of cases, with Epstein-Barr virus (EBV) infection smoking among 204 countries and territories in 2021
accounting for 70% of infection-related HLH. The clinical manifestations Figure 2.The burdens of NAFLD attributable to smoking of different age
of EBV-HLH are complex and diverse, and the diagnosis lacks specific groups from 1990 to 2021
indicators, making it extremely difficult to correctly identify patients
early on. If early recognition and effective treatment are not achieved
PP0021
in time to block the progression of the inflammatory cytokine storm, the
condition will progress rapidly, and the risk of death will greatly increase. Trends, Inequalities, and Projections of Acute Viral Hepatitis in the
Therefore, finding effective prognostic indicators to accurately predict Elderly: the Global Burden of Disease Study 2021
the prognosis of EBV-HLH, in order to improve the early identification of Qi Chen1, Yaqi Deng1, Jieyu Peng1, Ping Wang1, Yan Peng1, Xiaowei
patients with poor prognosis, is worth further research. Tang1
Method: Clinical data of 56 patients with EBV-associated 1
Department of Gastroenterology, the Affiliated Hospital of Southwest
Hemophagocytic lymphohistiocytosis (EBV-HLH) diagnosed in Xiangya Medical University, Luzhou, China
Hospital from March 2018 to March 2023 were collected.Based on the Background: Acute viral hepatitis significantly impacts global health,
results of multivariate Cox regression analysis, a prognostic evaluation especially among older adults. This study aimed to analyze the global
model was constructed and its predictive efficacy was verified. burden of acute viral hepatitis among individuals older than 70 years
Result: Patients with high EBV DNA load had more severe disease, from 1990 to 2021.
worse clinical indicators and significantly higher mortality than those with Method: Using the Global Burden of Disease (GBD) 2021 data, we
low EBV DNA load.Low platelet count, high alanine aminotransferase, calculated incidence and disability-adjusted life years (DALYs),
low albumin, gastrointestinal symptoms, steroid only, symptomatic analyzing trends with estimated annual percentage change (EAPC).
treatment and EBV DNA≥5×105 copies/mL were independent risk We also made projections, health inequality analysis and estimated
factors for prognosis, and 1994 regimen+hematopoietic stem cell the relationship between the sociodemographic Index (SDI) and acute
transplantation was protective factor for prognosis.
viral hepatitis disease burden. of medical resources to address this issue in the future.
Result: From 1990 to 2021, the global trend for acute viral hepatitis Table and Figure:Figure 1.(A) The ASR of incidence in 2021; (B) The
among older adults showed a significant decline in DALYs, with an trend (EAPC) in ASR of incidence from 1990 to 2021; (C) The ASR of
increase observed in the incidence number. The highest DALY rates DALYs in 2021; (D) The trend (EAPC) in ASR of DALYs from 1990 to
were observed in Eastern Sub-Saharan Africa and countries, such as 2012; of AHE in older adults for 204 countries and territories.
Somalia, Afghanistan, and Ethiopia. Hepatitis B was the leading cause,
followed by hepatitis A, C, and E. While both sexes experienced a
PP0023
decline in the hepatitis burden, males showed a more substantial
reduction in DALYs. Projections indicated continued declines in DALY Analysis of screening and promoting referral of patients with
rates but rising incidence numbers over the next two decades. There chronic hepatitis B in a large-scale tertiary hospital in China.
was a negative association between the SDI levels and burden of acute Yijing Cai1, Haibo Jia1, Hang Han1, Mingqin Lu1
viral hepatitis. Cross-country inequality analysis highlighted improved 1
The First Affiliated Hospital of Wenzhou Medical University
disparity measures, yet significant inequalities remain. Background: China bears a heavy burden of chronic hepatitis B
Conclusion: Despite a decreasing trend in DALYs, the rising incidence (CHB), and tracking progress towards the 2030 WTO hepatitis B virus
number of acute viral hepatitis among older adults, along with regional (HBV) elimination targets is crucial. Patients commonly undergo HBV
disparities and gender differences, underscored the urgent need for marker testing during hospitalization or before invasive procedures.
targeted public health interventions, which are vital for achieving the Facilitating the notification and referral of patients with positive HBV
World Health Organization 2030 elimination goals. marker tests from non-specialized departments to specialized
Table and Figure:Figure 1. physicians is highly beneficial for the CHB clearance project.
Figure 2. Method: We analyzed data on hepatitis B screening and referral in
each department of a large tertiary hospital from 2021 to 2024. In 2023,
PP0022 a short message early notification system was established for doctors
to enhance the notification and referral of HBVDNA-positive patients
Global trends and cross-country inequalities of acute hepatitis E
to infectious disease physicians, and its effectiveness was evaluated.
in older population, 1990–2021: A comprehensive analysis
Result: From 2021 to 2024, 160,458 HBsAg-positive patients were
Deliang Huang1, Zhibin Zhu1, Jinghan Peng1, Jun Chen1 detected across all hospital departments. The top five departments
1
The Third People’s Hospital of Shenzhen, The Second Affiliated were infectious diseases, gastroenterology, hepatobiliary and
Hospital of Southern University of Science and Technology pancreatic surgery, physical examination center, and gynecology. The
Background: To assess the global burden, trends, and health mean HBsAg positive rate in non-specialized departments was 9.0%
inequalities of acute hepatitis E (AHE) among the older adults over the (91,152/1,013,124). Department of Pediatrics had the lowest HBsAg
past three decades, and to further predict its changes by 2030. positive rate at 4.2% (675/16,016). The mean HBVDNA- positive rate in
Method: Data on the incidence and Disability-Adjusted Life Years non-specialized departments was 28.9% (30,005/104,956). The rate of
(DALYs) of AHE in the elderly were obtained from the Global Burden HBVDNA testing in patients with HBsAg positive was significantly lower
of Disease (GBD) 2021. A descriptive epidemiological analysis at the in Surgical departments than those in Internal medicine departments
global, regional, and national levels was conducted. The trends were (50.6% vs 80.5%, P<0.001). Internal medicine departments had a
analyzed using the estimated annual percentage change (EAPC) and significantly higher referral rate for hospitalized patients to specialized
joinpoint regression models. The burden was decomposed using department than surgical departments (HBsAg positive:13.8% vs
population size, aging, and epidemiological changes. The cross- 3.9%, P< 0.001; HBVDNA positive:31.7% vs 12.4%). The referral rate of
country inequalities was quantified using current standard health hospitalized patients with positive HBVDNA to specialized departments
equity methods, and the changes in burden up to 2030 were predicted. increased from 29.5 % to 35.2 % in Internal medicine departments (P
Result: In 2021, the global incidence and Disability-Adjusted Life Years < 0.001) but remained unchanged in Surgical departments (12.4 % vs
(DALYs) for AHE among the elderly were recorded as 1,130,013.35 12.5%, P = 0.931). Similar results were observed for HBsAg-positive
and 20,084.77, respectively. Although there are significant differences patients.
in the incidence and DALYs of elderly AHE across countries and Conclusion: Conclusions: The number of patients with CHB in
regions worldwide, the overall burden of incident cases has gradually non-specialized departments is substantial. However, in Surgical
increased from 1990 to 2021, with a slight rise in Age-Standardized departments, the HBVDNA testing rate and referral rate to specialized
Rates (ASR), while the number and ASR of DALYs showed a declining department are relatively low. The short message early notification
trend. The highest ASR of incidence and DALYs were found in the system can improve the inpatient referral rate, yet its impact on
Low SDI region, with ASR gradually decreasing as SDI increased. surgeons is not significant. Enhancing communication with surgeons
Decomposition analysis revealed that population growth and aging are and their cognitive level of CHB is urgently needed.
the main drivers of changes in the AHE burden, while epidemiological Table and Figure:Figure 1.Distribution of HBsAg-Positive Patients in
changes somewhat offset the positive changes in DALYs driven by Each Department of the Hospital (2021 - 2024, n = 160,458)
population growth. Analysis of transnational inequalities showed that Figure 2.Referral Rate of Specialized Department for Hospitalized
low SDI countries bear a disproportionate burden of elderly AHE, Patients with HBsAg-Positive (A) and HBVDNA-Positive (B) in Internal
although inequalities related to SDI have narrowed over time. Notably, Medicine Departments and Surgical Departments from 2021 to 2024.
from 2022 to 2030, the number of incidence and DALYs is expected
to continue increasing, although the ASR of these is expected to
PP0024
remain relatively stable, with a slight upward trend. Gender subgroup
analysis indicates that the burden of AHE in elderly women is more Trends and cross-country inequalities in the global burden of
challenging than in men, suggesting a need for increased focus on acute hepatitis A 1990–2021: A population-based study
female populations in future plans. Deliang Huang1, Xiangchang Zeng1, Qinxian Cai1, Jun Chen1
Conclusion: From 1990 to 2021, the burden of AHE among the 1
The Third People’s Hospital of Shenzhen, The Second Affiliated
elderly, as a major public health issue, remains substantial. Countries Hospital of Southern University of Science and Technology
with lower SDI levels bear a disproportionate burden of elderly AHE, Background: To evaluate the trend and transnational inequality of the
and while health inequities related to SDI among different countries global burden of AHA over the past 30 years and further predicts its
have been somewhat alleviated over time, the pressure on low SDI changes by 2030.
countries to control the disease remains high. The issue of AHE in Method: Data for AHA were extracted from the Global Burden of
elderly women requires further attention. This study highlights the Disease study 2021. The epidemiology of AHA was described at the
significant challenges in controlling and managing elderly AHE, global, regional, and national levels. The trends in the burden from 1990
including the growing number of cases and distributional inequalities, to 2021 were analyzed from a multidimensional perspective, including
calling for better tailored public health policies and rational allocation
overall and local levels. The burden of AHA was decomposed based potassium ≤3.5 mmol/L, direct bilirubin >6.8 mmol/L, hemoglobin <110
on population size, age structure, and epidemiological changes. g/L, and glutamic-pyruvic transaminase >40 U/L were the protective
The transnational inequality of AHA burden was quantified using the factors in HCC patients. Based on these factors, a
standard health equity method recommended by the World Health nomogram was constructed, showing an area under the curve (AUC)
Organization, and the changes in burden by 2030 were predicted. of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly
Result: The GBD estimated the global number cases of AHA incidence higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766).
and DALYs for the year 2021 to be 160860121.69and 1817363.17, Compared with several ML algorithms, the XGBoost model had an
respectively, with age-standardized rates (ASR) of 2273.72 and 24.95 AUC of 0.832 (sensitivity = 0.745, specific?
per 100000. According to the World Health Organization’s regions ity=0.766) and an independent validation AUC of 0.829 (sensitivity =
classification, the the highest cases of incidence and DALYs number 0.766, specificity = 0.737), making it the top-performing model in both
were both in South-East Asia Region in 2021, and the highest age- sets. The external validation results have proven the accuracy of the
standardized rates (ASR) were in the African and South-East Asia XGBoost model.
Regions, respectively. From 1990 to 2021, a general continuous decline Conclusion: The proposed XGBoost demonstrated a promising ability
in the global number cases and ASR of incidence and DALYs of AHA, for individualized prediction of HCC in HBV-related cirrhosis patients
with the fastest decline occurring in the last decade. Decomposition with low-level AFP.
analysis revealed a significant decrease in the incidence and DALYs Table and Figure:Figure 1.tables of the article
burden of global AHA. Population growth and epidemiological Figure 2.figures of the article
changes were the main positive and negative drivers of AHA disease
burden, respectively, and the changes in epidemiology could largely
PP0026
offset the disease burden caused by population increase. The relative
inequality index suggested that the Socio-demographic Index (SDI) Global Burden of Chronic Liver Disease and Temporal Trends: A
was inversely to inequality, with inequality gradually decreasing as Population-Based Analysis from 1990 to 2021 with Projections to
SDI increased. The incidence gap between the highest and lowest 2050
SDI countries decreased from -1242 in 1990 to -1992 in 2021, and Yunyu Zhao1, Yajing Bo1, Zixuan Xing1, Jian Zu2, Zhanpeng Yang2,
the DALYs gap decreased from -78 in 1990 to -15 in 2021. Absolute Yue Zhang2, Yujiao Deng1, Yi Liu1, Lanting Zhang1, Xiao Yuan1, Yuan
inequality analysis also indicated that the gap between the highest Wang1, Henry Linda3, Fanpu Ji1, Mindie H Nguyen3
and lowest SDI countries narrowed from 1990 to 2021. Notably, it is 1
The Second Affiliated Hospital of Xi’an Jiaotong University, 2Xi’an
predicted that from 2022 to 2030, the number and ASR of incidence Jiaotong University, 3Stanford University Medical Center
and DALYs will continue to decline, with a particularly significant Background: Prior data up to 2019 suggested several changes in
decrease in DALYs. the epidemiology of chronic liver disease (CLD) globally, highlighting
Conclusion: From 1990 to 2021, the burden of AHA as a major public the need for more updated real-time data and forecasted estimates
health issue has shown a continuous downward trend, primarily driven to inform medical practice and future public health planning. We
by changes in epidemiological factors. Countries or regions with investigated the global burden of CLD (included cirrhosis) updated to
lower SDI levels bear a disproportionately high AHA burden, but the 2021, forecast to 2050 and analysis for inequalities by country income
inequality related to SDI among different countries has decreased over levels.
time. This study highlights that over the past three decades, the control Method: Using the Global Burden of Disease (GBD) 2021 database, we
and management of AHA have significantly improved. analyzed the CLD prevalent, incident, death cases and corresponding
Table and Figure:Figure 1. age-standardized rates from 1990-2021. We calculated average annual
percent change (AAPC) by joinpoint regression model and quantified
PP0025 inequalities according to World Health Organization-recommended
health equity standards. We predicted the global burden of CLD until
Development of machine learning-based personalized predictive
2050 based on time series prediction models.
models for risk evaluation of hepatocellular carcinoma in hepatitis
Result: In 2021, the number of prevalent, incident CLD and related
B virus-related cirrhosis patients with low levels of serum alpha-
deaths globally were 1.7 billion (95% uncertainty interval (UI): 1.6-
fetoprotein
1.8), 58.4 million (95% UI: 54.2-62.8) and 1.4 million (95% UI: 1.3-
Xu Yuan1, Zhang Bei1, Zhou Fan1, Yi Ying Ping1, Yang Xin Lei1, 1.5), respectively. During 1990-2021, age-standardized prevalence
Ouyang Xiao2, Hu Hui1 (ASPR) of CLD was stable (AAPC: 0.01%; 95% confidence interval
1
the 2nd Hospital of Nanchang University , 2Quiclinic Technology Co., (CI): -0.03% to 0.05%), age-standardized incidence rate (ASIR)
Ltd., Nanchang, PR China increased, especially in those aged 15-49 (AAPC: 0.49%; 95% CI:
Background: The increasing incidence of hepatocellular carcinoma 0.45%-0.53%), in Europe (AAPC: 0.41%; 95% CI: 0.41%-0.42%)
(HCC) in China is an urgent issue, necessitating early diagnosis and and the Americas (AAPC: 0.41%; 95% CI: 0.39%-0.42%), and age-
treatment. This study aimed to develop personalized predictive models standardized death rate (ASDR) decreased globally (AAPC: -1.26%;
by combining machine learning (ML) technology with a demographic, 95%CI: -1.35%-(-1.17%)) and across subgroups. In 2021, metabolic
medical history, and noninvasive dysfunction-associated steatotic liver disease (MASLD) accounted
biomarker data. These models can enhance the decision-making for 74.7% of prevalent and 82.7% of incident CLD cases globally.
capabilities of physicians for HCC in hepatitis B virus (HBV)-related The ASIR of MASLD increased the most in those aged 15-49 (AAPC:
cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. 0.72%; 95% CI: 0.67%-0.77%) and in the Western Pacific region
Method: A total of 6,980 patients treated between January 2012 and (AAPC: 0.73%; 95% CI: 0.59%-0.86%). Socio-demographic index
December 2018 were included. Pre-treatment laboratory tests and (SDI)-related inequalities decreased for ASPR and ASIR of CLD but
clinical data were obtained. The significant risk factors for HCC were increased for ASDR, placing a disproportionately heavier burden on
identified, and the relative risk of each variable affecting its diagnosis low-SDI countries. By 2050, the ASIR of CLD is projected to increase
was calculated using ML and univariate regression analysis. The data globally to 763.4 (95% CI: 680.9-853.5) per 100,000, with an increase
set was then randomly partitioned into validation (20 %) and training of about 5.6% and primarily driven by the increase in MASLD, which is
sets (80 %) to develop the ML models. estimated to surge by roughly 19.2%, while the ASDR is projected to
Result: Twelve independent risk factors for HCC were identified using decrease to 9.5 (95% CI: 6.9-12.1) per 100,000.
Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random Conclusion: This study findings highlight the need for targeted
forest, and least absolute shrinkage and selection operation regression interventions and strategies to address the disparities in the global
models. Multivariate analysis revealed that male sex, age >60 years, burden of CLD, with a particular focus on MASLD management, the
alkaline phosphate >150 U/L, AFP >25 ng/ younger population (15-49 years), and socio-demographic inequalities.
mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L Table and Figure:Figure 1.Figure 1. Global burden, trend, and cross-
were the risk factors, whereas hypertension, calcium <2.25 mmol/L, country inequality of chronic liver disease from 1990 to 2021, with
projection to 2050. (A) Global ASPR, ASIR and ASDR of CLD from Mortality Burden of HBV/HCV-related Liver Cancer: A Comparative
1990 to 2021 and further forecasted to the year 2050, overall and by Analysis of Temporal and Spatial Trends from 1990 to 2050
sex. (B) Average annual percent change (AAPC) of ASPR, ASIR and Yujiao Deng1, Jingyue Tan2, Jian Zu2, Zixuan Xing3, Zhanpeng Yang2,
ASDR of CLD from 1990 to 2021 overall, by sex, by age, by WHO Yue Zhang2, Yajing Bo3, Xu Gao1, Enrui Xie3, Fanpu Ji3, Yuan Wang3
region and by liver disease etiology. (C) Socio-demographic Index 1
Division of Gastroenterology, the Second Affiliated Hospital of
(SDI)-related health inequality regression curves and concentration Xi’an Jiaotong University, Xi’an, China, 2School of Mathematics and
curves for ASPR, ASIR and ASDR of CLD worldwide, 1990 and 2021. Statistics, Xi’an Jiaotong University, Xi’an, China, 3Department of
Figure 2.Figure 2. Global age-standardized prevalence, incidence Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong
and death rates of chronic liver disease from 1990 to 2021 and further University, Xi’an, China
forecasted to the year 2050 by liver disease etiology. Background: Liver cancer (LC) is one of the most common causes of
cancer-related deaths worldwide. This study estimated the mortality of
PP0027 hepatitis B/C virus (HBV/HCV)-associated LC.
Risk of advanced liver disease among individuals with hepatitis B Method: We analyzed the temporal and spatial trends of HBV/HCV-
virus infection with low level viremia compared to individuals with associated LC mortality from 1990-2021 and forecasted to 2050.
no evidence of hepatitis B virus infection The BAPC model was used to predict the age-standardized mortality
rate (ASMR) of LCB/LCC in 2020-2050 globally and in the six WHO
Paul Y Kwo1, Laura E Telep2, Leland J Yee2, James Chuo2, Betty
subregions, accounting for gender differences.We calculated average
Chiang2, Sarjita D Naik2, Catherine T Frenette2, Amanda W Singer2,
annual percent change (AAPC) by joinpoint regression model and
Anand P Chokkalingam2, Camilla S Graham3,4
quantified inequalities. We also evaluated the factors impacted the
1
Stanford University, 2Gilead Science, Inc., 3Harvard University, 4Beth
mortality used decomposition analysis.
Israel Deconess Medical Center
Result: Global deaths from LC doubled from 238,969 in 1990 to
Background: Current hepatitis B virus (HBV) treatment guidelines do 483,875 in 2021. Compared with 1990, HBV and HCV etiologies
not recommend antiviral therapy for individuals with low level viremia accounted 37.45% and 30.28%, corresponding to a 7.13% decrease
(LLV; defined as HBV DNA ≤ 2,000 IU/mL) unless cirrhosis has been and 3.44% increase, respectively. During 1990-2021, the global ASMR
diagnosed; however, the association between LLV and advanced liver of LC (AAPC: -0.11, 95% CI: -0.35 to 0.12) and LC due to HCV (LCC)
disease is unclear. In this study, United States (US) electronic medical (AAPC: 0.05, 95% CI: -0.26 to 0.36) presented a stable trend, and had
record (EMR) and administrative claims data were used to characterize decreased for LC due to HBV (LCB) (AAPC: -0.54, 95% CI: -0.81 to
individuals with HBV LLV compared to those with no evidence of HBV, -0.27). The ASMR of LCB showed an overall downward trend worldwide
and to evaluate the risk of two outcomes in these groups: compensated (AAPC1990-2050=-0.94), from 2.5/100000 in 1990 to 2.09/100000 in
cirrhosis (CC) and a composite outcome of advanced liver disease 2021, and it is expected to further decrease to 1.37/100000 in 2050. As
events (defined as: CC, decompensated cirrhosis (DC), hepatocellular for LCC, the global ASMR showed a stable and fluctuating trend, from
carcinoma (HCC), and liver transplant (LTx)). 1.7/100000 in 1990 to 1.74/100000 in 2021, and is expected to remain
Method: Using Health Verity Marketplace EMR and claims data from stable at 1.71/100000 in 2050. The death burden of males was higher
2015 – 2023, two cohorts of adults (18+ years at index date) with than that of females (LCB for females: ASMR2021=0.76, 95% CI: 0.61
(1) HBV LLV and (2) no evidence of HBV (controls) were identified. to 0.94; LCB for males: ASMR2021=3.54, 95% CI: 2.87 to 4.41; LCC
Chronic HBV infection was defined as ≥ 2 positive lab results (HBsAg for females: ASMR2021=1.54, 95% CI: 1.30 to 1.76; LCC for males:
or HBV DNA) at least 6 months apart. Individuals with < 365 days of ASMR2021=1.99, 95% CI: 1.69 to 2.33). There were significant spatial
continuous insurance enrollment prior to index, nucleot(s)ide analogue distribution differences in ASMR of LCB/LCC in different regions.
(NA) treatment in the 6 months prior to index, or baseline evidence of Despite the highest ASMRs of LC and LCB in the Western Pacific
CC, DC, HCC, LTx, hepatitis C or D, or HIV were excluded. Absolute Region (WPR), itsit had been rapidly declining. And the highest ASMR
rates per 100 person-years (PY) and corresponding 95% confidence of LCB and LCC shifted from the WPR to the Eastern Mediterranean
intervals were calculated for each cohort, and Cox proportional hazards Region. The global ASMR of LC is predicted to decline until 2050
methods were used to estimate the risk of CC or of the composite (AAPC: –0.34, 95% CI: –0.46 to –0.23). During 1990-2021, in the five
outcome among those with HBV LLV vs. no evidence of HBV after most populated countries, the ASMR of LC increased the fastest in the
adjusting for demographic factors and baseline health conditions. United States (AAPC=2.44, 95% CI: 2.09 to 2.78), and only decreased
Result: After applying the inclusion and exclusion criteria, 1,139 in China (AAPC=–0.68, 95% CI: –1.25 to –0.10). Population growth and
individuals with HBV LLV, and 232,795 individuals with no evidence age structure were the main reasons for the increase in LC mortality
of HBV were identified. Those with LLV were older, more likely to be globally and in Southeast Asia from 1990 to 2021. Age structure is likely
Asian, and had significantly higher rates of diabetes, hypertension, to be key to the increase in LC mortality worldwide during 2022–2050.
hyperlipidemia, and MASH (see Table). After adjustment for age, Conclusion: The disease burden of hepatitis virus-related LC remains
sex, race, and baseline health conditions, HBV infection with LLV was high, and etiological and geographical variations exist. Asia accounts
associated with a significant increased risk of cirrhosis compared to no for most LC-related deaths worldwide. The WPR consistently had the
evidence of HBV (HR: 8.39, 95% CI: 5.28 – 13.34). An increased risk of highest ASMR of LC, and the Americas had the highest increase of
the composite outcome was also observed (HR: 2.68, 1.82 -3.93). The ASMR.
risk of cirrhosis and of any advanced liver disease events remained Table and Figure:Figure 1.Figure 1. Temporal trends of LCB/LCC-
elevated in a subgroup analysis including only individuals with no ASMR worldwide in the six WHO subregions, 1990-2050.
evidence of NA treatment or HBV DNA > 2,000 IU/mL during the follow Figure 2.Figure 2. Spatial distribution of LCB/LCC-ASMR in 2021 and
up period (71.5% of the original cohort; CC HR: 6.72 (3.86 – 11.71); 2050 in 204 countries and territories. (A) the ASMR of LCB in 2021, (B)
composite outcome HR: 2.10 (1.31 – 3.38)). the ASMR of LCB in 2050, (C) the ASMR of LCC in 2021, (D) the ASMR
Conclusion: In this analysis of US EMR and claims data, individuals of LCC in 2050.
with HBV LLV had a significant increased risk of liver-related events
relative to those with no evidence of HBV. These results support the
need for additional studies to determine whether starting antiviral PP0029
therapy could be a mechanism to mitigate advanced liver disease risk Multi-omics analysis reveals causal relationships and potential
among individuals with HBV LLV. mediators between dietary preferences and risk of NAFLD
Table and Figure:Figure 1. Shisheng Wu1, Qingan Fu1, Nuobei Zhang1
1
The Second Affiliated Hospital, Jiangxi Medical College, Nanchang
PP0028 University, Nanchang, Jiangxi, China
Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent
condition closely associated with obesity and metabolic syndrome,
with its global incidence on the rise. This study aims to explore the PP0031
causal relationship between dietary preferences and NAFLD risk Global Distribution and Trends of Liver Cancer due to Nonalcoholic
using multi-omics analysis, and to comprehensively explore possible Steatohepatitis from 1990-2021
mediating factors and their underlying mechanisms.
Jiawang Lu1, Gang Qin, Jun-Tao Shu, Chun-Hu Li
Method: We analyzed data from genome-wide association studies
(GWAS) to assess the potential genetic links between various dietary
1
Department of Infectious Diseases, Affiliated Hospital of Nantong
University
preferences and NAFLD. A two-step Mendelian randomization (MR)
analysis was conducted to evaluate whether dietary preferences affect Background: The increasing disease burden of non-alcoholic
NAFLD risk by regulating inflammatory factors. Further, co-localization steatohepatitis (NASH)-related liver cancer (NALC) has become a
analysis was used to identify gene loci driving the causal relationships growing concern. This study aims to comprehensively analyze and
between dietary preferences and NAFLD risk. Finally, clinical cross- predict the global distribution of NALC disease burden.
sectional data from the National Health and Nutrition Examination Method: Disease burden indicators and risk factors for NALC from
Survey (NHANES) and bioinformatics analysis were used to validate 1990 to 2021 were collected from the Global Burden of Disease (GBD)
the findings. study, stratification analysis was performed. Joinpoint regression,
Result: MR analysis revealed that a preference for low-calorie diet machine learning, decomposition analysis, frontier analysis and other
significantly reduces NAFLD risk by modulating DNER. Co-localization methods are used for comprehensive analysis.
analysis identified the FTO gene variant rs28429148 as a key driver of Result: From 1990 to 2021, NALC age-standardized incidence (ASIR),
the causal relationship between soft cheese and fruit juice preferences, prevalence (ASPR), disability-adjusted life years (ASDR), and mortality
with soft cheese increasing and fruit juice reducing NAFLD risk. (ASMR) rates all showed upward trends, with a consistently higher
These findings were further validated by clinical cross-sectional and burden in males. Projections for 2022 to 2030 indicate ASIR, ASPR, and
bioinformatics analysis. ASDR will keep rising, while ASMR may slightly decline. Decomposition
Conclusion: This study, for the first time, comprehensively elucidates analysis indicated that global increases in NALC burden from 1990 to
the causal relationship between dietary preferences and NAFLD 2021 were largely driven by population growth (43.16%), with males
risk from a multi-omics perspective and identifies FTO and DNER as experiencing a higher absolute increase than females (315,406.2 vs.
potential therapeutic targets. These findings provide new insights into 276,055.7 cases). Frontier analysis identified Mongolia as having the
the importance of personalized dietary interventions in the prevention largest gap from benchmarked health outcomes (effective difference
of NAFLD and informs clinical treatment. = 130.42), highlighting a substantial potential for improvement, while
Somalia showed minimal deviation from the benchmark (effective
difference = 0.56), suggesting limited additional intervention potential.
PP0030
Among risk factors, high fasting plasma glucose accounted for a
A persistent global inequality in HBV-related liver cancer burden larger proportion of NALC burden than smoking (21.39% vs. 8.68%).
from 1990 to 2021: a secondary analysis of the global burden of Conclusion: The burden of NALC is anticipated to intensify as
disease study 2021 demographic and societal shifts continue. Reliable epidemiological
Siqi Gao1, Qiuyu Guo1, Zijun Liu1, Shu Wang1, Fanqi Kong1, He Li 2 data on NALC are critical to informing clinical strategies, optimizing
1
China Medical University, 2The First Hospital of China Medical patient management, and shaping effective public health policies.
University Table and Figure:Figure 1.
Background: Hepatitis B Virus (HBV)-related liver cancer remains a Figure 2.
global health challenge, with remarkable disparities across different
Socio-demographic Index (SDI). This study aimed to assess the PP0032
temporal trends in the global burden of HBV-related liver cancer and Estimates and trends in the global burden of hepatocellular
cross-country inequalities across SDI levels between 1990 and 2021. carcinoma by NASH from GBD Study between 1990 to 2021
Method: Global disability-adjusted life years (DALY) data due to HBV-
Jing Liu1, Mingwei Wang2,3,4, Junping Shi1
related liver cancer were extracted from the Global Burden of Diseases
2021. The age-standardized DALY rate (ASDR) was used to assess
1
Affiliated Hospital of Hangzhou Normal University, 2Department
of Cardiology, Affiliated Hospital of Hangzhou Normal University,
the burden of HBV-related liver cancer. The slope index of inequality
Zhejiang Key Laboratory of Medical Epigenetics, School of
(SII) and the concentration index were applied to estimate the absolute
Basic Medical Sciences, Hangzhou Institute of Cardiovascular
and relative cross-country inequalities, with positive values indicating a
Diseases,Engineering Research Center of Mobile Health
higher burden in higher SDI countries, and vice versa.
Management System&Ministry of Education, Hangzhou Normal
Result: From 1990 to 2021, the ASDR of HBV-related liver cancer University,Hangzhou, 310015, China;, 3Hangzhou Lin‘an Fourth
decreased from 416.37 (95% uncertainty interval [UI]: 366.90, 477.53) People‘s Hospital, Hangzhou,311321, China, 4Jiande First People‘s
to 252.48 (95% UI: 219.37, 285.18) per 100,000 population globally. Hospital, Hangzhou, Zhejiang, China
Countries with high, high-middle, middle, low-middle, and low SDI had
Background: The prevalence of non-alcoholic steatohepatitis (NASH)-
a decline of ASDR of 46.24%, 44.19%, 49.74%, 35.11% and 39.82%,
driven hepatocellular carcinoma (HCC) is rising rapidly, which not only
respectively. Globally, ASDR burden persistently concentrated in lower
causes economic burden to patients, but also increases the social
SDI countries over the past three decades. The SII of ASDR in HBV-
burden. This study aimed to estimate the global burden of HCC due to
related liver cancer declined from -804.00 (95% confidence interval
NASH over the past 30 years.
[CI]: -895.46, -712.53) to -520.82 (95% CI: -584.70, -456.93). The
Method: The number and rate of deaths, disability-adjusted life years
relative inequality for global HBV-related liver cancer remained stable
(DALYs), and age-standardized rates (ASRs) for NASH-induced HCC
between 1990 and 2021, with the concentration index of -0.22 in 1990
were extracted. The estimated annual percentage changes (EAPCs)
and -0.23 in 2021.
for ASRs were calculated using a generalized linear model with a
Conclusion: Although the DALY burden of HBV-related liver cancer
Gaussian distribution to quantify the temporal trends in the global
decreased across all SDI regions, a remarkable inequalities cross-
burden of NASH-attributed HCC. The strength and direction of the
national health inequality persisted during the past 30 years, exhibiting
association between the sociodemographic index (SDI) and the DALY
with higher burden in lower SDI countries. More attention must be paid
rate were measured using Spearman’s rank-order correlation.
to reducing the HBV-related liver cancer burden and achieving equity
Result: Approximately 9.63% of the global DALYs of HCC in 1990
globally, especially in lower regions and countries.
were associated with NASH, which increased to 11.5% in 2021. From
Table and Figure:Figure 1.The number of DALYs (A) and age-
1990 to 2021, the global DALY cases of HCC caused by NASH and the
standardized DALY rates (B) of HBV-related liver cancer from 1990 to
global burden of DALYs increased, whereas the DALY rate decreased
2021, by SDI levels
with a higher SDI regional grade. The ASR of HCC with NASH increased
Figure 2.Absolute and relative cross-country inequality in DALY burden
with age, reaching the highest in the >85-year-old age group.
of HBV-related liver cancer, 1990–2021
Conclusion: The burden of HCC caused by NASH has increased over Result: In 2021, the ASIR of GBTC is 3.50 / 100,000 population (95%
the past three decades, especially in regions with a low SDI and in UI, 3.11-3.80/100,000 population). From 1990 to 2021, the global ASIR
old-age groups. decreased by 14% (95% UI: 8%-11%). The ASDR of GBTC is 2.23
per 100,000 population (95% UI: 1.99-2.38/100,000 population). The
global ASDR decreased by 20% (95% UI: 16%-28%) from 1990 to
PP0033
2021. And the age-standardized DALYs of GBTC is 43.22/100,000
Global, regional, and national burdens of hepatitis E from 1990 to population (95% UI: 37.71-46.08/100,000 population). The global ASR
2021 and forecasted incidence in 2030: Results from the Global decreased by 22% (95% UI: 17%-30%) from 1990 to 2021.Whether in
Burden of Disease Study 2021. terms of ASIR or ASDR, high-SDI regions exhibit significantly higher
Baiyun Wu1, Yuxin Tian1, Jing Zuo1, Jieru Yang1, Yuchen Fan1 values compared to other regions. However, compared with males,
1
Qilu Hospital of Shandong University females show significantly higher ASIR, ASDR, and age-standardized
Background: Hepatitis E (HEV) is a liver inflammation caused by the DALYs. The countries with the highest ASIR (4.40-9.01/100,000
Hepatitis E virus, found worldwide, contributing to the global disease population) are Chile, Japan, South Korea, and Thailand. However,
burden. We aimed to assess the evolving disease burden of Hepatitis some African countries near the South Atlantic, such as Angola,
E virus (HEV) across different age groups, spanning global, regional, Namibia, and the Republic of the Congo, as well as Madagascar near
and national levels from 1990 to 2021, and to predict the 2030 HEV the Indian Ocean, and Asian countries like Uzbekistan, have the lowest
incidence rates. ASIR levels (0.00-0.66/100,000 population). Similar to ASIR, ASDR and
Method: Drawing from the Global Burden of Diseases (GBD) Study age-standardized DALYs also show similar distribution trends. For both
(2021), we analyzed the incidence of HEV along with the associated male and female, the age group 70-74 years old had the highest death
disability-adjusted life years (DALYs). We quantified the incidence, numbers. Furthermore, the age-specific mortality rates for both male
calculated the average annual percentage changes (AAPCs) and and female showed an upward trend. In the next 30 years, the ASIR for
pinpointed the years that marked the most substantial shifts in the females is expected to continue decreasing, while the ASIR for males
global trajectory of HEV incidence. Furthermore, we dissected these is expected to keep rising. The ASDRs for both male and female is
global trends by considering variables such as age, sex, and the expected to remain largely unchanged, with females continuing to
sociodemographic index (SDI). We subsequently utilized the Bayesian have a higher ASDR than males.
Age-Period-Cohort (BAPC) model to predicted the 2030 HEV incidence Conclusion: In 2021, the global burden of GBTC incidence and
rates. mortality remained heavy. Although the overall incidence and mortality
Result: On a global scale, the incidence rate of HEV infection decreased of GBTC showed a declining trend from 1990 to 2021, the incidence
from 269.68 per 100,000 individuals (95% uncertainty interval [UI], rate of GBTC in males is expected to rise in the next 30 years, making
224.04 to 322.68) in 1990 to 260.41 per 100,000 individuals (95% UI, them a key target for future health policy interventions.
215.39 to 312.21) in 2021, with an AAPC of -0.1 (95% CI, -0.1 to -0.1).
Notably, the incidence of HEV significantly decreased in 1995, 2006, PP0035
2009, and 2014. The predicted global HEV infection incidence in 2030
Disproportionately Increase in Alcohol-related Liver Disease and
is 267.44 per 100,000 people (95% uncertainty interval [UI] 235.27 to
Alcohol Use Disorder in Asia
299.6).
Conclusion: From 1990 to 2021, the global HEV incidence declined, Pojsakorn Pojsakorn Danpanichkul1, Yanfang Pang2, Kanokphong
mirroring the spread of antiretroviral therapy and preexposure Suparan3, Pimtawan Jatupornpakdee4, Preenapun Saokhieo4,
prophylaxis. Nevertheless, annual HEV increases persist in some Natchaya Polpichai5, Tanawat Attachaipanich6, Thanathip
regions and nations. Swift action on disease control is crucial for Suenghataiphorn7, Andrew F Ibrahim1, Polathep Vichitkunakorn8,
the 2030 targets amid considerable global disparities in burden and Sakkarin Chirapongsathorn9, Ashok Choudhury10, Anand V Kulkarni11,
advancement. Karn Wijarnpreecha12, Suthat Liangpunsakul13, Apichat Kaewdech14
Table and Figure:Figure 1.The global and national incidence burden
1
Texas Tech University Health Sciences Center, 2Affiliated Hospital
of HEV of Youjiang Medical University for Nationalities, 3Immunology Unit,
Department of Microbiology, Faculty of Medicine, Chiang Mai
University, 4Faculty of Medicine, Chiang Mai University, 5Department of
PP0034 Internal Medicine, Weiss Memorial Hospital, 6Department of Internal
The disease burden of gallbladder and biliary tract cancer from Medicine, University of Missouri-Kansas City School of Medicine,
1990-2021: a population-based observational study from 2021
7
Department of Internal Medicine, Griffin Hospital City School of
GBD database Medicine, 8Department of Family and Preventive Medicine, Faculty of
Medicine, Prince of Songkla University, 9Phramongkutklao Hospital,
Xiaoxiao Wang1, Zixing Wang1, Huiying RAO1 1
0Department of Hepatology and Liver Transplant, Institute of
1
Peking University People‘s Hospital, Peking University Hepatology Liver and Biliary Sciences, 11Department of Hepatology and Liver
Institute, Infectious Disease and Hepatology Center of Peking Transplantation, Asian Institute of Gastroenterology AIG Hospitals,
University People‘s Hospital, Beijing Key Laboratory of Hepatitis 1
2Division of Gastroenterology and Hepatology, Department of
C and Immunotherapy for Liver Diseases, Beijing International Medicine, University of Arizona College of Medicine, 13Division of
Cooperation Base for Science and Technology on NAFLD Diagnosis, Gastroenterology and Hepatology, Department of Medicine, Indiana
Beijing 100044, China. University School of Medicine, 14Gastroenterology and Hepatology
Background: Gallbladder and biliary tract carcinoma (GBTC) is highly Unit, Division of Internal Medicine, Faculty of Medicine, Prince of
fatal malignancy that may arise from the gallbladder or the biliary tract. Songkla University
Only less than 25% patients have access to safe, timely, and high- Background: As alcohol consumption continues to rise rapidly in
quality cancer surgery in the world. GBTC is one of only a few cancers Asia, research into its significant consequences, alcohol-associated
that generally is more common in female than in male. However, to liver disease (ALD) and alcohol use disorder (AUD), is still limited. This
date, the global studies on the cancer burden of primary GBTC was study aims to examine the burden of ALD and AUD in Asia from 2000
insufficient. to 2021.
Method: All GBTC cancers (except intrahepatic bile duct cancer, Method: We analyzed data from the Global Burden of Disease (GBD)
C22.1) were coded as C23 through C24.9 based on the ICD 10th. Study 2021 to assess age-standardized prevalence, incidence, and
In this study, we used age-standardized incidence rates (ASIRs), mortality rates for ALD and AUD in Asia from 2000 to 2021.
age-standardized death rates (ASDRs), age-standardized DALYs, Result: In 2021, there were approximately 1.40 million cases of ALD,
and EAPCs to quantify global GBTC burden. We used a generalized resulting in 175,370 deaths, and 53.18 million cases of AUD, with
additive model adjusted for the SDI Index to estimate the relationship 57,110 deaths. Asia accounted for 46.35% of the global prevalence
between the SDI and ASDRs of GBTC in different locations of the world of ALD (an increase of 6.87% since 2000) and 47.86% of the global
from 1990 to 2021.
prevalence of AUD (an increase of 0.82% since 2000). Despite a 91.2% Togtuunbayar1,2, Batgerel Zagdragchaa3, Erkhembayar Dimaa1,4,
increase in crude ALD prevalence, incidence, and mortality from 2000 Enkhbold Chinbold5,3, Enkhtuya Damba3, Oidov Baatarkhuu6,3,
to 2021, age-standardized rates declined in most subregions. South Amarsanaa Jazag7,3
Asia exhibited the highest crude burden of ALD, while Central Asia had 1
Mongolian Association for the Study of Liver Diseases, 2Happy
the highest age-standardized rate. Notably, ALD prevalence increased Veritas Hospital, 3Mongolian Associaton for the Study of Liver
in South Asia (Annual Percent Change [APC]: 0.10%, 95% CI: 0.08 to Diseases, 4National University of Health Sciences University affiliated
0.13) and Central Asia (APC: 0.88%, 95% CI: 0.79 to 0.97), even as Hospital, 5Second General Hospital, 6Department of Infectious
other regions experienced declines. Diseases, National University of Health Sciences, 7Otoch Manramba
Conclusion: This study reveals a disproportionately increasing University
burden of ALD and AUD in Asia compared to global trends, with Background: In Mongolia, some patients diagnosed with liver cancer
significant variability across subregions. Central Asia and South Asia experinece delay treatment, which increases the risk of death due to
are identified as the primary drivers of the burden associated with ALD tumor growth and metastasis to other organs. In this study we aimed
and AUD in this region. to determing the time before getting treatment and causes of delay in
Table and Figure:Figure 1.The trend in the burden of alcohol-associated approximately 500 patients with HCC.
liver disease in Asia Method: We used A-HOC database of 558 Mongolian patients to
Figure 2.The trend in the burden of alcohol use disorder in Asia determine the time until starting cancer treatment. The study included
453 patients diagnosed with liver cancer at Happy Veratis Hospital
PP0036 between 2017 and 2024, and analyzed using anamnesis-synthesis
method
Global burden of cirrhosis in childhood and adolescence, 2000–
Result: Of the 453 patients selected, 63.7% were male and 363% were
2021: a systematic analysis of the global burden of disease study
female. Of the 453 people surveyed, 75.9% (344) entered treatment
2021
immediately, 9.4% (43) entered after 1 month, 5.5% (25) entered after
Xueqi Yang1, Baiyun Wu1, Yuzhen Wang1, Xinjing Yang1, Yuchen 2 months, 2.4% (11) entered after 3-4 months, 3% (14) entered after
Fan1 5-6 months, and 3.5% (16) entered after 7-12 months. The reasons for
1
Department of Hepatology, Qilu Hospital of Shandong University, not entering treatment right away are shown in the graph.
Jinan, China Conclusion: 3/4 of patients entered the treatment without any delay,
Background: Cirrhosis is a major cause of morbidity and mortality which is a very good result. But the delay in starting HCC treatment in
globally,but data on the burden and trends were sparse in children Mongolia was caused by following top 5 reasons: 1. Went abroad for
and adolescents.We aimed to determine the trends and changes in treatment or second opinion, 2. Financial causes, 3. Trying traditional
the global burden of cirrhosis among adolescents and young adults alternative remedies, 4. Sending and waiting for second opinions, 5.
using Global Burden of Disease (GBD) data (2000–2021). Could not belive the diagnosis.
Method: Data on cirrhosis was collected by the Global Burden of Table and Figure:Figure 1.
Disease (GBD) 2021 database from 2000 to 2021. We reported the
numbers and rates of incidence and prevalence of cirrhosis among
PP0038
adolescents and young adults at the global, regional, and national
levels.The age-period-cohort (APC) model was applied to analyze An Analysis of Gender, Age Distribution, and Temporal Trends in
trends across different age groups, periods, and birth cohorts, and the Cholangiocarcinoma Mortality in the United States: A Population-
Bayesian Age-Period-Cohort (BAPC) model was utilized for forecasting based Study
future epidemiological trajectories. Xindi Huang1, Yuxin Guo1, Xinyuan He1, Zhanpeng Yang2, Sikai Qiu1,
Result: Globally, from 2000 to 2021, the incidence rate of cirrhosis Yajing Bo1, Xin Liu1, YeeHui Yeo3, Fanpu Ji1, Ning Gao1
among the 5-9 and 10-14 age groups decreased from 221.93 (173.4 1
The Second Affiliated Hospital of Xi ‘an Jiaotong University, 2School
to 283.55) per 100,000 and 169.49 (133.12 to 207.26) per 100,000 to of Mathematics and Statistics, Xi’an Jiaotong University, 3Division of
110.93 (81.22 to 148.29) per 100,000 and 77.83 (58.31 to 101.7) per General Internal Medicine, Cedars-Sinai Medical Center
100,000, respectively. Meanwhile, the incidence rate of cirrhosis among Background: Cholangiocarcinoma is a highly lethal malignancy. While
the 15-19 and 20-24 age groups increased from 1076.95 (867.47 to the mortality rate of hepatocellular carcinoma (HCC) has stabilised,
1311.49) per 100,000 and 1139.98 (900.81 to 1408.18) per 100,000 particularly with a significant decrease in HBV/HCV-related HCC, the
to 1176.6 (926.16 to 1460.32) per 100,000 and 1284.89 (1009.04 to temporal trends of cholangiocarcinoma mortality and its differences
1598.04) per 100,000, respectively.From 2000 to 2021, the proportion between different sites, age groups and gender subgroups remain
of cirrhosis prevalence caused by hepatitis B decreased(15-19:11% unclear. Investigation of cholangiocarcinoma mortality trends is
to 4%,20-24:35% to 23%) ,while increases in cirrhosis prevalence essential to optimise public health policies and early interventions.
were driven by the proportion caused by NAFLD (15-19:87%-93%,20- This study aims to analyze the age-standardized mortality rate (ASMR)
24:55% to 67%). The age, period, and cohort effects of cirrhosis trends of intrahepatic and extrahepatic cholangiocarcinoma-related
among children and adolescents were consistent across SDI regions deaths from 2006 to 2023 based on the National Vital Statistics System
and globally, showing an increase with age, while period and cohort (NVSS) database, and the impact of the COVID-19 pandemic on
effects showed a decline. However, the period and cohort effects of ASMR.
cirrhosis caused by NAFLD increased across both SDI regions and Method: The study data were obtained from the National Vital
globally. Statistics System (NVSS) database, covering cholangiocarcinoma-
Conclusion: From 2000 to 2021, the incidence of cirrhosis decreased related deaths from January 2006 to December 2023. It evaluates
significantly in younger age groups (5-9 and 10-14 years) but increased mortality trends in adults aged 25 years and older and the impact of
in older adolescents and young adults (15-19 and 20-24 years). The the COVID-19 pandemic, with subgroup analyses based on bile duct
proportion of cirrhosis caused by hepatitis B declined globally, while location, age groups (25-44, 45-64, ≥65), and sex (male, female).
NAFLD emerged as the leading cause, with its burden increasing Result: This cross-sectional study included a total of 61,560
substantially. cholangiocarcinoma deaths, including 54,280 intrahepatic
Table and Figure:Figure 1.The global burden of cirrhosis in childhood cholangiocarcinoma cases and 7,280 extrahepatic cholangiocarcinoma
and adolescence cases. The ASMR of cholangiocarcinoma showed an increasing
trend from 2006 to 2023. The Annual Percentage Change (APC)
PP0037 of intrahepatic cholangiocarcinoma was 3.72%, while the APC of
extrahepatic cholangiocarcinoma accelerated during the pandemic
Determining the length of time before receiving HCC treatment
(APC=5.32%). For intrahepatic cholangiocarcinoma, the APC of male
and assessment of reasons of delay in Mongolia
was consistently higher than the female (3.88% vs. 3.50%). The elderly
Gantsetseg Ulziibat1,2, Erdenebayar Gonchig1,2, Byambatsetseg
group (≥65 years) had the highest ASMR with the most significant PP0040
increase (APC=5.05%, 2006-2014; APC=3.06%, 2014-2023). The Branding as a Traditional Healing Practice for Jaundice: Remedy
ASMR has increased from 7.1 per 100 000 in 2006 to 13.2 in 2023, with or Risk?
the prediction model showing a high degree of accuracy, suggesting
Md Ismail Gazi1,2, Mohammad Salauddin Mia1, Hema Binte Hamid3,
that the trend is reliable. The remaining age groups had lower ASMR
Mohammad EmrulHasan Khan1,2
but showed an increasing trend (Figure 1).
Meanwhile, extrahepatic cholangiocarcinoma showed no significant
1
National Gastroliver Institute and Hospital, Dhaka, 2ScopeBD
Laparoscopic Training and Research Center, Dhaka, 3Institute of
gender differences. The elderly group (≥65 years) had a slightly
Public Health, Dhaka
higher ASMR, but the increase was slow, with no significant trend. The
rest of the age groups remained stable. No significant fluctuations in Introduction: Traditional healing practices for jaundice remain common
ASMR were observed during the pandemic, with actual mortality rates in Bangladesh despite limited evidence of efficacy. Among these
aligning closely with predicted values, suggesting limited impact of the practices, branding (applying heated metal to the abdomen) has been
pandemic on cholangiocarcinoma mortality (Figure 2). observed in patients on several occasions during our clinical practice.
Conclusion: The ASMRs for intrahepatic cholangiocarcinoma have However, no report of this practice has been published in Bangladesh
increased significantly, especially in older and male populations, while until now. This case report presents the first detailed documentation of
changes in extrahepatic cholangiocarcinoma have been more stable branding as a traditional treatment for jaundice in Bangladesh.
but show regional differences in specific populations. The results Case description: A 51-year-old male presented to the gastroenterology
suggest that increased screening and early intervention in high-risk department of a tertiary care hospital in Dhaka with a 4-month history of
populations is key to reducing cholangiocarcinoma mortality. progressive jaundice, itching, dark-colored urine, anorexia, and weight
Table and Figure:Figure 1.Age standardized Mortality Rate of loss. Three months earlier, he had sought treatment from a traditional
Intrahepatic bile duct carcinoma (Per 100,000 persons) healer, who performed branding by pressing a heated metal coin onto
Figure 2.Age standardized Mortality Rate of Extrahepatic bile duct his upper right abdomen, claiming it would cure the jaundice within a
carcinoma (Per 100,000 persons) month. His jaundice did not improve, and a second branding was done
12 days prior to the hospital presentation. However, his symptoms
worsened, prompting him to seek medical care.
PP0039 On examination, the patient had icteric sclera and skin, right upper
The Prevalence and Incidence of Urinary Tract Infections in the abdomen tenderness, a scar, and a superficial dermal burn with post-
Past Decade – A Meta-Analysis and Systematic Review burn wound infection. Laboratory results showed elevated bilirubin
Wenjing Wang1, Yan Wang1 (16.2 mg/dL), AST (567 IU/L), ALT (127 IU/L), ALP (721 IU/L), and
1
8 Xishiku Dajie, Xicheng District, Beijing CA 19.9 (356.5 U/mL). Serologies for hepatitis A, B, C, and E were
Background: Urinary tract infections (UTIs) are among the most negative. MRCP and CT scan revealed a mass at the terminal part of
prevalent infectious diseases worldwide, posing a significant burden the common bile duct, causing mild dilatation and biliary obstruction
on public health. Despite extensive research, the global incidence (distal cholangiocarcinoma). The patient was referred to the surgery
trends of UTIs over the past decade remain unclear. This meta-analysis department. The burn was treated with antibiotics and regular
aims to evaluate the incidence of UTIs globally and among specific dressings. Initially, a Whipple procedure was planned. However,
populations during the last ten years. during surgery, a palliative triple bypass was performed as the tumor
Method: PubMed, Scoups and Web of Science databases were was unresectable with vascular encasement. He was discharged and
systematically searched for studies published in 2014 and later. Cross- referred to an oncologist for further care.
sectional, case-control, and cohort studies reporting the incidence of To understand the branding process, we visited and interviewed the
UTI in community and hospital Settings were included. Random effects traditional healer with consent. The healer claimed that intense heat
models were used to estimate the pooled incidence, and subgroup applied to the liver region destroys jaundice-causing substances but
analyses were performed according to region and type of disease. could not explain the mechanism or provide a scientific rationale.
Heterogeneity was assessed using the I² statistic. Interestingly, although the branding therapy failed to improve his
Result: A total of 71 studies involving 169,343 individuals were condition, the patient reported experiencing short-term relief and
included in this meta-analysis. The pooled global incidence of urinary peace following the procedure. This transient relief was likely due
tract infections (UTIs) was 18.7% (95% CI: 17.7%–19.6%). Among to the release of endogenous opioid peptides triggered by painful
these, the incidence of hospital-acquired UTIs was 17.3% (Figure 1). stimuli, which can induce temporary euphoria and analgesia without
Within hospital-acquired UTIs, the highest incidence was observed addressing the underlying disease.
in kidney transplant recipients (30.7%), followed by pregnant This case highlights the importance of raising awareness about the
women (25%). Catheter-associated UTIs accounted for 15.1%, while risks of unproven and harmful traditional practices, which can lead to
ICU patients had an incidence of 5.6%. Surgical procedures were diagnostic and treatment delays, resulting in poorer disease outcomes.
associated with a 3.2% increase in UTI incidence, and patients with
liver cirrhosis had a UTI incidence of 9.6%(Figure 2). PP0041
Regional analysis revealed that the incidence of UTIs was highest Risk of cancer associated with HBV, HCV, MASLD, alcohol and
in Africa (8.9%) compared to Asia (2.2%) and Europe, where the smoking
incidence was the lowest (1.2%). Due to the inclusion of only one study
Carolyn Wallace1, Samantha Hall1, Devin Razavi-Shearer1, Homie
from North America and Oceania, data from these regions lacked
Razavi1
representativeness. 1
Center for Disease Analysis Foundation
Conclusion: UTIs remain a significant and widespread global health
problem, especially in high-risk populations such as pregnant women, Background: Numerous studies have followed cohorts and reported
patients with indwelling catheters, and hospitalized patients. The the likelihood of developing liver cancer associated with hepatitis B
increased incidence observed in the African region may be attributed virus (HBV) and hepatitis C virus (HCV) infections, as well as metabolic
to factors such as limited access to health care resources, inadequate syndrome-like liver disease (MASLD) and alcohol consumption. The
infection-control measures, and antibiotic resistance. These results objective of this study was to collect and report this data in comparison
highlight the need to implement comprehensive prevention strategies to a well-established risk factor, such as smoking.
for high-risk populations, including strict catheter management Method: A comprehensive literature review was conducted on PubMed
practices, timely screening for UTIs in susceptible populations, and (publications prior to September 2024) to identify studies that assessed
rational use of antibiotics. the risk of developing lung cancer associated with smoking (current or
Table and Figure:Figure 1.Figure 1.Prevalence of hospital-acquired ≥1 pack/day), liver cancer attributed to alcohol consumption (highest
UTIs alcohol use group reported), HBV, HCV, and MASLD in Asian countries.
Figure 2.Figure 2. Prevalence of UTI in different diseases Included studies were cohort, case-control, and nested case-control
designs that reported odds ratios (ORs), relative risks (RRs), or hazard 2
Happy Veritas Hospital, 3Otoch Manramba University, 4Second
ratios (HRs) along with corresponding confidence intervals (CIs). The General Hospital, 5Mongolia-Japan teaching hospital, 6Department of
pooled OR was calculated using variance weighting, where variance infectious diseases, MNUMS
served as a surrogate for study size. Background: Liver cancer incidence in Mongolia is 63.2 per 100,000
Result: In Asian countries, 20 studies reported an increased risk population, or 6.5 times higher than the world average. During the last
of liver cancer associated with heavy alcohol consumption, 20 for 12 years, 26,543 cases of liver cancer were registered between 2010
HBV infection, 11 for HCV infection, 7 for MASLD, and 9 for the risk and 2022, which accounts for 36.3% of all malignancies detected in
of developing lung cancer from smoking. The study sample size Mongolia, mortality-wise 21,312 deaths were caused by HCC, 42.2%
ranged from 28,000 to 920,000 for alcohol consumption, 190,000 to of all cancer deaths. The 12 year cumulative survival rate of HCC is
497,000 for HBV infection, 190,000 to 12,000 for HCV infection, 13,448 19.8%.
to 6,400,000 for MASLD, and 1,400 to 4,100,000 for smoking. The Method: Currently Mongolia is an active participant of A-HOC studies,
odds ratio of developing liver cancer in Asia was: alcohol 2.0 (95% supported by APASL. Data from Ministry of Health and A-HOC
confidence interval: 1.4–3.0); MASLD 2.1 (0.8–5.9); HCV 11.0 (5.5– registration platform was used to update HCC status in Mongolia
21.9); HBV 16.3 (8.8–30.1); and the risk of developing lung cancer Result: If the liver cancer in Mongolia is classified by regions, it is 27.2%
from smoking ≥1 pack per day was 4.0 (2.8–5.7). in the Western region, 18.3% in the Central region, 24.8% in the Gobi
Conclusion: A substantial body of research has already been region, and 31.2% in the Eastern region. Tests and equipment currently
published on the association between heavy alcohol consumption, used to detect liver cancer in Mongolia: US, dynamic CT, EOB-MRI,
MASLD, HCV, and HBV, and the risk of liver cancer. Compared to Pathology, Angiography, tumor markers AFP, Pivka-ll, L-3. Treatment
very heavy smoking, HCV and HBV infections have a 2.75- and 4.1- of liver cancer in Mongolia: Liver transplantation, Hepatectomy, RFA/
fold increased risk of developing cancer. MASLD and heavy alcohol MWA, TAE/TACE, Sorafenib, Lenvatinib, Atezolizumab/Bevacizumab.
consumption have approximately half the risk of cancer relative to The peak age of liver cancer in Mongolia is 61-66 years for women
heavy smoking. This study highlights the significant risk of liver cancer and 56-60 years for men. Also, the youngest age at which liver cancer
associated with HBV, HCV, MASLD, and heavy alcohol consumption. was diagnosed was 32 years for men and 34 years for women. A-HOC
Only when compared to the risk of developing lung cancer from heavy reveals 37.6% of HCCs are primary and 63.4% are recurrent. Etiology
smoking do we fully comprehend the severity of liver cancer as a risk of HCCs are 18% is of non-viral origin, 7% of alcoholic origin, and 75%
factor. are of viral origin, but this trend is slowly changing. The number of
Table and Figure:Figure 1.Odds ratio of developing cancer by risk registered HCC cases by the time of abstract submission stands at
factor 586
Conclusion: HCC registration and follow up is growing in number and
PP0042 quality. More hospitals are joining APASL initiative.
The longer the occupational exposure to liver toxins, the higher
the risk of NAFLD PP0044
Xiaoliang Li1,2,3, Junrong Li4, Zhongwen Feng 4, Taolong Zhou1, Tao Utilization of Fecal Immunochemical Test in a Tertiary Government
Luo1, Kefeng Li4, Mingxing Huang1 Hospital: A Retrospective Cohort Study
1
The Third People‘s Hospital of Zhuhai, 2Huazhong University of Bea Regine Panganiban1, Jayson Villavicencio1, Eric Yasay1
Science and Technology, 3University of Macau, 4Macao Polytechnic 1
Philippine General Hospital
University
Background: Background: The only validated indication for fecal
Background: Occupational exposure to hepatotoxicants has been immunochemical test (FIT) is colorectal cancer (CRC) screening.
implicated in the development abnormal liver function, but the impact No local studies have explored FIT practice trends. We examined
on non-alcoholic fatty liver disease (NAFLD) is not clear. This study aims FIT utilization, focusing on its indications and impact on clinical
to investigate the relationship between the duration of occupational management and outcomes.
hepatotoxicants exposure and the risk of NAFLD. Method: Methodology: This retrospective cohort study involved
Method: We conducted a longitudinal study involving 1978 control chart reviews of adult patients who underwent FIT from January 1
subjects and 3721 exposed individuals.Data on demographic to December 31, 2023. Logistic regression analysis was used to
characteristics and health indicators were collected.Chi-square determine the association of FIT positivity with gastroenterology
tests and logistic regression analysis were performed to assess the referrals, endoscopic procedures, and findings.
association between exposure duration and NAFLD risk. Result: Results: A total of 701 patients were analyzed, with 516
Result: The exposure group showed a higher prevalence of NAFLD (73.6%) from outpatient clinics and 317 (60.47%) for CRC screening.
compared to the control group,with significant differences in NAFLD Inappropriate FIT requests were common, with 204/516 (39%)
N(27.7%vs.22.0%,P<0.001).Notably,the exposure year was identified outpatient and 180/185 (97%) inpatient tests ordered outside evidence-
as a significant predictor of NAFLD risk,with 4% higher risk of NAFLD based indications; outpatient tests had a significantly lower rate of
per increasing exposure year(95%CI:1.02-1.06,P<0.001). Present inappropriate requests (Z-score-4.39,p<0.05). Among inpatients,
evidence also shows that age,hypertension,and elevated liver 162/185 (87.57%) were for anemia, while only 5 (2.7%) were for CRC
enzymes associated with an increased risk of NAFLD. screening. Of the positive FITs for anemia, only 10/237 patients (4.22%)
Conclusion: Our findings suggest that the occupational exposure had a potential gastrointestinal cause identified. Notably, 63% (85/136)
duration to hepatotoxicants is associated with an increased risk of FIT-positive inpatients were not referred to gastroenterology. None
of NAFLD. These results highlight the importance of considering underwent annual serial FIT after a negative result. While FIT positivity
exposure in public health strategies and further research is warranted correlated with increased gastroenterology referrals (OR 13.84, 95%CI
to elucidate the underlying mechanisms. 8.92,21.48, p<0.001) and subsequent endoscopy (OR 6.60, 95%CI
Table and Figure:Figure 1.Table 1 Basic characteristics of the 4.09,10.66, p<0.001) in outpatients, it did not significantly relate to
population inpatient endoscopy. Importantly, majority of inpatients who underwent
Figure 2.Table 2 Logistic regression results FIT were critically ill.
Conclusion: Conclusion: FIT was often ordered in clinically
PP0043 inappropriate settings and did not consistently translate to effective
clinical management or follow-up endoscopy particularly among
Update of A-HOC in Mongolia
inpatients, confirming limited clinical utility in this setting
Amarsanaa Jazag1,2,3, Erdenebayar Gonchig1,2, Byambatsetseg
Togtuunbayar1,2, Enkhbold Chinbold4,1, Erkhembayar Dimaa5,1,
Enkhtuya Damba2,1, Oidov Baatarkhuu6,1 PP0045
1
Mongolian Association for the Study of Liver Diseases (MASLD),
The HBV immunization status of college students and the optimal were performed to assess the robustness of the results.
booster immunization strategies for susceptible students: a study Result: During a median follow-up of 197 months, 331 all-cause
including four universities in China deaths occurred among nasal S. aureus colonization. The fully
Yarong Song1, Yongliang Feng2, Feng Jiang3, Xingyan Xu4, Peijuan adjusted survey-weighted Cox PH model indicated that high NLR (1.43
Yang5, Jie Wang1, Jie Li1 [1.01, 2.02], P = 0.045) and SIRI (2.10 [1.41, 3.13], P < 0.001) were
1
Department of Microbiology & Infectious Disease Center, School of significantly associated with an elevated risk of fatality. This correlation
Basic Medical Sciences, Peking University Health Science Center, persisted in subgroup analyses based on sex, age, education, race,
Beijing 100191, China, 2Department of Epidemiology, School of family PIR, smoking, drinking and diabetes. ROC results displayed
Public Health, Shanxi Medical University, Taiyuan 030001 China, that both NLR and SIRI exhibited a high predictive ability in mortality
3
Department of Disease Prevention and Control, Zhengzhou risk. Kaplan-Meier curves indicated that high NLR and SIRI groups
University Hospital, Zhengzhou 450001, China, 4Department had better survival rates than low groups. Additional RCS analysis
of Epidemiology and Health Statistics, School of Public Health, identified that NLR and SIRI were non-linearly associated with all-
Fujian Medical University, Fuzhou 350122, China, 5The Student cause mortality (P < 0.05).
Psychological Counseling Center of the Student Affairs Department, Conclusion: This study innovatively indicated that higher NLR and
China West Normal University, Nanchong 637000, China SIRI levels were positively associated with increased risks of long-term
Background: People who have not been effectively immunized are all-cause mortality in the general population with nasal colonization of
vulnerable to hepatitis B virus (HBV) infection, and the annual reported S. aureus.
incidence of acute hepatitis B in China was mainly in young adults Table and Figure:Figure 1.Figure: The ROC curves of the NLR (A) and
since 2012. Universal screening for HBV and vaccination of susceptible SIRI (B) for predicting all-cause mortality at 3, 5,10 years.
populations are important measures to achieve the goal of eliminating Figure 2.Figure: The KM analysis of all-cause mortality based on NLR
viral hepatitis as a public health threat by 2030. We aim to understand (A) and SIRI (B) groups among individuals with nasal colonization of
the HBV immunization status of college students and explore optimal S. aureus.
booster immunization strategies for susceptible students.
Method: 3242 freshmen from four colleges were initially tested for PP0047
hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody
Residual rate of mother-to-child transmission of HBV: findings
(anti-HBs) using colloidal gold test strips. The freshmen who were
from a newly introduced programme on post-vaccination serologic
initially tested positive for HBsAg and/or negative for anti-HBs were
testing in Hong Kong SAR, China
further tested using Abbott reagents. Then, the freshmen with negative
anti-HBs and HBsAg as measured by Abbott reagents received two Chin Man Poon1, Patrick Shingkan Chong1, Vivien Waiman Tsui2,
doses of CHO hepatitis B vaccine (HepB) at 0 and 1 month, and those Jeffrey Cinghon Lai2, Zenith Hinyam Wu1, Bonnie Chunkwan Wong1
who were anti-HBs negative after the second dose of HepB would
1
Department of Health, 2Hospital Authority
receive the third dose CHO HepB at 6 months. Background: In Hong Kong, universal antenatal screening for
Result: 2329 (71.84%) freshmen were initially tested negative for anti- hepatitis B surface antigen (HBsAg), childhood hepatitis B vaccination,
HBs and HBsAg, and 46 (1.42%) freshmen were tested positive for and administration of hepatitis B immunoglobulin for babies born to
HBsAg. A total of 1263 freshmen with negative anti-HBs and HBsAg HBsAg-positive mothers have been in place since 1980s. Following
detected by Abbott reagents received HepB booster vaccination. the introduction of antiviral prophylaxis for pregnant women with high
Over 90%, nearly 99%, and over 99.9% freshmen obtained protective HBV viral load in 2020, an initiative of post-vaccination serologic
anti-HBs after the first, second, and third dose of HepB, respectively. In testing (PVST) was implemented in 2022 for babies born to HBsAg-
addition, one dose of HepB could provide protective anti-HBs to over positive mothers, aiming to identify babies with immunoprophylaxis
99% of freshmen with baseline anti-HBs levels of 2-10 mIU/mL. failure or inadequate immune response after hepatitis B vaccination for
Conclusion: Two doses of HepB are sufficient to provide protection for further management. This also provides systematic data for evaluating
the freshmen with negative anti-HBs, and those with baseline anti-HBs the effectiveness of the overall mother-to-child transmission (MTCT)
levels of 2-10 mIU/mL only need one dose of HepB booster. prevention strategy.
Method: Since January 2022, Maternal and Child Health Centres
PP0046 (MCHC) have been arranging PVST for babies born to HBsAg-positive
mothers in or after April 2021. From June 2022, mop-up PVST was
Neutrophil–lymphocyte ratio (NLR) and systemic inflammatory arranged for those born in or after October 2020 before the age of 24
response index (SIRI) as predictors for all-cause mortality of nasal months. The PVST consists of blood tests on both HBsAg and hepatitis
colonization of Staphylococcus aureus in the community setting: B surface antibody (anti-HBs), usually conducted at the age of 9-12
Evidence from NHANES 2001-2004 months. Data collected under the PVST initiative were reviewed for
Ju Zou1, Yuanyuan Xiao1, Biyue Tian1, Siyao Chen1, Anhua Wu1, evaluating the progress of eliminating MTCT of HBV in Hong Kong.
Chunhui Li1 Result: Out of the babies attending MCHC eligible for PVST, the
1
Department of Infection Control Center of Xiangya Hospital, Central acceptance rate for testing was 78.0% in 2022, 89.8% in 2023 and
South University 95.6% in 2024 (January to June). As of 30 September 2024, 2582
Background: There is no evidence illustrating the correlation between babies received PVST after primary hepatitis B vaccination. Of these,
the emerging inflammatory markers—neutrophil-to-lymphocyte ratio 2455 (95.1%) were sero-protected, 120 (4.6%) were tested negative
(NLR) together with systemic inflammatory response index (SIRI)—and for both HBsAg and anti-HBs, requiring the second series of hepatitis
long-term fatality risk of the general population with nasal colonization B vaccination, and seven (0.3%) were found infected with HBV
of Staphylococcus aureus (S. aureus). In this study, we aimed to and referred to paediatrician for hepatitis management. Among 93
prospectively evaluate this association to provide timely intervention babies who completed the second course of hepatitis B vaccination
and reduce unfavorable outcomes. with another PVST done, 92 (98.9%) were found sero-protected.
Method: A cohort of 1637 individuals with nasal S. aureus colonization Review of the seven infected babies found that none of their mothers
from the National Health and Nutrition Examination Survey (NHANES) received maternal antiviral prophylaxis, where three declined or self-
2001–2004 was included. Survey-weighted Cox proportional hazards discontinued the antiviral treatment during pregnancy despite having
and restricted cubic spline (RCS) models were used to evaluate high HBV viral load.
associations of NLR and SIRI with all-cause mortality, respectively. The Conclusion: The PVST programme was successfully rolled out with
predictive accuracy of NLR and SIRI for mortality risk was quantified by increasing acceptance in Hong Kong. An integrated analysis of the
the receiver operating characteristic (ROC) curve. The Kaplan-Meier PVST results and local epidemiology suggested that the MTCT rate of
curves were employed for comparing the survival probability between HBV had been reduced to a very low level, likely reaching the impact
groups of low and high groups of NLR and SIRI. Subgroup analyses target for MTCT elimination at ≤0.1% HBsAg prevalence in children ≤5
years old. To realise a hepatitis B-free generation in Hong Kong, the
effectiveness and safety of the use of maternal antiviral prophylaxis hepatitis C virus(HCV) infections in US, but access to diagnose(40%)
shall be further promoted. and receive treatment(1/3) was low. We aimed to develop HCV
infection screening algorithms using easily accessible demographic
parameters.
PP0048
Method: Methods We obtained data from National Health and Nutrition
Interventions to Improve Medication Adherence in Patients with Examination Survey(NHANES 1990-2020), and divided them into
Chronic Liver Diseases: A Systematic Review training(6-cycles; n=46243) and testing(5-cycles; n=37060) cohort.
YooJeong Shin1,2, Isaac HengBIn Moh1,2, Neha Sheriff2, Angela Then, logistic regression was applied to calculate the odds ratio(OR)
Webster3,4, Emily He2,5, Karen Waller2,3,4 of 4 demographic factors(sex, ethnicity, blood transfusion history, birth
1
Concord Clinical School, Faculty of Medicine and Health, University year). Next, we developed and compared 9 machine learning(ML)
of Sydney, Australia, 2Department of Gastroenterology, Concord algorithms to diagnose HCV infection. Finally, we adopted the selected
Repatriation General Hospital, Australia, 3Sydney School of Public algorithm to establish the model and test the performances.
Health, Faculty of Medicine and Health, University of Sydney, Result: Results The overall cohort(n=83303) was 49.0% male; 8.8% of
Australia, 4NHMRC Clinical Trials Centre, Faculty of Medicine and participates had a history of blood transfusion; with a mean birth year of
Health, University of Sydney, Australia, 5The Daffodil Centre, Faculty of 1972±23. The positive rates of anti-HCV and HCV RNA were 1.3% and
Medicine and Health, University of Sydney, Australia 0.8%(unweighted). In multivariate analysis, all four parameters were
Background: Chronic liver disease (CLD) affects 1.5 billion people significantly correlated with HCV infection: male(OR 2.01; P<0.001);
globally and causes significant morbidity and mortality, primarily Black versus White(OR 1.96; P=0.008); blood transfusion history(OR
through complications such as cirrhosis and hepatocellular 2.14; P<0.001); born 1970 and before(OR 8.98; P<0.001). Comparing
carcinoma. Effective medical therapies can treat CLDs or prevent the AUC values of 9 ML algorithms in the training cohort, XGBoost was
their complications, including antivirals to control hepatitis B, curative selected as the best prediction model. The AUC of the XGBoost model
treatments for hepatitis C, or beta-blockers to reduce the risk of cirrhosis was 0.891(95%CI 0.880-0.903) in the training set. In the testing set, the
decompensation. Yet, suboptimal medication adherence is common in AUC was 0.843(0.827-0.858), and the sensitivity, specificity, PPV and
CLD. Improving medication adherence in CLD patients could enhance NPV were 0.78, 0.78, 0.288 and 0.967, respectively.
health outcomes and reduce healthcare costs. This study aimed to Conclusion: Conclusion To predict HCV infection in general
systematically review interventions that improve medication adherence population, only 4 easily obtained demographic features are needed
in patients with CLD. using our ML model.
Method: Medline, Embase and The Cochrane Central Register of Table and Figure:Figure 1.Figure 2 ROC curves of 9 machine learning
Controlled Trials were searched for interventional studies on medication models in the diagnosis of HCV infection. (A) Birth year, sex, ethnicity,
adherence in CLD (4th of June, 24th of June 2024). The inclusion and blood transfusion history distribution in anti-HCV positive and
criteria were: populations with hepatitis B, hepatitis C, alcohol-related negative participates; (B) training cohort; (C) validation cohort.
liver disease, autoimmune hepatitis, primary biliary cholangitis, Wilson’s Figure 2.Figure 3 Performance of XGBoost model in the diagnosis of
disease, or cirrhosis; and study design: randomised controlled trials, HCV infection. (A) ROC curves in training cohort; (B) ROC curves in
non-randomised trials or prospective cohort studies with comparator validation cohort; (C) ROC curves in testing cohort; (D) calibration
groups. Risk of bias was assessed using ROBINS-I tool. Study curve in testing cohort; (E) Decision Curve in testing cohort; (F) Shapley
population, study design, intervention characteristics, and adherence analysis for variable importance and explanation of predictions.
outcomes were extracted. Relative improvements in adherence were
calculated to determine the effectiveness of interventions.
PP0050
Result: After screening 5241 records, 30 studies were included. Most
studied hepatitis C (17/30) or hepatitis B (9/30); two studies addressed The awareness of the link between liver cancer and hepatitis as a
cirrhosis, one study each examined autoimmune hepatitis and motivation for action – results of a globally representative survey
primary biliary cirrhosis and no studies examined alcohol-related liver Cary James1, Jessica Hicks1, Alexandra Smith1
disease or Wilson’s disease. Interventions were mixed, but included 1
World Hepatitis Alliance
increased health care worker education/support (11), drug regimen Background: Viral hepatitis is the most common risk factor for liver
simplification (6), supervised medication administration (3), telehealth cancer. Chronic viral hepatitis can lead to hepatocellular carcinoma
(3), smartphone reminders and education (2), group/peer-support (2), (HCC), which accounts for 80% of all liver cancer cases. Asia is
financial incentives (2) and other (2). Many (9/30) studies were at risk of disproportionately burdened and the region accounts for 72% of the
serious bias. Significant improvement in at least one adherence measure total liver cancer deaths worldwide. Despite this, few studies have
was reported in 18/30 studies. Consistent improvements in medication been conducted on the awareness of viral hepatitis’ connection to liver
adherence were observed with enhanced nursing interventions (6/6 cancer in the general population. To gain a greater understanding of
studies) and directly observed therapy in opioid treatment programs public awareness on the link between liver cancer and hepatitis the
(3/3 studies). There were limited studies and inconsistent results for World Hepatitis Alliance undertook a globally representative survey in
other types of interventions, including pharmacist-led education and nine countries, with a focus on Asia.
counselling, drug regimen simplification, telehealth and group therapy. Method: The World Hepatitis Alliance developed a survey, consisting
Conclusion: Promising strategies to improve medication adherence of five multiple choice questions to assess awareness of the link
in CLD include enhanced nursing interventions and directly observed between viral hepatitis and liver cancer and if that knowledge affects
therapy in opioid treatment programs. Unfortunately, published their likelihood to be tested or vaccinated for viral hepatitis. The survey
interventions to date are limited in quality and comparability, and fail was fielded in nine countries, including four in Asia, that were selected
to study high-burden conditions such as alcohol-related liver disease. based on geographic representation, and their rates of liver cancer.
Further high-quality trials are needed. The survey was distributed by the Survey Monkey audience platform
Table and Figure:Figure 1.Number of Different Intervention Types, to the general public between 30 June to 4 July 2023.
Grouped by Disease Result: 569 participants responded to the globally representative
Figure 2.Relative Improvement in Medication Adherence by Study survey from Argentina, Germany, Ghana, Hong Kong SAR of China,
India, Nigeria, South Korea, Vietnam, and the United States of
PP0049 America. 217 of the 569 participants responded from the 4 countries in
Asia. The survey found that nearly half (42%) of people worldwide are
Optimizing a hepatitis C screening model for general population
unaware that one of the leading causes of liver cancer is viral hepatitis.
using simple demographic data
However, it found that awareness in Asia was much higher, with 70% of
Chi Zhang1, Yiqi Liu1, Hong Zhao1, Guiqiang Wang1 participants responding that they were aware of the link between viral
1
Peking university first hospital hepatitis and liver cancer. The survey also found in Asia that over three
Background: Background and aims An estimated 2.4 million chronic quarters (78%) of the participants responded that knowing hepatitis
causes liver cancer means that they are more likely to get tested 1
Menoufia university
and over four fifths (82%) responded that they are more likely to get Background: Helicobacter pylori (H. pylori) is one of the most
vaccinated. These findings were similar to but slightly higher than the important pathogens affecting humans, infecting about half of the
global survey results. population worldwide and about 90% in Egypt, Africa and developing
Conclusion: The survey indicated that a significant percentage of countries. The pathogenesis and disease progression are mediated by
people globally are unaware of the link between hepatitis and liver a group of environmental and bacterial virulence factors.
cancer, but overall awareness was found to be higher in Asia. The Method: The study included 310 patients with different GIT symptoms
survey also indicated that if people are aware of the connection, who were exposed to upper gastrointestinal endoscopy. Gastric
they felt more likely to get tested for hepatitis and to be vaccinated biopsies were taken from antrum and corpus. Histopathologic
against hepatitis B. The findings demonstrate why it is critical to raise examination was done to gastric biopsies taken from patients after
awareness that viral hepatitis is one of the leading causes of liver cancer which PCR assay was accomplished to biopsies using standard
to accelerate progress towards the World Health Organization’s goal to laboratory procedures.
eliminate hepatitis by 2030. Health systems should integrate hepatitis Result: From the 310 patients, 180 patients were confirmed to
services into their cancer prevention programmes to decrease cancer be infected with H. pylori Using histopathology method giving an
mortality and support the elimination of hepatitis as a public health overall prevalence of 58% (180/310). Upon endoscopy, Pangastritis
threat. represented about 119 (66.1%) patients of 60 H. Pylori positive
Table and Figure:Figure 1.Global key findings patients, whereas 39 (21.7%) patients had Peptic ulcer disease (PUD).
Figure 2.Key findings in Asia Cancer stomach was detected in 10(5.6%) patients of 60 H. Pylori
positive patients. The overall Vac A, and Cag A genes identified were
PP0984 97 (53.8%), 70 (38.8 %) respectively, by PCR-based molecular testing.
The vac A gene status was significantly found in 52.6% of H. pylori
A nomogram based on clinical indicators and enhanced CT for
infected patients with pangastritis (p = 0.001). Also, Cag A gene was
prediction of VETC metastatic pattern in hepatocellular carcinoma
highly significantly found in 77.1% of H. pylori infected patients with
Kai Zhang1, Yongquan Yu2
pangastritis (p <0.001).
1
Qilu Hospital of Shandong University, 2Weihai Central Hospital Conclusion: The study showed a significant association between
Affiliated to Qingdao University virulence genes (Vac A,Cag A) and certain gastrointestinal diseases.
Background: Hepatocellular carcinoma (HCC) ranks sixth in global Table and Figure:Figure 1.Relation between Cag A and socio-
cancer incidence and was the third leading cause of cancer-related demographic characteristics, complaint and endoscopic findings in
deaths in 2020. Studies show that the Vascular Endothelial Tumor positive cases (n=120)
Capsule (VETC) pattern correlates with lower differentiation, higher Figure 2.Relation between Vac A and socio-demographic
recurrence, and metastasis rates in liver cancer, particularly to the characteristics, complaint and endoscopic findings in positive cases
lungs. VETC is an independent predictor of disease recurrence and (n=120)
survival post-liver resection and transplantation.
Method: A retrospective study included 101 HCC patients
PP0053
confirmed by pathology from July 2018 to June 2024, all undergoing
preoperative enhanced CT. Patients were divided into VETC-positive Optimizing Induction Models for Acute Liver Failure in SD Rats
(46 cases) and VETC-negative (55 cases) groups based on CD34 Bin Niu1,2, Ao Lv1,2, Liaoyun Zhang1
immunohistochemistry results. Clinical data collected included 1
Department of infectious Diseases, The First Hospital of Shanxi
gender, age, hepatitis B status, CEA, and AFP levels. Enhanced Medical University, 2Graduate School, Shanxi Medical University
CT qualitative indicators observed were ascites, pseudo-capsule Background: Acute liver failure (ALF) is a critical condition with high
presence, intratumoral necrosis, artery, irregular margins, non-ring- mortality characterized by rapid hepatic dysfunction leading to multi-
like hyperenhancement in the arterial phase, and hypovascular organ failure. Due to limited clinical treatment options and donor
components. Quantitative indexes included maximum tumor diameter scarcity, effective animal models are essential for understanding ALF
and extracellular volume fraction (ECV). Independent samples t-test pathophysiology and evaluating potential therapies. This study aimed
or Mann-Whitney U test compared quantitative data between groups; to optimize induction protocols for ALF in Sprague-Dawley (SD) rats
χ² test compared qualitative data. Multifactorial logistic regression using carbon tetrachloride (CCl4) and D-galactosamine (D-Gal),
identified independent VETC predictors, and a nomogram model was focusing on reproducibility, safety, and clinical relevance.
established. ROC curves evaluated predictive performance, with AUC Method: ALF models were induced in SD rats using various doses and
differences compared using the DeLong test. administration methods of CCl4 (4 ml/kg and 8 ml/kg, intraperitoneal or
Result: Significant differences were found in AFP levels, intratumoral gavage) and D-Gal (1.5 g/kg, 2.0 g/kg, and 2.5 g/kg, intraperitoneal).
artery, hypovascular components, and ECV between VETC-positive The models were evaluated for survival rate, liver injury biomarkers
and VETC-negative groups (all p<0.05). Logistic regression showed (ALT, AST), histopathological changes, and the presence of
AFP, intratumoral artery, and ECV as independent predictors of positive therapeutic windows. Successful induction was defined by consistent
VETC expression (OR 2.695, 3.633, 1.061, all P<0.05). The nomogram ALF pathology without excessive mortality.
model for predicting VETC expression in HCC was established. The Result: CCl4 at 4 ml/kg failed to induce significant liver injury, while 8 ml/
AUCs for AFP, intratumoral artery, ECV, and the nomogram model were kg caused rapid mortality within 24 hours, limiting its utility. In contrast,
0.617, 0.679, 0.662, and 0.781, respectively. The nomogram model’s D-Gal at 2.0-2.5 g/kg successfully induced ALF with characteristic
diagnostic efficacy was significantly better than individual indicators hepatocellular necrosis, elevated ALT/AST levels, and a manageable
(Z=3.49, 2.759, 2.330, P<0.05). survival rate (33.3%-67.7%) within a 72-hour window. Histological
Conclusion: The nomogram combining clinical and enhanced CT analysis revealed extensive hepatocyte vacuolation, disorganized liver
indicators shows superior efficacy for preoperatively predicting HCC architecture, and inflammatory infiltration, aligning with ALF pathology.
VETC metastatic patterns compared to single indicators. The D-Gal model demonstrated higher reproducibility and provided an
Table and Figure:Figure 1. Figure optimal intervention window compared to CCl4.
Figure 2.Table Conclusion: This study establishes 2.5 g/kg D-Gal as an effective
dose for ALF induction in SD rats, balancing model reproducibility and
PP0052 therapeutic applicability. Compared to CCl4, D-Gal offers a more stable
and clinically relevant platform for ALF research. Future studies should
Impact of Helicobacter Pylori virulence genes (Cag A, Vac A) on
explore sex differences, anesthesia effects, and immune-modulatory
Endoscopic findings in upper gastrointestinal tract in Egyptian
agents to enhance the translational value of these models.
patients with different Upper GIT Symptoms.
Table and Figure:Figure 1.Serological Data for the CCl4 (4 ml/kg) Group
Mostafa Makram Arafa1
Figure 2.Serological Data for the D-galN Group Method: Hepatic progenitor cell-specific lineage tracing mice
(Sox9Cre-ERRosatdTomato) were given tamoxifen to label Sox9
PP0054 expressing cells and two injections of retrorsine (RS) to suppress
hepatocyte proliferation before 50% PH.
Acute Stress Disorder Injure Interstitial Cells of Cajal in Gallbladder Result: The liver weight and liver/body weight ratio at 2-week and
HUANG ZHENPENG1, HU QIU2, KE WANG3, JIWEI WAN3, ZHI 4-week post PH were markedly lower than that of the control mice.
YANG3 There was a transient increase in liver CD45+CD3－ immune cell
1
Guangxi University of Chinese Medicine, 2Renmin Hospital of Wuhan infiltration and extracellular matrix deposition at 2-week post PH.
University, 3Xi’an Medical University And, few Ki-67 and HNF4a double positive proliferating hepatocytes,
Background: Traffic accident is one of main challenges to public while many Ki-67 and Sox9 double positive proliferating progenitor
health in worldwide, and it would cause serious physiological stress. cells were detected at 2-week and 4-week post PH. The expanded
Both psychological and physical stresses have long been known hepatic progenitor cells mainly differentiated into cholangiocytes and
to affect gallbladder motility. ICCs are localized in gallbladder, made limited contribution to hepatocytes because of the unsuccessful
where they function as smooth muscle pacemaker cells, promoting inducement of p21 expression in preexisting hepatocytes by RS.
gallbladder electrical activity, mediating and regulating gallbladder Conclusion: Hepatocyte hypertrophy and progenitor cell-majored
neurotransmitters; besides, it also has relationships to various cholangiocyte differentiation are insufficient for quick liver recovery
gallbladder motility disorders. SCF/c-kit pathway is important for ICCs. after PH when hepatocyte proliferation is inhibited.
This study explored the mechanism underlying functions of gallbladder
ICCs under acute stress conditions. PP0056
Method: There were 36 adult rabbits were randomly divided into 1
Single-cell atlas identifies transporter-type hepatocytes as
healthy control group and 5 study groups. Each rabbit from the study
drivers of repair in acute liver failure mice treated with hBMSC
groups was subjected to a right chest puncture using a Hopkinson
transplantation
Bar with an acceleration of 2600g, and following which 1 study group
was subjected to surgery immediately, while other 2 study groups were Heng Yao1, Jing Zhang1, Hui Yang1, Suwan Sun1, Xi Liang1, Jing
held for 24h (24h group) and 72h (72h group), respectively. Besides, Jiang1, Jiaojiao Xin1, Dongyan Shi1, Xin Chen2,3, Jun Li1
dexamethasone sodium phosphate injection after puncturing via
1
State Key Laboratory for Diagnosis and Treatment of Infectious
auricular vein and keep 24h (Treatment 24h group) and 72h (Treatment Diseases, National Clinical Research Center for Infectious Diseases,
72h group), then subjected to laparotomy and cholecystectomy. National Medical Center for Infectious Diseases, The First Affiliated
Immunohistochemistry was used to determine the morphology and Hospital, Zhejiang University School of Medicine, 2Institute of
numbers of gallbladder ICCs, while immunohistofluorescence and Pharmaceutical Biotechnology and the First Affiliated Hospital
Department of Radiation Oncology, Zhejiang University School of
TUNEL assays were performed to detect apoptosis numbers of
Medicine, 3Joint Institute for Genetics and Genome Medicine between
gallbladder ICCs. RT-PCR was performed to detect changes in the
Zhejiang University and University of Toronto, Zhejiang University
SCF/c-kit signal pathway.
Result: There were no differences in ICCs morphology between Background: The regenerative mechanisms in acute liver failure (ALF)
groups. Gallbladder ICCs were lost after puncture, after which mice treated with hBMSC transplantation remain poorly understood.
acute stress was relieved, and the density of gallbladder ICCs have This study constructed a comprehensive hepatic cell atlas to uncover
recovered; meanwhile, the density of gallbladder ICCs in animals the repairing processes.
that were injected glucocorticoid were higher than animals that Method: hBMSCs were transplanted into immunodeficient Fah-/-Rag2-
without injection at the same time (P<0.05). Apoptosis of gallbladder /-IL-2Rγc-/- SCID (FRGS) mice with induced FHF. Single-cell RNA
ICCs increased in acute stress and then decreased after stress was sequencing (scRNA-Seq) provided a detailed cellular map of the liver.
alleviated, the density of death gallbladder ICCs in animals that were Pseudotime analysis captured the dynamic changes in hepatocyte
injected glucocorticoid were lower than animals that without injection subtypes during repair. Immunohistochemistry (IHC) validated the
at the same time (P<0.05). In addition, the SCF/c-kit pathway, which regulatory elements identified.
was down-regulated during acute stress, was enhanced following Result: Two hepatocyte subtypes were identified in regenerating
up-regulation of stress; besides, SCF/c-kit pathway in animals that livers, termed classic hepatocyte and transporter-like hepatocytes.
were injected glucocorticoid has recovered than animals that without The transporter-like hepatocytes, highly expressing Mlxipl, were
injection at the same time (P<0.05). enriched in transporter-related functions such as detoxification and
Conclusion: Acute stress injures gallbladder ICCs; however, bile acid handling, showing accelerated recovery post-transplantation.
gallbladder ICCs would recover after stress is relief or removal. Pseudotime trajectories indicated a transition from classic to
Table and Figure:Figure 1.Figure 1 Change of Density of Gallbladder transporter-like hepatocytes during regeneration, mediated by hepatic
ICCs and Death Cells stem/progenitor cells (HsPCs). Multi-color IHC verified the presence of
Figure 2.Figure 2 Change of SCF/c-kit pathway in Gallbladder Mlxipl-high transporter-like hepatocytes.
Conclusion: This study identifies a transporter-type hepatocyte
subtype driving liver repair by restoring essential bile acid and toxin
PP0055 transport functions. These hepatocytes, despite being severely
Impaired Liver Recovery in Retrorsine/Partial Hepatectomy impaired, are replenished through differentiation from typical
Mice by Hepatocyte Hypertrophy and Progenitor Cell-Majored hepatocytes, offering insights into regenerative processes driven by
Cholangiocyte Differentiation hepatocyte transformations.
Yan Cui1,2,3, Li Li1,2,3, Yu He1,2,3, Shan Shan1,2,3, Lin Liu1,2,3, Hongyi Li1,2,3,
Jiangbo Ren1,2,3, Hui Wang1,2,3, Miaoran Yang1,2,3, Xinyan Zhao1,2,3, PP0057
Jidong Jia1,2,3, Ping Wang1,2,3
Blocking PI3K/Akt signal pathway promotes FoxA2 low-
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
expressing liver progenitors to respond to differentiation reagent
University, Beijing 100050, China., 2National Clinical Research Center
of Digestive Diseases, Beijing 100069, China., 3Beijing Key Laboratory and differentiate towards hepatocytes.
of Translational Medicine in Liver Cirrhosis, Beijing 100069, China. Jiangbo Ren1,2,3, Li Li1,2,3, Ping Wang1,2,3
Background: Liver has an extensive proliferating capacity after
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
University, Beijing 100050, China., 2National Clinical Research Center
liver resection, while the known progenitor cell-majored liver
of Digestive Diseases, Beijing 100069, China., 3Beijing Key Laboratory
recovery process has controversies when hepatocyte proliferation is
of Translational Medicine in Liver Cirrhosis, Beijing 100069, China.
suppressed. So, it still needs further explorations to understand this
regeneration process after partial hepatectomy (PH). Background: To enhance the response to differentiation reagent of the
Forkhead box protein A2 (FoxA2) low-expressing hepatic progenitor
cells and promote their differentiation towards hepatocytes. the proportion of apoptotic cells increased. In addition, GPX4, FSP1
Method: FoxA2 was knocked down in rat liver progenitor cells by and SLC7A11 protein expression was decreased, while ASCL4 protein
FoxA2 shRNA and the mRNA transcriptions of albumin and hepatocyte expression was increased, accompanied by increased Fe2+, LPO and
nuclear factor (HNF)4a were analyzed by RT-PCR. Then, sodium MDA levels. The combination therapy was observed to enhance the
butyrate, a differentiation-inducing reagent, was used to treat FoxA2 therapeutic effect of PDT by inducing the ferroptosis pathway.
knockdown cells to reveal their response to the differentiation reagent Table and Figure:Figure 1.Effect of photodynamic action on
by testing glycogen synthesis and albumin expression. Furthermore, cholangiocarcinoma cell lines.
RNA sequencing, KEGG analysis, RT-PCR, and Western blot were Figure 2.PDT affected the changes in Ferroptosis‐related indicators.
used to detect the activating signal pathway in FoxA2 knockdown
cells. Finally, sodium butyrate and Ly294002, an inhibitor of PI3K/Akt
PP0059
signal pathway, were used to treat FoxA2 knockdown cells to reveal
the recovery of their differentiation response. Phosphatidylserine induce thrombotic tendency and liver damage
Result: Knocking down FoxA2 reduced hepatocyte-related gene in obstructive jaundice
transcription of albumin and HNF4a when compared to the control Muxin Yu1, Chuwei Zheng2, Xiaoguang Wang2, Jinming Zhang2, Rong
cells. The glycogen synthesis function and albumin expression were Peng1, Guoming Lu1
reduced in sodium butyrate-treated FoxA2 knockdown cells when 1
Department of Medicine, Jiaxing University, Jiaxing, 314001, China,
compared to sodium butyrate-treated control cells. RNA sequencing 2
Department of Gastroenterology, The Second Hospital of Jiaxing,
and KEGG analysis revealed that PI3K/Akt signal pathway was the Jiaxing, 314001, China
pathway with the most increased gene number after knocking down Background: Hypercoagulability contributes to the majority of deaths
FoxA2. RT-PCR confirmed the increased gene transcription of the PI3K/ and organ failure associated with obstructive jaundice (OJ). However,
Akt signal pathway, such as Lama1, Il6, PI3K and Myc and western the exact mechanism of the coagulopathy in OJ remains elusive. Our
blot verified the enhanced phosphorylation of Akt in FoxA2 knockdown objectives were to demonstrate whether phosphatidylserine (PS)
cells when compared to those in control cells. The combined treatment exposure on platelets (PLTs), neutrophils (PMNs), endothelial cells
with Ly294002 and sodium butyrate increased albumin expression (ECs) and microparticles (MPs) can account for the hypercoagulability
and HNF4a transcription in FoxA2 knockdown cells when compared and liver damage in OJ patients.
with sodium butyrate-treated FoxA2 knockdown cells. And, glycogen Method: We evaluated OJ patients (n = 30) at two time point, which
synthesis function in Ly294002 and sodium butyrate-treated FoxA2 before (Day 0) and 7 days (Day 7) after the endoscopic retrograde
knockdown cells was more than that in sodium butyrate-treated FoxA2 cholangiopancreatography procedure (ERCP), and compared
knockdown cells and similar to that in the Ly294002 and sodium with healthy controls (n = 30). Lactadherin was used to quantify PS
butyrate-treated control cells. exposure on PLTs, PMNs, ECs and MPs. Healthy PLTs, PMNs and
Conclusion: Blocking PI3K/Akt signal pathway contributes to enhance human umbilical vein endothelial cells (HUVECs) were treated with 0,
the response to differentiation reagent of FoxA2 low-expressing liver 25, 50 or 100µM unconjugated bilirubin (UCB) and PS exposure on cells
progenitor cells to differentiate towards hepatocytes. were evaluated. Meanwhile, HUVECs were incubated with serum of OJ
patients and the expression of PS, intercellular adhesion molecule-1
PP0058 and vascular cell adhesion molecule-1 expression were evaluated.
Procoagulant activity was evaluated by purified coagulation complex
Study on the synergistic mechanism of photodynamic therapy
assays, clotting time, and fibrin turbidity. In addition, we established a
combined with ferroptosis inducer to induce ferroptosis in
cholestatic mouse model by bile duct ligation to determine the potential
cholangiocarcinoma
role of PS in intrahepatic coagulation and liver damage.
Sifan Dong1, An Jiang1 Result: Using flow cytometry, we found that OJ patients exhibited
1
Xi ‘an Jiaotong University elevated levels of PS+ PLTs, PMNs and associated MPs compared to the
Background: Photodynamic therapy (PDT) induced lipid peroxidation controls, which partly due to elevated UCB. Furthermore, the number of
reaction can lead to necrosis and apoptosis of extrahepatic PS+ PLTs, PMNs and MPs in patients at Day 0 were significantly higher
cholangiocarcinoma (ECC) cells, reducing the tumor load. However, than in patients at Day 7. Similarly, we observed markedly elevated
the depth of action of PDT is shallow, and its therapeutic efficacy PS exposure on HUVECs cultured with serum from patients at Day
is weak, making it difficult to achieve eradication even with multiple 0 versus serum from patients at Day 7. Confocal microscopy images
treatments. demonstrated localization of PS on HUVECs. Moreover, PS+ PLTs,
Method: This study aims to investigate the mechanism and main PMNs, ECs and MPs contributed to greatly shortened coagulation time
pathways of ferroptosis in cholangiocarcinoma under Hematoporphyrin- and markedly enhanced coagulation Factor Xa, thrombin, and fibrin
mediated photodynamic therapy, and to compare the effects of generation. This procoagulant activity could be blocked approximately
different ferroptosis inducers on photodynamic therapy-induced 80%, by the addition of lactadherin. Linear regression analysis showed
ferroptosis in cholangiocarcinoma. To provide an experimental basis that levels of PS+ PLTs, PMNs and MPs were positively correlated with
for selecting appropriate ferroptosis-inducing agents and synergizing hypercoagulation markers (TAT, D-dimer, and fibrinogen) as well as
with photodynamic therapy during the clinical perioperative period. liver injury indicators (ALT, AST, ALP, and GGT) in patients. Moreover,
Result: The combination of PDT with Lenvatinib or Erastin resulted cholestatic mice exhibited significantly increased levels of liver tissue
in increased ROS levels, and decreased GSH content, tumor cells necrosis, fibrin deposition, and thrombophilia compared to sham
were inhibited in the G2 phase, and the proportion of apoptotic cells mice. The enhanced intrahepatic coagulation and liver injury could be
increased. Additionally, GPX4, FSP1, and SLC7A11 protein expression reversed by inhibiting PS with lactadherin.
decreased, whereas ASCL4 increased This was accompanied by Conclusion: These results highlight the pathogenic activity of PS+
heightened levels of Fe2+, LPO, and MDA. Induction of the ferroptosis PLTs, PMNs, ECs and MPs in promoting a prothrombotic environment
pathway was observed to enhance the therapeutic efficacy of PDT. and liver damage in OJ. As such, lactadherin, a PS blockade, may be
Conclusion: 1. Photodynamic therapy can inhibit cholangiocarcinoma a viable therapeutic strategy for treating such patients.
cells by increasing the content of ROS, MDA, LPO and Fe2+, reducing Table and Figure:Figure 1.Experimental flowchart
the content of glutathione (GSH), and inhibiting the expression of Figure 2.Pattern Diagram
Xc-/GSH/GPX4 pathway and FSP1-CoQ10-NADPH pathway. It can
reduce the reduction ability of antioxidants in tumor cells and induce PP0060
ferroptosis in cholangiocarcinoma cells. When ferroptosis inhibitors are
used, the opposite effect is produced, so the induction of ferroptosis Brown adipose tissue derived extracellular vesicles administration
pathway can improve the effectiveness of PDT. alleviate acute liver injury in mice
2. After PDT combined with lenvatinib or Erastin, ROS level increased, Leyu Zhou1, Li Yang1
GSH content decreased, tumor cells were inhibited in G2 phase, and
1
West China Hospital, Sichuan University
Background: Brown adipose tissue (BAT) not only improves the liver understanding of the molecular mechanisms underlying tsRNA
microenvironment through metabolic regulation but also mediates inter- function.
organ signaling via extracellular vesicles (EVs), thereby modulating
liver immune response and promoting liver repairment. Previous PP0062
studies have reported that BAT-derived EVs (BAT-EV) reduce liver fat
accumulation and exhibit therapeutic effects in metabolic-associated Gankyrin-Deficiency Reprograms Intrahepatic Glucose And Lipid
liver diseases. However, research on the innovative therapeutic role of Metabolism To Delay Liver Regeneration
BAT-EVs in acute liver injury remains limited. Liu Yitian1
Method: We conducted experiments using three animal models of liver 1
225,Changhai Road,Shanghai
injury which was induced by concanavalin A (Con A), acetaminophen Background: Effective liver regeneration is indispensable for the
(APAP) or carbon tetrachloride (CCl4). First, we validated the BAT-liver recovery of patients with hepatic injuries. Gankyrin serves as a master
axis in vivo through BAT resection and BAT activation. Then we isolated regulator of cell growth and apoptosis to promote liver fibrosis and
BAT-EVs and cultured primary brown adipocyte in vitro. BAT-EVs or hepatocarcinogenesis. We examined the physiological function of
primary brown adipocyte was administrated into Con A, APAP, and Gankyrin in the metabolic and proliferative hepatocytes during liver
CCl4 mice, with liver function and histology assessed. Inflammatory regeneration.
levels were also analyzed using qPCR and ELISA. Further in vitro Method: We used hepatocyte-specific Gankyrin knockout mice
experiments were performed to explore the underlying mechanisms. to assess the impact of Gankyrin deficiency on liver regeneration
Result: Our results showed that after BAT removal, liver injury in post-hepatectomy. Biochemical assays were conducted to evaluate
Con A mice worsened, with increased hepatic inflammatory cell glycogenolysis and fatty acid transport in vitro and in vivo. The
infiltration. However, activating BAT with the selective β3-adrenergic molecular mechanism were explored by chromatin immunoprecipitation
receptor agonist CL 316243 reduced CCl4-induced hepatocyte death. and rescue experiments. Then, we assessed the impact of Pygl
Additionally, both BAT-EVs and primary brown adipocyte administration pharmacological inhibition on progression of liver regeneration. Finally,
significantly lowered peripheral ALT and AST levels, reduced liver we confirmed the Gankyrin-Foxo1 axis in vitro and in vivo.
necrosis area and apoptotic hepatocyte count, decreased inflammatory Result: Hepatic deficiency of Gankyrin (GankΔHep/Y) led to liver
cell infiltration, and lowered inflammatory cytokine levels, such as enlargement, glycogen accumulation, hypoglycemia and impaired
interleukin-6 and tumor necrosis factor-alpha. Further in vitro results glycogenolysis in mice. GankΔHep/Y PHx mice exhibited a delay
revealed that brown adipocyte-derived EVs suppressed macrophage in liver regeneration and disruption of the glucose-lipid metabolic
inflammatory responses, potentially by modulating macrophage homeostasis by altering the expression of PYGL and CD36 during
mitochondrial metabolism through mitochondrial protein transfer. liver regeneration. Mechanistically, Gankyrin interacts with Foxo1 and
Conclusion: There is BAT-liver protective axis in vivo. BAT-EVs and promotes its ubiquitination and proteasomal degradation, thereby
brown adipocyte significantly alleviate Con A, APAP, and CCl4- eliminating the FOXO1 -mediated transcriptional repression of PYGL
induced acute liver injury, suggesting a novel therapeutic strategy. and CD36 to enhance hepatocyte proliferation.
Modulating macrophage mitochondrial metabolism may represent a Conclusion: Gankyrin is a vital regulator of liver regeneration,
potential therapeutic target. However, the possible mechanism is still reprogramming glucose and lipid metabolism by governing FOXO1/
under exploration. PYGL and FOXO1/CD36 regulatory axes. Regulating the Gankyrin/
Foxo1 axis for governing glycogenolysis and lipid transport might
PP0061 provide the therapeutic advantages for facilitating liver regeneration.
Transfer RNA-derived small RNA tsRNA-20 mediates activation of
the ACPH/GRHL1 axis to facilitate liver cell regeneration in acute- PP0063
on chronic liver failure Bile Acid Receptor S1PR2-GSDMD Mediated Pyroptosis of Ly6C+
Mingxue Yu1, Qiyi Zhao1 Macrophages in Regulating Liver Inflammation
1
The Third Affiliated Hospital, Sun Yat-sen University Meng Chen1, Xueqin Li2, Hongyan Huang1, Kunpeng Huang1, Zhili
Background: Transfer RNA (tRNA)-derived small RNAs (tsRNAs) Wen1
represent a new class of small non-coding RNAs, with their biological 1
Department of Gastroenterology, The Second Affiliated Hospital of
functions gaining increasing attention. We previously reported that Nanchang University, 2Nursing department, the Second Affiliated
tsRNA-20 exhibits differential expression in patients with acute-on- Hospital of Nanchang University
chronic liver failure (ACLF), suggesting its potential as a biomarker Background: Bile acids have been reported to be involved in the
for ACLF. This study aimed to elucidate the role and underlying regulation of macrophage pyroptosis, among which FXR/TGR5 are the
mechanisms of tsRNA-20 in ACLF. most widely reported bile acid receptors. However, whether the newly
Method: We performed small RNA sequencing on plasma exosomes discovered bile acid receptor S1PR2 participates in the regulation of
collected from three healthy individuals and six patients with ACLF, pyroptosis and consequently modulates liver inflammation remains to
with validation using quantitative real-time polymerase chain reaction be elucidated.
(qRT-PCR) in plasma exosomes and tissues from patients with ACLF. Method: We injected the inhibitor JTE-013 to verify the regulatory
The biological function of tsRNA-20 was assessed by measuring effect of S1PR2 on liver sterile inflammation. Identified the liver cells
hepatocyte proliferation. Mechanistic studies involved tRNA pull-down, expressing S1PR2 through immunofluorescence co-localization.
RNA immunoprecipitation, western blotting, immunofluorescence, and Constructed CD11b-DTR mice to verify the regulatory effect of
co-immunoprecipitation assays. S1PR2 in myeloid macrophages. Applied transcriptome sequencing
Result: tsRNA-20 levels were significantly decreased in both plasma and IPA software to analyze the gene regulation of S1PR2 on
exosomes and tissues from patients with ACLF. Clinically, ectopic macrophages. Used CB-DOCK2 to simulate the binding of bile acids
expression of tsRNA-20 promoted liver cell proliferation, whereas its to S1PR2. Explored the association between myeloid S1PR2 and liver
downregulation had the opposite effect. Mechanistic investigations inflammation in the cholestasis model.
revealed that tsRNA-20 promotes liver cell regeneration by activating Result: We found that inhibiting S1PR2 significantly alleviated liver
the grainyhead-like 1 (GRHL1) transcription factor. Specifically, sterile inflammation. Through immunofluorescence experiments at the
tsRNA-20 directly binds to the RNA-binding protein acylpeptide tissue level, we identified that S1PR2 was mainly expressed in Ly6C+
hydrolase (ACPH), which activates the rat sarcoma (Ras)/extracellular infiltrating macrophages rather than Kupffer cells. Subsequently,
signal-regulated kinase (ERK) pathway. Subsequently, ACPH activates by using CD11b-DTR mice, we discovered that inhibiting S1PR2 on
GRHL1 and promotes its nuclear translocation. myeloid macrophages could remarkably reduce liver inflammation.
Conclusion: tsRNA-20 directly binds to ACPH and promotes liver Furthermore, we verified the regulatory effect of S1PR2 on macrophage
regeneration via the ACPH/GRHL1 axis, highlighting a potential pyroptosis in vitro, and analyzed the macrophage signaling pathways
therapeutic target for ACLF. This novel model enhances our
mediated by S1PR2 through transcriptome sequencing combined with Nanchang University
IPA software. Finally, we also examined the expression association Background: Adverse events and microbiota dysbiosis caused by
between S1PR2 and Ly6C+ macrophages in the cholestasis model. the eradication therapy of Helicobacter pylori (H. pylori) have become
Conclusion: Bile acid receptor S1PR2 significantly regulates increasingly evident. This study aims to investigate the adjunctive
macrophage pyroptosis and mainly affects liver inflammation through therapeutic effects of Lactiplantibacillus plantarum MH-301 in the
Ly6C+ macrophages. eradication therapy of H. pylori, as well as its impact on the gut and
Table and Figure:Figure 1.Bile Acid Receptor S1PR2-GSDMD Mediated vaginal microbiota.
Pyroptosis of Ly6C+ Macrophages in Regulating Liver Inflammation Method: In this study, sexually active, premenopausal women aged
18-50 years, diagnosed with H. pylori infection and concomitant
PP0064 chronic gastritis, were randomly assigned to receive either a bismuth-
containing quadruple therapy (amoxicillin, furazolidone, potassium
Endotoxin tolerance inhibits NLRP3 inflammasome activation
bismuth citrate, rabeprazole) combined with probiotics (L. plantarum
in macrophages 1 of septic mice by restoring autophagic flux
MH-301) or a placebo for 14 days. The primary clinical endpoint was
through TRIM26
the incidence of gastrointestinal adverse events, while the secondary
Shiwen Wu1, Jiawen Chen1, Chenyi Liu1, Shu Li1, Chao Cai1, Mingqin
clinical endpoints included the incidence of vaginal adverse events,
Lu1
treatment tolerability, and the H. pylori eradication rate. Stool samples
1
The First Affiliated Hospital of Wenzhou Medical University and vaginal swabs were collected before and after treatment for high-
Background: Sepsis is a life-threatening organ dysfunction caused throughput sequencing analysis
by the host’s exaggerated response to infection, and its complex Result: The probiotic group exhibited a significantly lower incidence
pathogenesis poses challenges for diagnosis and treatment. Therefore, of bloating (10.2% vs 19.4%, P=0.037), constipation (2.3% vs 7.8%,
it is crucial to thoroughly understand the pathogenesis of sepsis and P=0.048), and excessive vaginal discharge (3.1% vs 9.3%, P=0.040)
explore therapeutic approaches. compared to the placebo group. Furthermore, the probiotic group
Recent studies have shown that macrophages and the NLRP3 demonstrated better treatment tolerability than the placebo group
inflammasome play a key role in the pathogenesis of sepsis. In (P<0.05). However, there was no statistically significant difference
sepsis, autophagy exerts a protective effect by regulating the in the eradication rates between the two groups. High-throughput
activation and polarization of macrophages to mitigate the activation of sequencing revealed that H. pylori eradication therapy led to a decrease
inflammasomes and the release of inflammatory mediators. in the diversity of both gut and vaginal microbiota, with a reduction
Endotoxin tolerance (ET) is an immunotolerant state characterized by in the relative abundance of Prevotella in the gut microbiota, and an
low responsiveness to endotoxins. Some studies suggest that ET is increase in Streptococcus and Haemophilus. In the vaginal microbiota,
associated with the upregulation of CD64 receptors on macrophage there was a decline in Lactobacillus and an increase in Gardnerella.
surfaces, downregulation of MHC class II molecules, modulation of Compared to the placebo group, the probiotic group exhibited higher
inflammatory cytokines, upregulation of anti-inflammatory cytokines, relative abundances of Megamonas, Prevotella, and Lactobacillus
and enhancement of phagocytic activity and pathogen clearance. in the gut microbiota, and lower abundances of Streptococcus and
However, the precise mechanism by which ET regulates changes in Haemophilus. In the vaginal microbiota, the probiotic group had a
immune function remains largely unclear. lower relative abundance of Gardnerella (P<0.05). Correlation analysis
This study aims to elucidate how ET modulates macrophage autophagy indicated a positive relationship between gastrointestinal and vaginal
and inhibits NLRP3 inflammasome activation through the regulation of adverse events, and similarly, a positive correlation was found between
TRIM26, with the hope of providing new insights and targets for clinical the abundance of Lactobacillus in the gut microbiota and Lactobacillus
treatment of sepsis. in the vaginal microbiota (P<0.05).
Method: An in vivo sepsis model was generated using cecal ligation Conclusion: This study concludes that L. plantarum MH-301 can
and perforation (CLP), while an in vitro model of inflammatory injury reduce adverse events such as bloating, constipation, and excessive
was induced via lipopolysaccharide (LPS) administration. ET was vaginal discharge during H. pylori eradication therapy, with the gut-
established through pretreatment with low-dose LPS. Subsequent vaginal axis potentially being a crucial pathway for its therapeutic
analyses were conducted to assess the presence of the NLRP3 effects. Moreover, L. plantarum MH-301 had a positive regulatory
inflammasome, autophagic flux, and the expression levels of TRIM26. effect on the alteration of gut and vaginal microbiota, which may be a
Result: Heightened inflammation was observed in the TNF-伪 levels potential mechanism underlying its therapeutic effects.
and various organs of the sepsis group; conversely, inflammation was Table and Figure:Figure 1.
reduced in the group receiving ET treatment. Upon stimulation with
LPS, primary mouse peritoneal macrophages exhibited activation of the
PP0066
NLRP3 inflammasome and autophagy, accumulation of mitochondrial
reactive oxygen species (ROS), compromised membrane Baicalein induces hepatic stellate cell senescence via inhibiting
potential,resulting in cell apoptosis, and decreased expression of glycolysis by CEBPZ/p53/HK2 signaling pathway to inhibit liver
TRIM26. ET was found to enhance autophagy, suppress the activation fibrosis
of NLRP3 inflammasomes, and upregulate the expression of TRIM26. Shuling Chen1, Yang Wang1, Ruiqi Li2, Anyin Yang3, Hongli Liu2, Hao
Interestingly, modulation of autophagy levels either reversed or Ren1, Jing Fan4, Dandan Yin5, Qingfang Xiong1, Caiyun Zhang4,
intensified the protective effects of ET on macrophages in vitro. Xixuan Wang2, Yongfeng Yang1,2,4
Knockdown of TRIM26 using small interfering RNA (siRNA) resulted in 1
Department of Hepatology, The Second Hospital of Nanjing,
increased NLRP3 inflammasome activation and accumulation of P62. Affiliated to Nanjing University of Chinese Medicine, 2Department of
Conclusion: We reveal that ET restore the autophagic flux in Gastroenterology, Medical School, Southeast University, 3Department
macrophages, inhibit NLRP3 inflammasome activation, and mitigate of Pharmacy, Gaochun Hospital Affiliated to Jiangsu University,
inflammatory damage in septic mice,potentially through the regulation
4
Nanjing Key Laboratory of Hepatology, Nanjing University of Chinese
of TRIM26. Medicine, 5Clinical Research Centre, The Second Hospital of Nanjing,
Affiliated to Nanjing University of Chinese Medicine

PP0065 Background: Liver fibrosis is a condition in which abnormal

proliferation of connective tissue occurs in the liver. Baicaliein (BA)
Lactiplantibacillus plantarum MH-301 Reduces Helicobacter is a flavonoid compound extracted from the dried root of Scutellaria
pylori Treatment-Related Adverse Events via Gut-Vaginal Axis: A baicalensis, which can inhibit the mechanisms of cancer development
Randomized, Double-Blind, Placebo-Controlled Study such as metastasis, angiogenesis, and inflammation without harming
Zhang Kai Ge1, Zeng Yu Yu2, Xie Zheng Yuan1 healthy cells. However, there has been little research on its effects in
1
The Second Affiliated Hospital, Jiangxi Medical College, Nanchang liver fibrosis. This study aimed to investigate the protective effect of BA
University, 2The First Affiliated Hospital, Jiangxi Medical College, on liver fibrosis and elucidate its potential mechanisms.
Method: Serum markers for liver injury, liver tissue histochemical Wilson’s disease
staining, tissue immunofluorescence, tissue immunohistochemistry, Figure 2.Replenishment with Akkermansia Muciniphila decreased liver
Western blotting analysis, real-time quantitative polymerase chain N2 neutrophils and reversed liver lesion in Wilson’s disease.
reaction (qRT-PCR), β-galactosidase staining, cell cycle detection,
enzyme-linked immunosorbent assay (ELISA), Cellular Thermal PP0068
Shift Assay (CETSA), Cleavage Under Targets and Tagmentation
(CUT&Tag), Small Molecule pull-down (SM pull-down) and Surface Aryl hydrocarbon receptor signaling activation in macrophages
Plasmon Resonance (SPR) were utilized to identify the targets of BA, prevents cellular senescence and liver aging
as well as to detect the expression of proteins associated with cellular Huishi Tan1, Yongjian Zhou1
senescence, fibrosis markers, and signaling pathways. 1
Guangzhou First People‘s Hospital
Result: Serum liver injury indicators, fibrosis markers, and histochemical Background: Aging raises the risk of chronic liver disease and hepatic
staining results indicated that BA treatment significantly ameliorated fibrosis.Chronic liver disease and liver fibrosis are associated with
liver injury, inflammation, and fibrosis in vivo. Concurrently, BA markedly aging. Liver aging shows increased immune cell infiltration, hepatic
inhibited the activation of human hepatic stellate cell (HSC) line (LX2 stellate cell activation, and low-grade, chronic inflammation due to
cell line). The results further suggested that BA significantly promoted immunosenescence. Aryl hydrocarbon receptor (Ahr) plays a crucial
the senescence of activated HSCs, with cell cycle arresting at the G1 role in apoptotic cell processing, inflammatory response regulation,
phase. BA could promote cellular senescence by inhibiting glycolysis and immune function maintenance in macrophages.
in activated HSCs. Mechanistic studies demonstrated that BA could Method: The expression of macrophage Ahr in the liver of aged mice
directly bind to CEBPZ and regulate p53/HK2 signaling pathway at the was analyzed utilizing the GEO dataset. Additionally, mice with a
transcriptional level. The pharmacological inhibitor of p53, pifithrin-α specific deletion of Ahr in macrophages were employed to investigate
hydrobromide, significantly suppressed the anti-fibrotic effects of BA. the effects on liver aging. 16S rRNA sequencing and untargeted
Conclusion: Our findings suggested that BA had a protective effect metabolomics were performed to study the differential microbiota and
on liver fibrosis, and the underlying mechanism might be related to the their derived Ahr agonists during aging. Subsequently, identified Ahr
CEBPZ/p53/HK2 signaling pathway. agonists were investigated both in vitro and in vivo to examine their
Table and Figure:Figure 1. anti-aging and anti-inflammatory properties.
Result: Here, we performed an in-depth analysis of the single-cell
PP0067 RNA sequencing (scRNA-seq) dataset and identified the upregulation
of chronic inflammation-related genes and impaired macrophage Ahr
The role of gut-liver axis in the pathogenesis of Wilson’s disease
signaling during aging. In particular, the absence of Ahr in macrophages
Xiaoxiao Mi1, Junping Shi1 accelerates the aging process of the liver in mice, demonstrated by
1
The Affiliated Hospital of Hangzhou Normal University elevated production of pro-fibrotic genes, inflammatory cytokines,
Background: Wilson’s disease is an inherited disorder caused by the and senescent markers. Moreover, macrophages with Ahr deficiency
absence of the copper transport protein ATP7B, leading to abnormal exhibited heightened activation of cellular senescence signaling
copper accumulation in the liver. Existing chelation therapy drugs often pathways, marked by cell-cycle arrest, elevated propensity for
occupy with neurodegenerative side effects. The role of gut-liver axis inflammation, and defective efferocytosis capacity. Age-related
in the pathogenesis of Wilson’s disease remains unclear. Therefore, it is decreases in the gut microbiota-derived Ahr ligand, indolelactic
necessary to clarify the relationship between the intestinal microbiome acid (ILA), were observed in mice. Furthermore, the ILA supplement
and the liver disease progression and copper deposition. effectively activates Ahr signaling to prevents cellular senescence and
Method: Microbiome was analysed by Metagenomic sequencing liver aging.
and microbial culture in Atp7b-/- mice. Gut content, liver, blood and Conclusion: Collectively, our study emphasizes the key characteristics
liver neutrophils were tested by inductively coupled plasma-mass and potential mechanisms of Ahr signaling in the prevention of
spectrometry, qRT-PCR, immunoblot and immunohistochemistry macrophage senescence and liver aging, providing novel and
for expression of fibrogenic and neutrophil polarization markers. practical therapeutic strategies for liver aging and its related disorders.
Neutrophil response in atp7b-/- zebrafish was tested by live imaging, Table and Figure:Figure 1.Graphical Abstract
movement tracking, and transcriptional analysis in sorted cells. Figure 2.16S rRNA sequencing and untargeted metabolomics
Result: Metagenomic sequencing showed that, in Wilson disease
mice, Bacteroidota decreased while Firmicutes and Actinobacteria PP0069
increased at the Phylum level. At the class level, Bacteroidia
decreased, while Erysipelotrichia and Actinomycetia increased. At The role and mechanism of intestinal epithelial ZO-1 protein in
the Orders level, Bacteroidales and Verrucomicrobiales decreased acute-on-chronic liver failure
and Erysipelotrichales increased. At the species level, Bacteroidales Xu Lingyun1, He Yingli1
bacterium decreased by 43% and Akkermansia muciniphila 1
1 Department of Infectious Diseases, The First Affiliated Hospital of
decreased by 80%. Short-chain fatty acids were detected in the colon Xi’an Jiaotong University, Xi’an, China
contents of Wilson’s mice and wildtype mice, and it was found that the Background: Intestinal barrier injury is closely related to ACLF
levels of propionic acid and caproic acid in Wison’s disease mice were (acute-on-chronic liver failure, ACLF) and its complications, such as
significantly reduced. Further, by observing the livers of Wison’s disease spontaneous bacterial peritonitis and hepatic encephalopathy. The
mice and zebrafish, we found that both the mice liver and the zebrafish development of ACLF can further lead to the destruction of intestinal
liver had a large number of neutrophil infiltration. Furthermore, liver N2 barrier, forming a vicious cycle. ZO-1 (zonula occludens 1, ZO-1) and
neutrophils were observed in Wilson’s disease mice and zebrafish, and tight junctions play important roles in the intestinal barrier. However,
pharmacologically targeted transforming growth factor b1 reduced changes in tight junctions and molecular biology mechanisms in the
liver N2 neutrophils and improved liver function and alleviated liver intestine of ACLF have not been reported.
inflammation and fibrosis in ATP7B-knockout mice. Further, ATP7B- Method: 1)Evaluated the colon injury of traditional and “3-stage” ACLF
knockout mice treated with Akkermansia Muciniphila by oral gavage mice model: mainly including colon length, morphological changes,
showed reduced liver N2 neutrophils and alleviated liver inflammation WB and IF were used to detect the expression of colon tight junction
and fibrosis. protein. 2) Constructed LPS induced Caco-2 epithelial inflammation
Conclusion: The development of liver disease in Wilson’s disease is model. Used chloroquine and silencing of autophagy key genes to
accompanied by a shift from Bacteroides/verrucobacteria to Firmicutes- inhibit autophagy, and induced autophagy to clarify the relationship
dominated community in gut. Liver N2 neutrophils stimulated fibrosis, between ZO-1 and autophagy.Clarified the interaction between ZO-1
and replenishment with Akkermansia Muciniphila decreased liver N2 and autophagy key proteins.3) Explored the protective effects and
neutrophils and reversed liver lesions in Wilson’s disease. mechanisms of endocytic inhibitors such as Amiloride, Chlorpromazine,
Table and Figure:Figure 1.Liver N2 neutrophils was observed in
and Methyl-β-cyclodextrin on the autophagic degradation of ZO-1 liver inflammation, steatosis, and fibrosis, along with increased
protein by plasma membrane separation, WB, IF, and other methods. proteins involved in PPAR signaling, cholesterol metabolism, oxidative
Evaluated the effects of endocytosis inhibitor intervention on survival phosphorylation, and a decrease in necroptosis. Thus, pre-educating
time, liver pathology, colon length, histological morphology, expression the FMT donor microbiota with a high-protein diet holds a promising
of tight junction proteins (ZO-1, Claudin-1, and Occludin), and intestinal strategy in treating ALD.
permeability in “3-stage” ACLF mice. Table and Figure:Figure 1.Liver injury biomarkers and enriched hepatic
Result: 1) The colon length of ACLF mice was shortened (P<0.05) pathways
and the arrangement of colon glands was disordered. 2) Autophagy
inhibitors such as bafflomycin, chloroquine and silencing the key
PP0071
autophagy gene ATG13 ATG5 could rescue the downregulation
effect of LPS on ZO-1 (P<0.05). Various autophagy agonists such as Fecal cell-free transplantation exhibits efficacy similar to fecal
rapamycin could downregulate the expression of ZO-1 in Caco-2 cells. microbiota transplantation in alleviating alcoholic liver disease in
IF results suggested that ZO-1 could co-localize and interact with LC3B a murine model.
and LAMP2. 3) Amiloride could reverse the autophagic degradation of Nishu Choudhary1, Ashi Mittal1, Anupama Kumari1, Jaswinder Maras1,
ZO-1 protein in Caco-2 cells by LPS and EBSS Amiloride intervention Kavita Yadav1, Shvetank Sharma1, Shiv Sarin1
could improve the expression of ZO-1 in the colon and intestinal 1
Institute of liver and biliary sciences
permeability. Background: Fecal Microbiota Transplantation(FMT) is effective in
Conclusion: 1) Both ACLF mouse models showed significant treating alcohol-related liver disease(ALD). The microbiota of the
downregulation of ZO-1 protein in the colon. 2) ZO-1 could be donor, along with gut environment, contributes to disease remission.
degraded through the autophagy-lysosome pathway. 3) Amiloride Thus, factors other than bacteria in the gut may also have a role in
inhibited the internalization of membrane protein ZO-1 which could the remission of the disease. To confirm, we compared the efficacy of
improve liver pathology, and prolong survival time. bacterial cell free transplantation(CFT) against FMT.
Table and Figure:Figure 1.ACLF mouse models showed significant Method: Male C57BL/6N mice were pair-fed control or ethanol (22%)
downregulation of ZO-1 protein in the colon Lieber-DeCarli diet with thioacetamide for 8 weeks to induce ALD.
Figure 2.Amiloride inhibited the internalization of membrane protein FMT and CFT(stool-slurry filtered from 0.22 micron filter) from healthy
ZO-1 which could improve liver pathology, and prolong survival time. donors was performed in ALD animals. Samples collected at baseline
and post-FMT(day7). Liver injury was assessed by histopathology,
PP0070 biochemistry and RT-PCR. Fecal-microbiota was assessed by
16SrRNA sequencing. Hepatic metabolome was assessed by high-
Impact of Donor Protein Intake on FMT Outcomes in Alcoholic
resolution LC-MS.
Liver Disease Treatment
Result: Liver histology in both the groups showed significant overall
Ashi Mittal1, Nishu Choudhary1, Anupama Parasar1, Kavita Yadav1, improvement from ALD: with reduction in steatosis(9-fold, p=0.002),
Jaswinder Singh Maras1, Shiv Sarin1, Shvetank Sharma1 fibrosis(5-fold, p=0.005),AST(~2-fold, p=0.002),ALT(~5-fold,
1
Institute of liver and biliary sciences p=0.0001), bilirubin(~4-fold,p=0.03). Hepatic pro-inflammatory markers
Background: Alcohol-associated liver disease (ALD) patients are IL6(~3-fold,p<0.05) and Tnfa(~3.5-fold,p<0.05) reduced simlarlyin
often recommended a high-protein diet. Fecal microbiota transfer FMT and CFT. There was an associated decrease in opportunistic taxa
(FMT) has proven to be an effective alternative for ALD treatment. We Staphylococcus(2.8-fold,p=0.001) and Sporosarcina(2-fold,p=0.01)
investigated if pre-educating the donor microbiota with protein could in FMT but Desulfovibrio(1.5-fold,p=0.0001), Mucispirillum(10-
improve the remission of ALD in an animal model. fold,p<0.0001) and Escherichia-Shigella(9-fold,p<0.0001) in CFT. FMT
Method: Donor C57BL6N mice were pair-fed standard and protein altered 56, while CFT altered 190 metabolites significantly(p<0.05). In
(20% increased) diet for 2 weeks. FMT was performed in ALD mice FMT metabolites were involved in upregulation of Taurine-hypotaurine
(developed in 8 weeks using Lieber-DeCarli diet with incremental metabolism(p=0.01) and Cysteine and methionine metabolism(p=0.05)
ethanol and twice weekly i.p. thioacetamide-150mg/kg body weight). and downregulation of Pyruvaldehyde Degradation(p=0.05) and
Serum biomarkers of liver injury, histopathology, and gene expression pantothenate and CoA biosynthesis(p=0.02). Metabolic change
of inflammation were assessed by RT-PCR. Gut microbiota and its in CFT resulted in an upregulation of beta oxidation of long chain
effect on hepatic proteome were assessed by 16s-rRNA sequencing fatty-acids(p=0.02), spermidine and spermine biosynthesis(p=0.04)
and LC-MS/MS, respectively. and Taurine-hypotaurine metabolism(p=0.05) and downregulation
Result: Protein FMT (PF) reduced the liver injury significantly compared of androstenedione metabolism(p=0.002) and alpha linolenic-acid/
to Standard FMT (SF) with the reduction in serum biomarkers- ALT linoleic-acid metabolism(p=0.05).
(-1.5 fold change [FC], p=0.02), AST (-1.34FC, p=0.04); steatosis Conclusion: In ALD, whereas both FMT and CFT reduce the
(-1.8FC, p=0.01) and fibrosis (-1.4FC, p=0.04). PF also reduced opportunistic-taxa, the species targeted are different. The metabolic
the gene expression of hepatic pro-inflammatory markers- TNFα pathways modulated by the two strategies differ, but result in similar
(1.5FC, p=0.003) and IL6 (1.6FC, p=0.02), whereas it increased the amount of remission from disease. Thus, CFT appears to be a
anti-inflammatory IL10 (2FC, p=0.008). PF increased intestinal tight promising alternative to FMT.
junction claudin-4 (2FC, p=0.001) and occludin (1.6FC, p=0.007) Table and Figure:Figure 1.Pathway enrichment for upregulated and
along with the reduction in plasma endotoxin levels as compared to SF downregulated hepatic metabolites
(1.6FC, p=0.03). SF and PF led to significant variation in gut microbiota
composition (81%, p=0.001). PF increased Shannon diversity over SF
PP0072
(1.08FC, p=0.06). PF also significantly increased the abundance of
anti-inflammatory and SCFA producer- Muribaculum (2.4FC, p=0.002). Histone deacetylase 6 inhibitor affects gut microbiome
PF reduced the abundance of opportunistic pathogens- Staphylcoccus composition in alcoholic liver mice
(-6.7FC, p<0.001) and Aerococcus (-3.7FC, p<0.001). In PF, hepatic Yuqi Zhao1, Ruyi Peng1, Zengrong Wu1, Deliang Liu1, Yuyong Tan1
proteins involved in PPAR signaling, fatty acid degradation, cholesterol 1
The Second Xiangya Hospital of Central South University
metabolism, and oxidative phosphorylation were upregulated Background: Alcohol-associated liver disease is a series of disorders
significantly (FC>2,p<0.05), whereas, necroptosis, HIF-1 signaling & caused by the absorption, and metabolism of alcohol, which causes
biosynthesis of unsaturated fatty acids were downregulated. damage to liver cells. Studies suggested that the gut is also an
Conclusion: FMT from a high-protein diet donor alleviated the ALD important organ for alcohol metabolism. In addition to liver damage,
injury compared to that from a standard donor FMT. It increased the systemic metabolic changes often accompany alcohol consumption.
abundance of beneficial bacteria Muribaculum while decreasing the Histone deacetylase 6 (hdac6) has been implicated in glucose and
opportunistic pathogen Staphylococcus, concomitantly maintaining lipid metabolism, and the metabolic effects of ACY1215, a selective
the intestinal integrity barrier. It further improved liver injury by reducing
inhibitor of hdac6, are also of interest. inhibiting HCC progression and remodeling the TME.
Method: We divided 8-week-old C57/B6L mice into three groups: Result: In this study, we revealed that bufalin induced DNA damage
control, model, and treat groups with four mice in each group. We and release in HCC cells in a dose-dependent manner. The damaged
used the Gao-binge model. The mice in the control group were fed dsDNA released by HCC functioned as a signal factor to stimulate the
a standardized liquid diet, and the remaining two groups were fed activity of cGAS-STING signaling in macrophages, which increased
an equal-volume, equal-calorie lieber-decarli diet. The mice in the the levels of IFN-β, leading to tumor suppression by activating
control group were strictly controlled to consume an equal volume of cytotoxic CD8+ T cells. Moreover, activation of cGAS-STING signaling
liquid diet as the other two groups. The mice in the treatment group promoted M1 macrophage polarization, with the production of
were injected intraperitoneally with 30ug/g body weight of ACY1215 immunostimulatory cytokines and chemokines to enhance antitumor
starting on Day 8. At the end of the modeling period, mouse feces were immunity. The immunostimulatory effects of bufalin was counteracted
collected for the macro-genomics of the gut microbiome using Next by the STING inhibitor H151, confirming the role of cGAS-STING
Generation Sequencing. signaling in mediating the immunomodulation of bufalin. In orthotopic
Result: Sample analysis based on the number of genes suggested that HCC mouse models, bufalin was further confirmed to suppress HCC
the differences among groups were significantly greater than among development through the remodeling of the TME by activating cGAS-
samples within group, suggesting good comparability. The results STING signaling.
suggested that at the phylum level, the ratio of Bacillota/Bacteroidota Conclusion: Our results demonstrated that bufalin activated cGAS-
gradually decreased in the three groups (1.67, 0.85 and 0.20, STING signaling in macrophages by inducing DNA damage and release
respectively). At the species level, the gut microbiome composition in HCC cells, thereby triggering an immune response against HCC
of control mice Erysipelotrichaceae bacterium (3.85%), Eubacterium through macrophage-driven remodeling of the TME. These findings
(3.56%), Ructibacterium gallinarum (2.90%), Muribaculaceae provide valuable resources of expanding the immunotherapeutic
bacterium (2.95%) were more predominant. The model group was strategies for HCC treatment.
dominated by Muribaculaceae bacterium (4.49%), Ructibacterium Table and Figure:Figure 1.The schematic plot showed the mechanism
gallinarum (2.30%) and Chlamydia abortus (3.45%). Muribaculaceae of bufalin for anti-HCC immunomodulation.
bacterium (8.16%) was predominant in the gut microbiome of mice
in the treatment group. The results suggest that both alcohol and
PP0075
ACY1215 caused a decrease in gut microbiome abundance. Some
of the flora changes in the treatment group showed a superimposed Pheat, a Comprehensive T Cell Atlas of Human Pan-hepatic
effect of these two treatments, such as an increase in Bacteroidota. Disease at Single-cell Resolution
By comparing the KEGG database with the eggNOG database, the Siyuan Chen1, Chao Zhang1, Fusheng Wang1
results suggested that genes related to lipid metabolism, intestinal 1
The Fifth Medical Center of Chinese PLA General Hospital
defense mechanisms, etc., were upregulated in the treatment group, Background: Various hepatic diseases collectively lead to over
while genes related to carbohydrates were downregulated. two million human deaths annually worldwide. Advances in
Conclusion: By analyzing the gut microbiome of mice, we found immunotherapeutic strategies have ushered in a dawn for patients.
that the effects of alcohol and the HDAC6 inhibitor ACY1215 on the However, the efficacy remains suboptimal. It is urgent to exploit safer
composition of the mouse gut microbiome were significant, with some and more effective immunotherapeutic strategies further.
changes in the gut microbiome related to both glucose and lipid Exhausted CD8+T (Tex) cells with functional exhaustion phenotype
metabolism. This sheds some light on the systemic changes caused and regulatory CD4+T (Treg) cells with immunosuppress function are
by HDAC6 inhibitors in vivo and may be involved in the progression of obstacles to T cell-mediated hepatic adaptive immunity. Meanwhile,
alcohol associated liver disease. these populations are promising targets for innovative therapies.
Table and Figure:Figure 1.KEGG heatmap Commonalities and differences between these populations across
Figure 2.eggNOG heatmap different hepatic diseases remain poorly understood, hindering the
discovery of comprehensive immunotherapeutic strategies.
PP0074 Method: Large-scale single-cell RNA sequencing (scRNA-Seq)
datasets were prefetched from public database. Data were processed
Bufalin Induces Macrophage-governed cGAS-STING Signaling
using the Seurat pipeline with a two-step clustering approach: the first-
Pathway to Remodel Immune Microenvironment in Hepatocellular
round for major immune cell type assignment and the second-round
Carcinoma
for T cell type annotation.
Shi Han Yu1, Wen Lan Zheng1, Xue Mei Zhang1, Jia Shi1, Wu Rong Result: 1. Construction of the Pheat and transcriptional heterogeneity
Du1, Li Ming Zheng1, Hao Liu1, Hai Feng1, Zhuo Yu1 of T cells
1
Shuguang Hospital Affiliated to Shanghai University of Traditional (1) A total of 255 scRNA-Seq data from 12 studies were integrated,
Chinese Medicine including healthy control individuals and different hepatic disease
Background: Hepatocellular carcinoma (HCC) shows the resistance patients covering HBV infection, HCV infection, AH, MASH, cirrhosis,
to immunotherapy, largely attributed to the immunosuppressive and HCC (Fig1A).
nature of tumor microenvironment (TME). The cyclic GMP-AMP (2) T cells deposited in Pheat include CD4+, CD8+, γδ T, natural killer
synthase (cGAS)-stimulator of interferon genes (STING) signaling T, mucosal-associated invariant T and proliferative T cells (Fig1A).
is an evolutionary-conserved pathway that provokes the immune (3) CD8+T and CD4+T cells were divided into five transcriptional
response against tumor by improving the TME. Bufalin, the main active states, respectively (Fig1A).
component of traditional Chinese medicine Chansu, has been reported (4) Tex and Treg display an enrichment in the liver. Intrahepatic Tex
to have antitumor activity on various cancers including HCC. But in CHB patients presents a higher cell frequency than other hepatic
the mechanism through which bufalin stimulates anti-HCC immunity diseases, while intrahepatic Treg exhibits more heterogeneity in the
remains inadequately understood. liver (Fig1B).
Method: DNA damage and release in bufalin-treated human Huh7 2. Immunological features of Tex and Treg populations and multiple
and mouse Hepa1-6 HCC cells were assessed using comet assay, immunotherapeutic strategy discovery
immunoblotting and immunofluorescence for detecting γ-H2AX and Rb (1) Tex cells were annotated as three subpopulations with different
expression, and dsDNA quantification kit. Human THP-1 and mouse phenotypes and functions, developing along a trajectory from Texpre,
RAW264.7 macrophages were treated with conditioned medium (CM) through Texint, to Texterm (Fig2A-C).
from bufalin-treated HCCs, and the components of cGAS-STING (2) Intrahepatic Tex cells show a dominant frequency compared to
signaling and released cytokines were detected by immunoblotting, PBMC cells. Except for CHB, the frequency of Texpre is higher. Co-
quantitative PCR and ELISA. Flow cytometry was used to determine expression constructed by DEGs and 101 immune checkpoint genes
the phenotypes of macrophages treated by bufalin CM. Orthotopic (ICGs) identified hub ICGs in different hepatic diseases (Fig2D-G).
HCC mouse models were employed to assess the effect of bufalin on (3) Treg cells were classified into nTreg and eTreg. The frequency of
intrahepatic eTreg cells increases in patients compared to HC donors PP0077
(Fig2H-I). Expression of ORC1 Gene in the Histology of HBV-associated
(4) IL2-STAT5 signaling is enriched in all hepatic diseases, while Hepatocellular Carcinoma
different manifestations are presented in CHB, cirrhosis, and HCC,
Qingmei Li1, Jianning Jiang1
uncovering discrepant immunotherapeutic strategies in these diseases
(Fig2G-K).
1
The First Affiliated Hospital of Guangxi Medical University
Conclusion: Pheat serves as a valuable data resource for elucidating Background: To explore the expression of ORC1 gene in the
the commonalities and differences among T cell subsets, providing histology of HBV-associated hepatocellular carcinoma (HCC) at the
critical insights to advance immunotherapy across a spectrum of histological level, and to analyse the relationship between ORC1 and
hepatic diseases. the occurrence and development of HBV-associated HCC
Table and Figure:Figure 1.Fig1. Construction of the Pheat and Method: In this study, the experimental subjects were divided into
transcriptional heterogeneity of T cells CHB group (n=42), HBV-associated LC group (n=33), HBV-associated
Figure 2.Fig2. Immunological features of Tex and Treg populations and HCC group (n=49), normal liver tissue group (n=18) and non-HBV-
multiple immunotherapeutic strategy discovery associated HCC group (n=35). The expression of ORC1 protein in liver
tissues of each group was detected by immunohistochemical staining
(IHC), and the levels of ORC1 protein in the peripheral serum of 17
PP0076
patients with HBV-associated HCC were detected by enzyme-linked
Gut-liver-barrier dysfunction induced bioenergetic dysfunction in immunosorbent assay (ELISA). The integrated optical density value
hematopoietic stem cell accounting for defective maturation and (IOD) of the immunohistochemical staining intensity of ORC1 protein
functional impairment of monocyte-macrophage in cirrhosis can in each section of tissue was calculated by using the Fiji-win64 image
be ameliorated by mitoquinol analysis system, and the larger IOD value represented the higher level
Deepanshu Maheshwari1, Nidhi Nautiyal1, Manisha Bhardwaj1, of ORC1 protein.
Sunidhi Diwakar1, Nikita Sharma1, Chhagan Bihari1, Shiv Kumar Result: 1.(1) The liver tissue ORC1 protein level was higher in the
Sarin1, Anupam Kumar1, Anupam Kumar1 HBV-infected group than in the non-HBV-infected group (0.24±0.09 vs
1
Institute of liver and biliary sciences 0.15±0.08, P=0.000).(2) ORC1 protein levels increased sequentially
Background: Demand adapted myelopoiesis is central to effective from the CHB, HBV-associated LC, and HBV-associated HCC groups,
clearance of injury/infection. Despite increased myelopoiesis, why and were lower in the CHB group than in the HBV-associated LC group
liver clearance of infection and injury is compromised, leading to (0.22±0.05 vs. 0.23±0.05, P=0.337), and in the CHB group than in
progressive injury and onset of hepatic decompensation in chronic the HBV-associated HCC group (0.22±0.05 vs. 0.27±0.12, P=0.006)
liver injury is not well understood. We studied mechanistic basis for The HBV-associated LC group was lower than the HBV-associated
loss of functional macrophage populations in cirrhosis and evaluate HCC group (0.23±0.05 vs 0.27±0.12, P=0.035)(3) The liver tissue
the potential of Mitoquinol (MQ) in improving macrophage function ORC1 protein level was higher in the non-HBV-associated HCC
during cirrhosis. group than in the normal liver tissue group (0.16±0.09 vs 0.12±0.03,
Method: Kinetic changes in liver monocyte-macrophage dynamics P=0.050).2.ORC1 protein levels were higher in cancer tissues than in
and hematopoiesis were analyzed in a carbon tetrachloride (CCl4)- paracancerous tissues in the HBV-associated HCC group (0.27±0.12
induced chronic liver injury model. Bioenergetics of HSPCs and vs 0.12±0.03, P=0.000), and in the non-HBV-associated HCC group
macrophages were assessed using Seahorse Bioanalyzer. Gut-liver (0.16±0.09 vs 0.09±0.04, P=0.000), with P<0.05(3) The level of
barrier dysfunction was mimicked in healthy animals using GDCL3- ORC1 protein in cancer tissues of HBV-associated HCC group was
induced Kupffer cell depletion and DSS-induced intestinal injury. In higher than that in cancer tissues of non-HBV-associated HCC group
vivo, cirrhotic mice received oral MQ (50 µM) treatment for 2 weeks (0.27±0.12 vs. 0.16±0.09, P=0.000), and the level of ORC1 protein
following 8 weeks of CCl4 injury. in paraneoplastic tissues of HBV-associated HCC group was higher
Result: The liver exhibited a progressive decrease in macrophage than that in paraneoplastic tissues of non-HBV-associated HCC
population (p<0.01) and an increase in immature monocyte recruitment group (0.12±0.03 vs. 0.09±0.04, P=0.001).3.ORC1 protein levels in
(p<0.001). Chronic liver injury led to a myeloid-biased differentiation of hepatocellular carcinoma tissues of 17 patients with HBV-related HCC
HSCs. In the transition from healthy to steatosis, immature monocytes, showed a moderate positive correlation with peripheral serum ORC1
myeloid progenitors (MyP), and multipotent progenitors (MPP) protein levels (rs=0.554, P=0.021).
increased in the bone marrow (BM) without loss of LT-HSCs. From Conclusion: 1. the expression level of ORC1 gene gradually
steatosis to fibrosis and cirrhosis, MyP and MPP expanded at the increases with the progression of HBV-associated liver disease;2.the
expense of LT-HSCs. During this progression, immature monocytes high expression of ORC1 gene in liver tissues may be correlated with
increased, but mature monocytes declined along with their phagocytic the occurrence of HBV-associated HCC;
and efferocytic functions. The liver showed an influx of immature Table and Figure:Figure 1.
monocytes (p<0.01), loss of mature monocytes (p<0.01), and impaired Figure 2.
functionality (p<0.05). BM-HSCs and monocytes exhibited rising
cellular and mitochondrial (mt) ROS, loss of mt biomass, and potential PP0078
during cirrhosis. Gut-liver barrier disruption exacerbated mitochondrial The association of hepatitis B virus with extrahepatic tumors,
damage and bioenergetic dysfunction in HSPCs, resulting in immature mainly pancreatic cancer
monocytes unable to differentiate into functional macrophages.
YUCHAO LU1,2, LAI WEI1,2
MQ treatment reduced monocyte infiltration and macrophage loss while
increasing glucose uptake and mt biomass in HSCs. Treated HSCs
1
Tsinghua University, 2Beijing Tsinghua Changgeng Hospital
showed lower TLR2 expression and increased functional monocyte Background: Hepatitis B virus (HBV) infection is a pervasive global
production (p<0.01) with reduced immature monocytes (p<0.01). health issue, affecting over 350 million individuals worldwide. It is
Bone marrow-derived macrophages (BMDMs) from MQ-treated mice increasingly recognized for its association with extrahepatic tumors,
displayed improved mitochondrial respiration and ATP-linked oxygen particularly pancreatic cancer, which is highly aggressive and the
consumption. MQ-treated mice also demonstrated reduced liver injury eighth leading cause of cancer-related mortality. Despite its poor
and fibrosis compared to controls prognosis and increasing incidence, research on the relationship
Conclusion: This study demonstrates that gut barrier dysfunction between HBV and pancreatic cancer, including its impact on
during liver injury worsens bone marrow endotoxemia, causing prognosis and metastasis, remains limited. Currently, studies on
mitochondrial dysfunction in BM-HSPCs. This drives immature HBV infection and pancreatic cancer prognosis are relatively scarce,
monocyte production, impairing their maturation into functional especially regarding the influence of HBV infection on the metastasis
cells and hindering infection and injury resolution despite increased patterns of pancreatic cancer. This gap in knowledge is significant
myelopoiesis. as understanding the prognostic implications of HBV infection could
inform treatment strategies and improve patient outcomes. 6.758; 95% confidence interval [CI], 1.899–24.055; P=0.003), while
Method: This comprehensive analysis adhered to the PRISMA HBsAb titer was not significantly related to HBsAg seroreversion.
guidelines to systematically review recent literature on the association Conclusion: Trace serum HBsAg is associated with a higher risk of
between HBV and pancreatic cancer. The study included a longitudinal HBsAg relapse following PEG-IFN-induced HBsAg loss. Ultrasensitive
cohort of 93,402 subjects tracked for nearly 14 years, utilizing the COX HBsAg testing should be considered when evaluating the cessation of
proportional hazards model, competitive risk analysis, and subgroup antiviral therapy to better prevent potential HBsAg seroreversion.
analysis to compare incidence densities between HBsAg-negative Table and Figure:Figure 1.Table 1. Results of multivariable logistic
and HBsAg-positive groups. Additionally, a retrospective cohort study analysis for predictors of HBsAg seroreversion
and multiple meta-analyses were conducted to further substantiate the
association.
PP0080
Result: The study confirmed HBV infection’s link to pancreatic cancer,
with HBsAg-positive individuals showing a higher incidence. A 2013 Literature review of the epidemiology of chronic hepatitis B (CHB)
meta-analysis found increased hazard ratios for chronic HBV carriers infection in the paediatric population
(1.39), those with prior exposure (1.41), and active infections (3.83), all Myriam Drysdale1, Grace Dolman1, Saifuddin Kharawala2, Pooja
correlating with pancreatic cancer risk. HBsAg presence in pancreatic Malhotra2, Arnand Nair2, Dickens Theodore1, Marjan Hezareh1
tissues and HBx’s role in hepatic tumorigenesis indicate a promotional 1
GlaxoSmithKline, 2Bridge Medical Consulting
effect on pancreatic cancer. Chronic HBV infection possibly raises Background: Chronic hepatitis B virus (HBV) infection is a major
pancreatic cancer risk via liver-pancreas embryonic similarities, organ cause of liver disease and associated mortality worldwide. Infection
targeting, and pancreatic cell inflammation. Interventional therapies in children typically occurs after mother-to-child transmission or
were effective in reducing HBV spread in the pancreas and improving during early childhood via horizontal transmission. About 90% of
function in advanced cancer. infants infected at birth develop a chronic infection (30-50% of those
Conclusion: HBV-associated pancreatic cancer is largely Asian, infected ≤5years-old), often characterized by high viral replication,
potentially due to high hepatitis rates. Research may undervalue low-inflammation phase of infection and normal/slightly raised
occult HBV’s impact on cancer due to reliance on serological testing. aminotransferases. Despite near-universal hepatitis B immunisation
Future studies are needed to define HBV’s pancreatic cancer link. at birth and in infancy, slow progress in equitable access, HBV
HBV is a substantial, independent pancreatic cancer risk factor, testing, treatment, cultural barriers and stigma have led to important
even accounting for mortality risks. Increasing cancer rates in HBV- disparities between regions. We conducted a review of the literature
endemic areas highlight the need for new prevention and treatment on the burden of disease, treatment patterns, HBsAg levels distribution
strategies. Further research is crucial to understand HBV’s influence and vaccination coverage in the paediatric population with CHB to
on cancer prognosis and metastasis, enabling more effective, targeted understand the unmet need in this population.
interventions for HBV-related pancreatic cancer. A global research Method: We performed structured systematic searches in databases
initiative is key to bridging knowledge gaps and enhancing early (Embase, PubMed) as well as supplementary searches including
detection and treatment strategies. reports/websites (WHO, CDA Polaris, national-level datasources),
conference papers to identify literature published from 01 January
PP0079 2014 to 20 August 2024. Clinical trials, case-reports and case-series
(<10 patients) were excluded.
Trace Serum HBsAg Is Associated with a Higher Risk of HBsAg
Result: A total of 44 articles as well as selected websites/reports
Seroreversion after PEG-IFN-Induced HBsAg Loss
were included for this review. Global HBsAg prevalence in ≤5-year-
Na Gao1, Haishi Wu2, Mezuo Nian3, Qiyi Zhao3, Zhiliang Gao3 olds was ~0.70% in 2024 with the highest prevalence in WHO African
1
Department of Infectious Diseases, Third Affiliated Hospital of Sun region (~1.4%). Asian Countries have seen a major decline in HBsAg
Yat-Sen University, Guangzhou, Guangdong 510630, China, 2Third prevalence since 2015 but disparities between regions remain (~1.3%
Affiliated Hospital of Sun Yat-Sen University, 3The Third Affiliated HBsAg prevalence in South-East Asian compared to ~0.1% in Central
Hospital of Sun Yat-sen University
and East-Asian regions). In contrast, the prevalence in <5-year-olds was
Background: While PEG-IFN (pegylated-interferon)-based therapy 0.1% in WHO European region and <0.1% in WHO American region.
offers a higher chance of HBsAg seroclearance, more than one- While prevalence remains low in the older group (12-18 years-old) in
fifth of patients who achieve HBsAg loss may experience HBsAg countries such as US and Germany, the prevalence increases with age
seroreversion. The potential of ultrasensitive HBsAg-Next assays in Central Asia from 0.3% in <5-year-olds to 1.0% in 5-18 years-old.
to refine antiviral treatment endpoints and predict HBV reactivation Majority of children were HBeAg positive with high HBsAg ranging from
remains unclear. This study aimed to investigate the role of ultrasensitive 3.2 to 4.7 log IU/mL and high HBV DNA (“immune tolerant”) ranging
HBsAg in HBsAg seroreversion and to identify factors influencing from 2.6 to 8.5 log IU/mL, with HBeAg seroconversion typically not
HBsAg seroreversion. occurring until adolescence or adulthood. Approximately two-thirds
Method: We enrolled patients who experienced serum HBsAg loss of paediatric CHB patients had HBsAg levels higher than 10,000 IU/
following PEG-IFN-based therapy and followed them for a median of mL. The use of antiviral treatment in children was typically reserved
203 weeks (quartile 1–quartile 3: 169.75–235.5 weeks). Serum samples for those with elevated ALT or signs of evolving fibrosis. Most of the
were collected at various time points: during PEG-IFN consolidation, at studies reporting anti-HBV treatment use were from Asian cohorts.
cessation of PEG-IFN, and during follow-up. HBsAg was measured Treatment was given in 11.0 – 39.9% of children and adolescents.
using a HBsAg-Next Qualitative assay with a cutoff of 0.005 IU/mL, Interferon (IFN)/PegIFN or combination IFN+nucleos(t)ide analogues
and HBV DNA was quantified with a cutoff of 10 IU/mL. Multivariate (NA) were commonly used in children.
logistic regression analysis was used to determine factors associated Conclusion: Despite public health interventions, prevention and
with HBsAg seroreversion. treatment of paediatric HBV remain an important area of unmet need,
Result: A total of 126 patients with HBsAg seroclearance were included with wide variations across global regions.
in the study. HBsAg seroreversion occurred in 32 patients, with a Funding: GSK
median recurrence time of 48 weeks (36–78 weeks). At the cessation
of PEG-IFN, 15 patients had detectable ultrasensitive HBsAg. The
PP0081
HBsAb titer was significantly higher in the HBsAg-Next negative group
compared to the HBsAg-Next positive group (1.97, [1.21, 2.54] vs. 1.11 Deep sequencing reveals extensive expression of HBV integration
[0.5–1.47]; P=0.001). The cumulative incidence of sustained HBsAg in different phases of chronic HBV infection
loss was significantly different between the HBsAg-Next positive and Xiaoqi Yu1, Demin Yu1, Qiming Gong1, Li Chen2, Xinxin Zhang1
negative groups (Log Rank, P<0.001). Multivariate analysis revealed 1
Department of Infectious Diseases, Research Laboratory of Clinical
that detectable ultrasensitive HBsAg at the cessation or follow-up time Virology, Ruijin Hospital, Shanghai Jiao Tong University School of
points was associated with HBsAg seroreversion (odds ratio [OR], Medicine, 2Department of Gastroenterology, Ruijin Hospital, Shanghai
Jiao Tong University School of Medicine of Sorafenib, and epidemiological studies. Less explored themes
Background: Hepatitis B virus (HBV) integration can occur in the early include research on prevention strategies, screening, and impact
phases of chronic HBV infection and contribute to hepatitis B surface on public health. While there is a general increase in output, most
antigen (HBsAg) expression. In this study, we aimed to explore the publications are published by authors from the same institution on
occurrence of HBV integration events in different phases of chronic country.
HBV infection and their correlation with clinical and viral indicators. Conclusion: The study highlights the increase in research productivity
Method: We included liver tissues from 40 untreated patients with on hepatocellular carcinoma in Southeast Asia. Thailand was shown to
chronic HBV infection, 14 and 8 of these were in the HBeAg-positive lead in publication rates. The main focus of research in this region is on
chronic hepatitis B (EPCHB) and HBeAg-positive chronic infection immunotherapy and epidemiological studies. While there is a general
(EPCI) phase, 6 and 12 of these were in the HBeAg-negative chronic increase in research output, the results highlight the need to foster
hepatitis B (ENCHB) and HBeAg-positive chronic infection (ENCI) collaborative research initiatives.
phase, respectively. The profiles of HBV integration were analyzed by
transcriptome deep sequencing. PP0083
Result: Virus-host chimeric reads were detected in all patients,
Establishment and application of a new method for dual detection
with a median (IQR) number of 2,152 (1,077-3,510) per patient. The
of HDV RNA and HBV DNA based on CRISPR technology
median number of chimeric reads was significantly higher in HBeAg-
Feng Ren1, Yuan Tian, Ling Xu, Zihao Fan, Yaling Cao
positive patients than in HBeAg-negative patients (3,016 vs. 1,137, p <
0.001). EPCI patients had the highest median reads number (3,253.5
1
Beijing Insitute of Hepatology/Beijing Youan Hospital, Capital
[1975.75-4,627.5]), followed by EPCHB patients (2,863 [2256.5- Medical University
4017.5]), ENCHB patients (1,305.5 [656.75-2783.25]), and ENCI Background: Hepatitis D virus (HDV) is a defective virus that is
patients (1114 [415-1,968.75]). HBV integration sites were randomly dependent on hepatitis B virus (HBV) for infection and replication, and
distributed on chromosomes and were found in mitochondrial genes. co-infection with HDV and HBV exacerbates the development of viral
Both the number of total chimeric reads and unique chimeric reads hepatitis. In this study, we used the clustered regularly interspaced
were significantly but not strongly correlated with serum HBV DNA and short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas)
HBsAg levels (p < 0.01), however, there was no significant correlation system to establish a method for the detection of HDV RNA and HBV
between the number of chimeric reads and inflammation grade or DNA, as well as dual detection.
fibrosis stage. Method: We constructed HDV and HBV plasmids by comparing
Conclusion: The findings suggested that HBV integration occurs conserved sequence regions; and we designed and screened RT-RAA
across all patients with chronic HBV infection, and is correlated with primer pairs to amplify the HDV plasmid and RAA primers to amplify
viral load. Whether these integrated sequences can be translated or the HBV plasmid, as well as corresponding crRNAs (CRISPR-derived
affect gene function needs further studies. RNAs), respectively; the conditions of the assay were optimized,
leading to the establishment of a new CRISPR-Cas13a/Cas12a-based
assay. Then the sensitivity and specificity of the new method was
PP0082
evaluated by fluorescence and lateral flow test strip method of the
Hepatocellular Carcinoma Research Productivity in Southeast “line elimination method”. The established new assay was validated by
Asia: A Bibliometric Analysis collecting HDV- and HBV-related clinical samples in comparison with
Jan Bendric Co Borbe1, Henzor Dauigoy1 RT-qPCR and RT-ddPCR methods.
1
University of the Philippines- Philippine General Hospital Result: RT-RAA-CRISPR-Cas13a/RAA-CRISPR-Cas12a fluorescence
Background: Liver cancer is the second most common cause of and “line elimination” lateral flow test strip assays were established
cancer-related death in Asia, the majority of which are reported in for HDV RNA detection and HBV DNA detection, respectively. The
Southeast Asia and East Asia. It has also been shown that incidence sensitivities of RT-RAA-CRISPR-Cas13a for detecting HDV plasmids
among Asians is the highest, doubling that of white Hispanics and positive samples were both 10 copies/μL, and the sensitivities
and more than four times higher than that of whites. Based on the of RAA-CRISPR-Cas12a for detecting HBV plasmids and positive
2020 GLOBOCAN data, Southeast Asian countries such as Laos, samples were both 1 copy/μL. Moreover, we established a RT-RAA-
Cambodia, and Thailand are only second to Mongolia in terms of age- CRISPR-Cas13a/Cas12a dual fluorescence and “line elimination”
standardized rate of incidence and mortality of liver cancer. The ever- lateral flow test strip assays for HDV RNA and HBV DNA. The sensitivity
changing landscape in the management of hepatocellular carcinoma for detecting HDV and HBV plasmids and positive samples was 10
necessitates constant research in this field, and by extension, copies/μL, and there was no cross-reactivity between the detection of
systematic analysis of these vast research outputs to assess emerging HDV and HBV and other related viruses; the RT-RAA-CRISPR-Cas13a/
trends, collaboration shifts, and overall scientific impact. This study Cas12a dual fluorescence and lateral flow test strip assays showed
aims to evaluate research productivity on hepatocellular carcinoma a detection rate of 70% and 65.7% for HDV RNA and HBV DNA,
specifically in Southeast Asia where the disease accounts for respectively.
considerable morbidity and mortality. Conclusion: We developed a novel CRISPR-Cas13a/Cas12a-based
Method: A systematic review will be conducted to retrieve studies assay for accurate, convenient, highly sensitive and specific detection
on hepatocellular carcinoma using PubMed, Scopus, and Google of HDV RNA and HBV DNA, providing a more effective alternative for
scholar. The authors will present an adapted Preferred Reporting Items early detection and treatment of HDV and HBV infections, as well as for
for Systematic Reviews and Meta-analyses (PRISMA) 2020 flowchart the guidance of medication administration and the evaluation of clinical
of study selection (Figure 1). All publications on hepatocellular therapeutic effects.
carcinoma with at least one author affiliated with a Southeast Asian Table and Figure:Figure 1.Schematic diagram of dual detection method
institution will be deemed eligible. The following study designs will be by RT-RAA-CRISPA-Cas13a/Cas12a for HBV DNA and HDV RNA
included: clinical trials, retrospective and prospective cohorts, case-
control studies, cross-sectional studies, case series, case reports, and PP0084
systematic reviews/ metaanalysis. Commentaries, letters to the editor, STING Activation Suppresses Viral Replication but Promotes Liver
book chapters, and conference papers will be excluded. Inflammation and Fibrosis in Chronic Hepatitis B Concurrent with
Result: The results show a surge in the number of publications since Metabolic Dysfunction-Associated Fatty Liver Disease
2021. China remains to produce the most research output per year
Wenhui Wu1, Suping Hai1, Xitang Li1, Qiang Gao1, Binghui Yu1,
globally, contributing over 50% of publications in the field. However
Feiyang Xu1, Xizhe Zheng1, Junjian Hu1, Xiaojing Wang1, Qin Ning1
in Southeast Asia, Thailand has been shown to be the most prolific
followed by Singapore and Vietnam. The analysis also revealed several
1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical
College and State Key Laboratory for Diagnosis and Treatment of
emerging themes within HCC research including immunotherapy, use
Severe Zoonostic Infectious Disease, Huazhong University of Science
and Technology, Wuhan, China increasing HBV replication. Mechanistically, Rot treatment elevated
Background: Concomitant Metabolic Dysfunction-Associated Fatty mtROS levels and reduced mitochondrial membrane potential (ΔΨ),
Liver Disease (MAFLD) is common in patients with Chronic hepatitis leading to deteriorated lysosomal membrane permeabilization and
B (CHB), but the implications on liver-related outcomes remain leakage of hydrogen ions, which elevated lysosomal pH. Additionally,
controversial. Stimulator of Interferon Genes (STING) plays a central Rot treatment inhibited mitochondrial ATP production and reduced
role in innate immune activation. Here, we aim to investigate the role of contact between mitochondria and lysosomes. Obstructing
STING in disease progression in CHB patients concurrent with MAFLD. mitochondrial ATP synthesis with Oligomycin A treatment or disrupting
Method: HBV transgenic mice and pAAV/HBV1.2 hydrodynamic mitochondria-lysosome contacts with VPS13A knockdown resulted in
injection mice fed with a high-fat diet (HFD) were both used to lysosomal alkalinization by modulating v-ATPase assembly.
establish mouse models of CHB concurrent with MAFLD. STING Conclusion: Mitochondrial function plays a crucial role in the
knockout, Tmem173-/- (Sting-/-) and macrophage STING deficiency, interaction between HBV and lysosomes, suggesting that targeting the
Tmem173f/fLyz2Cre+ (Stingf/fLyz2Cre+) and liver-specific STING mitochondria-lysosome axis could offer innovative antiviral strategies.
knock-in, Albcre+ Sting-IRSE-EGFPki/ki (Stingki/kiAlbcre+) mice
and their controls were used in this study. THP1 and HepG2/ PP0086
HepG2.2.15 co-cultured cells were stimulated with palmitic acid (PA)
Novel function of NUP153 in HNF4α transcriptional upregulation
or its control for 12 hours in vitro. Markers for STING, autophagy, and
contributes to promoting HBV replication
endoplasmic reticulum stress were assessed using Western blotting,
Qianqian Jiang1, Zhao Zhou2, Xinyu Du3, Yukun Li2, Guiwen Guan2,
immunohistochemistry, and immunofluorescence assays. The liver
Ting Zhang2, Xin Liu2, Danli Yang2, Lin Wang2, Xiangmei Chen2,
tissues obtained from patients and were used for clinical validation.
Hongsong Chen1, Fengmin Lu1,2
Result: Compared with CHB or MAFLD mice, the concurrent presence
of CHB and MAFLD in mice resulted in a significantly accelerated
1
Peking University People’s Hospital, Peking University Hepatology
progression of liver inflammation and fibrosis, despite a decrease in Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy
for Liver Disease, Beijing International Cooperation Base for Science
HBV DNA levels observed within this group. Concomitant with disease
and Technology on NAFLD Diagnosis, 2Department of Microbiology
progression, CHB mice concurrent with MAFLD exhibited impaired
and Infectious Disease Center, School of Basic Medical Sciences,
autophagic flux and the upregulate of macrophage STING. The STING
Peking University, 3Precision Medicine Center, Academy of Medical
activation impaired the function of RAB7, thereby preventing STING
Sciences, Zhengzhou University
from entering lysosomes for degradation. Damaged degradation
of STING leads to its secretion via vesicles, which are subsequently Background: Nucleoporin 153 (NUP153) is known to facilitate
captured by hepatocytes, triggering endoplasmic reticulum stress and the nuclear entry of the human immunodeficiency virus (HIV)
exacerbating the progression of liver disease. Macrophage STING nucleocapsids, and recent studies suggest it also plays a role in
deficiency restored RAB7 function, enhanced autophagic flux, and hepatitis B virus (HBV) nucleocapsids nuclear import. Herein we
consequently mitigated liver inflammation and fibrosis. The expression aimed to investigate the impact of NUP153 on HBV replication and its
of STING, RAB7, and autophagy-related proteins was confirmed in underlying mechanism.
liver tissue samples derived from patients. Method: NUP153 was knocked down by RNA interference or CRISPR/
Conclusion: The significant upregulation of macrophage STING Cas9-mediated gene disruption, or overexpressed using an expression
expression in CHB concurrent with MAFLD disease can inhibit HBV plasmid in HBV-replicating cells and animal model. Luciferase reporter
virus replication and exacerbate liver inflammation by activating assays were employed to assess the activities of viral or host factor
antiviral and pro-inflammatory signals. Meanwhile, it impairs RAB7 promoters. Cytoplasmic and nuclear fractionation experiments were
function, impeding STING degradation and promoting its release conducted to analyze the subcellular distribution of proteins and HBV
through vesicles, which are then captured by liver cells and further RNA.
exacerbates disease progression. Result: Knockdown of NUP153 significantly inhibited HBV replication
without affecting the levels of covalently closed circular DNA
(cccDNA) pool in both the prcccDNA/Cre recombinant plasmid
PP0085 system and HepG2-NTCP cells. Consistent results were observed
Mitochondrial Regulation of Hepatitis B Virus Autophagic in a mouse model hydrodynamically injected (HDI) with 1.2×HBV
Degradation through Dual Modulation of Lysosomal acidification plasmid. Conversely, NUP153 overexpression markedly increased
Zhiqiang Wei1, Yanying Yan1, Lingzhu Zhao1, Chen Li1, Jinjin Qi1, cccDNA transcription and progeny virus production. HBV promoter
Zhengyun Xiao1, Guohua Lou1, Zhenggang Yang1, Xueyu Wang1, Min assays revealed that NUP153 enhanced HBV core promoter activity,
Zheng1 likely through a hepatocyte nuclear factor 4α (HNF4α)-dependent
1
State Key Laboratory for Diagnosis and Treatment of Infectious mechanism. Mechanistically, ERK signaling was essential for NUP153-
Diseases, National Clinical Research Center for Infectious Diseases, mediated promotion of HNF4α and HBV replication. On the other hand,
Collaborative Innovation Center for Diagnosis and Treatment of HBV replication significantly upregulated NUP153 mRNA and protein
Infectious Diseases, The First Affiliated Hospital, College of Medicine, levels in both HBV cell models and HBV-infected patients.
Zhejiang University Conclusion: We identified that nucleoporin NUP153 as a novel
Background: The ultimate goal of anti-hepatitis B virus (HBV) therapy host factor that promotes HBV replication by enhancing cccDNA
is sustained viral control or clearance; however, effective drugs are still transcription through the upregulation of HNF4α, suggesting a potential
lacking. Enhancing autophagic degradation may significantly reduce therapeutic target for HBV replication.
the secretion of HBV particles and effectively increase the degradation Table and Figure:Figure 1.NUP153 promotes HBV transcription and
of viral proteins in host cells, which plays a key role in HBV clearance. replication in vitro
HBV infection inhibits lysosome-associated autophagic degradation to Figure 2.NUP153 promotes HBV replication through ERK-HNF4a
enhance its own replication. Therefore, this study aims to investigate pathway
the underlying mechanisms of this observation.
Method: Mitochondrial function and lysosomal activity were tested PP0087
in HBV-replicating hepatoma cell lines. Additionally, the activity of The Risk prognosis of withdrawal for Chronic Hepatitis B failure
mitochondrial respiratory complexes were measured both in vitro and to meet discontinuation criteria: A systematic review and meta-
in vivo. analysis
Result: Both mitochondria and lysosomes were apparently
Shuixian Du1, Kezhen Hu1
dysfunctional in HBV-replicating cells. Blocking mitochondrial function 1
Qingdao Municipal Hospital
using the mitochondrial electron transport inhibitor Rotenone (Rot) in
vitro and in vivo decreased autophagic degradation capacity while Background: Chronic hepatitis B virus infection is a major public
health problem, and antiviral therapy is essential. Clinical as well as
historical studies have shown that discontinuation without meeting the hepatitis B virus (HBV) infection have long been an intriguing question.
criteria for discontinuation can lead to serious consequences, and Given the wide physiological range of liver stiffness and the growing
there is no international systematic analysis that summarizes studies attention to the role of mechanical microenvironment in homeostasis
that do not meet the criteria for discontinuation, so we conducted a and diseases, we investigated how physical matrix cues impact HBV
systematic review and meta-analysis to describe the risk of death and replication.
related influencing factors. Method: Using various cell and mouse models, along with single-cell
Method: n this study, we screened studies published in PubMed and RNA sequencing data from the liver tissues of HBV patients, the effects
Web of science up to July 18, 2024, and found that unauthorized of matrix stiffness and mechanosignaling activation on HBV replication
drug discontinuation in patients with chronic hepatitis B has a poor have been comprehensively studied.
prognosis. Six articles were selected for systematic review and meta- Result: High matrix stiffness significantly inhibited HBV replication
analysis. and activated YAP (Yes-associated protein), a key mechanosignaling
Result: The mortality rate of liver failure in chronic hepatitis B patients molecule, in primary human hepatocyte HBV infection model.
who discontinued medication without authorization was 47%; 57% YAP activation notably suppressed HBV transcription and antigen
of patients with liver failure who discontinued medication without expression. Several YAP-induced genes exhibited strong anti-HBV
authorization had cirrhosis; and the risk of death in patients with effects. Meanwhile, YAP significantly inhibited the expression levels of
cirrhosis from chronic hepatitis B who discontinued medication without HNF4A (Hepatocyte nuclear factor 4 alpha), a host factor supporting
authorization who developed liver failure was 1.67 times higher than HBV replication. Single-cell analysis of liver tissue from individuals with
that in patients without cirrhosis. active HBV replication revealed a strong significant negative correlation
Conclusion: Patients with chronic hepatitis B virus infection who between YAP signature activation and HBV transcript levels. Activating
developed liver failure after unauthorized drug discontinuation had a YAP by small molecules potently controls HBV in mouse models.
poor prognosis and high mortality. Cirrhosis is a statistically significant Conclusion: These findings unveil a novel mechanism that involves
risk factor in patients who die of liver failure after unauthorized drug the mechanical environment of hepatocytes and YAP to clear HBV
withdrawal. infection in the liver, providing new perspectives for HBV cure studies
and antiviral development.
Table and Figure:Figure 1.A schematic model of antiviral action through
PP0088
liver mechanosignaling via YAP.
GDH1-dependent α-ketoglutarate promotes HBV transcription by
modulating histone methylation on the cccDNA minichromosome
Shengtao Cheng1, Hui Zhang1, Ming Tan1, Juan Chen1
PP0090
1
Chongqing Medical University ATG16L1-mediated Autophagy Affects the Anti-HBV Effect of
Dendritic Cells
Background: Hepatitis B virus (HBV) hijacks host cell metabolism,
especially host glutamine metabolism, to support its replication. Futing Liu1
Glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme crucial
1
The Second Affiliated Hospital of Anhui Medical University
for glutamine metabolism, can interact with histone demethylases Background: Given the important role of dendritic cells in the anti-
to regulate gene expression through histone methylation. However, HBV immune response, it is known that dendritic cells can efficiently
the mechanisms underlying GDH1-mediated glutamine metabolism activate the STING pathway upon recognition of HBV infection, and the
reprogramming and the roles of key metabolites during HBV infection activation of STING proteins may also be associated with the induction
remain unclear. of autophagy. However, the effect of autophagy on the antiviral
Method: Transcriptomic and metabolomic analyses of HBV-infected effects of dendritic cells and its underlying mechanisms are not fully
cell were performed. Both HBV-infected cells and humanized understood.
liver chimeric mice were used to elucidate the effect of glutamine Method: Here, we investigated the relationship between STING
metabolism on HBV. pathway activation and autophagy by directly agonizing dendritic
Result: HBV infection leads to the abnormal activation of glutamine cells using HBV-concentrated viral particles and the STING agonist
metabolism, including upregulation of key enzymes and metabolites diABZI, and examined the effects of autophagy inhibitors or inducers
involved in glutamine metabolism. The viral core protein (HBc) mediates on dendritic cells. The expression of dendritic cell surface molecules
the translocation of GDH1 into the nucleus, where GDH1 activates was analyzed using flow cytometry, and the effect of dendritic cells
covalently closed circular DNA (cccDNA) transcription by converting on the anti-HBV effects of CD8+ T cells was analyzed by co-culture
glutamate to α-ketoglutarate (αKG). Mechanistically, the promoting technique with lymphocytes. In addition, the role of ATG16L1 in STING
effect of GDH1-derived αKG on cccDNA transcription is independent activation-induced autophagy was analyzed to better understand
of its conventional role. Rather, αKG directly interacts with the lysine- the mechanisms by which autophagy affects the antiviral effects of
specific demethylase KDM4A and enhances KDM4A demethylase dendritic cells.
activity to regulate αKG-dependent histone demethylation, controlling Result: By agonizing dendritic cells it was demonstrated that
cccDNA transcription. autophagy formation increased with increasing agonization time,
Conclusion: Our findings highlight the importance of glutamine STING expression decreased, and autophagy formation was reduced
metabolism in HBV transcription and suggest that glutamine by knockdown of STING. Inhibition of autophagy upregulated the
deprivation is a potential strategy for silencing cccDNA transcription. STING pathway effector molecules phosphorylated STING and
Table and Figure:Figure 1.Graphic abstract phosphorylated TBK1 in agonized dendritic cells. However, mRNAs
Figure 2.Key Data such as IL-6, TNFa, IFNβ, and CXCL10 were downregulated in
dendritic cells after inhibition of autophagy by chloroquine, and the
surface molecules CD40, CD80, CD86, MHC-I, MHC-II, and PD-L1 did
PP0089
not show a trend of upregulation. In addition, TNFa, IL-2, and IFNγ
Liver Mechanosignaling as a Natural Anti-Hepatitis B Virus secreted by CD8+ T cells were also down-regulated after inhibition of
Mechanism autophagy and co-culture with lymphocytes. In contrast, the ability of
Jianyu Ye1, Faghong Li2, Ting Hua1, Zhenghong Yuan1, Jiming dendritic cells to inhibit the secretion of HBsAg and HBeAg by AML12
Zhang2, Jieliang Chen1 cells transfected with pHBV1.3 was enhanced after knockdown of the
1
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), ATG16L1 molecule, implying that STING activation-induced autophagy
School of Basic Medical Sciences, Shanghai Medical College Fudan is dependent on ATG16L1.
University, Shanghai, China, 2Department of Infectious Diseases, Conclusion: Dendritic cells activate the STING pathway to induce
Huashan Hospitall, Fudan University, Shanghai, China autophagy formation after recognizing HBV. However, the resulting
Background: The mechanisms underlying the natural control of degradation of the effector protein STING is inhibited by knockdown
of ATG16L1 and attenuates the ability of hepatocytes transfected
with pHBV1.3 to secrete HBsAg and HBeAg and thus exert anti-HBV resulted in decrease of the above HBV virological markers. Consistently,
effects. overexpression of NIK inhibited HBV replication and transcription, as
well as core promoter activity, in a dose-dependent manner in HBV
transfection and infection cell models. Further studies have found
PP0091
that the anti-HBV effect of NIK depends on its kinase activity, while
Expression of TIM-3 on the DC surface inhibits the antiviral effects KK429/430AA sites mutation abolished its anti-HBV effect in vitro and
of the HBV-DNA-induced cGAS-STING pathway in vivo. To identify the downstream pathways involved in NIK-mediated
Mengqi Ruan1 HBV inhibition, we performed RNA-seq screening of NIK induced
1
Anhui genes expression and confirmed the kinase dependent activation of
Background: In the tumor microenvironment, tumor-infiltrating DCs type I/III IFN response pathway and NF-κB signaling pathway. Finally,
highly express TIM-3 protein, which competes with nucleic acids although NIK was reported to activate IRF3-dependent IFN pathway
released by tumor cells for binding to HMGB1, blocking the entry of and NF-κB2 dependent non-canonical NF-κB pathway, we found that
nucleic acids into the endosomes and thus inhibiting nucleic acid- the anti-HBV effect of NIK in hepatocytes was significantly weakened
stimulated STING signaling pathway activation in DCs. As a result, the after IRF1 and IRF9 knockout, but not NFKB2 or IRF3 knockout.
activation and impaired function of innate immune cells. Blocking TIM- Conclusion: Our study suggests that NIK represents a novel host
3 promoted activation of the cyclic GMP-AMP synthase and stimulator factor in hepatocytes restricts HBV replication and transcription by
of interferon genes pathway, expression of type I interferons, and activating IFN pathway through IRF1/9. Activation of NIK-mediated
secondary expression of chemokines. However, the mechanism by pathway may serve as a new strategy for HBV therapy.
how TIM-3 regulates the STING pathway within DC to initiate innate Table and Figure:Figure 1.Figure.1
immune responses in chronic hepatitis B is not clear. Figure 2.Figure.2
Method: DC2.4 cells were stimulated with HBV virus particles, and the
activation level of STING pathway was detected by Western Blot, PCR, PP0093
and the expression of DC cell phenotypes (TIM-3, CD80, CD86, CD40)
Ubiquitinated Hepatitis D Antigen Induced Specific CD8+T Cell
by flow cytometry. Knockdown of TIM-3 expression was followed by
Inhibited HDV Replication via JAK/STAT Pathway in HDV Infected
HBV stimulation to detect the level of STING pathway activation.
Liver Organoids
A mouse model of slow hepatitis B was constructed and TIM-3
expression was inhibited in mice, and the maturation degree of DC Leer Shen1, Luying Tian1, Qingxin Guo1, Jinmei Chen1, Xiaohua
cells as well as the level of specific T-lymphocyte response were Chen1
detected.
1
Shanghai Jiao Tong University Medicine School Affiliated Shanghai
Result: Upon knockdown of TIM-3 in DC cells, the level of intracellular Sixth People’s Hospital
STING pathway activation was up-regulated and the ability to secrete Background: Hepatitis D virus (HDV) infection induces the most
interferon was enhanced. severe form of human viral hepatitis. Poor adaptive immune responses
In vivo inhibition of TIM-3 in mice resulted in increased maturation of could result in persistent HDV infection, and virus-specific CD8+T cell
DC cells, upregulation of the level of specific T-cell responses, and response seems to play a significant role in the eradication of HDV.
decreased serum levels of HBsAg, and HBeAg. However, the impact of Ub-S-HDAg on CD8+T cells in HDV is unknown.
Conclusion: During chronic HBV infection, high expression of TIM-3 Here, we aimed to unveil the anti-viral effect and mechanisms of Ub-S-
on the DC surface inhibited the activation of the STING pathway, and HDAg in HDV infected liver organoids.
its downstream expression of interferon and inflammatory cytokines Method: Induced pluripotent stem cells were differentiated into
decreased, activating the antiviral capacity of T lymphocytes. Blockade hepatocyte-like cells (HLCs) and subsequently seeded onto inverted
of TIM3 resulted in increased maturation and immune activation of colloidal crystal (ICC) scaffolds. The HLC-ICC liver organoid system
DCs, which may help to reverse the tolerance state in patients with was co-infected with HBV and HDV particles. The ubiquitinated small
chronic hepatitis B. Hepatitis D antigen (Ub-S-HDAg) recombinant lentiviral plasmid was
constructed and transfected into human dendritic cells (DCs), which
were then co-cultured with T cells. The levels of cytokine secretion by
PP0092
CD8+ T cells and their antiviral efficacy were subsequently evaluated.
NF-κB-inducible kinase expression activates type I/III interferon Additionally, transcriptomic sequencing and bioinformatics analyses
signaling via IRF1 to inhibit HBV replication and transcription in were conducted to elucidate the antiviral mechanisms of Ub-S-HDAg.
hepatocytes Result: In this study, we successfully established a model capable
Ziying Liu1, Xiaoyong Zhang1 of stably expressing HDV for approximately three weeks. The results
1
Department of Infectious Diseases, Nanfang Hospital, Southern demonstrated that Ub-S-HDAg significantly promoted DC maturation,
Medical University, Guangzhou, China; State Key Laboratory of enhanced CD8+ T cell proliferation, and strengthened HDV-specific
Organ Failure Research; Key Laboratory of Infectious Diseases cytotoxic T lymphocyte (CTL) responses. Additionally, in the Ub-S-
Research in South China, Ministry of Education; Guangdong HDAg group, CD8+ T cells exhibited significantly elevated secretion
Provincial Key Laboratory for Prevention and Control of Major Liver of IFN-γ, IL-2, IL-12, and TNF-α, while HDV RNA viral load and HDAg
Diseases; Guangdong Provincial Clinical Research Center for Viral levels were markedly reduced compared to other groups. Both KEGG
Hepatitis; Guangdong Institute of Hepatology; Guangdong Provincial pathway enrichment analysis and GSEA analysis suggested that Ub-
Research Center for Liver Fibrosis Engineering and Technology S-HDAg exerted its antiviral effects in CD8+ T cells through the JAK/
Background: NF-κB-inducing kinase (NIK) is a key factor in the STAT pathway, which was further validated by Western blot (WB) and
activation of cellular non-canonical NF-κB pathway, thus it plays qPCR analyses.
critical role in host defense of pathogens infection. This study aims Conclusion: Overall, our findings suggest that in the HDV-infected liver
to investigate the hepatocyte intrinsic role of NIK in regulation of HBV organoid model, Ub-S-HDAg may promote CD8+ T cell differentiation
infection. and induce a specific cellular immune response through the JAK/STAT
Method: NIK was knocked down by RNA interference and over- pathway, thus providing a potential therapeutic approach for HDV
expressed by lentiviral or plasmid. C57BL/6 or hepatocyte-deficient eradication.
NIK (NIKΔhep) mice were hydrodynamically injected with pAAV- Table and Figure:Figure 1.Establishment of HDV infection in HLC-ICC
HBV1.2 plasmids. HBV DNA, HBsAg, HBeAg, HBcAg, 3.5kb HBV organoids
RNA and capsid DNA were used to evaluate HBV replication and gene Figure 2.The antiviral effect of Ub-S-HDAg
expression.
Result: Using the pAAV-HBV1.2 hydrodynamic injection mouse model,
PP0094
hepatocyte-specific NIK knockout resulted in increased levels of serum
HBV DNA, HBsAg, HBeAg and liver HBcAg, while overexpressing NIK
Hepatocyte-enriched miRNA-193b-3p Promotes Hepatitis B Virus coagulation failure and the number of organ failure in the CMA+APASL
Replication by Dual Activation of Viral Core Promoter Activity and group was lower than that of the CMA-APASL group (P<0.05) ,and
Autophagy Induction by Targeting IGF-1R the proportion of hepatic encephalopathy, liver function, renal function,
Yingying Deng1, Jiaxin Zheng1,2, Yong Lin1 coagulation function, proportion of coagulation failure, number
1
Chongqing Medical University, 2Sichuan Tianfu New Area People‘s of organ failure, 28-day and 90-day morbidity and mortality, and
Hospital prognostic scores were higher in CMA+EASL group than CMA-EASL
group (P<0.05) .Among HBV-ACLF patients, age, NLR, MLR, TBil, INR,
Background: HBV infection is a principal cause of severe liver
PT, D-Dimer, Lac, complications (ascites, hepatic encephalopathy,
disease in humans and is associated with increased levels of specific
and infections), coagulation failure, number of organ failures, 90-day
serum or intracellular miRNAs. Among these, miR-193b-3p is a liver-
morbidity and mortality, and prognostic scores were higher in the
enriched miRNA; however, its role in HBV replication remains unclear.
CMA+APASL group than in the CMA-APASL group (P <0.05); several
This study aimed to investigate the influence of chronic HBV infection
inflammatory indicators, INR, PT, TBil, Lac, complications,and organ
on miR-193b-3p levels in the peripheral blood and liver tissues of
failure, prognostic scores, 28-day and 90-day morbidity and mortality
patients with chronic hepatitis B, evaluate the effect of miR-193b-3p
were higher than those in the CMA-EASL group (P <0.05).
on HBV replication both in vitro and in vivo, and elucidate the potential
Conclusion: Regardless of ALD-ACLF or HBV-ACLF, patients who
underlying mechanisms.
met both CMA and EASL diagnostic criteria had a more severe
Method: To determine whether HBV infection upregulates miR-193b-
condition and worse prognosis, and the combined EASL diagnostic
3p expression, we conducted real-time PCR analysis to measure
criteria reassessment could further differentiate the severity of ACLF;
miR-193b-3p serum levels in different patient groups. Additionally, we
whereas, the combined APASL diagnostic criteria were only applicable
conducted in vitro and in vivo experiments to determine whether miR-
to differentiate patients with HBV-ACLF, and could not differentiate the
193b-3p promotes HBV replication. Bioinformatics and mechanistic
severity of the condition of ALD-ACLF patients. The prognostic scores
studies were conducted to investigate these mechanisms.
of the patients were compared to the prognostic scores of the patients.
Result: Hepatic miR-193b-3p levels in patients with chronic hepatitis
B were significantly elevated compared with those in healthy
controls. Ectopic expression of miR-193b-3p significantly enhanced PP0096
HBV replication and transcription in different hepatoma cell lines. Study of the underlying mechanism of liver fibrosis based
Bioinformatic analysis of transcriptomic sequencing following miR- on a combination of network pharmacology, transcriptomics,
193b-3p overexpression identified IGF-1R as a direct target through metabolomics, and experimental validation strategies
which miR-193b-3p regulates HBV replication. Mechanistically, miR- Bei Gui1, Lin Xiao Chi2
193b-3p increased HBV core promoter activity via the IGF-1R/FXRα 1
Guangdong Province Traditional Chinese Medical Hospital, 2
axis, thereby enhancing HBV transcription. Additionally, miR-193b-3p Guangdong Province Traditional Chinese Medical Hospital
increased IGF-1R/AKT/MDM2/p53 signalling-mediated autophagy
induction, which in turn facilitated increased HBV post-transcriptional Background: Liver fibrosis (HF) is a necessary pathological process in
activity. the occurrence and development of a variety of chronic liver diseases.
Conclusion: Collectively, miR-193b-3p exerts a proviral effect on If not blocked in time, it can further develop to cirrhosis, liver cancer,
HBV replication through dual synergistic mechanisms that affect both and even life-threatening. HHSYF is an effective empirical formula for
transcriptional and post-transcriptional stages. This study offers novel HF in a clinical setting and has been shown to be effective in liver
insights into the role of hepatocyte-enriched miR-193b-3p in HBV fibrosis. In a previous study, we demonstrated that HHSYF upregulated
replication and its potential therapeutic implications in chronic HBV miR-29a-3p expression and inhibited NOD-like receptor protein 3
infection. (NLRP3) to reduce inflammatory cytokines and relieve HF. Targetscan
prediction found that HMGB 1 is a target gene of miR-29a-3p. In this
study, we investigated the mechanism of HHSYF in more detail from
PP0095 the perspective of macrophage pyroptosis.
Comparison of the value of different clinical diagnostic criteria in Method: Mouse model of liver fibrosis was established by CCI4
patients with ALD and HBV-related acute-on-chronic liver failure induction. Levels of miR-29a-3p in mice with liver fibrosis were
Yanping Chen1, Lingxia Wang2, Zuxiong Huang2 overexpressed by a lentiviral vector. Mouse liver tissue morphology was
1
Fujian Medical University, 2Meng Chao Hepatobiliary Hospital of assessed using Sirius Red, staining, and H & E staining. Transcriptome
Fujian Medical University sequencing analysis and network pharmacology were used to reveal
possible targets and mechanisms. Finally, the effects of mice and mice
Background: To compare the applicability of the diagnostic criteria of
on HMGB 1-NLRP 3 pathway, mRNA expression and IL-1, IL-1 β, and
the European Association for the Study of the EASL-CLIF Collaborative
IL-18.
Group and APASL in patients with ALD-ACLF and HBV-ACLF who
Result: The protein-protein interaction (PPI) core gene network
conform to the diagnostic criteria of the Chinese Medical Association
consists of NLRP3, CASP1 (caspase-1), TP 53, and MAPK8. Pathway
(CMA) in China.
enrichment analysis revealed a significant enrichment of inflammatory
Method: The clinical data of 43 ALD-ACLF patients and 208 HBV-
responses associated with pyroptosis. We further performed in vivo
ACLF patients who met the diagnostic criteria of CMA in our Hospital
experiments and showed that the HHSYF suspension administration
from January 2019 to December 2022 were retrospectively analyzed.
had less hepatic fibrosis damage in the HHSYF group than in the model
According to whether the EASL-CLIF diagnostic criteria were met,
group. The level of miR-29a-3P was increased in the liver tissues of the
they were categorized as simultaneously meeting the EASL diagnostic
HHSYF group. In addition, the levels of NLRP3, HMGB 1, caspase-1,
criteria (CMA+EASL group) versus not meeting the EASL diagnostic
GSDMD-N, IL-1 β, and IL-18 were reduced to varying degrees at both
criteria (CMA-EASL), and according to whether they met the APASL
the mRNA and protein levels.
diagnostic criteria, they were categorized as simultaneously meeting
Conclusion: In conclusion, our study demonstrated that the function
the APASL diagnostic criteria (CMA+APASL group) versus not meeting
of miR-29a-3p in liver fibrosis and its targeting HMGB 1 to mediate the
the APASL diagnostic criteria (CMA- APASL group).To compare the
NLRP 3 inflammasome pathway to exert therapeutic effects against
applicability of combining different diagnostic criteria in ALD-ACLF
liver fibrosis.
and HBC-ACLF.
Table and Figure:Figure 1.Workflow of the HHSYF investigation strategy
Result: Comparison of the applicability of different diagnostic criteria in
the treatment of HF
patients with ACLF who met the CMA diagnostic criteria: the proportion
of patients with HBV-ACLF who met both CMA and APASL diagnostic
criteria was higher than that of ALD-ACLF (P=0.027). And there was no PP0097
significant difference in the proportion of those who met both CMA and
EASL diagnostic criteria.Among ALD-ACLF patients, the proportion of
AUF1 is a novel negative regulator for hepatitis B virus replication reporter assays are employed to assess the impact of UBF1/2 on the
acting through a post-transcriptional manner transcriptional activity of HBV promoters.
Chenxiao Qu1, Jing Zhang2, Danjuan Lu1, Yi Wang1, Wenhui Song1, Result: First, we confirmed that UBF1/2 are cccDNA-binding proteins
Yuxin Song3, Jia Liu1, Ting Zhang1, Fengmin Lu1, Xiangmei Chen1 through DNA pull-down and cccDNA ChIP assays. Second, the in
1
Peking University Health Science Center, 2Capital Medical University vitro transfection systems and HBV replication systems showed that
Beijing Tongren Hospital , 3Shihezi University School of Medicine UBF1/2 suppress HBV replication by reducing transcriptional activity
of multiple HBV promoters. Furthermore, the phosphorylation status
Background: As a hepatotropic DNA virus, HBV is tightly regulated by
of UBF1/2 were found to be involved in their regulatory role in HBV
both viral and host factors. Understanding the molecular mechanisms
replication.
underlying HBV-host interactions and identifying effective therapeutic
Conclusion: The host factors UBF1/2 could directly bind to cccDNA to
targets for HBV are of significant importance. This study aims to
suppress cccDNA transcription and HBV replication through inhibiting
investigate the interaction and mechanisms between HBV and the
multiple HBV promoters activity, in a UBF1/2 phosphorylation status
RNA-binding protein AU-rich element RNA-binding protein 1 (AUF1).
dependent manner.
Method: The interaction and mechanism between HBV and AUF1 were
investigated in both HBV replication cell models and the HepG2-NTCP
HBV infection cell model. The levels of HBsAg, HBeAg, and HBV DNA PP0099
in the culture supernatant were quantified using chemiluminescence The host factor RBM25 promotes HBV cccDNA transcription and
immunoassay and quantitative real-time PCR (qPCR). Western replication by regulating Yin Yang 1
blot was performed to assess intracellular core and HBs proteins. Yukun Li1, Tianhao Mao1, Liwei Zheng1, Zhao Zhou1, Qianqian
Southern blot and qPCR were employed to detect intracellular capsid- Jiang2, Xinyu Du3, Ziyuan Ma4, Xin Liu1, Ting Zhang1, Guochao Wei1,
associated HBV replicative intermediates and HBV DNA. Northern blot Yongzhen Liu5, Lin Wang1, Xiangmei Chen1, Fengmin Lu1
and reverse-transcription qPCR were used to evaluate intracellular 1
Department of Microbiology & Infectious Disease Center, School of
levels of HBV RNA. The impact of AUF1 on the transcriptional activity Basic Medical Sciences, Peking University, Beijing, China, 2Peking
of HBV RNA was assessed through a luciferase assay, while an RNA University People’s Hospital, Peking University Hepatology Institute,
turnover assay was conducted to analyze its effect on the stability of Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver
HBV RNA. Ribo-seq analysis was utilized to investigate the influence of Disease, Beijing International Cooperation Base for Science and
AUF1 on the translation efficiency of both host genes and HBV RNA. Technology on NAFLD Diagnosis, Beijing, China, 3Precision Medicine
The binding ability of AUF1 to HBV RNA was examined using RNA Center, Academy of Medical Sciences, Zhengzhou University,
immunoprecipitation (RIP) as well as RNA pulldown assays. Zhengzhou, China, 4School of Medical Sciences, University of Sydney,
Result: Our findings demonstrated that AUF1 inhibited HBV Sydney, Australia, 5Model Animal Research Center, Medical School of
replication and expression in both HBV replication and infection Nanjing University, Nanjing, China
models. Mechanistically, AUF1 primarily reduced the stability of HBV Background: The persistence of covalently closed circular DNA
RNA at the post-transcriptional level, leading to decreased RNA levels, (cccDNA) in HBV-infected hepatocytes remains a major obstacle
while translation efficiency remained unaffected. AUF1 interacted with functional cure of chronic hepatitis B. Understanding the molecular
multiple binding sites on HBV RNA. However, there was no competition mechanisms regulating HBV cccDNA transcription is essential for
between AUF1 and HuR for binding to HBV RNA, and they did not developing novel therapeutic strategies. The aim of this study is to
exhibit opposing effects in regulating HBV RNA. Additionally, we investigate the role of RNA-binding protein RBM25 in HBV replication,
observed that HBV reduced intracellular AUF1 protein levels without with focusing on its interaction with cccDNA and its regulation of host
affecting AUF1 mRNA, likely due to enhanced protein degradation. transcription factors.
Conclusion: This study unveiled the inhibitory role of AUF1 in Method: RBM25 function was studied through loss- and gain-of-function
HBV replication through its binding to HBV RNA and subsequent approaches in HBV-replicating and infection cell models, as well as in
destabilization, while conversely, HBV promoted degradation of AUF1 an HBV-replicating mouse model. The effects of RBM25 knockdown
protein levels. These findings provide novel insights into the interaction and overexpression on HBV replication, cccDNA transcriptional
between AUF1 and HBV, positioning AUF1 as a post-transcriptional activity, and host transcription factor expression were evaluated
negative regulator of HBV replication. using Southern blot, Northern blot, RT-qPCR, immunohistochemistry,
and luciferase reporter assays. The interaction between transcription
PP0098 factors, histone modifications and cccDNA were examined by DNA
Host factors UBF1/2 binding to Hepatitis B virus cccDNA suppress pull-down and ChIP assays.
HBV replication by inhibiting HBV promoters Result: RBM25 knockdown markedly inhibited HBV replication, as
confirmed by the changes of levels of HBsAg, HBeAg, HBV DNA,
Xinyu Du1, Tianhao Mao2,3, Lin Wang2, Xiangmei Chen2, Fengmin
HBV RNA, and L-HBs. Meanwhile, constant overexpression of ectopic
Lu1,2
RBM25 significantly enhanced these markers, though with decreased
1
Precision Medicine Center, Academy of Medical Sciences,
core protein stability. Mechanistically, RBM25 promoted HBV promoter
Zhengzhou University, Zhengzhou 450052, China., 2Department of
activities by binding to cccDNA through its RERD and PWI domains.
Microbiology &Infectious Disease Center, School of Basic Medical
This effect was mediated by increased YY1 expression and recruit
Sciences, Peking University Health Science Center, Beijing 100191,
it to cccDNA, which in turn enhanced acetylation of cccDNA-
China., 3Department of infectious disease and liver disease. The
second Hospital of Nanjing, Affiliated to Nanjing University of Chinese bound histones, promoting HBV transcription. In a mouse model,
Medicine, Nanjing, 210003, China; RBM25 knockdown decreased YY1 expression and HBV replication.
Furthermore, RBM25 expression was upregulated and translocated to
Background: Our previous laboratory study has shown that upstream the nucleus following core protein expression and accumulation.
transcription factor 1/2 (UBF1/2), as host factors, may be potential Conclusion: This study demonstrated that RBM25 is a host factor
cccDNA-binging proteins, significantly affecting the levels of HBsAg that enhances HBV replication by upregulating YY1-dependent
and HBeAg in cell culture supernatants. This study aims to investigate transcriptional activation of cccDNA. It also revealed a reciprocal
whether UBF1/2 serve as cccDNA-binding proteins, and further regulatory mechanism between the HBV and RBM25, which helps
explore the potential mechanisms in regulating Hepatitis B Virus(HBV) sustain HBV replication at a moderately high level.
replication. Table and Figure:Figure 1.RBM25 promotes HBV replication
Method: DNA pull-down and cccDNA ChIP assays are used to confirm Figure 2.RBM25 promotes YY1 expression and facilitates HBV
the binding of UBF1/2 to HBVcircle, a construct to mimic the naked transcription through YY1-mediated acetylation of cccDNA-associated
cccDNA. The siRNAs knocking down and ectopic overexpression of histones
UBF1/2 or their variants, are used to study the effect of UBF1/2 on
HBV replication in in vitro HBV replication cell models. Luciferase
PP0100
Nuclear receptor binding protein 1 enhances the activity of found between the HCC and HDs. There was no statistical difference
Hepatitis B virus core promoter to promote the replication of between the groups (P > 0.05).
Hepatitis B virus Conclusion: Conclusion: Siglec-9 expression on CD56dimNK cells
Zhao Zhou1, Lin Wang1, Xiangmei Chen1, Fengmin Lu1 in chronic HBV-infected patients with different clinical regressions was
1
Department of Microbiology and Infectious Disease Center, School of higher than in the healthy population, suggesting that the prognosis
Basic Medical Sciences, Peking University Beijing, China of patients can be assessed by detecting siglec-9 molecules in the
assay as well as the treatment of HBV infection by inhibiting siglec-9
Background: Nuclear receptor binding protein 1(NRBP1) is a kind
molecules.
of pseudokinase, which functions differently in various diseases’
progression. It may change its cellular distribution in Dengue virus
infection and promote the existence of virus in cells. However, the PP0102
effect of this protein in hepatitis B replication has not been reported. DNAJC9 binds to and enhances the transcription of Hepatitis B
Method: Construct exogenous expression plasmid of NRBP1 and virus cccDNA by recruiting histone H3.3
transfect it transiently into HBV cell models to overexpress NRBP1 in Tianhao Mao1,2, Xinyu Du1, Yukun Li1, Zhao Zhou1, Deyao Li1, Liwei
the present of prcccDNA/pCMV-Cre recombinant system. Use siRNA Zheng1, Danli Yang1, Ting Zhang1, Guixin Li1, Xiangmei Chen1,
to knock down endogenous expression of NRBP1 in the present of Fengmin Lu1,3,4
prcccDNA/pCMV-Cre recombinant system. Real-time fluorescence 1
Department of Microbiology &Infectious Disease Center, School of
quantitative PCR and chemiluminescence immunoassay were used Basic Medical Sciences, Peking University Health Science Center,
to detect the level of HBV DNA, HBeAg and HBsAg in the cellular Beijing 100191, China., 2Department of Infectious Disease, The
supernatant. Reverse transcription-real-time fluorescence quantitative Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese
PCR was used to detect the content of various types of HBV RNA in Medicine, Nanjing 210003, China., 3Precision Medicine Center,
cells. Western blot was used to detect the content of HBV core protein Academy of Medical Sciences, Zhengzhou University, Zhengzhou
in cells. Dual luciferase reporter gene assay was used to detect the 450052, China., 4Shenzhen Blood Center, Shen Zhen 518035,
effect of NRBP1 on core promoter(CP) activity. Guangdong, China.
Result: Exogenous expression of NRBP1 can increase the content of
Background: Hepatitis B virus (HBV) covalently closed circular DNA
HBV DNA, HBeAg and HBsAg in the cellular supernatant. Exogenous
(cccDNA), the transcriptional template in HBV replication, is regulated
expression of NRBP1 can also significantly increase the content of
by multiple host proteins such as epigenetic factors and transcription
core protein in cells and the content of various types of HBV RNA in
factors. This study aims to identify novel host proteins interacting with
cells. Exogenous expression of NRBP1 can significantly activate the
cccDNA and regulating its activity in HBV life cycle.
activity of HBV core promoter, and can significantly activate the activity
Method: Mass spectrometry analysis identified host proteins
of transcription factors CREB2 and c-jun.
associated with biotinylated cccDNA surrogate HBVcircle. Following
Conclusion: NRBP1 promotes HBV transcription and replication,
this, an siRNA library screening was applied to identify candidate
which may be related to its ability to up-regulate the activity of HBV-
proteins affecting HBV replication. We confirmed the interaction
related transcription factors CREB2 and c-jun.
between cccDNA and host protein through DNA pull-down, cccDNA
Table and Figure:Figure 1.Exogenous expression of NRBP1 promotes
ChIP, and immunofluorescence. Quantification of HBV nucleic acids
HBV RNA transcription
and antigens demonstrated the influence of the host protein on HBV
life cycle. Via Co-IP and cccDNA ChIP experiments, we discovered the
PP0101 specific mechanism by which the host protein changes the epigenetic
Regulatory effects of siglec-9 on CD56dimNK cells in chronic status of cccDNA.
HBV-infected patients and their different clinical regressions Result: The captured host proteins were mainly enriched in ribosome
biogenesis and chromosome assembly pathways. Among the
Zhihao Zhao1,2, Huijie Jiang1,2, Xianggen Kong1,2, Shiyu Cui1,2, Xuemei
chromatin-associated proteins, knockdown of DnaJ homolog subfamily
Jiang1,2
C member 9 (DNAJC9) in HepG2 cells transfected with HBVcircle
1
Shangdong University, 2Shandong public health clinical center,
had the most significant inhibitory effect on hepatitis B surface
Jinan, China
antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cell culture
Background: Background: To study the expression of siglec-9 supernatant. DNAJC9 can bind to cccDNA in a manner independent
molecules on NK cells and their role in regulating their functional state of histones and specific DNA sequences. In different HBV replication
and to provide new strategies for clearing HBV infection and blocking cell models, knockdown of DNAJC9 significantly reduced the levels
the chronicity of HBV infection. of supernatant HBV DNA, HBsAg, and HBeAg, as well as intracellular
Method: Method: In this study, clinical specimens were enrolled HBV RNA levels. The effects of the overexpression experiments were
using a consecutive enrollment method in patients with chronic in contrast to these findings. DNAJC9 knockdown did not disturb the
hepatitis B(CHB), HBV-associated cirrhosis(LCC), HBV-associated conversion from relaxed circular DNA (rcDNA) to cccDNA, but reduced
hepatocellular carcinoma(HCC), and HBV-associated slow plus the transcriptional activity of HBV promoters and enhancers. DNAJC9
acute liver failure(ACLF) who were admitted to the Public Clinical can bind to histone H3.3, and knockdown of DNAJC9 reduced active
Centre of Shandong Province from March 2023 to December 2023, chromatin marks on cccDNA, such as histone H3.3, tri-methylation
and the employees who underwent a health check-up in our hospital of histone H3 at lysine 4 (H3K4me3), and acetylation of histone H3
as healthy controls(HDs). Basic personal information of the enrollees at lysine 27 (H3K27ac). Finally, HBV replication led to a decrease of
was collected, and fresh EDTA-anticoagulated peripheral blood was DNAJC9 in the cytoplasm and an increase in the nucleus.
retained for flow cytometry. All patients underwent liver biochemistry, Conclusion: Histone chaperone DNAJC9 can bind to cccDNA
blood routine, HBV DNA, hepatitis B five quantitative, liver tumor in a histone-independent manner. DNAJC9 upregulates cccDNA
indexes, and liver ultrasound examination. transcription and viral replication by increasing the density of H3.3,
Result: Results:The median percentage of Siglec-9 expression on H3K4me3, and H3K27ac on cccDNA, thereby activating its promoters
CD56dim NKcells from patients with CHB, LCC, HCC, ACLF, and HDs and enhancers. HBV replication may promote the nuclear localization
were (20.1%, 12.4%, 11.8%, 19.5%, and 4.2%), respectively, and of DNAJC9 protein, thus facilitating active transcription and replication
statistically significant differences were found between the four groups of HBV.
of CHB, LCC, HCC, and ACLF, and HDs (p-value less than 0.05 for
all). The median mean fluorescence intensity of Siglec-9 expression
on CD56dim NK cells from patients with CHB, LCC, HCC, ACLF, and PP0103
HDs was (1464, 1314, 1361, 3413, and 297) and statistically different Revealing HBV quasispecies at the single-cell level
between the four groups of CHB, LCC, and ACLF, and HDs (P values Yanfang Huang1, Yongping Liu2, Jinhang He1, Qiran Zhang1, Wenhong
were less than 0.05), but no statistically significant difference was Zhang1, Qiu Chao3
1
Huashan Hospital, Fudan University, 2Hangzhou Xixi Hospital, lipid droplet-mitochondria tethering. RIL-175 cells reconstituted with
3
Institutes of Biomedical Sciences, Fudan University wild-type rVDAC1 or rVDAC1(K161R) were injected intrahepatically
Background: HBV quasispecies emerge as the result of the complex into mice to assess the impact of K161R mutation on VDAC1-APOE
interplay between the virus and the host immunity. Previous studies interaction and associated downstream cascades.
regarding HBV quasispecies were predominantly performed at the Result: Spatial transcriptomic analysis revealed that patients in
bulk level through cloning or second/third-generation sequencing, concurrent group exhibited markedly exacerbated mitochondrial
without observing the virus quasispecies at the single-cell level. dysfunction and aberrant immune cell infiltration. Although all
Hence, the diversity of HBV quasispecies at the single-cell level was enrolled CHB patients were in the immune-tolerant phase, concurrent
traced based on the previously established targeted capture single- MASLD significantly increased the infiltration of tumor-associated
cell sequencing technology, facilitating a deeper understanding the macrophages (TAMs) within the lesion areas (Fig. 1). Compared
virus mutant repository. with CHB or NAFLD patients, concurrent CHB and NAFLD patients
Method: Targeted capture single-cell sequencing technology was presented upregulated Voltage-Dependent Anion Channel 1
employed on liver biopsy specimens from two HBeAg-positive and (VDAC1) localized on mitochondria, accompanied by a marked
two HBeAg-negative patients with chronic hepatitis B (CHB). By increase in VDAC1 oligomerization (Fig. 2). VDAC1 subsequently
using pyranges, consensus reads from Read2 of four probes (S, interacted with the lipid droplet protein Apolipoprotein E (APOE),
X, pgRNA, rcDNA) were extracted. To avoid artifacts, variants with resulting in lipid droplets-mitochondria tethering, oxidative stress and
nucleotide substitutions higher than 0.1% and 2 reads of a single UMI markedly exacerbated mitochondrial dysfunction, which developed a
were selected. Phylogenetic analysis was carried out by the MEGA tumorigenic microenvironment by increasing lactate production and
11 software using the maximum likelihood method, and quasispecies inhibiting apoptosis. Interfering with this cascade through blocking
complexity was calculated using Shannon entropy (Sn). VDAC1-APOE interaction mitigated mitochondrial dysfunction,
Result: A total of 33, 68, 54, and 33 variants of four patients with CHB inhibited lactate production, promoted apoptosis and suppressed the
were detected in the HBV S (321-470 nt), X (1531-1680 nt), pgRNA development of a pro-tumorigenic hepatic microenvironment in mice.
(2259-2408 nt), and rcDNA (1099-1248 nt) regions, respectively. The Meanwhile, oligomerization of VDAC1 in MASLD promoted the release
total number of variants in HBeAg-positive patients was significantly of mitochondrial DNA (mtDNA), which inhibitted HBV replication by
greater than that in HBeAg-negative CHB patients. Phylogenetic activating the ISG-mediated innate immune response (Fig. 2).
analysis indicated that HBV in these four patients with CHB was under Conclusion: Concurrent MASLD promotes VDAC1-mediated lipid
constant evolutionary selective pressure. droplet-mitochondria tethering, which is associated with higher risk of
Overall, the average Sn at the single-cell level was similar to that at the HCC and lower HBV replication in CHB patients.
global level. As the HBV UMI increases, the diversity of viral variants Table and Figure:Figure 1.Fig. 1 Concurrent MASLD aggravates
within a single cell decreases, indicated by smaller Sn. This indicated mitochondrial dysfunction in CHB patients
that most cells were dominated by a single HBV variant, with only a Figure 2.Fig. 2 Elevated VDAC1 expression promotes lipid droplet-
small fraction of cells carrying multiple HBV variants. Specifically, the mitochondria tethering
hepatocytes of one HBeAg-positive CHB patient were predominantly
characterized by a single variant, while the hepatocytes of another PP0105
HBeAg-positive CHB patient were characterized by the coexistence
Intrahepatic CD161hiCD8+T cell recruitment has a pathogenetic
of multiple variants.
potential in chronic HBV infection
Conclusion: Our results indicate that the diversity of HBV quasispecies
Wanlu Duan1, Jianfei Li2, Qin Wang1
exhibits significant heterogeneity at the single-cell level.
Table and Figure:Figure 1.
1
Anhui
Background: Backgrounds & aims: CD8+T cells are crucially
associated with the fight against hepatitis B virus (HBV) infection.
PP0104
CD161 has been shown to express remarkably on HCV-specific
VDAC1-mediated Lipid Droplet-mitochondria Tethering Promotes CD8+T cells. However, the accurate function of CD161+CD8+T cells
Tumorigenesis and Inhibits HBV Replication in CHB Patients in HBV immunity or pathogenesis remains undetermined.
Concurrent with MASLD Method: Methods: Blood samples were collected from 25 chronic
Zhe Dai1, Yin Gao2, Guangde Zhou3, Xiaoman Liu1, Zhe Wang1,4, hepatitis B (CHB) patients. Peripheral blood levels of CD161+CD8+T
Xianwei Liu1, Huijun Chen1, Yijin Wang1 cells and their correlation with serum ALT levels were analyzed in CHB
1
School of Medicine, Southern University of Science and Technology, patients. To analyze the in vivo CD161+CD8+T cell’s number, function,
Shenzhen, Guangdong, China., 2Department of Biochemistry, Key and intrahepatic recruitment characteristics, HBV replication mouse
Laboratory for Molecular Enzymology and Engineering of Ministry models were established. The expression of CD161 on HBV-specific
of Education, School of Life Sciences, Jilin University, Changchun, CD8+T cells was also detected by analyzing CD161+CD8+ T cell’s
China., 3Department of Pathology, Beijing YouAn Hospital, Capital functions during infection.
Medical University, Beijing, 100069, China., 4Life Sciences Institute, Result: Results: Patients with CHB infection had a markedly lower
Zhejiang University, Hangzhou, 310058, China. peripheral blood frequency of CD161+CD8+T cells than did healthy
Background: The prevalence of metabolic dysfunction-associated controls, and negatively correlated with serum ALT level. Furthermore,
steatotic liver disease (MASLD) has increased among the general compared to the control mice, the frequency of CD161+CD8+T cells
population and chronic hepatitis B (CHB) patients worldwide. The was significantly decreased in the blood of acute and chronic HBV-
clinical impacts of MASLD on CHB progression are controversial replicating mice. Moreover, CHB-replicating mice had significantly
from different studies and their interaction seem complex. We aimed increased hepatic levels of CD161+CD8+T cells, which was not
to explore the impact and the underlying mechanism of concurrent observed in the acute group of mice. Additionally, the CD161+CD8+T
MASLD in CHB pathogenesis. cells were categorized into CD161hi and CD161intCD8+T cells and
Method: Spatial transcriptome sequencing were performed on liver it was revealed that in the liver of CHB-replicating mice the primary
biopsies from healthy controls and patients with MASLD, CHB, and CHB recruited cells were CD161hiCD8+T. Intrahepatic CD161hiCD8+T cells
concurrent with MASLD to systematically investigate the heterogeneity demonstrated increased CXCR6 expression, enhanced production of
and ecosystem of CHB patients with and without MASLD. rAAV8-1.3 cytokine IL-17 and TNF-α, and reduced IFN-γ secretion. Accordingly,
HBV hydrodynamic injection mice fed with high-fat diet (HFD)- or high- the CXCL16 mRNA expression in the liver tissue of CHB-replication
fat methionine-restriction choline-deficient diet (HFMRCD) were used mice was markedly higher than in acute HBV-replicating and control
to establish CHB concurrent with MASLD models. HBV-transfected mice. The study also revealed that HBV-specific CD8+T cells were
HepG2.2.15 and RIL-175 cells were stimulated with palmitic acid mainly CD161-CD8+T cells.
and oleic acid (PAOA) in vitro. Liquid chromatography-tandem mass Conclusion: Conclusion: During HBV infection, the intrahepatic
spectrometry (LC–MS/MS) were used to screen proteins involved in recruitment of CD161+CD8+T cells was mainly CD161hiCD8+T cell
subpopulation, which has a weak antiviral response, but increased pro- NTCP cells, we found that isotretinoin (ISO), ciprofibrate (CIP), and
inflammatory effect, suggesting that CD161 may serve as a potential caffeic acid (CAF) reduced HBV infection efficiency and inhibited HBV
marker of liver-damaging T cells. expression when treated concurrently with HBV infection. The similar
results were obtained in primary human hepatocytes infection assays.
Given that the envelope of HDV is primarily composed of the hepatitis
PP0106
B virus surface antigen (HBsAg), it follows the same mechanisms as
Long-term antiviral treatment in patients with chronic hepatitis B, HBV during the initial entry process into hepatocytes. We examined the
normal alanine aminotransferase, and mild liver inflammation and effect of ISO, CIP and CAF in the HDV infection model using HepG2-
fibrosis NTCP cells and found that they effectively reduced HDV infection
Youwen Tan1 efficiency as well.
1
The Third Hospital of Zhenjiang Affiliated Jiangsu University Conclusion: In conclusion, our research results suggest that ISO,
Background: To study the long-term benefits of antiviral treatment CIP and CAF are prospective candidate agents for anti-HBV and
prognosis in chronic hepatitis B (CHB) with normal alanine HDV targeting L-HBsAg directly. These compounds contribute to the
aminotransferase (ALT) levels and mild inflammation and fibrosis. development of a well-tolerated and broadly active inhibitor of viral
Method: Baseline clinical and pathological data were collected from infection.
patients with CHB who underwent liver biopsy. The follow-up endpoint Table and Figure:Figure 1.Screening of small molecule compounds
was the date of a clinical serious liver outcomes (CLV) or the last binding with L-HBsAg
follow-up. Univariate and multivariate analyses of HCC and cirrhosis Figure 2.Identification of Entry Inhibitors for HBV Infection
were performed using Cox proportional hazard regression. Kaplan–
Meier survival analysis was used to evaluate the risk of liver HCC and PP0108
cirrhosis.
CD300A+CD8+T cells promote functional cure in patients with
Result: A total of 149 CHB cases with normal ALT accompanied by
chronic hepatitis B under PEG-IFN-α
mild inflammation or fibrosis were included; 86 cases were treated
with antiviral therapy, and 63 were not. The median follow-up time was Peng Zhang1, Chao Zhang1
82.00 (45.50–153.00) months. The endpoint CLV were four cases of
1
The Fifth Medical Center of Chinese PLA General Hospital
cirrhosis (5.4%) in the antiviral group (no HCC cases) and five cases Background: Functional cure (FC) is the optimal therapeutic outcome
of cirrhosis (13.1%) in the non-antiviral group (two HCC cases). The for patients with chronic hepatitis B (CHB), in which CD8+ T cells
Kaplan–Meier survival analysis showed no significant increase in the play a vital part. However, the critical immunological characteristics
cumulative risk of CLV in the non-antiviral group (log-rank, p = 0.677). of CD8+ T cells in FC under pegylated interferon alpha (PEG-IFN-α)
A normal-high baseline ALT level and the presence of liver fibrosis remain unclear.
were also associated with an increased risk of CLV (log-rank, p = Method: We collected peripheral blood mononuclear cells (PBMCs)
0.0432 and 0.0172, respectively). Cox multivariate analysis showed from a cross-sectional cohort for 10X Genomics single-cell RNA
that baseline age, high ALT levels, and liver fibrosis were independent sequencing (scRNA-seq). 8 CHB patients with serum HBsAg levels
risk factors for SAE. <3000 IU/ml at baseline were undergoing PEG-IFN-α therapy and
Conclusion: No clinical benefit from antiviral treatment was observed 3/8 achieved FC, and 5/8 did not after follow-up. FC was defined as
in patients with CHB, normal ALT levels, and mild liver inflammation sustained clearance of serum HBsAg and HBV DNA after a finite course
and fibrosis. of treatment. By determining the transcriptional profiles of immune
Table and Figure:Figure 1. Kaplan–Meier survival analysis assessed cells coupled with assembled T cell receptor (TCR) sequences, we
the risk of clinical serious liver outcomes (CLV) elucidated the functional properties of CD8+ T cells associated with
FC vs. non-FC. Relevant findings were validated by flow cytometry
analysis in another longitudinal cohort, including 5 FC and 5 non-FC
PP0107
patients after 48 weeks of PEG-IFN-α therapy.
Screening and Identification of Entry Inhibitors for HBV Infection Result: The scRNA-seq data revealed that CD300A+ CD8+ T cells
Chen Chuyuan1, Ziying Liu1, XuanYi Li1, XiaoYong Zhang1 were enriched in FC patients and expressed higher levels of cytotoxic
1
Department of Infectious Diseases, Nanfang Hospital, Southern genes (GNLY, GZMB, and PRF-1), and genes enriched in cell
Medical University, Guangzhou, China; State Key Laboratory of migration, cytokine production, such as IL-2, TNF, and IFNγ. Besides,
Organ Failure Research; Key Laboratory of Infectious Diseases the SCENIC analysis indicated that the activities of BATF and TBX21,
Research in South China, Ministry of Education; Guangdong associated with effector functions, predominated in CD300A+ CD8+ T
Provincial Key Laboratory for Prevention and Control of Major Liver cells. Analysis of paired scRNA and TCR sequencing data revealed that
Diseases; Guangdong Provincial Clinical Research Center for Viral CD300A+ CD8+ T cells displayed more pronounced clonal expansion
Hepatitis; Guangdong Institute of Hepatology; Guangdong Provincial than CD300A- CD8+ T cells and tended to exhibit high activity in TCR
Research Center for Liver Fibrosis Engineering and Technology. signaling. In addition, HBV-specific CD8+ T cells predicted by GLIPH
Background: Chronic hepatitis B virus (HBV) infection is a serious highly expressed CD300A. Flow cytometry analysis in the longitudinal
global health issue. The current first-line treatments, including cohort validated that CD300A+ CD8+ T cells with enhanced cytotoxic
pegylated interferon and lifelong nucleoside analogues therapy, activities were enriched in FC patients before and undergoing PEG-
can inhibit HBV expression. However, they rarely achieve functional IFN-α therapy. Remarkably, the frequency of CD300A+ CD8+ Tcm
cure, and they cannot elimination the covalently closed circular DNA cells at baseline was negatively correlated with the time to achieve FC.
(cccDNA) or prevent reinfection of new hepatocytes. Therefore, the Conclusion: Functional cure is associated with the enrichment of
development of new anti-HBV agents is imperative. CD300A+ CD8+ T cells, which may serve as new therapeutic targets
Method: Focuing on L-HBsAg as the target, we employed Virtual and promote higher rates of functional cure in patients with CHB.
Screening (VS) and activity-based Probes (ABPs) to identify potential
small molecule compounds that may interact with L-HBsAg. To explore
PP0109
the potential antiviral mechanisms, these compounds were added
at different time points during the HBV infection of HepG2-NTCP Optimization of the preparing protocol improves human
cells. Ultimately, we verified their anti-HBV effects in primary human hepatocyte engraftment in humanized mice that support high
hepatocytes. infection of HBV
Result: In this study, we screened out 38 small molecule compounds Zhenchuan Miao1, Boyao Nie1, Tianyu Zhang1, Junhao Liu1, Ziqian
from a compound library that may interact with L-HBsAg, and we Yu1, Binbin Yu1, Yijuan Nie1, Ming Yin1
confirmed that 6 small molecule compounds may bind to L-HBsAg 1
Beijing Vitalstar Biotechnology Co., Ltd
through ABPs experiments. By adding these small molecule Background: Humanized liver mouse models are of significant value
compounds at different time points during the HBV infection of HepG2-
in studying human hepatocyte-specific functions and liver diseases. related liver diseases, characterized by negative serum HBsAg and
URG mice, which are highly immunodeficient mice with a TetOn- positive Anti-HBc. The diagnostic capability of OBI was evaluated by
regulated uPA transgene, can be induced liver damage by expressing comparing it with the conventional four-parallel nested PCR method.
uPA gene specifically in the liver upon Doxycycline administration, Result: A total of 153 patients with HBV-related liver disease who
allowing the engraftment of exogenous hepatocytes including experienced loss of HBsAg, the detection rate of repDNA detected
human’s. Although URG mice have the advantages of easy breeding, using the over-gap ddPCR method was significantly higher compared
good health status, and low maintenance costs, early experiments to the four parallel nested PCRs methods employed for OBI detection
showed that the human hepatocyte replacement rate was rarely more (88.24% vs. 75.16%, P<0.01). A moderate positive correlation was
than 50%, or the human serum albumin (HSA) content rarely exceeded identified between serum HBcrAg levels and intrahepatic repDNA
6 mg/mL. Despite continuous induction with Dox, the chimeric rate in HBsAg-negative CHB patients (r=0.470, P<0.001). However, this
tended to decline after 8 weeks transplantation. Here reports that correlation was not observed in patients with liver cirrhosis (LC). In
optimizing the protocol for preparing Hu-URG (URG mice transplanted CHB patients, The area under the receiver operating characteristic
primary human hepatocytes) significantly increased the chimerism that (ROC) curve (AUC) for predicting the intrahepatic repDNA state
supports high infection of HBV. was 0.773 for serum HBcrAg and 0.803 for Anti-HBc. Notably, the
Method: The Dox induction scheme after the transplantations in URG combination assessment of serum HBcrAg and Anti-HBc enhanced
mice was changed from a fixed concentration of Dox in drinking the AUC to 0.913.
water to a gradual increase from 0.1 mg/mL at the start to 0.5 mg/ Conclusion: The quantitative system utilizing the over-gap ddPCR
mL after 5 weeks, intending to cause a chronic liver damage and thus method for detecting intrahepatic repDNA demonstrated greater
extending the proliferation time window for exogenous hepatocytes. sensitivity compared to the conventional approach of four parallel
The diet for URG mice was changed from breeding feed to a low- nested PCRs in the diagnosis of OBI..The serum HBcrAg[1] level may
fat feed with <4% crude fat content. HSA content measurement and serve as a predictor of intrahepatic repDNA state in patients with CHB
immunohistochemical staining were employed to exhibit the chimerism who have experienced HBsAg loss. Furthermore, integrating the anti-
of human hepatocytes. Hu-URG mice then were inoculated with HBc level could enhance the diagnostic accuracy for OBI.
different sources of HBV and detected for viral indicators in the serum Table and Figure:Figure 1.Figure 1. Comparison of diagnostic
and livers. performance between the over-gap repDNA-ddPCR and conventional
Result: After optimization, the HSA contents in Hu-URG significantly nested PCR assays for OBI in paraffin-embedded liver biopsies. (A)
increased, the highest up to 20 mg/mL. IHC analysis showed that the Distribution of patients with nested PCR assay positive (no less than two
positive staining areas of human albumin, CK-18, CYP3A4, etc., in the regions positive) and repDNA-ddPCR assay positive in 153 patients.
liver sections could occupy up to 95%, and uniformly distributed in (B) A comparative analysis of the positive detection rates between the
every lobe. In Hu-URG mice that did not change to low-fat diet, human nested PCR assay and the repDNA-ddPCR assay was conducted.
hepatocytes usually accumulated a large amount of fat as showed in (C) Distribution of patients’ positive results from the repDNA-ddPCR
the sections, and became steatotic after 8 weeks of transplantation. assay, categorized by the number of positive regions identified using
The low-fat feed significantly reduced lipid droplet liver sections, and the nested PCR assay. (D) Correlation between the repDNA levels and
enable the HSA level stable nearly 12 months. HuURG mice were easily positive regions detected by nested PCR assay in paraffin-embedded
infected with HBV isolates either from clinical hepatitis B patient serum, liver biopsies. RepDNA, replication-competent HBV DNA; +, positive;
HBV transgenic mouse serum, or HepAD38 cell culture supernatant, -, negitive.
producing long-term high viremia. HBcAg, HBsAg and HBV cccDNA Figure 2.Figure 2. Evaluating serum HBcrAg and anti-HBc for
could be detected in the liver tissues. diagnosing intrahepatic repDNA in patients with HBsAg loss. (A)
Conclusion: The use of low-fat feed can improve the steatosis of Serum HBcrAg levels in liver tissue repDNA positive vs. negative
engrafted human hepatocytes, increase chimerism and extend the groups, (B) Serum anti-HBc levels in liver tissue repDNA positive vs.
stable period. The optimized Hu-URG mouse model supports long- negative groups, (C) ROC curves for serum HBcrAg and anti-HBc were
term stable infection of various genotypes of HBV, providing an ideal in created to diagnose liver tissue repDNA state in total 153 patients ,(D)
vivo model for HBV biological research and evaluation of anti-hepatitis ROC curves for serum HBcrAg and anti-HBc to diagnose liver tissue
B drugs. repDNA state in CHB patients, (E) ROC curves for serum HBcrAg and
Table and Figure:Figure 1.Continuous monitoring of human serum anti-HBc to diagnose liver tissue repDNA state in LC. AUC, area under
albumin (HSA) in the blood and immunohistochemical staining of drug- the curve. *, P < 0.05.
metabolizing enzymes in liver tissue of of optimized Hu-URG mice.
Figure 2.Comparison of HE staining and virological blood markers of
PP0111
Hu-URG mice infected with different subtypes of HBV before and after
dietary adjustment in Hu-URG mice HBsAg Glycan Isomer (HBsAgGi): A Potential Circulating
Biomarker for Monitoring cccDNA and Predicting Virologic
Response in Chronic Hepatitis B
PP0110 Zhiqing Hu1,2,3, Jin Li2, Yuanlan Ji3, Min Wu4, Fan Chen2, Chuanwu
Serum HBcrAg and Anti-HBc predict as Predictorsthe state of Zhu2, Li Zhu1,2,3
intrahepatic replication-competent HBV DNA in chronic hepatitis 1
The Affiliated Infectious Disease Hospital, Suzhou Medical College,
B patients with HBsAg loss Soochow University, Suzhou, Jiangsu 215123, China, 2Department
Guangxin Yu1, Yan Liu2, Jiuxin Qu3, Fengming Lu1, Hao Liao3 of Infectious Diseases, The Affiliated Infectious Disease Hospital,
1
Department of Microbiology & Infectious Disease Center, School of Suzhou Medical College, Soochow University (Suzhou Fifth People‘s
Basic Medical Sciences, Peking University Health Science Center, Hospital), Suzhou, Jiangsu 215131, China, 3Suzhou Medical College,
Beijing, 100191, China, 2Department of Infectious Diseases, The Fifth Soochow University, Suzhou, Jiangsu 215123, China, 4Shanghai
Medical Center of Chinese PLA General Hospital, Beijing, 100039, Public Health Clinical Center, Fudan University, Shanghai 200083,
China, 3Department of Clinical Laboratory, Shenzhen Third People‘s China
Hospital, National Clinical Research Center for Infectious, Southern Background: Previous studies have suggested that the O-glycosylated
University of Science and Technology, Shenzhen, China form of middle HBsAg (HBsAgGi) specifically presents in infectious
Background: We investigated the effectiveness of serum HBcrAg and HBV virions containing HBV DNA or RNA, exclusively in patients with
Anti-HBc in detecting intrahepatic replication-competent HBV DNA, chronic hepatitis B (CHB) of genotype C. HBsAgGi has been proposed
including cccDNA and rcDNA, in chronic hepatitis B patients who have as a potential novel glycol-biomarker to monitor viral kinetics in CHB
lost HBsAg. patients during therapy. This study aimed to evaluate the utility of
Method: An Over-gap droplet digital PCR (ddPCR) method was HBsAgGi as an innovative circulating marker for covalently closed
developed for the detection of the repDNA. Serum viral biomarkers circular (ccc) DNA and its potential to predict virologic response (VR)
were assessed in a cohort of 153 patients diagnosed with HBV- in CHB patients undergoing nucleos(t)ide analogue (NA) therapy.
Method: Sixteen untreated CHB patients of genotype C with paired PP0113
serum and liver biopsy samples were included. Serum levels of HBsAg, HDV Full Genome Sequencing and Sensitive HBV Genotyping
HBV DNA, HBV RNA, and HBsAgGi were quantitatively measured. from a Large Cohort of HBV/HDV Co-infected Patients
HBsAgGi was quantified using a commercially available ELISA kit
Savrina Manhas1, Silvia Chang1, Ross Martin1, Andrew Lopez1, Harish
(RCMG Inc) with a monoclonal antibody targeting the O-glycosylated
Gopalakrishna2, Brooke Swanson3, Thomas Aeschbacher1, Simin
PreS2 domain of middle HBsAg. Intrahepatic cccDNA was assessed
Xu1, Roberto Mateo1, Yang Liu1, Chunfeng Li1, Stephanie Narguet4,
by quantitative PCR with specific primers and probes. Correlations
Dzhamal Abdurakhmanov5, Pietro Lampertico6, Dmitry Manuilov1,
between these serum markers and intrahepatic cccDNA levels were
William Meyer3, Christopher Koh2, Tarik Asselah4, Tomas Cihlar1,
analyzed. In addition, we retrospectively included 18 CHB patients
Hongmei Mo1, Evguenia Maiorova1
receiving NA treatment and measured serum levels of HBsAgGi,
HBsAg, HBV DNA, and HBV RNA at baseline and after 48 weeks of
1
Gilead Sciences Inc, 2National Institutes of Health, 3Quest
Diagnostics, 4Université de Paris Cité, 5First Moscow State Medical
NA therapy.
University, 6Foundation IRCCS Ca‘ Granda
Result: In the untreated CHB cohort, serum HBsAgGi showed the
strongest correlation with intrahepatic cccDNA levels (r=0.7436, Background: The most severe form of viral hepatitis is caused by
p=0.0014), followed by HBV RNA (r=0.4963, p=0.0523), HBsAg co-infection of Hepatitis Delta virus (HDV) and Hepatitis B virus
(r=0.3311, p=0.2092), and HBV DNA (r=0.3173, p=0.2294). In the (HBV). Phylogenetic analyses classify HBV and HDV into eight major
cohort of CHB patients receiving NA therapy, patients were categorized genotypes: HBV GTA to GTH and HDV GT1 to HDV GT8. Currently,
into two groups based on virologic response (VR), defined as serum HBV and HDV sequencing data from patients with chronic hepatitis
HBV DNA <100 U/ml at week 48. Thirteen patients achieved VR, delta (CHD) is limited.
and serum levels of HBsAg, HBV DNA, HBV RNA, and HBsAgGi at Method: HDV and HBV sequencing were attempted for 639 HDV/HBV
baseline were significantly lower in the VR group compared to the non- participants originating from Europe, Africa, and the United States (US).
VR group. The area under the ROC curve (AUC) for baseline HBsAgGi For HDV, full genome (FG) amplification and next generation sequencing
in predicting VR was 0.9538, outperforming HBsAg (AUC=0.9385), (NGS) or total RNA sequencing of plasma was performed. Participant
HBV DNA (AUC=0.8769), and HBV RNA (AUC=0.8615). HDV consensus sequences were used to determine genotype based
Conclusion: Serum HBsAgGi demonstrated a stronger correlation on BLAST analyses against an HDV genotyping reference library.
with intrahepatic cccDNA than traditional viral markers such as For HBV, amplification of fragments across large hepatitis B surface
serum HBsAg, HBV DNA, and HBV RNA. It represents a promising antigen followed by NGS was performed. HBV consensus sequences
novel circulating marker for intrahepatic cccDNA and may serve as from NGS were used to determine HBV genotypes based on BLAST
a valuable predictor of virologic response during NA therapy in CHB analyses against a diverse set of HBV sequences representing all
patients with genotype C. HBV genotypes. If amplification was unsuccessful, HBV genotype was
Table and Figure:Figure 1.Correlation of liver cccDNA with HBsAgGi determined using an enzyme immunoassay, designed to determine
Figure 2.Receiver operating characteristic curve analyses for HBV genotype by detecting genotype-specific epitopes in the PreS2.
predicting virologic response in 18 CHB patients receiving NA therapy Result: Out of 639 participants, 516 (81%) were assigned an HBV
genotype. HBV GTs were: GTD (n=397, 77%), GTA (n=77, 15%), GTE
(n=24, 5%), and <2% each for GTB, GTC and GTH. For HDV, 505 out
PP0112 of 639 participants were assigned a genotype. HDV GTs were mostly
5′ preS1 deletions enhance HBV replication and transcription by GT1 (n=464, 92%), followed by GT5 (n=29, 6%), and <2% each for
upregulating the viral polymerase expression GT2, GT6 and GT7. Both HBV and HDV genotype combinations were
Weicheng Xu1,2, Ruijie Yang1,2, Jing Li1,2, Yingli He1,2 determined for 432 participants with D/1 being most prevalent (n=347,
1
Department of Infectious Diseases, The First Affiliated Hospital of 80%), followed by A/1 (n=46, 11%) and <2% each for E/5, E/1, A/5,
Xi’an Jiaotong University, Xi’an, China, 2National Regional Infectious C/1, D/5, A/2, D/2, E/6, B/1 (see Table). While D/1 was most prevalent
Diseases Center Co-constructed by National Health Commission of in Europe (89%) and the United States (49%), Africa had both D/1,
PRC and People‘s Government of Shaanxi Province, Xi’an, China A/1 and E/1 present at 29%, 21% and 17%, respectively. Phylogenetic
Background: 5′ preS1 deletions frequently arise during chronic analyses identified four novel HDV GT1 provisional subgenotypes,
infection with hepatitis B virus (HBV) genotypes B and C, which HDV GT1fp to GT1ip, supported by high bootstrap proportions (see
are associated with liver cirrhosis and hepatocellular carcinoma. Figure). Although genetically diverse, HDV viral loads were similar for
Although it has been reported that the deletions increase viral loads participants across HDV GT1 subgenotypes.
in HBV-infected liver cancer cell lines, the underlying mechanisms Conclusion: Sequencing and genotyping of HDV and HBV from 639
remain to be elucidated. This study aimed to investigate the role of participants from 25 countries were determined here with HBV/HDV
polymerase truncation in 5′ preS1 deletion-induced HBV replication genotypes D/1 being most prevalent in Europe and the United States
and transcription. while D/1, A/1 and E/1 were more prevalent in Africa. Phylogenetic
Method: Replication competent 1.1mer and 1.3mer HBV constructs analyses showed new HDV GT1 subgenotypes that have not been
of genotype C were modified to introduce deletions in the 5′ preS1 previously reported suggesting an even greater genetic diversity of
region, resulting in polymerase truncations. Wild-type or deletion HDV GT1 than previously recognized.
mutants of HBV polymerase were co-transfected into HepG2 cells Table and Figure:Figure 1.HBV/HDV Genotypes from Co-infected
along with the 1.1mer construct, which lacks polymerase expression. Participants by Region
HBV RNA, DNA, and protein levels were monitored. Figure 2.Expansion of HDV GT1 subgenotypes through phylogenetic
Result: 5′ preS1 deletions significantly increased replicative DNA, analysis of HDV sequences
extracellular virions, and HBV RNA, with the 18-nt and 21-nt deletions
showing particularly pronounced effects. Co-transfection of deletion- PP0114
type polymerase with the 1.1mer construct, which does not express CCR2 of CD4+CD8+CXCR5+ T cell regulated IL-21 and TNF-α
polymerase, at ratios of 1:1, 1:2, and 1:3 resulted in substantially higher secretion in CHB patients
levels of HBeAg, virion HBV DNA, and replicative DNA compared to
Xin Tong1, Shengxia Yin1, Qi Gu1, Jie Li1
wild-type polymerase. Both RNA and protein levels produced by the
truncated polymerase were consistently higher, independent of RNA
1
Department of Infectious Disease, Nanjing Drum Tower Hospital,
and protein stability. Additionally, conformational changes may occur Affiliated Hospital of Medical School, Nanjing University
in the polymerase, as predicted by AlphaFold. Background: Follicular helper T cells (Tfh), which high express C-X-C
Conclusion: 5′ preS1 deletions enhance HBV RNA, replicative DNA, chemokine receptor type 5 (CXCR5), can assist the function of B cells.
and virion production. Truncated polymerase promotes HBV replication There are multiple subtypes of CXCR5+ T cells and they are found to
and infection by increasing RNA and protein levels. have influence to the progress of HBV. The aim of this study is to find
the difference between subtypes of CXCR5+ T cells in CHB patients
and investigate their surface protein features and potential role. associated with cytokine secretion, inflammatory progression, and the
Method: We collected peripheral blood from CHB patients without progression of HBV-related liver diseases. In addition, gene sequencing
antiviral therapy and healthy controls, and performed single-cell RNA of samples co-immunoprecipitated with CTCF, H3K27me3, H3K27ac,
sequencing of CXCR5+ T cells. Peripheral blood mononuclear cells and p300 indicated that the number of peaks and gene distribution in
(PBMCs) in peripheral blood of 67 CHB patients in 4 different phases macrophages treated with HBeAg were altered compared with control
and 12 healthy controls were collected and we analyzed the surface macrophages.
protein features of CXCR5+ T cells and HBsAg-special B cells by flow Conclusion: In conclusion, we demonstrate 3D genomic and epigenetic
cytometry. We collected CD4+CD8+CXCR5+ T cells from peripheral differences between control and HBeAg-treated macrophages.
blood of CHB patients and were treated with or without 200nM CCR2 Importantly, this work provides a high-resolution 3D genomic
inhibitor, and assessed IL-21 and TNF-α at 48 hours. interaction resource of HBeAg-induced activated macrophages,
Result: In the single-cell RNA sequencing, we found a group of providing insights into novel mechanisms of the pathogenesis of HBV-
CD4+CD8intCXCR5+ T cells. The percentage of CD4+CD8intCXCR5+ related liver disease and may offer new perspectives for the treatment
T cell in CHB patients was higher than healthy controls (7.64% vs of HBV-related liver disease.
0.96%). Analyzed by flow cytometry, it was found that the expression Table and Figure:Figure 1.Three-dimensional chromatin landscape of
of CC chemokine receptor 2 (CCR2) in CD4+CD8+CXCR5+ T cells control macrophages and HBeAg-stimulated macrophages.
was significant higher than CD4+CD8-CXCR5+ T cells and CD4-
CDa8+CXCR5+ T cells, respectively (58.83% vs 26.35%, P<0.001;
PP0116
58.83% vs 31.00%, P<0.001). Further analysis revealed that CCR2
had a positive correlation with HBsAg+ B cells (P=0.030, r=0.256). For MMP-9 Suppresses the Anti-HBsAg B Cell Response During
patients in different CHB phases, the patients in immune tolerant phase Chronic HBV Infection
and inactive HBV carrier state had higher expression of CCR2 than Dilhumare Ablikim1, Yuhang Chen1, Dongliang Yang1, Xin Zheng1, Jia
healthy controls respectively (72.18% vs 40.50%, P=0.0125; 65.01% Liu1
vs 40.50%, P=0.0429). After inhibited CCR2 for 48 hours, the treated 1
Department of Infectious Diseases, Union Hospital, Tongji Medical
group had higher levels of IL-21 (598.6 vs 792.9 pg/ml, P=0.017) and College, HuazhongUniversity of Science and Technology, Wuhan
TNF-α (571.4 vs 1676 pg/ml, P=0.04) than control group. 430022, China
Conclusion: Our study found that CCR2 was up regulated in Background: Chronic Hepatitis B (CHB) infection poses a significant
CD4+CD8+CXCR5+ T cells of CHB patients and the expression of IL- threat to global health, and current treatment regimens are insufficient
21 and TNF-α increased significantly after inhibited CCR2. That might for achieving a cure for the disease. Virus-specific T-cell and B-cell
provide a new direction of HBV therapy. responses are crucial in the clearance of Hepatitis B Virus (HBV)
infection. Our previous research indicated that Matrix Metalloproteinase
PP0115 (MMP)-9, together with MMP-2, are involved in the regulation of
intrahepatic anti-HBV effector T cell responses in acute self-limiting
High-resolution Mapping of Chromatin Conformation Reveals the
HBV infection. However, it remains unclear if MMP-9 also plays a role in
Mechanism of HBeAg-induced Macrophage Activation in HBV-
regulating anti-HBV immune responses and mediating HBV clearance
related Liver Disease
in the scenario of chronic HBV infection.
Tiantian Liu1, Xiaoyu Xie1, Shujun Ma1, Huiling Cao1, Hongjun Bian1, Method: We addressed this question by employing MMP-9 gene
Wanhua Ren1,2, Jianni Qi1 knockout (KO) and RNA interference techniques in chronic HBV
1
Shandong Provincial Hospital Affiliated to Shandong First Medical replication mouse models.
University, 2National medical center for infectious diseases Result: The absence of MMP-9 in FVB mice led to significantly
Background: We have demonstrated that macrophage activation is accelerated clearance of Hepatitis B surface antigen (HBsAg) in
closely related to HBV-related liver disease, in which HBeAg, but not peripheral blood and increased production of Hepatitis B surface
HBsAg and HBcAg, plays a key role in inducing macrophage activation. antibody (HBsAb) in pAAV-HBV1.2 or BPS plasmids hydrodynamic
However, how the changes in the 3D genome during HBeAg-induced injection (HDI) mouse models. Adoptive transfer of spleen immune
macrophage activation and its correlation with macrophage function cells from MMP-9 KO mice to wild-type mice could also accelerate
remain unknown. serum HBsAg clearance and enhance HBsAb production in the
Method: To explore changes in the 3D genome following HBeAg pAAV-HBV1.2 HDI mouse model, suggesting that the anti-HBV effect
activation of macrophages, high-throughput chromosome of MMP-9 KO is mainly mediated by immune cells. RNA-seq analysis
conformation capture (Hi-C), RNA-sequencing (RNA-seq), and showed that MMP-9 KO significantly induced enrichment of genes
chromatin immunoprecipitation-sequencing (ChIP-seq) assays were related to the B-cell receptor signaling pathway in the splenocytes of
performed in control macrophages and HBeAg-treated macrophages. mice post pAAV-HBV1.2 HDI compared to wild-type mice. MMP-9 KO
Result: High-resolution 3D chromatin interaction maps revealed intra- mice also showed significantly enhanced B cell activation, as well as
genome interactions between control macrophages and HBeAg- increased numbers of germinal B cells and follicular helper CD4+ T
treated macrophages, thereby demonstrating differences between cells infiltration in the liver post pAAV-HBV1.2 HDI compared to wild-
the two groups of macrophages in distinct 3D genome hierarchies. type mice. Importantly, in vivo knockdown of MMP-9 expression by
In HBeAg-stimulated macrophages, 982 Compartment regions on 21 RNAi also resulted in significantly accelerated serum HBsAg clearance
chromosomes were converted (A-B or B-A), resulting in differential in wild-type FVB and C57BL/6 mice post pAAV-HBV1.2 HDI.
expression of 198 genes, including 164 up-regulated genes and 34 Conclusion: Our results suggest that MMP-9 may play a role in
down-regulated genes. These genes were mainly enriched in pathways negatively regulating anti-HBV B cell responses during chronic HBV
such as endocytosis and cytokine-cytokine receptor interaction. infection. Targeting MMP-9 could serve as a novel strategy for the
6062 specific TAD boundaries were found in HBeAg-stimulated treatment of chronic HBV infection.
macrophages. At the same time, based on the TADs in HBeAg-
stimulated macrophages, the 10,110 TADs identified in the control PP0117
group macrophages were divided into four categories: stable (4,964),
merge (2,258), split (931) and rearrangement (1,957). Compared Characterization of various genotype HBV carrier mouse models
with control macrophages, HBeAg-stimulated macrophages had generated by AAV vector delivery
the largest number of loop anchors within chromosomes chr1, chr2, Zhenchuan Miao1, Boyao Nie1, Junhao Liu1, Xue He1, Weifeng Yang1,
chr11, and chr12, and the largest number of loop anchors between Shujun Liu1, Ming Yin1
chromosomes chr1–chr2, chr1–chr3, chr1–chr4, and chr1–chr9, 1
Beijing Vitalstar Biotechnology Co., Ltd
resulting in differential expression of 2,101 genes. These genes were Background: Functional cure (also known as clinical cure) is the ideal
significantly enriched in pathways such as PI3K-Akt signaling pathway, treatment goal recognized by the prevention and treatment guidelines
phagosome, and chemokine signaling pathway, and were significantly
for chronic hepatitis B (CHB). Hepatitis B virus (HBV) includes at least Result: We mapped the mononuclear phagocytes (MPs) system
8 genotypes and more variants, which cause different symptoms in within the HBV infected, NUC treated human liver to 11 clusters (Figure
infected individuals with different genetic backgrounds. To develop 1A, B), among which we identified an erythrophagocytic macrophage
new effect drugs and realize personalized treatment for this disease, (EryMac) cluster featured by SEPP1, C1QC, CD5L, MARCO, SLC40A1
it is necessary to establish clinically relevant animal models of HBV and IFI27 (Figure 1C). The transcriptomic fingerprints of EryMac highly
infection. AAV-HBV mouse model prepared by injection of rAAV viral resemble the TREM2+ lipid-associated macrophage (LAM) reported
vectors carried the entire HBV genome demonstrate a good HBV elsewhere.
carrier and useful in anti-HBV drug evaluation in vivo. This study aims The EryMac cells were metabolically hijacked compared to other
to compare the virological indicators, hepatic damage, and immune components of the MP compartment including monocytes, dendritic
tolerance characteristics of models established by injecting different cells and Kupffer cells, represented by a significant downregulation
doses of AAV-HBV constructed with 1.3 fold length of HBV genome of electron transport chain, aerobic respiration and oxidative
sequences of different genotypes into mice, in order to explore the phosphorylation genes in untreated HBV infected livers compared to
implications of the models for hepatitis B research and new therapy normal livers (Figure 1D).
development. After NUC initiation, the EryMac cells were the most responsive MP
Method: Different doses of genotypes B, C, and D AAV-HBV were component with the highest DEGs and pathway enrichment index with
injected into C57BL/6 and immunodeficient NPG mice, and the levels aerobic respiration restoration feature (Figure 2A).
of HBV DNA, HBsAg, HBeAg, HBsAb, and ALT in serum of the mice EryMac at week 4 after NUC stop showed a significant upregulation
were measured. Pathological section analysis of the mouse liver was of vesicle mediated transport, intracellular transport and protein
also conducted. localization pathways (FDR < 1*10-4) compared to week 0, and a
Result: The levels of viremia indicators in the mouse models marginal downregulation of lipid metabolism pathway (FDR < 0.05)
established by each type of AAV-HBV were dose-dependent. (Figure 2A).
Genotype D AAV-HBV could establish a stable HBV carrier state at The EryMac displays innate immune phenotype with its top biomarker
an injection dose even as low as 1E8 vg/mouse, while genotype C genes enriched in neutrophil degranulation, scavenger receptor and
AAV-HBV could only maintain HBV viremia in immunocompetent mice classical complement pathways (Figure 2B). In particular, they showed
at an injection dose more than 2E9 vg/mouse. Lower dose C-type AAV- increased activity in scavenger receptor mediated ligand binding and
HBV deliveries only sustained viremia for a few weeks in the mice, in uptaking featured by a significantly increased CD163, HBB and HBA2
which HBs antibodies were detected and ALT levels elevated, while expression at week 4 after NUC stop (Figure 2C, 2D).
in immunodeficient mice, HBV viremia remained stable. It was found Conclusion: We identified a cluster of intrahepatic macrophages
difficult for Type-B AAV-HBV to establish a stable HBV infection state that were metabolically hijacked by hepatitis B virus infection. Their
in immunocompetent mice even at dose of 1E11 vg/mouse, except metabolic drive was modulated by NUC initiation and NUC cessation
for using a mutant Type-B HBV sequence. In mice with spontaneous with different metabolic pathways. The cells showed increased
decline of HBV, hepatocyte damage and immune cell infiltration were scavenger receptor mediated activity after NUC stop.
observed in liver pathological sections. Table and Figure:Figure 1.Figure 1
Conclusion: The efficiency of establishing AAV-HBV mouse models Figure 2.Figure 2
varies with HBV genomes of different genotypes, and the levels of
HBV viremia are related to the capacity of HBV antigens to induce
PP0119
immune tolerance, in addition to the viral replication efficiency. The
decline in HBV virological indicators in the model is due to immune Association of HLA-DRB1 Alleles with Chronic Hepatitis B and Its
clearance. The ability of each genotype of HBV to induce immune Related Diseases
tolerance in mice is in an order of D > C > B. The results suggest that Bin Niu1,2, Qiongjie Li1, Rong Wang1,2, Liaoyun Zhang1
the polymorphism of HBV antigens is related to the different clinical 1
Department of infectious Diseases, The First Hospital of Shanxi
characteristics of hepatitis B. Medical University, 2Graduate School, Shanxi Medical University
Table and Figure:Figure 1.The HBsAg levels with different genotypes Background: Chronic hepatitis B virus (HBV) infection affects over
and different injection doses of AAV-HBV mice. 200 million people worldwide and is a leading cause of cirrhosis and
Figure 2.The HBV DNA and HBeAg levels with different genotypes and hepatocellular carcinoma (HCC). Approximately 20–30% of chronic
different injection doses of AAV-HBV mice. HBV patients progress to severe complications such as liver cirrhosis
or HCC. Host genetic factors, particularly HLA-DRB1 alleles, play a
PP0118 crucial role in determining the outcome of HBV infection. This study
aimed to explore the association of HLA-DRB1 alleles with HBV-
Metabolic Reprogramming of Intrahepatic Mononuclear
related diseases, providing insights into disease pathogenesis and
Phagocytes in Nucleos(t)ide Analogues Treated Chronic Hepatitis
personalized therapeutic approaches.
B Virus Infection
Method: A total of 88 HBV-infected patients and 121 healthy
Fengge Zhu1, Liqiong Yang1, Deliang Yang1, Han Xiao1, Xue Li1, Wai controls were genotyped for HLA-DRB1 alleles using a polymerase
Kay Seto1, Man Fung Yuen1, Lung Yi Mak1 chain reaction-sequence-specific primer (PCR-SSP) method. Allele
1
The University of Hong Kong frequencies were compared between HBV patients and controls,
Background: Recent evidence demonstrated Hepatitis B virus (HBV) as well as among chronic hepatitis B (CHB), cirrhosis, and HCC
induced metabolic reprogramming of macrophages via mitochondrial subgroups. Statistical analysis was conducted to identify significant
pathways that led to attenuated antiviral response. We aimed to associations between HLA-DRB1 alleles and HBV-related diseases.
characterize the metabolic feature of intrahepatic mononuclear Result: Significant differences were observed in the frequency of
phagocytes (MP) in HBV infected patients with regards to nucleos(t) certain HLA-DRB1 alleles between HBV patients and controls. HLA-
ide analogues (NUC) treatment. DRB1*03:01, 13:02, and 14:01 showed a negative association with
Method: Single cell RNA sequencing (scRNA-seq) data of liver tissues HBV infection, suggesting a protective role, whereas HLA-DRB1*12:01
from 6 healthy donors (GSE182159) and 10 patient donors of chronic and 14:54 were positively associated with HBV infection, indicating
HBV infection under NUC treatment (GSE216314, GSE252863) were increased susceptibility (P < 0.05). Subgroup analysis revealed that
retrieved from the Gene Expression Omnibus (GEO) database. High HLA-DRB1*08:03 was significantly enriched in patients with HCC
resolution, unsupervised clustering and t-distributed stochastic compared to CHB and cirrhosis cases (P < 0.05). Additionally, clinical
neighbour embedding (t-SNE) were used to reveal the clustering of parameters showed that disease severity correlated with age, reduced
intrahepatic mononuclear phagocytes (MPs) system. Differential hemoglobin, and lower albumin levels across HBV-related subgroups.
expression genes (DEGs) were calculated with Hurdle model, false Conclusion: This study highlights the critical role of HLA-DRB1
discovery rate (FDR) <0.01, fold change>2. Gene Ontology enrichment alleles in influencing HBV infection outcomes and progression to
analysis was performed with GSEA. severe liver diseases. HLA-DRB1*12:01 and 14:54 may serve as
potential genetic markers for increased HBV susceptibility and risk of Study on the correlation between HLA-DR+CD38+CD8+ T cell
progression to HCC, while HLA-DRB1*03:01, 13:02, and 14:01 could changes and efficacy in the treatment of hepatitis B virus with
indicate protective effects. These findings provide a foundation for interferon
personalized risk prediction and tailored therapeutic strategies for Yanjie Lin1, Guiqiang Wang1,2
HBV-related diseases. 1
Department of Infectious Disease, Center for Liver Disease, Peking
University First Hospital, 2Department of Infectious Diseases, Peking
PP0120 University International Hospital
Functional Insights into Gut Microbiota-Metabolite Associations Background: Interferon (IFN) plays a dual role of direct antiviral and
in Chronic Hepatitis B Under Tiaogan Buxu Jiedu Formula immune regulation in anti-hepatitis B virus (HBV) therapy. Some patients
Intervention can obtain early hepatitis B surface antigen (HBsAg) response in the
Xiaoke Li1,2, Tingyu Zhang1, Shuo Li3,4, Xin Sun1, Yizi Ao1, Shuying early stage of IFN treatment, but the decline of HBsAg level stagnates
Hu1, Jinyu Li1, Hongbo Du1,2, Yongan Ye1,2 in the later stage, and the antiviral effect cannot be continued even if
IFN treatment is continued. Currently, how to further explain the cause
1
Dongzhimen Hospital, Beijing University of Chinese Medicine,
of this phenomenon from the immunological level is still a problem to
Beijing 100700, China;, 2Beijing University of Chinese Medicine, Liver
Diseases Academy of Traditional Chinese Medicine, Beijing, China, be solved. Thus, we aim to investigate changes in phenotype and
3
Department of Traditional Chinese Medicine, Peking University function of CD8+ T lymphocytes in chronic hepatitis B (CHB) patients
Shougang Hospital, Beijing, China., 4No. 9, Jin Yuanzhuang Road, undergoing IFN and correlation with clinical response.
Shijingshan District, Beijing. 100144 Method: CHB patients were divided into three groups according to
antiviral treatment. PegIFNα was then administered to Naïve group
Background: Chronic Hepatitis B (CHB) is a major global health
and nucleos (t) ide analogues (NAs)-treated group. For Plateau
concern, characterized by persistent liver inflammation. While Western
group, whose HBsAg decline reached a plateau, IFN therapy was
medicine targets HBV replication, the gut microbiome’s role in CHB is
stopped and was resumed after an interval. Peripheral blood samples
increasingly studied. Traditional Chinese Medicine (TCM), known for
were collected to detect clinical indexs, and T lymphocyte related
its gut regulation and liver health improvements, is under scrutiny for
phenotypes and functions using flow cytometry at corresponding
its potential in CHB treatment. This research focuses on the Tiaogan
detection points of three groups.
Buxu Jiedu formula (TGBXJD), examining its impact on gut microbiota
Result: A prospective cohort of 151 CHB patients participated in this
and metabolites in CHB patients, offering insights into new therapeutic
study. During IFN treatment, HLA-DR+CD38dim subset of CD8+ T cells
strategies.
increased and then markedly decreased, while the HLA-DR+CD38hi
Method: This study, granted by the National Natural Science Foundation
subgroup increased significantly in both Naïve and NAs-treated groups
of China’s General Program (No.82174341), was conducted as part
(p all < 0.0001). For Plateau group, the HLA-DR+CD38dimCD8+ T
of the “Thirteenth Five-Year Plan” project on “Research on Integrated
cells increased significantly and the HLA-DR+CD38hiCD8+ T cells
Traditional Chinese and Western Medicine Treatment Plan for HBeAg-
greatly decreased after IFN intermittent treatment (p all < 0.0001). The
positive Chronic Hepatitis B.” analyzed gut microbiota, metabolites,
changes of HLA-DR+CD38dim and HLA-DR+CD38hi subsets during
and clinical indicators in 100 CHB patients who achieved HBeAg
IFN intermittent treatment were strongly positively correlated with the
seroconversion from January to September 2019. Patients, pre-treated
changes of HBsAg during IFN retreatment, respectively (r = 0.4843,
with entecavir (ETV) and either the TGBXJD or placebo, were followed
p = 0.0066; r = 0.4588, p = 0.0315). Compared with activated HLA-
for 24 weeks post-treatment after discontinuing both treatments at 96
DR+CD38dimCD8+ T cells, HLA-DR+CD38hi subgroup expressed
weeks. The cohort was divided into relapse (CHB_R) and non-relapse
lower level of co-stimulatory molecules and killing ability.
(CHB_N) groups, with 50 healthy individuals as controls. Blood plasma
Conclusion: IFN treatment made activated HLA-DR+CD38dimCD8+
and stool samples were analyzed for differential microbiota and
T cells gradually differentiated into HLA-DR+CD38hi subset that
metabolites, with Spearman correlation and correlation heatmaps
indicated impaired killing function. IFN intermittent therapy can reverse
created. RDA and Monte Carlo permutation tests were used to assess
this trend and help restore antiviral efficacy of IFN.
gut microbiota-physicochemical factor relationships.
Result: Figures A and B reveal that fecal metabolites like (2S,3R)-3-
Hydroxy-2-methylbutanoic acid and 2’-Deoxyinosine 5’-phosphate PP0122
correlate with certain microbiota. Figure C shows metabolites like Dissecting antibody-mediated effects of NK cell reveals a cytotoxic
4-Guanidinobutanoate significantly affect gut microbiota abundance, CX3CR1+KLRC2-CD16hi subset linked to favorable outcomes in
with R2 at 15.22%. Figure D indicates Loliolide has the most impact chronic HBV infection
on gut microbiota at the genus level, with R2 at 67.50%. Figure Libo Tang1, Yuhao Wang1, Zhaofeng Zeng1, Yurong Gu2, Zihan Jin1,
E shows plasma metabolites’ correlations with pathways, with Linnan Song1, Xuan Yi1, Lingtao Zhang1, Yujing Zhang1, Weiying He1,
Guanidinoacetate negatively linked to mismatch repair and Proline Liping Wang1, Weixin He1, Jianru Sun1, Xiaoqin Lan1, Xiangyong Li2,
betaine to riboflavin metabolism. Figure F reveals fecal metabolites’ Shihong Zhong1, Yongyin Li1
correlations with pathways, with (S)-Chiral alcohol positively linked to 1
Department of Infectious Diseases, Nanfang Hospital, Southern
ribosome pathways. Figure G indicates PLT’s positive correlation with Medical University, Guangzhou, China, 2Department of Infectious
Chitinophaga-related microbiota. Figure H shows plasma metabolites’ Diseases, The Third Affiliated Hospital of Sun Yat-Sen University,
correlations with clinical indicators, with Proline betaine negatively Guangzhou, China
linked to ALT and AST, and Trigonelline to TBIL. Figure I depicts fecal
Background: Natural killer (NK) cell function is generally considered
metabolites’ correlations with clinical indicators, with WBC positively
dampened in chronic hepatitis B virus (HBV) infection; however, the
linked to Loliolide and (2S,3R)-3-Hydroxy-2-methylbutanoic acid.
pool of NK cells exhibits phenotypic and functional heterogeneity, and
Conclusion: This study elucidates the complex interplay between
the antibody-mediated effect of NK cells has been less characterized.
the gut microbiota and host metabolism, providing a scientific basis
Here, we evaluated the dynamic changes in antibody-mediated effect
for targeted interventions using the gut microbiota to improve the
of NK cells and the heterogeneous responses of NK subsets engaged
recurrence of CHB patients after drug discontinuation.
in this process at distinct stages of chronic HBV infection, as well as in
Table and Figure:Figure 1.Figure 1 The interaction between the gut
patients undergoing anti-HBV treatment.
microbiota and host metabolism.
Method: A T-cell receptor-like antibody specific for HBV core 18-27
peptide (cTCRL-Ab) was used to detect the antibody-mediated effect
PP0121 of NK cells, and an array of NK cell surface markers were analyzed in
cross-sectional and longitudinal cohorts of patients with chronic HBV
infection. Single-cell RNA sequencing (scRNA-seq) was performed to
identify the heterogeneity of NK subsets.
Result: The cytolytic effect and IFNγ production of NK cells could be Key Laboratory of Digital Medical Engineering
evaluated using the cTCRL-Ab, Notably, cTCRL-Ab-mediated NK cell Background: Chronic hepatitis B (CHB) is a major public health
responses were compromised in chronically HBV-infected patients, with concern, and patients with compensated cirrhosis are at risk for
a particularly pronounced effect observed among those receiving Peg- significant liver complications. Pegylated interferon alpha-2b (Peg-
IFNα therapy, which was associated with the downregulation of CD16 IFN-α-2b) in combination with nucleos(t)ide analogs (NAs) has shown
expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated promise in enhancing antiviral efficacy and improving liver fibrosis. The
NK cell function by reducing CD16 expression in vitro. scRNA-seq CHESS-SAVE score is a noninvasive approach to assess the risk of
analyses revealed that Peg-IFNα treatment-induced decline of CD16 decompensated events. CHESS-SAVE score = 0.036* stiffness- 0.152*
in NK cells occurred within a CD16hi dysfunction subset that exhibited albumin- 0.011* platelets+ 1.177* [Varices: 0 if absent, 1 if present],
properties of exhaustion. In contrast, a subset of activated CD16hiNK the liver stiffness unit was Kpa, the albumin unit was g/L, and the
cells cells (CX3CR1+KLRC2-CD16hiNK cells, CD16hi_Activated2) platelet count unit was ×109/L. Score < -1.5 is low risk, score < 0 is
with high cytotoxicity demonstrated a significant increase in frequency medium risk, score ≥0 is high risk. This study aimed to evaluate the
and function, which were associated with a favorable treatment differences in liver stiffness, virological response, and safety profiles
response. Furthermore, the intrahepatic CX3CR1+KLRC2-CD16hi between patients (whose CHESS-SAVE scores were low and medium
subset showed a trend towards functional restoration in HBsAg loss risk) receiving Peg-IFN-α-2b combined with NAs and those receiving
individuals, as compared to chronic HBV-infected patients. NAs alone.
Conclusion: Our data contribute to the understanding of antibody- Method: This prospective, non-randomized observational study
mediated responses of NK cells in chronic HBV infection, and highlight included 134 patients with compensated hepatitis B virus-related
a previously unappreciated functional CX3CR1+KLRC2-CD16hiNK cirrhosis in the CHESS-SAVE guided group receiving Peg-IFN-α-2b
subset as a potential therapeutic target. alongside NAs, and 185 patients in the control group receiving only
Table and Figure:Figure 1. NAs. Patients were followed for 24 weeks, with assessments made for
liver stiffness via transient elastography and monitoring for adverse
PP0123 drug reactions.
Result: The most baseline characteristics from two groups were
Comparative Analysis of Peg-IFN-α-2b andplus Nucleos(t)ide
comparable (Table 1). Notably, liver stiffness in the CHESS-SAVE
Analog Therapy in Patients with Compensated Hepatitis B virus-
guided group reduced from a baseline of 12.91 kPa to 7.65 kPa at week
related Cirrhosis: Results from the CHESS2306 Studycohort
24, with a change of -5.26 kPa (p< 0.05). Conversely, liver stiffness
Taoran Geng1, Qun Zhang1, Haifang Cao2, Ying Guo3, Wenhua
in the control group slightly decreased from 10.66 kPa to 10.23 kPa,
Zhang4, Lan Ma5, Liping Wang5, Rui Zhao6, Wei Wang6, Wei Gou7,
with a change of -0.43 kPa (p=0.50) (Figure 1). The comparative liver
Hui Wang7, Qingge Zhang8, Shihua Zhang9, Limao Xu9, Qingfa
stiffness reduction between the two groups was statistically significant
Ruan10, Binbin Lin10, Xiangzhong Liu11, Hongli Wang11, Yongning Xin12,
(p < 0.01). HBV-DNA was completely suppressed in both groups,
Yanzhen Bi12, Haiyan Kang13, Pengbin Gao13, Ming Liang14, Fenxiang
and there was no significant difference in the decrease of HBsAg
Li15, Caiyun Wu15, Musong Li16, Huiling Xiang17, Qing Ye17, Huixing
between the two groups. No patients had HBeAg seroconversion in
Chen18, Tao Ren19, Yujin Jiang20, Dianjie Dang21, Chuan Liu22,23,
the 6 months after treatment in both groups. No serious adverse drug
Xiaolong Qi22,23
reactions were reported in the CHESS-SAVE guided group during the
1
Liver Disease Center of Integrated Traditional Chinese and Western 24-week follow-up.
Medicine, Department of Infectious Diseases, Zhongda Hospital, Conclusion: The addition of Peg-IFN-α-2b to NAs therapy
Southeast University, 2Department of Hepatology,The Fourth People’s demonstrated a more substantial decrease in liver stiffness and no
Hospital of Qinghai Province, 3Department of Hepatology, The
serious adverse reactions in patients with compensated hepatitis
Third People‘s Hospital of Taiyuan, 4Hepatobiliary Center, Gansu
B virus-related cirrhosis whose CHESS-SAVE scores were low and
Wuwei Tumor Hospital, 5Department of Infectious Diseases, The
medium risk.
People’s Hospital of Bozhou, 6Department of Infectious Diseases,
Table and Figure:Figure 1.Table 1
The Sixth People’s Hospital of Shenyang, 7Department of Metabolic
Hepatology, Qingdao Public Health Center Clinical Sub-center, Figure 2.Figure 1
8
Department of Hepatology, Xingtai People‘s Hospital, 9Department
of Gastroenterology, Pidu District People‘s Hospital, 10Hepatology PP0124
Center, Xiamen Hospital of Traditional Chinese Medicine,
Inhibition of ACAT1 could promote HBV-specific T cell response
1
1Department of Hepatology, Yantai Qishan Hospital, 12Department
and HBsAg clearance via up-regulation of biosynthesis of
of Infectious Diseases, Qingdao Hospital, University of Health and
pantothenic acid and coenzyme A in mice.
Rehabilitation Sciences(Qingdao Municipal Hospital), 13Department
of infectious diseases, The Fifth Hospital of Shijiazhuang, Wanqin Qian1, Ziying Liu1, Xiaoran Li1, Shangfei Peng1, Xiaoyong
1
4Department of infectious diseases, The Second Affiliated Hospital Zhang1, Wei Zhu1, Jikun Qian2, Yuan Ma2, Xuan Huang1
of Harbin Medical University, 15Department of Hepatology, The 1
Guangdong Provincial Key Laboratory for Prevention and Control of
Third People‘s Hospital of Linfen, 16Department of Liver Diseases Major Liver Diseases., 2Division of Orthopaedic Surgery, Department
and Gastroenterology, Baoding People‘s Hospital, 17Department of of Orthopaedics, Nanfang Hospital, Southern Medical University.
Gastroenterology and Hepatology, Tianjin Third Central Hospital, Background: Acyl coenzyme A: cholesterol acyltransferase-1
Tianjin Key Laboratory of Extracorporeal Life Support for Critical (ACAT1), a key enzyme converts free cholesterol to cholesterol
Diseases, Institute of Hepatobiliary Disease, 18Department of esters for storage, has been reported to enhance adaptive immunity
Hepatobiliary Surgery, Fujian Institute of Hepatobiliary Surgery, Fujian by modulating cholesterol metabolism in hepatocarcinoma study.
Medical University Union Hospital, 19Department of Gastroenterology,
However, the role of ACAT1 in chronic hepatitis B (CHB) is unclear yet.
The Hospital of Chengdu Office of the People‘s Government of
Method: Avasimibe (AVA), a kind of ACAT1 inhibitors, was applied in
the Tibet Autonomous Region, 20Department of Liver Diseases,
the mouse model with pAAV/HBV1.2 plasmid hydrodynamic injection
National Clinical Research Center for Infectious Disease, Shenzhen
(HI). Hepatitis B virus (HBV) serological markers were detected at the
Third People’s Hospital, The Second Affiliated Hospital, School of
Medicine, Southern University of Science and Technology, 21Office indicated time-points. The proportion of cells from non-parenchymal
of the Hospital Director, Handan Infectious Disease Hospital, 22Liver liver cells were analyzed by flow cytometry, and HBV specific CD8+ T
Disease Center of Integrated Traditional Chinese and Western cells responses were detected by intracellular cytokine staining (ICS).
Medicine, Department of Radiology, Zhongda Hospital, Medical Frequency and distribution of multiple immune cells were observed in
School, Southeast University, Nurturing Center of Jiangsu Province for the liver tissues by immunofluorescence. The RNA sequencing assay
State Laboratory of AI Imaging & Interventional Radiology (Southeast and untargeted metabolomic analysis in liver tissues were detected.
University), 23Basic Medicine Research and Innovation Center of The phospho-Akt expression level was determined in primary
Ministry of Education, Zhongda Hospital, Southeast University, State hepatocytes with or without AVA stimulation by western blot.
Result: Compared with the control group, the serum HBV surface development of hepatocellular carcinoma (HCC) associated withHBV
antigen (HBsAg) levels were significantly lower in the AVA group from infection. Furthermore, the risk of HCC in the offspring of mothers
day 4 after HI, and HBsAg clearance was earlier in the AVA group. infected with HBV is notably increased, although the underlying
The frequency of T cells were increased in the liver tissues of the mechanisms remain unclear. This study aimed to investigate whether
AVA group in the immunofluorescence assay, whereas there were no vertical transmission of HBsAg contributes to the development of HCC
significant differences in other non-parenchymal liver cells subgroup in offspring and to explore the potential mechanisms involved.
between the two groups . Meanwhile, the frequency of IFN-γ+ or Method: To address this, we generated HBsAg-exposed offspring
TNF-α+ CD8+ T cells of were significantly higher in both intrahepatic mice by mating HBsAg-positive female mice with wild-type male mice.
lymphocytes and splenocytes upon HBV peptide stimulation in the Wild-type control mice were obtained by mating wild-type mice. RNA
AVA group. Furthermore, The immune and metabolism associated sequencing of fetal liver tissues was performed to identify differentially
pathways were also showed enrichment in AVA group by RNA-seq. expressed genes, followed by validation through RT-qPCR. Additionally,
Untargeted metabolomics analysis revealed that AVA acts on the hepatocytes (H2.35) were cultured in vitro and exposed to HBsAg to
biosynthesis of pantothenic acid and coenzyme A pathway, which validate the differential gene expression.
increased coenzyme A levels via activating PI3K/Akt pathway. The Result: The sequencing results revealed 1,769 genes with more than
phospho-Akt expression was elevated in the primary hepatocytes with two-fold differential expression between the two groups. Of these, 917
AVA stimulation by Western Blot. genes were upregulated and 851 genes were downregulated in the
Conclusion: Inhibition of ACAT1 could promote HBV-specific CD8+T HBsAg-exposed group compared to the wild-type group. Specific
cells and accelerate HBsAg clearance in mice HBV model. The analysis indicated that these differentially expressed genes were
ACAT1 inhibition may up-regulate biosynthesis of pantothenic acid and enriched in processes such as viral infection, tumorigenesis, and lipid
coenzyme A in hepatocytes via PI3K/Akt pathway activation, which metabolism. Notably, genes such as HBEGF, BCL-xL, and c-myb were
may potentiate HBV-specific T cell response. Thus, ACAT1 inhibition significantly upregulated. These findings were confirmed by RT-qPCR.
is a potential therapeutic target may benefit the HBV functional cure. In vitro experiments further demonstrated that HBEGF expression was
significantly increased following HBsAg exposure.
Conclusion: In summary, our results suggest that HBsAg may play
PP0125
a critical role in the development of hepatocellular carcinoma by
Peripheral Helper CD4+ T Cell Functionality distinguishes between modulating the expression of HBEGF, offering a potential target for
Acute Resolving and Chronic Hepatitis B therapeutic intervention in HCC.
Chao Zhang1, Xiaoyu Li1, Peng Zhang1, Qiaolan Lv1, Fusheng Wang2 Table and Figure:Figure 1.HBsAg Exposure Promotes the Expression
1
The Fifth Medical Center of Chinese PLA General Hospital, 2The Fifth of HBEGF
Medical Center of Chinese PLA General Hospital
Background: CD4+ T cells are crucial in mediating viral control and PP0127
pathogenesis in HBV infection, but their phenotypical and functional
Correlation Analysis Between HBV DNA and cccDNA Levels in
characteristics remain incompletely understood in patients with both
Liver Tissues of HBV-HCC Patients and Tumor Markers
acute and chronic HBV infection.
Method: We utilized single-cell RNA sequencing (scRNA-seq), single- Yuanlang Ji1,2, Xiaoyuan Hu3,2, Zhiqing Hu1,2, Xiaolong Zhu3,2,
cell multiplex secretome analysis, and multicolor immunohistochemistry Chuanwu Zhu1, Li Zhu1, Hua Xiao Yang3, Jin Li1
(mIHC) to analyze intrahepatic and blood CD4+ T cells from HBV-
1
The Affiliated Infectious Diseases Hospital of Soochow University,
infected patients at various disease phases, including immune
2
Medical College of Soochow University, 3the First Affiliated Hospital of
tolerant (IT), immune activation (IA), acute resolving (AR), and chronic Soochow University
resolved (CR). Functional experiments were conducted to validate the Background: Globally, approximately 296 million individuals are
phenotypes of peripheral helper CD4+ T cells (Tph) and assess the chronically infected with HBV, with China as a high-prevalence
impact of Ursodeoxycholic acid (UDCA) on Tph cell functionality. region. Each year, China reports about 466,000 new hepatocellular
Result: We identified ten distinct CD4+ T cell subsets with different carcinoma (HCC) cases, 85% of which are HBV-related. HCC ranks as
tissue preferences and functional profiles. Intrahepatic Tph cells were the fourth leading cause of cancer mortality worldwide, with a 5-year
enriched in both AR and IA patients, but not in IT and CR patients. The survival rate of only 18%. Without treatment, HBV-HCC patients have a
frequency of Tph cells was positively correlated with liver inflammation. median survival of just 3–6 months. While HBV virological factors have
Tph cells exhibited distinct functional polarization preferences in AR been linked to HCC development, the expression levels and clinical
and IA. In AR, Tph cells secreted high levels of IL-2, IL-7, IL-21, IFN-γ, significance of HBV DNA and cccDNA in liver tissues require further
and IL-10, which promoted CD8+ T cell responses. In contrast, in IA, investigation.
Tph cells produced higher levels of TNF-α, GZMB, IL-4, and IL-9, which Method: This study analyzed liver cancer and adjacent non-tumor
were more closely associated with tissue damage. The functional tissues from 30 HBV-HCC patients, collecting demographic data,
polarization of Tph cells was regulated by ER stress and BHLHE40. laboratory results, and tumor markers. Quantitative PCR was used
Furthermore, UDCA treatment alleviated ER stress and improved Tph to measure HBV DNA and cccDNA levels, and their correlations with
cell functional polarization and CD8+ T cell dysfunction in IA patients. tumor markers and disease progression were assessed.
Conclusion: Our study indicates that Tph cell functionality differs Result: HBV DNA and cccDNA levels in liver cancer tissues were
between acute and symptomatic chronic HBV infections. UDCA significantly correlated (p=0.0107). HBV DNA levels in liver cancer
treatment restores the function of Tph cells and may represent a tissues also correlated with HBV DNA and cccDNA levels in adjacent
therapeutic approach to the treatment of CHB. tissues (p=2.14E-06, p=0.0354, respectively), and similar correlations
Table and Figure:Figure 1.Figure 1 were observed between cccDNA in cancer tissues and HBV DNA/
Figure 2.Figure 2 cccDNA in adjacent tissues (p=0.0019, p=0.0069). Adjacent tissue
HBV DNA and cccDNA were also significantly correlated (p=0.0056).
Further analysis revealed that HBV DNA and cccDNA levels in cancer
PP0126
tissues, as well as HBV DNA in adjacent tissues, were positively
HBsAg Exposure Promotes Hepatocellular Carcinoma in Offspring associated with TNM staging (p=0.0006, p=0.0250, p=0.0014).
Through Upregulation of HBEGF HBV DNA in cancer tissues correlated with microvascular invasion
Jing Ning1, Chao Zhang1, Shigang Ding1 (p=0.0409), and cccDNA levels correlated with histological grade
1
Peking University Third Hospital (G-stage) (p=0.0043). Significant differences in HBV DNA and cccDNA
Background: Hepatitis B virus (HBV) infection is a significant global levels across TNM stages were also observed.
public health issue. Previous studies have shown that levels of Conclusion: This study highlights significant correlations between
hepatitis B surface antigen (HBsAg) are strongly correlated with the HBV DNA and cccDNA levels in cancer and adjacent tissues of
HBV-HCC patients. These levels were closely associated with TNM
staging and tumor progression. Monitoring HBV DNA and cccDNA ChIP-Seq Validation of Histone Modifiers in Seroconversion
in liver tissues may provide valuable insights for evaluating disease Associated with Hepatitis B Reactivation
progression and prognosis in HBV-HCC patients. Nirupma Trehanpati1, Jayesh Kumar Sevak1, Gayantika Verma1,
Table and Figure:Figure 1.The comparison between different TNM Mojahidul Islam1, Gayatri Ramakrishna1, Shiv Kumar Sarin1
staging groups of HBV DNA and cccDNA 1
Institute of liver and biliary sciences
Background: Hepatitis B virus (HBV) infection remains a global health
PP0128 challenge, with functional cure being rare. Epigenetic modifications
Hedyotis chrysotricha (Palib.) Merr aqueous extract inhibits play a crucial role in driving seroconversion and achieving a functional
hepatitis B virus, especially HBsAg via HNF4α regulated by PI3K- cure. We aimed to investigate the histone modifiers in hepatitis B
AKT and MAPK-ERK1/2 pathway reactivation patients leading to seroconversion.
Yina Yu1, Yan Lou2, Yunqing Qiu1,3 Method: Sixteen HBV reactivation (rHBV) patients were followed up
1
State Key Laboratory for Diagnosis and Treatment of Infectious till 24 weeks for seroconversion (HBsAg loss and anti-HBs >10 IU/ml).
Disease, and National Clinical Research Center for Infectious Peripheral blood mononuclear cells (PBMCs) from seroconverters (SC)
Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang and non-seroconverters (NSC) were analysed for global methylation
University, Hangzhou, 310000, Zhejiang, China., 23. Department of patterns and validated through chromatin immunoprecipitation
Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University sequencing (ChIP-seq) for H3K9 acetylation (H3K9ac) and methylation
School of Medicine, Zhejiang Provincial Key Laboratory for Drug (H3K9me).
Evaluation and Clinical Research, 79 Qingchun Road, 310058, Result: At baseline, seroconverters showed hypomethylation
Hangzhou, Zhejiang, P. R. China., 32. The First Affiliated Hospital, of histone modifiers and transcription factors including KDM4C,
Zhejiang University School of Medicine, Zhejiang Provincial Key KDM2B, HDAC4, JMJD1C, GATA6, RAD51B and NCOR2 which
Laboratory for Drug Evaluation and Clinical Research, 79 Qingchun was consistent through 24 weeks. Additional hypomethylation was
Road, 310058, Hangzhou, Zhejiang, P. R. China. observed in immune-related genes such as IL17RA, IFNGR2, TLR5,
Background: Hepatitis B virus (HBV) poses a significant challenge IRF8, STAT5B, and TGF-beta. ChIP sequencing with H3K9ac revealed
to global public health due to its close association with liver cirrhosis increased acetylation of KDM4C, KDM5B, JMJD1C, HDAC2, HDAC4,
and hepatocellular carcinoma. Currently, existing antiviral treatment GATA6, NCOR2, RAD51B, and IL17RA, as well as IFNGR2, IL27,
strategies are unable to completely eradicate HBV. Traditional Chinese IL1RA, IL7R, IL15 and IL15RA in seroconverters at baseline and at
medicine offers unique advantages in treating chronic hepatitis B. 24 weeks. Similarly, decreased H3K9Me also leads to the activation
Various herbal texts, such as “Common Herbs Used in Zhejiang Folk of G6PD, IGFR2, IL15RA, IL17B, IL2RA, DNMT3A, ATP6VOA1,
Medicine” and “Traditional Chinese Medicinal Herbs from Fujian” ATP11C, ATP13A2 in seroconverters at baseline and 24 weeks. This
indicate that the aqueous extract of Hedyotis chrysotricha (Palib.) enhanced acetylation and decreased methylation is associated
Merr (HCM) may have potential anti-HBV activity. However, its exact with genes related to rapid immune metabolic activation, potentially
pharmacological effects and specific mechanisms of action have yet facilitating HBsAg seroconversion. Conversely, ChIP sequencing
to be thoroughly investigated. revealed increased H3K9 acetylation of exhaustion genes including
Method: We first identified the chemical components of HCM using LAG3, CTLA4, FOXP1, PDCD2L, PDCD10, TGFBR2, TGFBR3, and
UPLC-Triple-TOF/MS, combined with relevant reference standards. HIF1-alpha in non-seroconverters. This upregulation of exhaustion
We used a transgenic HBV mouse model along with the HepG2.2.15 related genes was observed both at baseline and 24 weeks. Similarly,
and HepAD38 HBV cell lines to assess its anti-HBV efficacy. Besides, increased H3K9 methylation was observed in non-seroconverters with
network pharmacology, molecular docking and transcriptomics were upregulation of PDCD11 and TOX2 at baseline and 24 weeks.
employed to explore the underlying anti-HBV mechanisms. Conclusion: Increased H3K9 acetylation and decreased methylation
Result: 19 major chemical components were identified in HCM through in rHBV patients at baseline and 24 weeks was associated with
UPLC analysis with reference standards, including isorhamnetin, immune metabolic activation driving HBsAg seroconversion. However,
monotropein, sesamoside and kaempferol, which were discovered non-seroconverters showed increased acetylation of LAG3, CTLA4,
in HCM for the first time. Our findings showed that HCM significantly FOXP1, PDCD2L, PDCD10, TGFBR2, TGFBR3, and HIF1-alpha which
inhibited HBV replication and transcription in both the transgenic HBV causes immune exhaustion and viral persistence.
mouse model and HBV cell lines, with a notable reduction in HBsAg
levels and the potential inhibition of cccDNA. Further analysis using PP0130
network pharmacology and transcriptomic approaches suggests
Identification of early biomarkers for acute-on-chronic hepatic
that the anti-hepatitis B mechanism may involve the upregulation of
dysfunction based on proteomics
the PI3K-AKT and MAPK-ERK1/2 pathways. And the corresponding
Jing Zuo1, Yuxin Tian1, Hangyu Ma1, Zhengjie Qu1, Jieru Yang1,
pathway inhibitors LY294002 and PD98059 significantly reduce the
Yuchen Fan1
anti-hepatitis B efficacy of HCM. Additionally, HCM can inhibit HNF4α
activity, which was shown to play a critical role in HBV replication and
1
Department of Hepatology, Qilu Hospital of Shandong University
transcription. Subsequently, we confirmed that HNF4α diminishes the Background: Acute-on-chronic liver failure (ACLF) is a syndrome
anti-hepatitis B efficacy of HCM in cell lines overexpressing HNF4α. that manifests as systemic inflammation and organ failure with
More interestingly, our research revealed that its activity was negatively extremely high short-term mortality rate. Acute-on-chronic hepatic
regulated by the PI3K-AKT and MAPK-ERK1/2 pathways. dysfunction(ACHD) which is defined by the COSSH, is characterized
Conclusion: The aqueous extract of HCM not only inhibits HBV by a poor prognosis with a high likelihood of progression to ACLF. Early
replication and transcription but also significantly suppresses HBsAg intervention in the disease process holds the potential to reduce the
levels. The underlying mechanism likely involves the concurrent mortality rate associated with ACLF. However, the early identification of
activation of the PI3K-AKT and MAPK-ERK1/2 pathways, resulting ACHD presents significant challenges. Therefore, the aim of our study
in the inhibition of HNF4α activity, which in turn suppresses HBV is to explore the use of Olink proteomics to identify early diagnostic
replication and transcription. biomarkers for ACHD, facilitating early disease intervention.
Table and Figure:Figure 1.Graphic abstract Method: We ultimately enrolled three groups of patients for Olink
Figure 2.Characterization of the chemical constituents in HCM by proteomic analysis: hepatitis B virus-related liver cirrhosis (HBV-LC,
UPLC-Triple-TOF/MS. n=26), hepatitis B virus-related acute-on-chronic hepatic dysfunction
(HBV-ACHD, n=14) and hepatitis B virus-related acute-on-chronic
liver failure (HBV-ACLF, n=18). Subsequently, we employed the Least
PP0129
Absolute Shrinkage and Selection Operator (LASSO) regression to
pinpoint five key differential proteins. Finally, we utilized the Enzyme-
Linked Immunosorbent Assay (ELISA) method to validate the
expression levels of the aforementioned five differential proteins. Correlation between PROK2 and Neutrophils markers.
Result: We identified 9 differentially expressed proteins(DEPs) in the
HBV-ACHD group that could be distinctly differentiated from HBV-
PP0132
LC and HBV-ACLF. The five key DEPs were AREG, DPP10, PRDX1,
PRDX3, ZBTB16 with LASSO regression. Reduction of Bacteroides fragilis in gut microbiome of CHB
Conclusion: The five key DEPs may serve as potential biomarkers patients promotes liver injury
for the early identification of HBV-ACHD, with the aim of reducing the Qiuhong You1, Kaifeng Wang1, Zhou Zhao1, Heqi Zhou1, Zhixian Lan1,
likelihood of progression to HBV-ACLF and decreasing mortality rates. Hongyan Liang1, Rui Deng1, Wanying Li1, Routing Wang1, Kaikai
Table and Figure:Figure 1. Zhang1, Dekai Zheng1, Jian Sun1
1
Department of Infectious Diseases, Nanfang Hospital, Southern
Medical University, Guangzhou, China; State Key Laboratory of
PP0131 Organ Failure Research; Key Laboratory of Infectious Diseases
CLU/PROK2 in chronic Hepatitis B: an exploratory study on its role Research in South China, Ministry of Education; Guangdong
as a potential diagnostic biomarker and therapeutic target with Provincial Key Laboratory of Viral Hepatitis Research; Guangdong
persistent positive in HBV DNA level receiving entecavir treatment Provincial Clinical Research Center for Viral Hepatitis; Guangdong
Jie Wei1 Institute of Hepatology
1
Zhuhai People‘s Hospital (Zhuhai Clinical Medical College of Jinan Background: In chronic hepatitis B (CHB) patients under antiviral
University) treatment, liver injury, as evidenced by on-treatment elevated ALT, was
Background: Despite notable improvements in the clinical treatment associated with unfavorable outcomes. Dysbiosis of gut microbiota
of hepatitis B virus (HBV) infection, there are still some shortcomings has been reported to be related with liver injury. However, the key
in treatments using nucleoside/nucleotide analogs, such as drug intestinal bacterial strains affecting liver injury in CHB patients with viral
resistance, subsequent virological relapse and. Treatment of CHB control remain unclear.
with entecavir suppresses virus replication and reduces disease Method: Using a case-control design, 28 cases with elevated ALT
progression, but could require life-long therapy. Required developing (serum ALT >35 U/L in males and >25 U/L in females) and 28 matched
novel diagnostic biomarker and therapeutic targe of CHB patients controls with normal ALT were randomly selected from consecutive
with persistent positive in HBV DNA level under entecavir treatment. CHB patients who have achieved hepatitis B virus (HBV) DNA
Therefore, the novel and effective therapies are urgently required to undetectable for at least 6 months after entecavir treatment. Shotgun
inhibit HBV by targeting essential mechanisms of viral replication and metagenomics on their fecal samples were performed to characterize
transcription. the composition of gut microbiota. Fecal microbiota transplantation
Method: We conducted a comprehensive bidirectional and multivariable (FMT) from case and control patients was conducted to assess the
Mendelian randomization (MR) study using sequencing data and roles of gut microbiota by lipopolysaccharide (LPS) and methionine
publicly available genetic data to explore the causal association choline-deficient (MCD) diet-induced liver injury models, respectively.
between host factors and CHB systematically. We investigated the Result: Characteristics of the cases were comparable to controls.
underlying mechanisms via gene set variation analysis (GSVA), gene Through linear discriminant analysis effect size analysis, we identified
set enrichment analysis (GSEA), and immune cell infiltration analysis. that Bacteroides fragilis was decreased in cases and exhibited the
Molecular docking and virtual screening were also performed to greatest disparity between cases and controls (Figure 1). FMT from
identify potential drug candidates through drug repositioning. cases exacerbated LPS-induced and MCD diet-induced liver injury,
Result: Univariate MR analyses demonstrated a significant link between as evidenced by higher serum ALT, AST and more severe histological
increased CLU and PROK2 levels and a heightened risk of CHB. This changes compared with FMT-control mice. Fecal reconstitution was
was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009–1.073, confirmed by 16S rDNA analysis in recipient mice. As expected,
P=0.012) as estimated using the inverse variance weighting (IVW) Bacteroides fragilis showed lower abundance in FMT-case mice.
method. In multivariable MR analysis, even after adjusting for host Notably, oral gavage of Bacteroides fragilis improved both LPS-
factors, elevated CLU and PROK2 levels continued to show a strong induced and MCD diet-induced liver injury.
correlation with an increased risk of CHB (IVW P=0.020, OR=1.037, Conclusion: Bacteroides fragilis was beneficial for alleviation of liver
95% CI=1.006–1.069). However, reverse MR analyses did not injury in mouse models. Residual liver inflammation in CHB patients
establish a causal relationship between CHB and various cathepsins. with viral control is possibly related to the reduction of Bacteroides
IHC staining and chemiluminescence immunoassay findings revealed fragilis in gut microbiome.
significant overexpression of CLU and PROK2 in both liver tissues and Table and Figure:Figure 1.Figure 1
serum of patients compared to controls, and this high expression was
unique to CHB compared with several other primary kidney diseases PP0133
such as membranous nephropathy, minimal change disease and
Efficacy of tenofovir alafenamide monotherapy compared to
focal segmental glomerulosclerosis. Investigations into immune cell
tenofovir disoproxil fumarate addition in chronic hepatitis B
infiltration, GSEA, and GSVA highlighted the role of CLU and PROK2
patients with low-level viremia after entecavir treatment
expression in the immune dysregulation observed in CHB. Molecular
docking and virtual screening pinpointed Camostat mesylate, c- Kit- Zhongxiang Yang1
IN-1, and Mocetinostat as the top drug candidates for targeting CLU
1
TIBET AUTONOMOUS REGION PEOPLE‘S HOSPITAL
and PROK2. Background: To observe the clinical efficacy of different treatment
Conclusion: Elevated CLU and PROK2 levels are associated with strategies in chronic hepatitis B(CHB) patients with low-level
an increased risk of CHB, and this enzyme is notably overexpressed viremia(LLV) after initial entecavir(ETV) therapy. Methods A total of
in CHB patients’ serum and liver tissues. CLU and PROK2 could 80CHB patients who experienced LLV after 48 weeks of initial treatment
potentially act as a diagnostic biomarker, providing new avenues for with ETV at Tibet Autonomous.
diagnosing and treating CHB. Method: A total of 80CHB patients who experienced LLV after 48
Table and Figure:Figure 1.Figure 3. Sensitivity analysis of Mendelian weeks of initial treatment with ETV at Tibet Autonomous Region People’s
randomization results. A Leave one out analysis of CLU. B Leave one Hospital from January 2020 to December 2023 were selected. Patients
out analysis of PROK2. C Leave one out analysis of ADGRE4P. D were divided into 40 cases each in the observation group and the control
Leave one out analysis of ITGB3. E Leave one out analysis of TREML1. group, according to the different treatment regimens. The observation
Figure 2.Figure 8. Hepatitis B single-cell annotation and expression group was converted to antiviral treatment with tenofovir alofovir(TAF)
of key genes. A Single-cell umap clustering map. B Single-cell for 48 weeks, while the control group received a combination of ETV
annotations. C Expression of key genes in single cells by featurePlot. and tenofovir disoprofoxil fumarate(TDF) for 48 weeks. The complete
D Expression of key genes in single cells by DotPlot. E Dotplot of the virological response(CVR) rate, HBeAg negative rate, estimated
Correlation between CLU and HSC G-CSF markers. F Dotplot of the glomerular filtration rate(eGFR), liver stiffness measurement(LSM),
liver function changes, and adverse drug reactions were compared serve as a useful reference for clinical decision-making.
between the two groups at 24 and 48 weeks post-treatment. Table and Figure:Figure 1.The patient flowchart
Result: There were no statistically significant differences in CVR rates Figure 2.Risk prediction model for HCC after HBsAg seroclearance
between the control group and the observation group at week 24(90.
00% vs 92. 50%, χ2=0. 215, P=0. 847) and week 48(92. 50% vs 97.
PP0135
50%, χ2=0. 347, P=0. 732). The difference in HBeAg-negative rates
between control and observation groups at week 24(9. 38% vs 15. The impact of switching from entecavir to tenofovir amibufenamide
15%, χ2=0. 556, P=0. 712) and 48(15. 63% vs 36. 36%, χ2=3. 660, on HBsAg levels in patients with chronic hepatitis B: A real-world
P=0. 099) was statistically significant. The improvement in eGFR and study
LSM in the observation group was better than that of the control group Liangliang Wang1, Xiaoyu Wang1, Jiaqi Yu1, Qingxi Wang1, Bing
at week 48(t=5. 642, t=7. 853, P<0. 001). There were no statistically Qiao1, Jun Yu1, Jing Chen1, Yidi Han1, Haifeng Zhang1
significant differences in alanine transaminase(ALT), aspartate 1
Qingdao Public Health Clinical Center, Department of Hepatology,
aminotransferase(AST), and total bilirubin(TBIL) values between the China
two groups at week 24 and week 48. No serious adverse reactions Background: Tenofovir amibufenamide (TMF) has shown strong
occurred in either group during the treatment period. antiviral efficacy in randomized clinical studies. TMF is recommended
Conclusion: TAF monotherapy demonstrates superior antiviral for first-line treatment of CHB in mainland China. The objective of this
efficacy, lowering LSM values, and renal safety compared to the study was to evaluate the impact of switching from entecavir (ETV) to
combination of ETV and TDF in CHB patients with LLV following initial TMF on HBsAg levels and antiviral efficacy in CHB patients.
ETV treatment, with fewer adverse reactions. Method: Treatment-naive CHB patients were included and treated
with ETV for 48 weeks. They were then randomly assigned in a 1:1
PP0134 ratio to either continue ETV treatment or switch to TMF treatment.
Continuous monitoring was conducted until 96 weeks. HBsAg levels
Risk of hepatocellular carcinoma after hepatitis B surface antigen
were compared between the two groups, and therapeutic effects were
seroclearance and a novel prediction model establishment
evaluated based on virological response, serological indicators, and
Shuaibing Ying1, Jinyao Dai1, Yunqing Qiu1, Yan Lou1 other relevant parameters.
1
State Key Laboratory for Diagnosis and Treatment of Infectious Result: A total of 96 patients in the ETV group and 98 patients in the
Diseases, National Clinical Research Center for Infectious Diseases, TMF group completed the 96-week follow-up. There were no statistically
China-Singapore Belt and Road joint Laboratory on Infection significant differences in baseline HBsAg, HBeAg, and HBV DNA
Research and Drug Development, National Medical Center for levels between the two groups at baseline and at 48 weeks (P > 0.05).
Infectious Diseases, Collaborative Innovation Centet for Diagnosis
In the ETV group, the HBsAg level decreased from 3.76±0.66 log10
and Treatment of Infectious Diseases, The First Affiliated Hospital,
IU/mL to 3.51±0.43 log10 IU/mL within 96 weeks (P < 0.05). In the
Zhejiang University School of Medicine
TMF group, the HBsAg level decreased from 3.74±0.46 log10 IU/mL
Background: Functional cure is accepted as ideal therapy target to 3.19±0.37 log10 IU/mL within 96 weeks (P < 0.05). At the end of the
and anti-virus drug research aims for CHB patients with functional 96-week follow-up, the HBsAg level in the TMF group was significantly
cure have lower risk of HCC. Risk of HCC remains after HBsAg lower than that in the ETV group (3.19±0.37 vs 3.51±0.43, P < 0.05).
seroclearance and accurate prediction of HCC risk in CHB is important The proportions of HBeAg-positive patients in the ETV group at
for determining antiviral therapy and HCC detection management. baseline, 48 weeks, and 96 weeks were 46.9% (45/96), 41.7% (40/96),
At present, the international prediction model of HCC for CHB is and 39.6% (38/96), respectively. The proportions of HBeAg-positive
mainly based on page-B, mPAGE-B, REACH-B, GAG-HCC, etc., but patients in the TMF group at baseline, 48 weeks, and 96 weeks were
the research objects of the above scoring models are patients with 48.0% (47/98), 42.9% (42/98), and 34.7% (34/98), respectively. There
chronic viral hepatitis B, and the optimal surveillance for HBsAg was no statistically significant difference in the HBeAg seroconversion
seroclearance patients has yet to be determined. This study aims to rate between the TMF group and the ETV group (15.6% vs 27.7%, P >
find out the independent risk factors that affect the prognosis of HBsAg 0.05). At the end of the 96-week follow-up, 79 patients (82.3%) in the
seroclearance patients to construct a simple, objective and accurate ETV group and 85 patients (86.7%) in the TMF group achieved HBV
risk prediction model. DNA negativity, with no statistically significant difference in the HBV
Method: A total of 6536 patients with chronic hepatitis B who achieved DNA negativity rate between the two groups (P > 0.05).
HBsAg seroclearance from January 2006 through June 2021 were Conclusion: Switching from entecavir to tenofovir amibufenamide
retrospectively analyzed, using clinical date reporting system of the in CHB patients resulted in a significant decrease in HBsAg levels.
First Affiliated Hospital of Zhejiang University. 3852 patients were Switching from entecavir to tenofovir amibufenamide in chronic
included in the final analysis. A prediction model was constructed by hepatitis B patients has good antiviral efficacy.
multivariable Cox model. Harell’s C-index and AUROC were used for
discrimination.
Result: Overall, 118 patients (3.1%) developed HCC after HBsAg PP0136
seroclearance during a follow-up of 12112 person-year (0.97%/ APRI, FIB4, FIB5, GPR, AND AGPR SCORE: WHICH ONE IS
year). Multivariate Cox regression analysis indicate that age at HBsAg BETTER IN EVALUATING FIBROSIS IN CHRONIC HEPATITIS B
seroclearance (HR=1.021, 95%CI: 1.006-1.036, P=0.007), male PATIENTS?
(HR=1.73,95%CI: 1.093-2.739, P=0.019), platelet (HR=0.997,95%CI: Yoshua Arif Putra1, Luciana Sophie Mariana Rotty2, Bradley Jimmy
0.994-1.000, P=0.022), albumin (HR=0.961, 95%CI: 0.933-0.989, Waleleng2, Fandy Albert Gunawan Gosal2, Jeanne Winarta2, Andrew
P=0.007), with or without cirrhosis (HR=3.648,95%CI: 1.246-2.838, Evron Pierre Waleleng2
P=0.003) are independent risk factors for the HCC occurrence. The 1
Department of Internal Medicine, Faculty of Medicine, Universitas
five independent variables were used for constructing the novel Sam Ratulangi, Prof. dr. R. D. Kandou Hospital, Manado, Indonesia,
prediction model. The C-index of the model was 0.769(95%CI: 0.748- 2
Department of Internal Medicine, Division of Gastroenterology
0.791). The novel model has a good predictive ability for HCC risk in the Hepatology, Faculty of Medicine, Universitas Sam Ratulangi, Prof. dr.
first year (AUC=0.797,95%CI: 0.749-0.846), third year (AUC=0.784, R. D. Kandou Hospital, Manado, Indonesia
95%CI: 0.732-0.836), and fifth year (AUC=0.791,95%CI: 0.739-0.843). Background: Viral hepatitis, especially hepatitis B, caused 1.3 million
Compared with PAGE-B, mPAGE-B prediction model, the novel model deaths in 2022, posing a global health issue. HBV leads to severe
could make a more accurate prediction for HCC. liver conditions, yet diagnosis and treatment rates are low. While liver
Conclusion: The independent risk factors of HCC occurrence are biopsy is the standard for assessing fibrosis, its risks and costs have
age at HBsAg seroclearance, sex, platelet level, albumin level, with prompted noninvasive alternatives like APRI, FIB-4, and FIB-5, which
or without cirrhosis.The novel model based on these five factors can use routine blood tests. Recent research suggests that FIB-5, GPR and
provide precise HCC prediction after HBsAg seroclearance and may AGPR models may better diagnose liver fibrosis in HBV patients. This
study aims to assess the effectiveness of FIB-5, GPR, and AGPR in Result: In the study, no statistically significant differences were
identifying fibrosis severity in CHB patients. observed in the cumulative probabilities of HBsAg loss among three
Method: This study at Prof. Dr R. D. Kandou General Hospital in Manado groups. However, significant differences in HBV DNA clearance
included patients with chronic hepatitis B (HBsAg-positive for over six rates were noted between the TDF combination therapy group and
months). Patients were evaluated for liver fibrosis using FibroScan and the ETV combination therapy group (P = 0.01). After propensity score
noninvasive scores (APRI, FIB-4, FIB-5, GPR, AGPR), with fibrosis matching, the TDF group showed a significantly higher undetectable
stages from F0 (mild) to F4 (cirrhosis). ROC curves assessed the HBV DNA rate compared to the IFN monotherapy group, while no
diagnostic accuracy of FIB-5, GPR, and AGPR in distinguishing non- significant differences in HBsAg clearance rates were found among
significant (F0–F1) from significant fibrosis (F2–F4). Statistical analyses the three groups. Both TDF and ETV combination treatment groups
were conducted using SPSS, with p < 0.05 indicating significance. demonstrated greater reductions in HBsAg level from baseline to week
Result: There were 83 patients, 56 males (67.5%) and 27 females 48 than the IFN-α group (P<0.05), with no significant difference between
(32.5%). The mean age of the patients was 53.35 years. The median the two combination therapy groups. Additionally, the ETV combination
scores of FibroScan, APRI, FIB-4, GPR, and AGPR were 9.40, 0.60, therapy group had a lower HBeAg clearance rate compared to IFN-α
1.99, 0.38, and 0.91, respectively. The mean for FIB-5 was -12.90 monotherapy (30% vs. 87.50%, P<0.05) but a higher ALT normalization
± 9.13. There were statistically significant differences between the rate (76.92% vs. 45.45%, P<0.05). The efficacy of the TDF combination
moderate fibrosis and advanced fibrosis in terms of age, hemoglobin, therapy group did not differ significantly from the other two groups.
leukosit, platelet, AST, albumin, γ-GT, APRI, FIB-4, FIB-5, GPR, and Conclusion: This study demonstrates that TDF and ETV combination
AGPR therapies are similarly effective for viral suppression, with TDF showing
There was a significant correlation between FibroScan results and the superior HBV DNA clearance but a higher rate of certain adverse
indices APRI, FIB-4, FIB-5, GPR, and AGPR (P < 0.001). FIB-5 had the events, while both therapies significantly reduced HBsAg levels
strongest inverse correlation (r = -0.784), followed by FIB-4 (r = 0.766) compared to IFN monotherapy. These results suggest that treatment
and AGPR (r = 0.704). Linear regression confirmed FIB-5 [β = -0.288 choice should consider patient-specific factors and long-term safety.
(95% CI: -0.457, -0.119), P = 0.001] and GPR [β = 2.551 (95% CI: Table and Figure:Figure 1.Cumulative probability of patients with
1.357, 3.745), P < 0.001] as significant markers. These results support undetectable HBV DNA according to antiviral therapy in the entire
FIB-5 as a reliable indicator of liver fibrosis alongside FibroScan. study population
Using Youden’s Index, the cutoffs were: APRI 0.56 (sensitivity 75.92%, Figure 2.Cumulative probability of (A) patients with HBsAg loss and
specificity 89.65%, PPV 93.18%, NPV 66.67%), FIB-4 1.65 (87.03%, (B) patients with undetectable HBV DNA according to antiviral therapy
93.10%, PPV 95.91%, NPV 79.41%), FIB-5 -10.17 (96.55%, 92.59%, after trimatch.
PPV 98.03%, NPV 87.50%), GPR 0.545 (64.81%, 93.10%, PPV 94.59%,
NPV 58.69%), and AGPR 0.83 (75.92%, 89.65%, PPV 93.18%, NPV
PP0138
66.67%).
Conclusion: APRI, FIB-4, FIB-5, GPR, and AGPR are useful scoring Exploration and new suggestions on stage criteria of natural
systems for assessing fibrosis in CHB patients. This study highlights history for chronic hepatitis B
FIB-5 as an effective tool for detecting and staging fibrosis, though Tongjing Xing1
further research is needed to expand understanding of FIB-5’s 1
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical
diagnostic potential. University
Table and Figure:Figure 1.The characteristics study Background: The recommended standards for the four classification
Figure 2.ROC curve generated by APRI, FIB-4, FIB-5, GPR, and AGPR indicators in guidelines are inconsistent. Significant differences of
for differentiation between advanced fibrosis and mild to moderate patient selection in clinical studies result in poor comparability of the
fibrosis research. According to the current standards of staging, there are still
a large number of patients in an uncertain period, and most of these
PP0137 patients require treatment.
Method: We summarize the relevant research on the natural stages
Comparative Efficacy and Safety of Pegylated Interferon-Alpha
of chronic HBV infection and existing problems. Some revision
Monotherapy versus Combination Therapies with Entecavir or
suggestions are proposed to guide the clinical practice of chronic HBV
Tenofovir in Chronic Hepatitis B Patients
infection better.
Huiqing Liang1, Xiaoting Zheng1, Qianguo Mao1, Jiaen Yang1, Qingfa Result: New suggestions for revisions to the stage criteria for CHB,
Ruan1, Chuncheng Wu1, Yaoyu Liu1, Siyan Chen2, Luyun Zhang2, Yan including three stages: immune tolerance stage, immune clearance
Dai2, Manying Zhang1, Hongli Zhuang3, Li Lin1, Shaodong Chen3 stage, and immune control stage. Patients with high levels of HBV DNA,
1
Xiamen Hospital of Traditional Chinese Medicine, 2Fujian University of HBsAg, and HBeAg, normal ALT levels, and no or mild inflammation or
Traditional Chinese Medicine, 3Xiamen University fibrosis in the liver tissue have been classified as being in the immune
Background: Chronic hepatitis B virus infection (CHB) is a major tolerance stage. The immune control stage is characterized by a
contributor to severe liver diseases. Current treatments primarily positive HBsAg, continuously negative HBV DNA, normal ALT, and
involve nucleos(t)ide analogs (NAs) and pegylated interferon-alpha no inflammation or varying degrees of liver fibrosis in the liver tissue.
(Peg-IFNα), with combination therapies showing promise for enhancing Between the two stages, all patients with HBsAg who are HBV DNA-
efficacy. This study aims to compare the effectiveness and safety of positive, HBeAg-positive or-negative and a normal or elevated ALT
Peg-IFNα monotherapy versus its combinations with entecavir (ETV) may be classified as being in the immune clearance stage and require
and tenofovir disoproxil fumarate (TDF) in managing CHB. antiviral treatment. According to the stage criteria, patients in the
Method: The study included 147 treatment-naïve patients from Xiamen immune tolerance stage and immune control stage can be followed up
Traditional Chinese Medicine Hospital with CHB, who were allocated and observed. Antiviral therapies should be used when these patients
into three groups after exclusions: Group A (31 patients) received a enter the immune clearance stage.
combination of Peg-IFNα-2b and ETV, Group B (59 patients) received Conclusion: Three stages were suggested for revisions to the stage
Peg-IFNα-2b and TDF, and Group C (57 patients) served as a criteria for CHB. These revision suggestions rationalize some of the
control group receiving monotherapy with Peg-IFNα-2b. All subjects existing problems with the stage criteria for CHB and can significantly
underwent evaluations at baseline and every 12 weeks up to 48 reduce the number of patients in the “uncertain stage” or “gray zone,”
weeks. Cumulative probabilities of hepatitis B surface antigen (HBsAg) which is particularly valuable in guiding clinical practice. However,
loss and undetectable HBV DNA were estimated using the Kaplan- further clinical studies with large samples are needed to confirm these
Meier method, with comparisons within groups made via the log-rank suggestions.
test. Univariate and multivariate Cox proportional hazards models
identified predictors for HBsAg loss. Propensity score matching was
PP0140
then applied to address selection bias.
The predictive model for HBsAg clearance in patients with non- collected their newborns’ umbilical cord blood (UCB) samples.
advantageous chronic hepatitis B treated with pegylated interferon HBV markers in maternal serum were screened at 24-28 weeks
Wentao Kuai1,2, Jia Xin Han2, LIANG XU1,2 of gestation. Women with detectable HBV DNA received tenofovir
1
Department of Hepatology, Tianjin Second People’s Hospital, disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) for pMTCT.
2
Clinical School of the Tianjin Second People’s Hospital, Tianjin Maternal and newborn UCB samples were analyzed for HBV markers.
Medical University Infants received hepatitis B immunoglobulin (HBIG) and the hepatitis B
vaccine at birth, with follow-up doses at 1 and 6 months. HBV-related
Background: The objective of this study was to develop a multi-
parameters were assessed at 7-12 months of age (Fig.1).
parameter predictive model for HBsAg clearance in non-advantageous
Result: A total of 171 pregnant women with chronic HBV infections
chronic hepatitis B (CHB) patients undergoing pegylated interferon
were included, with a mean delivery age of 31±4 years. UCB testing
(Peg-IFN) therapy.
showed positive rates of 21.1% for HBsAg, 12.9% for HBsAg with
Method: A total of 178 CHB patients receiving Peg-IFN-based antiviral
HBeAg, while all samples were positive for HBcAb and negative for HBV
therapy were enrolled from the Hepatology Department of Tianjin
DNA&RNA(Fig.2). 150 in 171 pregnant patients with log10DNA<5.3,
Second People’s Hospital between July 2020 and June 2024, forming
UCB testing showed positive rates of 19.3% for HBsAg, 10.0% for
the training cohort. An additional 182 patients from Tianjin Third Central
HBsAg with HBeAg. Logistic regression identified maternal HBsAg
Hospital were included as the external validation cohort. Baseline
and HBeAg positivity as risk factors for neonatal UCB HBsAg (P <
data were collected at the initiation of Peg-IFN therapy, with follow-
0.001), but the level of maternal HBV DNA was not a risk factor for
up conducted at 3-6 month intervals. LASSO-COX regression was
neonatal UCB HBsAg (P>0.05)(Tab.1). ROC analysis showed the
employed to construct the predictive model for HBsAg clearance in
maternal log10DNA level (≥2.22 IU/ml) low predicted neonatal UCB
the non-advantageous population. Model performance was assessed
HBsAg/HBeAg positivity(0.5<AUC≤0.70)while maternal HBeAg levels
using the C-index, area under the curve (AUC), calibration curves, and
(≥11.48 COI) strongly predicted neonatal UCB HBeAg positivity (AUC
decision curve analysis (DCA).
> 0.9) (Fig.3) Follow-up of 21.1% of infants with HBsAg positivity in
Result: The general characteristics and clinical features of the
neonatal umbilical cord blood until 7 months to 1 year showed that all
training and validation cohorts were comparable (P > 0.05). A novel
HBsAg in venous blood of the infants had turned negative.
nomogram was developed, incorporating baseline HBsAg levels,
Conclusion: Pregnant patients with HBV DNA ≤ 10 ^ 5IU/ml still
HBsAg levels at 3 months, HBeAg status at 3 months, and ALT levels
have the potential risk of MTCT. After expanding the indications
at 3 months to predict HBsAg clearance. In the training cohort, the
of antiviral therapy, TDF/TAF, can successfully block the MTCT of
C-index of the nomogram was 0.911, and time-dependent AUC
HBV DNA and HBV RNA in neonatal UCB of pregnant women with
values were consistently greater than 0.9. In the validation cohort, the
chronic HBV infection, but can not completely block the infection of
C-index was 0.946, with time-dependent AUC values again exceeding
neonatal umbilical cord blood by HBsAg through the placental barrier.
0.9, indicating strong discriminatory ability. Kaplan-Meier analysis
Serological follow-up of infants at 7-12 months indicated a 100% MTCT
showed that high-risk patients in both cohorts required significantly
prevention rate among those whose mothers adhered to expanded
longer median times for HBsAg serological clearance compared to
antiviral treatment guidelines with TDF/TAF, HBV vaccination and HBIG
low-risk patients (P < 0.001). Calibration curves demonstrated good
administration. Maternal HBeAg levels correlated with neonatal UCB
agreement with the ideal diagonal line in both cohorts, indicating high
HBsAg and HBeAg, particularly in high-titer HBeAg-positive mothers,
consistency between predicted and observed survival probabilities.
highlighting the need for active management in this group to prevent
DCA curves showed that the nomogram provided a higher net benefit
MTCT.
than the “None” and “All” strategies across all threshold probabilities,
Table and Figure:Figure 1.Figure
emphasizing its potential for clinical application and its value in real-
Figure 2.Table
world practice.
Conclusion: The predictive model for HBsAg clearance in non-
advantageous CHB patients receiving Peg-IFN therapy shows high PP0142
efficacy, robustness, and clinical applicability. This model holds Effectiveness and Safety of TAF in Chronic Hepatitis B Patients
promise as a valuable tool for clinicians in providing personalized Over 30 Years Old with Normal ALT Levels and Positive Hepatitis
management of CHB treatment. B Virus DNA
Table and Figure:Figure 1. The construction of a predictive model for Yanfang Li1, Jing Sun1, Xinxin Liu1, Haifeng Yu1, Youde Liu1, Ning
HBsAg clearance imn non-advantageous CHB patients. A: ROC curve Sun2
ofthe training cohort, B: Multivariate Cox regresion forest plot in the 1
Yantai Qishan Hospital, 2Yantai Yuhuangding Hospital
training cohort; C: ROC curve of the validation cohort; D: Nomogram
for predicing HBsAg clearance in non-advantageous CHB patient. Background: Antiviral therapy’s indications are gradually growing
as our understanding of hepatitis B grows. The Chinese Guidelines
for the Prevention and Treatment of Chronic Hepatitis B, updated in
PP0141 2022, recommend antiviral medication for patients over 30 years old
More aggressive initiation of antivral treatment contributes to who have HBV DNA-positive serum, regardless of ALT levels. At the
blockading mother-to-child transmission of HBV DNA&RNA in moment, a few clinicians express reservations about initiating antiviral
neonatal umbilical cord blood therapy and its long-term clinical benefits in patients without family
Huimin Liu1, Wenting Chen, Yongjie Liang, Lijian Ran, Jing Wang, history of liver cancer or cirrhosis. We aim to evaluate both the short-
Haotian Luo, Songtao Zhao, Yan Zhu, Jie Xia, Guohong Deng, Qing and long-term efficacy and safety of TAF in CHB patients over 30 years
Mao1 old who present with normal ALT levels and detectable HBV DNA.
1
Department of Infectious Diseases, Southwest Hospital, Third Military Method: A total of 103 patients from Yantai Qishan Hospital and Yantai
Medical University (Army Medical University) Yuhuangding Hospital were enrolled in this study. HBV DNA, HBsAg,
HBeAg, ALT and renal function were measured at baseline, 24 weeks
Background: The 2022 Chinese guidelines recommend antiviral
and 48 weeks of follow-up.
therapy for patients over 30 years with detectable HBV DNA. For
Result: ALT level was 23.53±8.57 U/L, and the mean age was
pregnant women with HBV DNA >2×10^5 IU/ml, treatment should
47.01±9.54. The median HBV DNA level was 2.17 (1.48~2.82) lg IU/
begin at 24-28 weeks of gestation. This study evaluates the effect
mL, and all 103 patients tested positive for HBsAg and 21.3% of them
of expanding antiviral indications in preventing mother-to-child
tested positive for HBeAg. The mean eGFR level was 130.70±41.64 ml/
transmission (pMTCT) in women aged >30 years with detectable HBV
(min/1.73m2). Of them, 82.5% were in stage 1 of CKD, 16.5% in stage
DNA.
2, and 1% in stage 3. Following TAF antiviral therapy for 48 weeks, 80%
Method: This retrospective study included pregnant women with
of patients had HBV DNA levels below 20 IU/mL, which is a statistically
chronic HBV infections who delivered at Southwest Hospital,
significant increase from baseline (c2=130.794, P<0.001). None of
Chongqing, China, between December 2021 and June 2024, and
those patients showed complete disappearance of serum HBsAg and
change of HBeA[EL1] g. There is no statistically significant difference before the start of the study at Beijing Ditan Hospital of Capital
in the change of CKD stage(c2=3.030, P=0.553). 61 patients Medical University were enrolled. Including demographic information,
completed 96 weeks treatment, and the HBV DNA undetectable rates disease history, physiological and biochemical tests, HBVDNA, and
of them were 78.7% and 85.2% at 48 and 96 weeks respectively, which other related treatments information were collected. The patients were
indicated a statistically significant difference in the virologic response followed up every 3 months. HCC was detected by ultrasonography
(c2=110.770, P<0.001)(Fig.1). The proportion of serum HBsAg and (US), computed tomography (CT), or magnetic resonance imaging
HBeAg positive remained mostly unaltered. There is also no significant (MRI).
changes in CKD stage(c2=2.678, P=0.756)(Fig.2). Result: A total of 764 CHB patients were included in this study, with
Conclusion: In CHB patients over 30 years old who present with a median follow-up time of 8.8 (6.7-10.6) years. During the follow-
normal ALT levels and detectable HBV DNA, short-term TAF therapy up period, a total of 38 patients developed HCC. Multivariate Cox
showed significant viral inhibition and renal safety. In future, We will regression analysis showed that age, family history of HCC, alcohol
continue to follow up patients to obtain longer-term research data. consumption, cirrhosis, and FIB-4 were all independent risk predictors
Table and Figure:Figure 1.DNA changes after 96 weeks treatment for HCC in CHB patients. Restricted cubic spline analysis indicated
Figure 2.CKD changes after 96 weeks treatment the risk of liver cancer increased with the increase of FIB-4 value.
Compared with the group with FIB-4 less than 1.4, the group with FIB-4
greater than 1.4 had an HR value of 8.89 (95%CI:3.16-25.07) for HCC,
PP0143
and after adjusting for multiple factors, the HR was 4.84 (95%CI:1.64-
Baseline Serum Medium HBsAg: A Simple and Strong Predictor 14.34). Compared to non-cirrhotic patients, the HR for HCC in patients
for Functional Cure of Chronic Hepatitis B with cirrhosis was 3.46 (95%CI:1.69-7.07). The mediation effect
Qiyi Zhao1, Zhishuo Mo1, Hang Si1, Mingzhu Liu2, Yuan Tang1, model analysis showed that FIB-4 index has a mediating effect on
Zhaoxia Hu1, Ning Wen1, Zhiliang Gao1 liver cirrhosis, with 40.25% indirectly affecting the occurrence of HCC
1
The Third Affiliated Hospital of Sun Yat-sen University, 2Sun Yat-sen through liver cirrhosis.
Memorial Hospital, Sun Yat-sen University Conclusion: FIB-4 index has advantages in predicting the risk of HCC
Background: Functional cure (FC) is an ideal therapeutic target in patients with CHB receiving antiviral treatment. It could be used
for chronic hepatitis B (CHB). Predicting FC after treatment remains in clinical practice to assist in decision-making for long-term HCC
challenging. We aimed to evaluate the predictive efficiency of FC monitoring strategies, especially for moderate and high-risk patients.
based on large hepatitis B (LHBs) and medium hepatitis B (MHBs)
surface proteins before treatment. PP0145
Method: A total of 1,526 patients with CHB (NCT04035837) were
Dynamic assessment of liver steatosis on the risk of hepatocellular
included in this study. Of these, 128 patients with sequential serum
carcinoma in patients with chronic hepatitis B by ultrasound
samples were available. The FC group was defined as patients with
serum Hepatitis B surface antigen (HBsAg) < 0.05 IU/mL, with or Mingyue Xiao1, Yuankai Wu2, Xiaomei Wang1, Nana Wang1, Yutian
without hepatitis B surface antibodies. Propensity score matching Chong2, Jie Ren1, Lili Wu1
(PSM) was used to balance the baseline characteristics; 78 patients
1
Department of Ultrasound, Third affiliation hospital of Sun Yat-sen
were included (39 FC and 39 non-FC). Levels of total HBsAg, LHBs, university, 2Department of Infectious Diseases, Third affiliation hospital
and MHBs were measured before and during pegylated interferon- of Sun Yat-sen university
alpha (peg-IFN) treatment. Background: Whether hepatic steatosis (HS) can aggravate the risk
Result: After PSM no significant differences were seen between the of hepatocellular carcinoma (HCC) in patients with chronic hepatitis
FC and non-FC groups, including in baseline HBsAg levels. Receiver B(CHB) is still controversial. Attenuation imaging (ATI) is a new
operating characteristic analyses indicated that both MHBs and LHBs ultrasound method that can quantify the degree of HS. Based on a
levels were better predictors of FC than the total HBsAg levels. MHBs long-term follow-up cohort, this study used ultrasound to evaluate the
levels were consistently lower in the FC group than in the non-FC group effect of HS on the risk of HCC in CHB population, aiming to guide
before and longitudinally during the 48-week peg-IFN treatment. MHBs clinical diagnosis and treatment.
significantly differed at baseline (P = 0.0177), while total HBsAg levels Method: CHB patients who were followed up in our hospital since
showed no significant change until 12 weeks. The baseline LHBs levels 2008 were enrolled. Baseline data (at the first ultrasound examination)
also differed (P = 0.0389); however, the difference was not statistically were collected. Ultrasound examination and laboratory tests were
significant between the two groups after four weeks of treatment. performed regularly. Ultrasound examination included conventional
Conclusion: Compared with total HBsAg, MHBs is a simpler and ultrasound, two-dimensional shear wave elastography to measure liver
stronger predictor of peg-IFN response in CHB patients as early as stiffness, and ATI to measure attenuation coefficient (AC). Delta-ATI=
baseline and longitudinally during treatment, aiding in increasing FC last AC value -baseline AC value. The end point of follow-up was the
rates. occurrence of HCC or the last follow-up. The subjects were divided
Table and Figure:Figure 1.The schematic representation of baseline into HS group and non-HS group according to ultrasound findings.
MHBs which is a strong predictor of FC in patients with CHB. Kaplan Meier method was used to draw the survival curve. Log-rank
test was used to compare the survival curves between the two groups.
Cox regression was used for survival analysis.
PP0144
Result: A total of 1862 patients with CHB were enrolled. The average
Correlation between FIB-4 index and the risk of hepatocellular follow-up time was 104±68 months. 82 patients (4.4%) developed HCC.
carcinoma in patients with chronic hepatitis B: A prospective There were 430 patients (23.1%) with HS and 197 patients (10.6%) with
cohort study liver cirrhosis at baseline. The survival rate of HS group was higher than
Gang Wan1,2, Xuesong Gao3,2, Xuefei Duan3,2 that of non-HS group, and the difference was statistically significant (χ2
1
Department of Medical Records, Beijing Ditan Hospital, Capital =6.083, P=0.014). HS was a protective factor for HCC in CHB patients,
Medical University, 2National Center for Infectious Diseases (Beijing), and HR was 0.69 (0.35-1.35), with no statistically significant difference.
3
International Medical Department, Beijing Ditan Hospital, Capital A total of 1059 patients underwent ATI examination more than 2 times.
Medical University The follow-up time was 29.3±10.9 months, and 10 patients developed
Background: This study aims to explore the predictive ability of FIB- HCC. Delta-ATI was a protective factor for the development of HCC in
4 index for the occurrence of hepatocellular carcinoma (HCC) in a CHB patients, HR: 0.001 (0.0-0.19), P=0.009.
prospective cohort of chronic hepatitis B (CHB) patients receiving Conclusion: It is feasible to evaluate the degree of HS based on
long-term antiviral therapy. ultrasound in CHB population. The increase of ATI value may be
Method: From October 2008 to July 2021, 829 adult patients with related to the reduction of the risk of liver cancer in CHB patients.
chronic hepatitis B who received oral antiviral therapy or treatment Table and Figure:Figure 1.Survival curves of HS group and non-HS
group
 PP0146 outcomes. This study aims to investigate the predictive clinical value
Prevalence and clinical characteristics of HBV-infected patients and response mechanisms of lymphocyte mitochondrial metabolism in
with HBsAg and anti-HBs coexistence PegIFN-α treatment of CHB patients.
Method: Peripheral blood samples were collected from untreated CHB
Xinru Wang1, Chuanmeng Zhang1, Wei Wang1, Li Xiao1, Yilin He2, Bo
patients, those treated with nucleos(t)ide analogues (NAs), and those
Wang3, Jianchun Xian3
receiving combined PegIFN-α and NAs therapy. Healthy individuals
1
The Affiliated Taizhou People‘s Hospital of Nanjing Medical were included as the control group. Distributions of various white blood
University, 2Centre for Disease Control and Prevention of Taizhou, 3The
cell types and mitochondrial metabolic characteristics in peripheral
Affiliated Taizhou People‘s Hospital of Nanjing Medical University
blood were analyzed. The study also evaluated differences between
Background: Hepatitis B virus (HBV) infection is a serious public health treatment groups in terms of HBV-related immune damage, liver injury,
problem worldwide. Typically, HBsAg and anti-HBs do not coexist and and treatment efficacy.
are not clearly staged in the natural history of HBV infection. However, Result: In a clinical cohort of 125 CHB patients, only 1 patient (3.03%)
the pattern of coexistence of HBsAg and anti-HBs is still common in treated with NAs alone achieved a clinical cure, whereas 23.81% (10/42)
the real clinical world, and there is a lack of clear understanding of the of patients treated with combined PegIFN-α and NAs achieved a clinical
epidemiological and clinical significance of this particular serological cure. Peripheral blood cell analysis showed no statistically significant
pattern. differences in white blood cell counts among the groups. However,
Method: Descriptive epidemiological methods and SPSS 23. 0 significant abnormalities in mitochondrial metabolism were detected in
software were used to retrospectively analyse the epidemiological and lymphocytes across all CHB patient groups. Specifically: (1) untreated
clinical characteristics of coexisting HBsAg and anti-HBs among those patients exhibited markedly reduced mitochondrial mass(MM) in
who were hospitalised in the Affiliated Taizhou People’s Hospital of peripheral immune cells, suggesting impaired mitochondrial reserves
Nanjing Medical University and had received HBV serum markers from and metabolic function; (2) during liver injury, phagocytic cells of the
1 January 2021 to 31 December 2022. innate immune system accumulated in the liver, while the percentage
Result: Of 127 119 patients enrolled , 61 149 patients (48.1%) were of helper T cell (Th) and cytotoxic T cell (Tc) with low mitochondrial
male, and the median age was 55 (42-68) years. The HBsAg positivity membrane potential(MMPlow) increased, indicating heightened
rate was 6.60% (8 395/127 119).A total of 402 patients (4.79%) had metabolic activity; (3) PegIFN-α therapy promoted differentiation into
coexistent HBsAg and anti-HBs, the median age was 61 (52, 71) years, monocytes, enhanced mitochondrial reserves(increased MM) in Th
82.1% of patients had HBsAg levels below 250 IU/mL and 51.7% of cells, and increased ATP production(decreased MMPlow%), reflecting
patients had HBsAg levels below 10 IU/mL.The coexistence of HBsAg heightened Th cell immune activity. The MM and MMPlow% of Tc cells,
and anti-HBs in the age groups 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 as well as monocyte numbers, were predictive of clinical cure following
- 69, 70 - 79, and 80+ accounted for 1.50%, 3.10%, 2.93%, 4.67%, PegIFN-α treatment.
5.22%, 6.78% and 10.11% of the HBsAg positive patients, respectively. Conclusion: In real-world clinical practice, changes in mitochondrial
Compared with those infected without anti-HBs, patients with anti- metabolism in peripheral blood lymphocytes occur significantly earlier
HBs were older (P<0.001) and had lower HBsAg levels (P<0.001). than changes in cell counts, providing a more sensitive reflection of
And with the negative of hepatitis B e antigen (HBeAg), the level of immune status. The mitochondrial metabolic response of Th and Tc
antibody to hepatitis B core antigen (anti-HBc) was lower ( P<0.001). cells is closely associated with PegIFN-α treatment, and improved
According to the HBeAg status, the patients with HBsAg and anti-HBs mitochondrial function in Tc cells, along with differentiation into
coexistence were divided into 37 HBeAg positive patients (9.2%) and monocytes, can serve as predictors of clinical cure outcomes.
365 HBeAg negative patients (90.8%). Patients with vs without HBeAg
were younger, had higher ALT levels , AST levels, HBsAg and hepatitis
B virus deoxyribonucleic acid (HBV DNA) levels (P<0.05) and lower
PP0148
platelet counts (P=0.001).Compared with patients without HBeAg, Dramatic paradigm shift in antidiabetic drug use in patients with
those with HBeAg had higher APRI scores (P<0.001), FIB-4 scores chronic hepatitis B and diabetes mellitus from 2000 to 2023: a
(P=0.03).Patients with HBeAg also had higher proportions of cirrhosis territory-wide study
(P= 0.001) and severe liver fibrosis (P= 0.002). Grace Wong1, Lililan Liang1, Terry Yip1, Jimmy Lai1, Vincent Wong1
Conclusion: The prevalence of coexistent HBsAg and anti-HBs was 1
The Chinese University of Hong Kong
4.79% of HBsAg positive patients, the HBeAg negative patients were Background: In view of aging population of patients with chronic
365(90.8%) predominant. Those with HBsAg and anti-HBs coexistence hepatitis B (CHB), comorbidities including diabetes mellitus (DM) are
were older and had lower levels of HBsAg and anti-HBc compared to increasing prevalent. We aimed to evaluate the disease burden of DM
those with anti-HBs (-) infection. The prevalence of this coexistence and the update of different classes of antidiabetic drugs in CHB-DM
gradually increases with age. The coexistence of HBsAg and anti- patients.
HBs appears to represent a transitional phase in the natural history Method: The drug records of consecutive CHB patients from 2000
of HBV infection, possibly indicating a phase of HBeAg clearance or to 2023 were retrieved. The secular trend of different classes of
pre-conversion in HBeAg positive patients, and a HBsAg clearance or antidiabetic drugs were analysed.
pre-conversion in HBeAg negative patients. Result: We recruited 234,865 CHB patients (mean age 48±11 years;
Table and Figure:Figure 1.Comparison of Clinical Features Between 62.4% men) in 2000-2023; 51,305 (21.8%) had received at least
Patients With and Without Anti-HBs one antidiabetic drug. In year 2000-2004, the three most commonly
Figure 2.Comparison of laboratory results of HBsAg and anti-HBs used classes of antidiabetic drugs include sulphonylurea (n=9,319),
coexistence by HBeAg Status metformin (n=7,360), and insulin (n=3,022). The usage has been
increased most dramatically for metformin (in 2005-2009: n=13,205;
PP0147 2010-2014: n=20,141; and 2015-2019: n=26,045; 2020-2023:
Lymphocyte Mitochondrial Metabolism as a Predictor of Clinical n=28,348); whereas only modest increase in using sulphonylurea
Cure in Chronic Hepatitis B Patients Treated with PegIFN-α (in 2005-2009: n=13,593; 2010-2014: n=15,706; and 2015-2019:
n=17,768; 2020-2023: n=16,597) (Figure). The newer classes of
Zutao Chen1,2, Qingzhen Han2
antidiabetic drugs, namely dipeptidyl peptidase 4 inhibitors (DPP-
1
the First Affiliated Hospital of Soochow University, 2the Fourth
4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have
Affiliated Hospital of Soochow University
dramatic increase in usage over last decade (Figure).
Background: PegIFN-α is among the most effective treatments for Conclusion: There has been a dramatic paradigm shift in antidiabetic
achieving a clinical cure for chronic hepatitis B (CHB) by modulating drug use in CHB-DM patients over last two decades. The impact of this
immune responses, reducing HBV RNA levels, and inducing cccDNA shift on glycaemic control, safety issue and adverse clinical outcome
degradation. However, there remains a lack of reliable biomarkers is to be evaluated.
to evaluate the response to PegIFN-α treatment and predict clinical Financial support: This work was supported by the General Research
Fund from the Research Grant Council grant to Grace Wong as the LOQ group. Data on patients’ sex, age, type of NAs used, routine
(Reference: 14106922). blood tests, liver and kidney function, quantitative hepatitis B serology,
Table and Figure:Figure 1.Secular trend of usages of A. the top three ultrasensitive HBV DNA, HBV pgRNA, abdominal ultrasound, CT or
different classes of antidiabetic drugs from 2000 to 2023 and B. two MRI imaging were collected. Differences between the two groups in
new classes of antidiabetic drugs in 2015 to 2023 in patients with terms of demographic data and HBV markers such as HBV pgRNA
chronic hepatitis B. were analyzed using t-tests, χ²tests, univariate, and multivariate logistic
Figure 2.Secular trend of usages of A. the top three different classes regression analysis.
of antidiabetic drugs from 2000 to 2023 and B. two new classes of Result: A total of 827 patients with chronic HBV infection treated with
antidiabetic drugs in 2015 to 2023 in patients with chronic hepatitis B. NAs were included in the study, with 536 patients in the TND group and
291 in the LOQ group. Compared with the TND group, the LOQ group
had a younger age (P < 0.001), and higher level of ALT, AST, HBeAg
PP0149
positive rate, HBsAg, and HBV pgRNA (all P < 0.001). Multivariate
The predictive value of bilirubin after in HBV-ACLF artificialpatients logistic regression analysis indicated that younger age, higher AST,
after artificial liver surgery liver surgery and its relationship with HBsAg, and HBV pgRNA levels were independent risk factors for the
liver regeneration LOQ group (all P < 0.05). Subgroup analyses stratified by HBeAg
Yuqi Chen1, Huaqian Xu1, Chunyan Li1, Shanhong Tang1 status, cirrhosis status, and sex showed that the LOQ group had
Background: Hepatitis B-associated Acute-on-Chronic liver failure significantly higher levels of HBsAg and HBV pgRNA compared to the
(HBV-ACLF) is the most common form of liver failure with rapid TND group in all subgroups (all P < 0.05).
progression and high mortality. The artificial liver support system Conclusion: The LOQ group had higher levels of HBV replication
(ALSS) is an important tool to reduce HBV-ACLF mortality, but there compared to the TND group. HBsAg and HBV pgRNA levels can serve
is no optimal time to observe its efficacy. Clinical prognostic scores as surrogate markers for HBV replication in cases with trace amounts
for patients with liver failure currently include Child-Pugh, MELD, of ultrasensitive HBV DNA. Further studies are needed to explore the
ALBI scores, etc., which only cover a single or partial dimension clinical significance of trace amounts of ultrasensitive HBV DNA.
of liver function and cannot evaluate the prognosis of patients as Table and Figure:Figure 1.Comparison of HBsAg and HBV pgRNA
a whole and comprehensively. Bilirubin, a common indicator to levels between TND and LOQ groups in subgroups
predict the prognosis of HBV-ACLF, often reflects liver damage and Figure 2.Correlation between serum HBV pgRNA and HBsAg levels in
biotransformation function. Liver regenerative function has been a hot overall patients (A, C), or HBeAg-positive patients (B, D)
topic in recent years. Therefore, evaluating the changes of hepatocytes
in vivo in different dimensions and at different time points can help us to
PP0151
better assess the prognosis of patients with liver failure. However, the
changes of bilirubin in patients with artificial liver and its relationship Establishment of a Bile Acid-based Risk Model to Predict the
with liver regeneration still need to be explored. Progression to Cirrhosis and Hepatocellular Carcinoma in
Method: To study the best detection time of bilirubin in ALSS Patients with Chronic Hepatitis B
treatment of HBV-ACLF and the relationship between bilirubin and liver Xue Mei Zhang1, Li Ming Zheng1, Wen Lan Zheng1, Jia Shi1, Shi Han
regeneration. Yu1, Wu Rong Du1, Hao Liu1, Hai Feng1, Zhuo Yu1
Result: The detection of bilirubin on the third day after artificial liver 1
Shuguang Hospital Affiliated to Shanghai University of Traditional
surgery can better predict the prognosis of HBV-ACLF patients, and Chinese Medicine
the prognosis of patients is better when the change rate of bilirubin is Background: Progressing to cirrhosis and hepatocellular carcinoma
40-50%, and the liver regeneration ability of patients is the strongest (HCC) is a severe epidemiological risk of chronic hepatitis B (CHB),
at this time. which is urgently required for effective monitoring strategies. The
Conclusion: Bilirubin can be used as an indicator to assess the dysregulation of bile acids (BAs) metabolism is crucial in aggravating
prognosis of HBV-ACLF patients after artificial liver surgery. Dynamic this pathological process of liver disease. In this study, we aim to
monitoring of bilirubin in combination with alpha-fetoprotein can develop a risk model based on BAs signature to predict the likelihood
multidimensionally evaluate the functional status of liver cells in HBV- of cirrhosis and HCC occurrence in patients with CHB.
ACLF patients and improve the reliability and accuracy of prognosis Method: A retrospective analysis was conducted on clinical data from
prediction. 608 patients suffering from CHB, HBV-related cirrhosis and HCC who
Table and Figure:Figure 1.Comparison of the K-M survival curves of were admitted to Shuguang hospital between 2018 and 2023. Patients
different bilirubin decline rates were randomly divided into a training set (n=425) and a validation
Figure 2.AFP of different bilirubin decline rates set (n=183). In the training set, univariate and multivariate logistic
regression analyses were performed to identify significant variables
PP0150 that were used to develop a Nomogram risk model for predicting the
progression of CHB to cirrhosis and HCC. The model’s accuracy,
Analysis of serum HBV pgRNA levels in chronic hepatitis B
calibration and clinical utility were separately assessed by the area
patients with HBV DNA below the detection limit and below the
under the receiver operating characteristic curve (AUC), calibration
quantification limit after long-term nucleotide analogues treatment
curves, decision curves and clinical impact curves. The risk predictive
Yiheng Zhang1, Tao Li, Yundong Qu, Lei Wang, Yan Wang1 model was further validated to ensure its reliability and applicability
1
The Sencond Hospital of Shangdong University using the validation set.
Background: This study aims to investigate the differences between Result: In the training set, univariate and multivariate logistic regression
two groups of patients treated with nucleos(t)ide analogues (NAs): analyses indicated that taurocholic acid (TCA) and age were identified
those with undetectable HBV DNA by ultrasensitive testing and those as independent risk factors for the progression to cirrhosis and HCC in
with HBV DNA below the quantification limit. The findings will provide patients with CHB, while serum albumin (ALB) was determined to be an
a basis for the clinical interpretation and rational use of ultrasensitive independent protective factor. A Nomogram risk model was developed
HBV DNA results. using these three indicators, demonstrating a highly accurate and
Method: This cross-sectional study included patients with chronic reliable ability to predict the progression from CHB to cirrhosis
hepatitis B (CHB) who were treated with NAs between May 2023 and and HCC (AUC=0.9151, 95%CI: 0.888-0.9421, P<0.001), which
December 2023 at the outpatient clinic and inpatient department of the outperformed the predictive capabilities of individual indicators (TCA:
Hepatology Department, The Second Hospital of Shandong University. AUC=0.8294, 95%CI: 0.787-0.8718, P<0.001; Age: AUC=0.7952,
All patients had ultrasensitive HBV DNA results that were either 95%CI: 0.787-0.8384, P<0.001; ALB: AUC=0.8703, 95%CI: 0.8335-
undetectable or less than 20 IU/mL. The group with undetectable 0.9071, P<0.001). The risk model’s predictive accuracy was further
ultrasensitive HBV DNA is defined as the TND (target not detected) validated in the validation set (AUC=0.9413, 95%CI: 0.9096-0.973,
group, while the group with HBV DNA levels below 20 IU/mL is defined P<0.001). Additionally, the calibration and clinical applicability of the
model was confirmed in both the training and validation sets. patients. It is well known that p53 gene mutation plays an important
Conclusion: This study developed a Nomogram risk model that role in the occurrence and development of HCC. This study aimed to
integrated bile acid markers, offering a precise tool for predicting to investigate the role of ESPL1 and p53 genes in the pathogenesis
and diagnosing cirrhosis and HCC in patients with CHB. The model of HBV-associated HCC and evaluate the potential of serum ESPL1
presents an accurate and user-friendly approach for early screening marker and p53 antibody as diagnostic indicators for HCC.
and prevention of cirrhosis and HCC. Nevertheless, to ensure the Method: A total of 115 patients from our hospital were enrolled and
model’s reliability and effectiveness, prospective, multicenter, large- divided into four groups: healthy control group, chronic hepatitis B
sample cohort studies are necessary. Our studies would assist (CHB) group, HBV-associated liver cirrhosis (LC) group, and HBV-
clinicians in the timely and accurate identification of high-risk CHB associated HCC group. Serum levels of ESPL1 and p53 antibodies
patients, facilitating precise prevention strategies and personalized were detected using enzyme-linked immunosorbent assay (ELISA),
management plans. and differences between these levels were compared. Clinical AFP
Table and Figure:Figure 1.The schematic diagram of study in the were collected to compare the ROC curve analysis and diagnostic
retrospective cohort reliability of peripheral serum ESPL1, p53 antibody, and AFP in
Figure 2.The establishment and verification of a Nomogram risk model evaluating their diagnostic value for HCC. Immunohistochemical
for CHB progression to cirrhosis and HCC results of p53 in HCC group were collected, and ESPL1 serum marker,
p53 antibody, AFP were analyzed, and their coincidence rate with p53
immunohistochemical diagnosis was analyzed.
PP0152
Result: The serum level of ESPL1 marker differed among the HCC
Efficacy of peginterferon alfa-2b monotherapy in initial treatment group, LC group, CHB group, with an increasing expression level
of patients with HBeAg negative chronic hepatitis B observed from healthy control to CHB to LC to HCC groups as disease
Jing Chen1, Jianmei Lin2 progression occurred (Figure1A). Only in the HCC group did we
1
Department of Healthcare-associated infection control center, observe an increase in p53 antibody levels which was significantly
Sichuan Provincial People‘s Hospital, University of Electronic Science higher than those found in CHB group , LC Group ,and healthy control
and Technology of China, 2Infectious Disease Department, Sichuan (Figure1B).
Provincial People‘s Hospital, University of Electronic Science and In HCC group there was a positive correlation between
Technology of China serum levels of both ESPL1 marker(p=0.009, r=0.351), but no
Background: To evaluate the efficacy of initial treatment with significant correlation was observed within either CHB or LC groups.
peginterferon alfa-2b (peg-IFN alfa-2b) monotherapy in patients with The area under curve (AUC ) of serum ESPL1 was 0.917
HBeAg negative chronic hepatitis B (CHB). which was significantly higher than that obtained by using p53 antibody
Method: This study included 59 HBeAg negative CHB patients from (AUC =0 .725 ) and AFP (AUC =0 .678) (Figure2). The sensitivity and
December 2019 to December 2023, who were treatment-naïve. consistency of serum ESPL1 marker in the diagnosis of HCC were
These patients had a willingness to receive interferon treatment, and significantly higher than that obtained by using p53 antibody or AFP .
after thorough examination to rule out relevant contraindications and The concurrence rate of serum ESPL1 marker with p53
sufficient communication, they received peg-IFN alfa-2b monotherapy. immunohistochemistry in the HCC group was significantly higher
At 4, 12, 24 and 48 weeks of treatment, the level of hepatitis B surface compared to that of p53 antibody and AFP.
antigen, continuous virological response, biochemical changes and Conclusion: 1. The ESPL1 gene may play a crucial role in the
adverse reactions during treatment were observed. These patients upstream regulation of the oncogenic cell pathway involving the p53
had treated for at least 24 weeks, of which 26 patients had completed gene; 2. The serum marker for ESPL1 exhibits an increasing trend
48 weeks of treatment. with disease progression, providing early warning indications for the
Result: The average age of these patients was 37.4 years, with 42 occurrence of early-stage liver cancer; 3.Considering factors such as
males accounting for 71.2%. There were 14, 13, 15, and 17 cases of cost, operational feasibility, and applicability, the ESPL1 serum marker
baseline HBsAg<20IU/ml, 20-100IU/ml, 100-1500IU/ml, and>1500IU/ demonstrates superior diagnostic efficacy compared to both p53
ml in these patients, respectively. After 24 weeks of treatment, HBV antibody and AFP in the diagnosis of HCC.
DNA decreased by 2.19 log10IU/ml relative to baseline, and HBsAg Table and Figure:Figure 1. Figure 1 Comparison between the
decreased by 1.02 log10IU/ml relative to baseline, with the most experimental group and healthy control group
significant decrease observed in patients with baseline HBsAg<20IU/ Figure 2.Figure 2 ROC curve of serum ESPL1, p53 antibody and AFP
ml, followed by patients with baseline HBsAg<100IU/ml. At 24 weeks
of treatment, 13 patients had HBsAg turned negative, accounting for PP0154
22.0%, and the baseline HBsAg of these 12 patients was all<100IU/
ml. 26 patients had completed 48 weeks of treatment and follow-up, The epidemiological characteristics of patients with chronic
and 11 patients (42.3%) achieved HBsAg clearance. Among the hepatitis B: a single-center retrospective study
population without HBsAg conversion, 60.0% of them had HBsAg<100 Yanqin Du1, Yandan Zheng1, Hua Wang1, Xin Zheng1
IU/mL after treatment. 1
Department of Infectious Diseases, Union Hospital, Tongji Medical
Conclusion: The lower the baseline HBsAg level, the greater the College, Huazhong University of Science and Technology
probability of HBsAg clearance in patients receiving initial interferon Background: To analyze the epidemiological characteristics and the
monotherapy. Even if clearance is not achieved, HBsAg levels will antiviral status of patients with chronic hepatitis B (CHB) infection in
significantly decrease. the outpatient clinic of a single center at Wuhan Union Hospital after
Table and Figure:Figure 1.Mean changes in HBV DNA the issue of the “Guidelines for the prevention and treatment of chronic
Figure 2.Changes in HBsAg from baseline hepatitis B (version 2022)” by Chinese Medical Association.
Method: We established structured electronic medical records of
PP0153 patients with CHB, including age, gender, history of mother-to-child
transmission, family history of cirrhosis or liver cancer, comorbidities,
To Explore the Relationship between ESPL1 Gene and p53 Gene in
and antiviral treatment status. Data were collected from CHB patients
HCC Patients and to Analyze Its Diagnostic Value for HCC
who visited the outpatient clinic of Department of Infectious Disease in
Yanfei Feng1, Jianning Jiang1 Wuhan Union Hospital from August 2023 to August 2024. Descriptive
1
Guangxi epidemiological methods were used to analyze the data.
Background: The fusion of some HBV genes with human genes has Result: A total of 1210 CHB patients were included, aged between 10
been found to form the HBV S-Human Extra spindle poles like 1 (ESPL1) and 80 years. 215 cases (17.77%, 215/1210) had a history of mother-
fusion gene and over-expression of ESPL1 protein, which plays a role to-child transmission, and 289 cases (23.88%, 105/1210) had a family
in promoting the development of hepatocellular carcinoma (HCC) history of HBV-related cirrhosis or HBV-related liver cancer. There
were 105 patients (8.67%, 105/1210) diagnosed with cirrhosis or HBV-
related liver cancer at the time of consultation, and 198 cases (16.35%, Table and Figure:Figure 1.Table 1. COX regression analysis of factors
198/1210) had comorbid metabolic diseases. Twelve patients (0.99%, related to HBsAg response
12/1210) achieved functional cure. Prior to the release of the 2022 Figure 2.Figure 1. Kaplan-Meier survival analysis of HBsAg response
guidelines, 648 patients (56.53%, 648/1210) had received antiviral A. K-M analysis comparing HBsAg response rate between the
treatment, while 550 patients (45.15%, 550/1210) had never received CHB+MASLD and CHB groups; B. K-M analysis of HBsAg response
antiviral treatment. After the release of the 2022 guidelines, among the incidence across varying MASLD severity levels in patients.
550 untreated patients, 120 cases (9.9%, 120/1210) began antiviral
treatment. Leaving 430 patients still untreated, including 223 cases
PP0156
(18.43%, 223/1210) who met the criteria for antiviral therapy for the
2022 guidelines. The proportion of males, patients with coexisting Evaluating the Added Value of MRI in Detecting Significant Hepatic
cirrhosis or liver cancer, and the number of cases with ALT levels Histological Changes in Chronic HBV Patients with Normal ALT
greater than the upper limit of normal (ULN) significantly increased in Levels
the group that started antiviral treatment compared to the untreated Jiarui Zhong1, Junhao Zha1, Shenghong Ju1
group after the issue of 2022 guidelines. Furthermore, the proportion of 1
Department of Radiology, Zhongda Hospital, Medical School of
HBeAg-negative patients and the HBsAg levels in untreated patients Southeast University
were significantly lower than those in treated patients. These results Background: A subset of chronic hepatitis B (CHB) patients with
suggested that female, relatively low HBsAg levels, and HBeAg- normal alanine aminotransferase (ALT) levels exhibit significant liver
negative status may be the reasons why these patients did not histological changes (SLHC), defined as fibrosis grade ≥ 2 and/or
temporarily consider antiviral treatment. inflammation grade ≥ 2. These changes meet the histological criteria
Conclusion: The antiviral treatment rate for CHB patients increased for initiating antiviral treatment. This study aimed to develop a non-
from 56.53% to 66.43% at one year after the issue of 2022 guideline invasive combined model to assess the additional value of MRI in
which expanded the treatment indications. However, there remains a detecting SLHC in CHB patients with normal ALT levels and predicting
gap to the WHO’s target treatment rate of 80% for the elimination of their prognosis after antiviral treatment.
viral hepatitis as a public health threat by 2030. Method: A total of 516 patients with CHB and normal ALT levels, who
underwent liver biopsy and MRI, were included in this multicenter
PP0155 retrospective study conducted between May 2015 and July 2022.
Patients from center 1 were randomly assigned to a training set (n =
Impact of Hepatic Steatosis on the Efficacy of Antiviral Treatment
299) and an internal testing set (n = 123) in a 7:3 ratio. The external
for Chronic Hepatitis B and the Establishment of a Predictive
testing set (n = 94) consisted of patients from center 2. Using T1
Model
delayed enhanced MR images, radiomics features were extracted from
Guanghui Ren1, Shi Yin1, Ying Zhu1 the entire liver region of interest to develop the MR model (FEA_RADI)
1
Department of Infectious Disease, Liver Disease Center of Integrated for diagnosing SLHC. Binary logistic regression analysis was employed
Traditional Chinese and Western Medicine, The First Affiliated to identify independent risk factors from clinical variables, which were
Hospital of Dalian Medical University, Dalian, Liaoning, China. combined with the FEA_RADI model to create the AAPFR model.
Background: Metabolic dysfunction-associated steatotic liver The final NEWMODEL combined the AAPFR model with FibroScan
disease (MASLD) and chronic hepatitis B (CHB) are prevalent chronic data. The diagnostic performance of these models was assessed by
liver conditions. Recent data indicate a rising incidence of MASLD comparing the area under the curve (AUC). Patients in center 1 with
coexisting with CHB, though the influence of MASLD on antiviral paired liver biopsies or FibroScan data (n=218) before and after 22-26
treatment outcomes for CHB remains under discussion, highlighting months of antiviral treatment were included in the longitudinal analysis.
the need for further investigation. Result: The distribution of SLHC across all three datasets was 51%,
Method: We analyzed a cohort of 250 CHB patients undergoing with no statistically significant differences (P=1.00). ALB, AST, and
antiviral therapy, divided equally into CHB+MASLD (n=125) and CHB PLT were identified as independent factors (all P < 0.05) for predicting
(n=125) groups. Patients received either nucleos(t)ide analogs (NAs) SLHC. The AUC of the AAPFR model for diagnosing SLHC was 0.80,
monotherapy, peginterferon α-2b monotherapy, or a combination of 0.80, and 0.72 in the training, internal testing, and external testing sets,
NAs and peginterferon α-2b. Response rates to antiviral treatment at respectively, which was superior to APRI (all P < 0.05) and comparable
24 and 48 weeks were compared between the groups. Additionally, to FibroScan (all P > 0.05). The IDI was 11.9%, 16.93%, and 12.9%
Kaplan-Meier survival and COX regression analyses were performed (all P < 0.001) respectively. The NEWMODEL model achieved AUCs
to assess the impact of baseline characteristics and MASLD on antiviral of 0.82 and 0.81, outperforming FibroScan (all P < 0.05) in the training
treatment efficacy, and a prognostic NOMO diagram was developed to and internal tests, while the IDI was 15.0% and 17.8% (all P < 0.001).
establish a predictive model. NEWMODEL had satisfactory performance in diagnosing SLHC
Result: At week 24 and 48, the CHB+MASLD group showed significantly regression after antiviral treatment (AUC=0.76; 95% CI: 0.70–0.82).
higher HBsAg response rates than the CHB group (24 weeks: 11.5% NEWMODEL could find more patients who can benefit from antiviral
vs. 3.3%, p=0.038; 48 weeks: 24.4% vs. 11.3%, p=0.005). By week treatment in this population.
48, pgRNA response rates were also significantly higher in the Conclusion: The radiomics-based combined model: NEWMODEL,
CHB+MASLD group compared to the CHB group (48.8% vs. 28.3%, demonstrated satisfactory performance in evaluating SLHC in CHB
p=0.049). Kaplan-Meier survival analysis demonstrated a reduced patients with normal ALT and had a great significance in prognosis.
median time to HBsAg response in the CHB+MASLD group compared Table and Figure:Figure 1.Schematic overview of the study design
to the CHB group (HR=3.40, 40 weeks vs. 42.5 weeks, p=0.002). Figure 2.Prognostic value of the models for SLHC
COX regression identified age (HR=0.952, p=0.008), antiviral regimen
(NAs+ peginterferon α-2b: HR=4.829, p<0.001), baseline HBsAg
PP0157
level (HR=0.650, p=0.010), and the presence of MASLD (HR=3.321,
p=0.022) as independent predictors of HBsAg response, facilitating Current status and challenges in the diagnosis, treatment and
model development. Time-ROC analysis confirmed age, antiviral management of hepatitis B virus infected patients
regimen, baseline HBsAg level, and MASLD as robust predictors for Yani Zhou1, Wei Wu1, Sisi Yang1, Yida Yang1
HBsAg decline (24 weeks: AUC=0.902; 48 weeks: AUC=0.890), with 1
State Key Laboratory for Diagnosis and Treatment of Infectious
strong model discrimination and clinical utility. Diseases, National Clinical Research Center for Infectious Diseases,
Conclusion: In CHB patients undergoing antiviral therapy, concurrent National Medical Center for Infectious Diseases, Collaborative
MASLD is associated with improved HBsAg response. Younger age, Innovation Center for Diagnosis and Treatment of Infectious Diseases,
NAs combined with peginterferon α-2b therapy, lower baseline HBsAg Department of Infectious Diseases, The First Affiliated Hospital,
levels, and MASLD presence can effectively predict positive treatment Zhejiang University School of Medicine, Hangzhou, China.
response. Background: Chronic hepatitis B virus (HBV) infection is a serious
global public health problem. There is still a large gap between the cell response. Moreover, among those who exhibited a reduction in
diagnosis and treatment rates of hepatitis B in China and the goals HBsAg above 0.5log within 12 weeks of treatment in HBeAg positive
set by the World Health Organization (WHO) to be achieved by 2030. group, elevated levels of CD80 and CD72 expression were observed
In order to achieve the goal of HBV elimination, the Department on B cells, along with increased expressions of CD86, CD80, and PDL-
of Infectious Diseases of our hospital, as a key department for the 1 on monocytes. The expressions of both CD25 on CD4 T cells and
prevention and treatment of HBV in China, statistics on the rate of HBV- HLA-DR on CD8 T cells remained consistently elevated throughout the
DNA detection in each department is very important to improve the entire follow-up period but showed a declining trend. However, these
treatment rate of hepatitis B. patients still did not exhibit a robust HBV-specific T cell response.
Method: A cross-sectional study of a total number of HBsAg-positive Conclusion: TMF antiviral treatment leads to a more pronounced
patients in the First Affiliated Hospital of Zhejiang University from HBsAg reduction in HBeAg positive naïve patients accompanied by
January 1, 2024 to June 31, 2024 was counted and analyzed for HBV- consistent activation of B cells and monocytes, as well as a gradual
DNA detection as well as departmental distribution. decline in T cell activation. Only the HBeAg negative group exhibits a
Result: The total number of HBsAg-positive patients in the First stronger HBV-specific T cell response. Our findings suggest potential
Affiliated Hospital of Zhejiang University was 23,913. HBsAg-positive differential immunological mechanisms underlying TMF’s antiviral effect
patients were distributed among various departments attending the between HBeAg negative and positive patients, along with significant
hospital, among which the department of infectious diseases had the reduction of HBsAg during the early stage of TMF treatment.
highest attending rate of 47.70%, followed by hepatobiliary surgery Table and Figure:Figure 1.Changes in clinical parameters during follow
with 10.00%. The total number of HBsAg-positive patients who further up
improved their HBV-DNA test was 10,564. The number of HBV- Figure 2.Changes in immune phenotype and functions during follow up
DNA tests performed in the departments of hematology, infection,
hepatobiliary surgery and nephrology were 1045, 6133, 1339 and 235,
PP0159
respectively, and the rates of HBV-DNA testing in these departments
were 77.46%, 53.73%, 55.81% and 53.53%, respectively. Association of High-Density Lipoprotein Cholesterol Levels with
Conclusion: About 47.70% of HBsAg-positive patients in the 90-day Mortality in Patients with HBV-ACLF
department of infection diseases, and still about half of the patients were Ke Shi1, Ying Feng1, Xianbo Wang1
distributed in the non-infection departments, only four departments 1
Beijing Ditan Hospital, Capital Medical University
in the hospital had HBV-DNA testing rates higher than 50%, and for Background: Hepatitis B virus-related acute-on-chronic liver failure
infectious departments, the HBV-DNA testing rate was not satisfactory. (HBV-ACLF) is linked to dyslipidemia and inflammatory responses.
Enhancing attending physicians’ awareness of HBV-DNA testing for This study aimed to investigate the correlation between high-density
HBsAg-positive patients is essential to improve the treatment rate of lipoprotein cholesterol (HDL-C) levels and 90-day transplant-free (TF)
hepatitis B. mortality in patients with HBV-ACLF.
Table and Figure:Figure 1.Figure 1 Method: A retrospective cohort of 412 patients with HBV-ACLF from
Beijing Ditan Hospital was enrolled. We evaluated the prognostic
PP0158 accuracy of lipid profile parameters using the area under the receiver
operating characteristic curve (AUC) and assessed the association
Immunological correlates of rapid HBsAg decline in chronic HBV
between HDL-C levels and mortality with restricted cubic spline
hepatitis patients undergoing Tenofovir Amibufenamide treatment
analysis. Kaplan-Meier curves and log-rank tests were used to analyze
Shu E Xiong1, Hang Jia1, Xu Feng Quan1, Bo Yun Liang1, Si Hong 90-day TF mortality. These results were validated internally.
Lu1, Yi Cheng1, Hua Wang1, Han Xin Li1, Ling Xu1, Su Meng Li1, Tong Result: Patients with HDL-C levels below 0.13 mmol/L had significantly
Wang1, Yi Wen Shu1, Jia Yu Yu1, Jia Liu1,2, Xin Zheng1,2 higher mortality rates (adjusted hazard ratio: 4.04, 95% CI: 1.35–11.85)
1
Union Hospital, Tongji Medical College, Huazhong University of compared to those with HDL-C above 0.36 mmol/L. An “L-shaped”
Science and Technology, 2Joint International Laboratory of Infection association was found between HDL-C levels and TF mortality. The
and Immunity, Huazhong University of Science and Technology prognostic value of HDL-C (AUC at day 90: 0.732) was similar to the
Background: While most chronic viral hepatitis B (CHB) patients model for end-stage liver disease score (0.729). In the training cohort,
undergoing Tenofovir amibufenamide (TMF) antiviral therapy 90-day TF mortality rates were 8.3%, 15.2%, 24.0%, and 43.2% for
experience a rapid decline in HBV DNA levels, the same is not extremely low, low, medium, and high-risk subgroups, respectively. In
observed for HBsAg decline in all patients, highlighting unclear the validation cohort, the rates were 4.5%, 18.5%, 31.2%, and 44.7%,
immunological mechanisms. This study aims to prospectively and respectively.
dynamically observe immunological changes during the initial stage of Conclusion: HDL-C levels < 0.13 mmol/L were associated with
TMF antiviral treatment. increased 90-day transplant-free mortality in patients with HBV-ACLF.
Method: A total of 37 CHB patients who will initiate antiviral treatment Table and Figure:Figure 1.Random forest analysis and predictive ability
with TMF were enrolled, comprising 18 HBeAg positive and 19 HBeAg of different indicators for 28- and 90-day TF mortality in patients with
negative individuals. Clinical assessment was performed over 48 HBV-ACLF. (A-B) Random forest analysis with tenfold cross-verification
weeks post-TMF treatment. The phenotypes of B cells, dendritic indicated that HDL-C came in second only to MELD score. (C-D) ROC
cells (DCs), monocytes, T cells, and HBV-specific T cell functions curves of HDL-C, LDL-C, TC, TG and MELD score predicting 28- and
were longitudinally assessed using freshly isolated peripheral blood 90-day TF mortality in training set. (E-F) ROC curves of HDL-C, LDL-C,
mononuclear cells (PBMCs). TC, TG and MELD score predicting 28- and 90-day TF mortality in test
Result: The study revealed a rapid decrease in HBV DNA and RNA set. TF, transplant-free; TC, total cholesterol; TG, triglyceride; HDL-C,
levels following TMF antiviral treatment among all CHB patients. high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein
Notably, the HBeAg positive group exhibited a significant decline cholesterol; MELD, Model for end-stage liver disease; ROC, receiver
in HBsAg levels, characterized by abnormal ALT levels at baseline. operating characteristic curve; HBV-ACLF, hepatitis B virus related
Immunological marker monitoring revealed elevated frequencies of acute-on-chronic liver failure; TF, transplant-free.
B cells and CD8 T cells in HBeAg positive group, while a significant Figure 2. (A) Cox proportional hazards analysis evaluating prognostic
decrease in T cells was observed in the HBeAg negative group, implication of HDL-C in differented subgroups. HR was adjusted
primarily due to a reduction in CD4 T cells. In general, both groups for age, sex, ascites, hepatic encephalopathy, total bilirubin, total
exhibited a transient upregulation in the expression of CD80, CD86, cholesterol, neutrophil-lymphocyte ratio, international normalized ratio,
and CD72 on B cells following 8 weeks of TMF treatment. The HBeAg and creatinine in the multivariate model. (B) Risk stratification of 90-
negative group showed a significant increase in the expression of CD80 day TF mortality rate according to HDL-C quartile in the training and
and PD-L1 on B cells and PD-L1 on monocytes, while demonstrating a the test sets. (Risk stratification: A: very low-risk group, HDL-C levels
decrease in CD72 on B cells expression compared to baseline levels. > 0.36mmol/L;B: low-risk group, HDL-C levels 0.20–0.36 mmol/L; C:
Furthermore, they also manifested a more robust HBcAg-specific T intermediate-risk, HDL-C levels 0.13–0.20 mmol/L; D: high-risk, HDL-C
levels < 0.13mmol/L; p < 0.0001 by log-rank test). age, sex, neutrophil–lymphocyte ratio, and model for end-stage liver
disease scores (P < 0.05).
Conclusion: JDLXJP significantly reduced the 90-day mortality rate of
PP0160
HBV-ACLF patients. Further prospective clinical studies are needed to
Dynamic Expression of IFI27 and IFI44L as Predictive Biomarkers confirm these findings.
for Clinical Cure in Chronic Hepatitis B Under Interferon Therapy Table and Figure:Figure 1.Baseline characteristics of the Jiedu
Xiyao Chen1, Liang Peng1 Liangxue Jianpi prescription (JDLXJP) and control groups and Cox
1
The Third Affiliated Hospital of Sun Yat-sen University hazards analysis for 90-day survival of patients with hepatitis B virus-
Background: Interferon (IFN)-based therapies are crucial for managing related acute-on-chronic liver failure (HBV-ACLF).
chronic hepatitis B (CHB), but treatment outcomes vary. Biomarkers Figure 2.Effect of Jiedu Liangxue Jianpi prescription (JDLXJP) on 90-
predicting clinical cure can guide personalized strategies. This study day mortality in patients with hepatitis B virus-related acute-on-chronic
examines the temporal expression patterns of two interferon-stimulated liver failure (HBV-ACLF). Blue line: JDLXJP group; red line:control
genes (ISGs), IFI27 and IFI44L, in peripheral blood mononuclear cells group.
(PBMCs) during Pegylated Interferon-α (PegIFN-α) therapy, assessing
their potential as predictive biomarkers. PP0162
Method: A total of 220 CHB patients were initially enrolled, with 86
Analysis of the Efficacy and Safety of TAF and TDF in Pregnant
matched pairs (172 patients) selected after 1:1 matching based on
Women with HBV Infection Across Different Age Groups
clinical parameters, including baseline HBsAg levels and age. Patients
were divided into a clinically cured group (n=86) and an uncured Xu Jiang1, Chengjing Tao1, Chun Zhao1, Tongtong Chen1, Liuyi Lu1,
group (n=86), defined by HBsAg clearance at week 48 of therapy. Shourong Liu1
PBMCs were collected at baseline, 12, 24, and 48 weeks, and total
1
xixi hospital of hangzhou
RNA was extracted. IFI27 and IFI44L expression levels were quantified Background: With the diversification of reproductive concepts among
by quantitative reverse-transcription PCR (qRT-PCR) and normalized young people, the age range of pregnant women has become more
using housekeeping genes. Relative mRNA changes were calculated complex. Women in different age groups have varying physical
via the 2^-ΔΔCt method. Clinical parameters such as ALT, HBV DNA, conditions, and the same drug can have different effects across these
and HBsAg levels were recorded. Statistical analyses used paired groups.Guided by evidence-based medicine, more precise selection
t-tests and repeated-measures ANOVA, with significance set at p < of antiviral drugs is required. Therefore, we conducted a meta-analysis,
0.05. integrating data from pregnant women across multiple regions and age
Result: At baseline, no significant differences in IFI27 or IFI44L groups, to explore the efficacy and safety of TAF in treating pregnant
expression were observed between groups. In the clinically cured women with HBV infection across different age groups, and comparing
group, both genes were significantly upregulated, peaking at week it with traditional therapeutic drugs.
24 (p < 0.01) and exhibiting markedly higher levels than the uncured Method: From January 1, 2016, to October 30, 2024, we conducted
group. In contrast, the uncured group showed modest upregulation a meta-analysis of databases including PubMed, Wanfang, Web of
at week 12, followed by a plateau or decline by week 24. The strong Science, and CNKI. We compared the efficacy and safety of TAF and
upregulation of IFI27 and IFI44L in the cured group correlated with TDF in preventing MTCT in pregnant women with HBV across different
HBsAg clearance at week 48, suggesting their predictive value for age groups. The analysis included indicators such as HBV DNA levels
clinical cure. at delivery, the effectiveness of MTCT prevention at the seventh month
Conclusion: These findings align with single-cell transcriptomics postpartum, and several newborn measurements and the 1-minute
studies showing broad activation of IFN-α downstream genes (e.g., Apgar score. Pregnant women were categorized into three age groups
IFI27 and IFI44L) during PegIFN-α therapy. IFN-induced immune based on their age data (mean ± standard deviation): Group A (≤28
activation likely contributes to HBV clearance, with IFI27 and IFI44L years), Group B (29–34 years), and Group C (≥35 years).
as promising biomarkers for predicting therapeutic outcomes. Their Result: This study included eight cohort studies and two randomized
dynamic expression could enhance personalized CHB treatment controlled trials (RCTs). A total of 587 mothers were treated with TAF,
strategies and improve interferon-based therapy efficacy. and 641 mothers were treated with TDF. The study results showed
Table and Figure:Figure 1. no difference in the effectiveness of MTCT prevention at the seventh
month postpartum (RR: 1.00 [95%CI: 0.98, 1.02]). In terms of newborn
safety: TAF and TDF showed no statistical differences in the 1-minute
PP0161
Apgar score, birth height, birth weight, and birth head circumference
Evaluation of Clinical Efficacy of Jiedu Liangxue Jianpi of newborns born to hepatitis B mothers in different age subgroups; in
Prescription in Patients with HBV-ACLF terms of safety and efficacy for pregnant women with HBV infection:
Ke Shi1, Ying Feng1, Xianbo Wang1 there was no difference in the overall reduction of maternal HBV DNA
1
Beijing Ditan Hospital, Capital Medical University levels between TAF and TDF (P = 0.25); however, in the age group of
Background: Hepatitis B virus-related acute-on-chronic liver failure ≥35 years, TAF was more effective in reducing HBV DNA levels, with
(HBV-ACLF) has significant morbidity and mortality due to limited a statistically significant decrease (MD: 0.48, 95% CI: -0.15, 0.81, P =
treatment options. This study aimed to assess the clinical effect of the 0.005); at the same time, TAF showed an advantage in blood creatinine
Jiedu Liangxue Jianpi prescription (JDLXJP) on patients with HBV- levels across all age groups, with a statistically significant difference
ACLF. compared to the TDF group, showing an overall mean difference of
Method: We prospectively collected data from 276 HBV-ACLF patients -2.74 μmol/L (95% CI: -4.72, -0.76, P = 0.007).
treated at Beijing Ditan Hospital from January 2018 to December Conclusion: TAF and TDF are both safe and effective in treating
2023. Patients were divided into Chinese medicine group (n=141) pregnant women with HBV infection and their newborns across
and control group (n=135) based on JDLXJP use. COX regression different age groups. Pregnant women aged ≥35 years can achieve
analysis identified independent factors affecting 90-day prognosis, a more significant reduction in HBV DNA levels with TAF treatment.
and mortality rates were compared between groups and different Additionally, pregnant women across different age groups can benefit
subgroups. from better kidney safety by choosing TAF treatment.
Result: Treatment with Chinese medicine was an independent Table and Figure:Figure 1.The impact of TAF and TDF on HBV DNA
protective factor against 90-day mortality in ACLF patients (P < levels in HBV-infected pregnant women during childbirth across
0.05). The Chinese medicine group had a significantly lower 90-day different age groups
mortality rate compared to the Western medicine group (14.9% vs. Figure 2.The impact of TAF and TDF on serum creatinine levels in HBV-
31.8%, P < 0.001). Additionally, mortality rates decreased significantly infected pregnant women during childbirth across different age groups
in the Chinese medicine group across different subgroups based on
 PP0163 Shenyang Sixth People’s Hospital from January 2019 to December
Changes of HBV RNA in HBeAg-Positive Chronic Hepatitis B 2023 were followed up for 48 weeks after delivery. According to the
Patients with Low-Level Viremia Following Maintenance or antiviral medication status after delivery, they were divided into the
Modification of Treatment Regimens with Nucleos(t)ide Analogues continued medication group and the discontinuation group (immediate
or Interferon Add-On Therapy discontinuation after delivery). The effects of discontinuation on HBV-
DNA levels and HBsAg quantification in the two groups after delivery
Yushuang Zhang1, Tao Li1, Lei Wang1
were observed.
1
the Second Hospital of Shandong University, 247 Beiyuan Road Result: A total of 138 patients with mother-to-child transmission
Background: The mechanisms underlying viral transcription and prevention were enrolled. Before delivery, 100% had HBV-DNA below
replication activity in HBeAg-positive chronic hepatitis B (CHB) patients the detection limit (≤5.0E+10² IU/mL) (P<0.05), and about 24.4% had
with low-level viremia (LLV), particularly under maintained or modified a quantitative decrease in HBsAg > 10%. During postpartum follow-
treatment regimens with nucleos(t)ide analogues (NAs) or interferon up, in the continuous medication group (28 cases), all HBV-DNA
add-on therapy, remain insufficiently understood. Circulating hepatitis remained below the detection limit. In the drug withdrawal group (110
B virus (HBV) RNA, a transcriptional product of covalently closed cases), 0 case had HBV-DNA re-positive at 12 weeks postpartum,
circular DNA (cccDNA), has recently emerged as a robust biomarker 68 cases (61.8%) had HBV-DNA re-positive at 24 weeks postpartum.
of viral transcriptional and replicative activity. This study aimed to Among the patients with HBV-DNA below the detection limit at 24
evaluate and compare circulating HBV RNA levels between patients weeks postpartum, 14 cases had HBV-DNA re-positive at 48 weeks
with LLV and those achieving maintained virological response (MVR) postpartum, and 26 cases had a continuous decrease in HBsAg >
and to analyze HBV RNA changes in patients undergoing different 10%, including 20 cases in the continuous medication group and 6
interventions. cases in the drug withdrawal group. In the patients with a continuous
Method: This prospective cohort study included 62 patients in decrease in HBsAg, all had a quantitative decrease in HBsAg > 10% at
the LLV group and 175 in the MVR group. Serum HBV RNA levels 12 weeks of mother-to-child transmission prevention. In the continuous
were measured using specific RNA target capture combined with medication group, no abnormality in liver and kidney function was
simultaneous amplification and testing methods. Propensity score observed during 48-week follow-up, and no adverse perinatal events
matching (PSM) was employed to balance baseline characteristics were reported, indicating relatively safety.
between groups. Conclusion: Continued antiviral treatment after mother-to-child
Result: The median HBV RNA levels were 6.8 log10copies/mL in the transmission prevention can effectively and continuously suppress
LLV group and 3.8 log10copies/mL in the MVR group. PSM analyses the virus. Meanwhile, a decrease in HBsAg quantification by more
yielded 62 matched pairs, demonstrating significantly higher HBV than 10% at 12 weeks postpartum may be a predictive factor for the
RNA levels in the LLV group (p < 0.001). Among the patients, 54 continuous decrease in HBsAg, which can help identify the populations
continued or modified NAs regimens (including single application of with advantages and disadvantages in response to antiviral treatment
tenofovir, tenofovir alafenamide fumarate, or tenofovir amibufenamide, and provide a reference direction for personalized treatment.
or combination therapy with entecavir), while eight modified their
regimens with interferon add-on therapy. Baseline antiviral duration,
PP0165
aspartate aminotransferase (AST), HBsAg, HBeAg, and HBV RNA
levels were similar between the NAs and interferon groups (p > 0.05). Early Antiviral Efficacy of Tenofovir Alafenamide Fumarate in the
After 48 weeks of treatment, the interferon group exhibited higher AST initial treatment of Normal Alanine Transaminase and hepatitis B
levels (34 vs. 22U/L, p = 0.022) but lower HBsAg (796.2 vs. 7861.7IU/ virus DNA positive chronic hepatitis B virus infection: a 48-week
ml, p = 0.002), HBeAg (24.5 vs. 265.4S/Co, p = 0.016), and HBV Multicenter and Retrospective Study from China
RNA levels (5.0 vs. 6.5log10copies/ml, p = 0.024). MVR rates were Qirui Song1, Wenkang Gao2, Qinzhi Deng3, Ling Yang2, Jianjun Lou4,
comparable between the two groups (100% in interferon group vs. Fan Du2, Jie Li5, Yue Chen2, Jianfeng Zhong6, Zhaowei Tong6, Jie Ye2,
69% in NAs group, p = 0.293). Jiangshan Lian1, Yida Yang1
Conclusion: HBeAg-positive CHB patients with LLV showed elevated 1
State Key Laboratory for Diagnosis and Treatment of Infectious
circulating HBV RNA levels compared to those achieving MVR. Diseases, Department of Infectious Diseases, National Clinical
Interferon add-on therapy appeared to reduce HBV RNA more rapidly Research Center for Infectious Diseases, National Medical Center for
than NAs, suggesting its potential therapeutic value in mitigating viral Infectious Diseases, Collaborative Innovation Center for Diagnosis
transcription and replication activity in LLV patients. and Treatment of Infectious Diseases, The First Affiliated Hospital of
Table and Figure:Figure 1.Figure 1. Baseline HBV RNA levels in MVR Zhejiang University School of Medicine, 2Division of Gastroenterology,
and LLV groups after PSM. Union hospital, Tongji Medical College, Huazhong University of
Figure 2.Figure 2. Changes of virological indicators in NAs and IFN Science and Technology, 3Ningbo No. 2 Hospital, Ningbo Institute of
groups. Liver Diseases, 4Yuyao people‘s hospital of zhejiang province, 5The
2th Affiliated Hosptial and Yuying Children‘s Hospital of Wenzhou
Medical University, 6Huzhou central hospital
PP0164
Background: Studies have confirmed that a considerable
Efficacy Analysis of Postpartum Discontinuation and Continued proportion of chronic hepatitis B (CHB) patients with normal alanine
Antiviral Therapy in Pregnant Women with Mother-to-Child aminotransferase (ALT) levels are characterized by inflammation and
Transmission Prevention fibrosis. The indication of CHB antiviral therapy is HBV-DNA positive
Rui Zhao1, Shengnan Sun1, XiaoLin Shi1 (HBV-DNA> 20 IU/mL), ALT≥ULN or ALT < ULN but meeting the
1
Shenyang Six People‘ Hospital relevant conditions(ULN: 50 U/L for male and 40 U/L for female).
Background: The impact of the altered immune status due to However, there is still a lack of clinical evidence on the efficacy and
childbirth on viral suppression and serological conversion of viral benefit of antiviral therapy in patients with normal ALT levels, and
markers remains unclear at present. This study aims to observe the the applicability and generalization of 30 U/L for male and 19 U/L
efficacy of postpartum discontinuation and continued antiviral therapy for female recommended by many international guidelines in China.
in pregnant women with mother-to-child transmission prevention, so as This study aims to evaluate the early efficacy and benefit of antiviral
to provide references for further achieving the clinical cure of hepatitis therapy in these patients, and to provide clinical evidence for the re-
B in pregnant and lying-in women. determination of ALT threshold in Chinese CHB patients.
Method: Pregnant women with chronic hepatitis B and high viral Method: From August 2022 onwards, a total of 607 treatment-naive
load (defined as HBV-DNA ≥ 1.0×105 IU/mL in the third trimester of patients with positive HBV-DNA and normal ALT levels were recruited
pregnancy) who received tenofovir disoproxil fumarate (TDF) or from six medical institutions to receive tenofovir alafenamide (TAF)
tenofovir alafenamide (TAF) for mother-to-child transmission prevention antiviral therapy. As of now, 265 patients have completed the 48-
in the third trimester of pregnancy and had regular consultations in week follow-up and clinical data collection. Changes in blood routine,
liver and kidney function, GPR, APRI, and FIB- 4, were assessed at week 12 had a sensitivity of 76.47% and a specificity of 72.55% for
baseline, 12, 24, and 48 weeks. The primary efficacy endpoint was predicting HBeAg SR.
achieving a complete virologic response (CVR), while secondary Conclusion: Baseline HBV RNA levels in HBeAg-positive CHB patients
endpoints included improvements in GPR, APRI, and FIB- 4. exhibited a significantly positive correlation with HBV DNA and HBsAg
Result: After TAF antiviral therapy, the rates of achieving HBV-DNA < levels, this correlation weakened following antiviral therapy. The serum
20 IU/mL at week 12, 24, and 48 were respectively 62.3% (203/326), HBV RNA level at the week 12 could serve as an early predictor for the
76.3% (219/287), and 86.0% (228/265), the difference between HBeAg SR in patients with CHB. HBeAg-positive CHB patients treated
groups was statistically significant (p< 0.001). At week 48, 15/57 with antiviral drug TAF showed a higher HBeAg SR rate compared to
(26.3%) patients achieved HBeAg serum clearance, and 5/49 (10.2%) ETV and TDF.
achieved HBeAb seroconversion. There was a significant decrease
from baseline in the level of ALT levels at week 48 (27.0 (18.0,36.0)
PP0167
vs. 22.0 (16.0,28.3), p< 0.001) and AST levels (24.0 (19.0,31.0) vs.
21.0 (18.5,25.5), p< 0.001), and there was a statistically significant Analysis of HBeAg Clearance Rates and Associated Factors in
decrease in the distribution interval of APRI for assessing liver fibrosis Treatment-Naïve HBeAg-Positive Chronic Hepatitis B Patients: A
(0.25 (0.22,0.42) vs. 0.26 (0.19,0.31), p< 0.001). It is noteworthy that Comparison Between Entecavir and Tenofovir Alafenamide.
GPR and FIB-4 levels generally exhibited a downward trend, FIB- 4 Yuliang Zhang1, Xin Wan1, Shipeng Ma1, Liang Wang1, Qian Liu1,
(1.00 (0.73,1.47) vs. 0.95 (0.72,1.32), p= 0.228), GPR (0.16 (0.11,0.24) Yulun Tang1, Shanfei Ge1
vs. 0.14 (0.10,0.22), p= 0.146). In subgroup analysis, there was a 1
The First Affiliated Hospital of Nanchang University
significant difference in the rate of CVR (92.9% vs. 81.0%, p= 0.006) Background: Chronic hepatitis B virus (HBV) infection is a major
and HBeAg clearance (41.7% vs. 22.2%, p= 0.015) between the global public health issue and a leading cause of complications such
low ALT group (ALT≤ 30 U/L for male and 19 U/L for female) and the as liver failure, liver cirrhosis (LC), and hepatocellular carcinoma
high ALT group (30-50 U/L for male and 19-30 U/L for female). The (HCC). In recent years, nucleos(t)ide analogs (NAs) have emerged
biochemical and fibrosis indicators the high ALT group showed varying as one of the first-line antiviral treatment strategies. These therapies
degrees of improvement. effectively inhibit HBV replication, improve the progression of liver
Conclusion: TAF antiviral therapy effectively reduces HBV-DNA levels fibrosis, and achieve favorable clinical outcomes. However, despite
and significantly improves inflammatory liver fibrosis in CHB patients these advances, the serum HBeAg seroconversion rate in HBeAg-
with ALT < ULN and HBV-DNA positive. positive chronic hepatitis B (CHB) patients remains relatively low.
Table and Figure:Figure 1.Efficacy assessment after 48-week treatment Method: A retrospective analysis was conducted on 138 chronic
by different ALT levels hepatitis B (CHB) patients who received at least 48 weeks of antiviral
Figure 2.Antifibrotic assessment after 48-week treatment treatment with entecavir (ETV) or tenofovir alafenamide (TAF). Patients
were divided into the ETV group (n=81) and the TAF group (n=57)
PP0166 based on the treatment regimen, with baseline clinical data balanced
using propensity score matching (PSM). At 48 weeks, patients were
linical value of serum HBV RNA in patients with chronic hepatitis
categorized into the HBeAg clearance group (n=23) and the HBeAg
B during antiviral therapy
non-clearance group (n=91) based on serum HBeAg levels.
Xiaojing Zhang1, Fengmin Lu2, Rui Wu1, Qiaofei Jin1, Yijun Zhou1, Result: 1, At week 48, the HBeAg clearance rate in the TAF group was
Chen Wang1, Huaguo Shao3, Shourong Liu1 significantly higher than in the ETV group (28.00% vs. 13.00%, χ² =
1
Department of Hepatology, Hangzhou Xixi Hospital, Hangzhou 4.412, P = 0.036).
Xixi Hospital Affiliated to Zhejiang Chinese Medical University, 2, Univariate analysis revealed that baseline HBV DNA (Z = -2.039,
2
Department of Microbiology and Infectious Disease Center, School P = 0.041), HBeAg levels (Z = -3.792, P < 0.001), HBsAg levels (Z
of Basic Medical Sciences, Peking University Health Science Center,
= -2.814, P = 0.005), treatment regimen (ETV/TAF) (χ² = 4.412, P =
3
Institute of Hepatology and Epidemiology, Hangzhou Xixi Hospital,
0.036), and age (χ² = 5.812, P = 0.016) were significantly associated
Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical
with HBeAg clearance.
University
3, Multivariate logistic regression analysis identified baseline HBeAg
Background: The correlation between hepatitis B virus (HBV) RNA, level (OR = 0.428, 95% CI = 0.223–0.820, P = 0.011), treatment
HBV DNA and HBsAg (hepatitis B surface antigen) during antiviral regimen (OR = 0.205, 95% CI = 0.060–0.702, P = 0.012), and age (OR
treatment and whether the detection of HBV RNA can be used to = 10.621, 95% CI = 2.583–43.683, P = 0.001) as independent factors
determine virological response and discontinue the treatment, are for HBeAg clearance.
still unknown. This study was to investigate the clinical significance 4, The area under the ROC curve for baseline HBeAg level predicting
of quantitative detection of HBV RNA in patients with HBeAg-positive HBeAg clearance was 0.757, with a cut-off value of 2.389 (log10 IU/
(hepatitis B e antigen) chronic hepatitis B (CHB) receiving antiviral mL), sensitivity of 61.5%, and specificity of 82.6%.
therapy, and to clarify its role in predicting HBeAg seroconversion (SR) 5, Kaplan-Meier analysis showed that patients aged <30 years, treated
in CHB patients. with TAF, and with baseline HBeAg <2.389 (log10 IU/mL) had higher
Method: A total of 138 patients with HBeAg-positive CHB who were cumulative rates of HBeAg clearance (P < 0.05).
newly diagnosed from January 2022 to December 2022 were enrolled Conclusion: In treatment-naïve HBeAg-positive CHB patients.
in this study. The patients were divided into the HBeAg SR group and 1, 48 weeks of TAF therapy resulted in a higher HBeAg clearance
the non-seroconversion (NSR) group. The dynamic changes and rate than ETV therapy. 2, Age <30 years and baseline HBeAg <2.389
correlations between HBV RNA, HBV DNA, HBsAg and HBeAg was (log10 IU/mL) independently predicted HBeAg clearance.
analyzed between the two groups and the predictive values of them Table and Figure:Figure 1.Table1 Baseline characteristics of the study
for HBeAg SR were calculated. population before and after propensity score matching
Result: The HBeAg SR rate was 23.9% (33/138), patients treated Figure 2.Table2 Clinical outcomes after 48 weeks of treatment
with TAF had higher SR rate than others (P < 0.001). The serum HBV
RNA levels of SR group decreased significantly after antiviral therapy
than in the NSR group. Baseline HBV RNA levels were significantly PP0168
correlated with HBV DNA, HBsAg and HBeAg in both groups, but GGT to PLT Ratio Rredicts Progression of Liver Fibrosis in NAs-
weakened after antiviral therapy. Univariate and multivariate regression treated Chronic Hepatitis B Patients with Advanced Fibrosis in
analysis showed that the serum HBV RNA levels at week 12 was an Combination with PEG-IFN α Therapy
independent predictor of HBeAg SR. The area under the receiver Ling Li1, Xia Wang2, Huili Li1, Yiru Zhao1, Guangde Yang2, Juanjuan
operating characteristic curve (AUROC) of the serum HBV RNA levels Fu2, Li Li2, Guojun Li3, Xiuchen Pan2
at week 12 had a higher value (AUROC = 0.8039, 95% CI: 0.691- 1
Xuzhou Medical University, 2The Affiliated Hospital Of Xuzhou
0.917). The cut off value of HBV RNA level with 5.68 lg copies/ml at Medical University, 3Shenzhen Third People’s Hospital
Background: Although antiviral treatment with nucleos(t)ide analogs ACHBLF patients in the developed model group The survival rate
(NAs) alone or combination with Peg‐IFNα can lead to regression curve of the patients with HBV-related ACLF in the developed model
of liver fibrosis or cirrhosis in chronic hepatitis B (CHB) patients, a group showed that the survival rate decreased significantly from day 1
substantial proportion of patients still fail in improvement of fibrosis. to day 100 and then plateaued, which means that the survival condition
The purpose of this study is to evaluated predictors of liver fibrosis within 100 days has important clinical significance. We speculate that
progression after PEG-IFN α add-on therapy in NAs-treated CHB patients with liver failure have large damage to liver cells, a huge
patients with advanced fibrosis. amount of toxin accumulation, and poor regeneration ability of liver
Method: A retrospective study was performed on NAs-treated cells. Thus, the liver may need around 100 days to regenerate to a
CHB patients with advanced liver fibrosis or compensated cirrhosis certain extent and restore the corresponding functions, which improve
in combination with PEG-IFNα therapy at two centers in china from liver function and tend to stabilize vital signs.
January 1st, 2019 to December 31st, 2022. All enrolled patients Figure 2.Figure 2. ROC curve Theoretically, an area under the curve
received PEG-IFN α treatment for 48 weeks and were followed up for (AUC) greater than 50% suggests the model utility, and greater than
24 weeks. Hepatic histopathologic examination, transient elastography, 70% indicates moderate utility.
and liver imaging were employed to evaluate the fibrosis changes in
patients before the initiation of interferon therapy and 24 weeks after PP0170
the completion of therapy. The primary endpoint was to assess the
outcome of liver fibrosis at 24 weeks after treatment, and the secondary The impact of metabolic dysfunction-associated steatotic liver
endpoints were to evaluate the seroclearance of HBsAg, change of disease on the efficacy of pegylated interferon treatment in
liver function indicators and adverse reactions. chronic hepatitis B: A real-world study
Result: A total of 102 patients were included in the study, with Jiaxin Han1, Liu Yang1, Wentao Kuai2, Yuqiang Mi2, Liang Xu2
35 HBeAg-positive and 67 HBeAg-negative patients at baseline 1
Clinical School of the Second People‘s Hospital, Tianjin Medical
respectiviely. At 24 weeks after the endpoint of PEG-IFN α treatment, University, Tianjin 300192, China, 2Tianjin Institute of Hepatology,
69 patients completed the comparison of liver fibrosis before and after Tianjin Second People’s Hospital, Tianjin 300192, China
treatment. Among them, 16 patients (23.2%) showed progression of Background: The impact of metabolic dysfunction-associated
liver fibrosis, 32 patients (46.4%) showed regression of liver fibrosis, steatotic liver disease (MASLD) on the efficacy and prognosis of
and 21 patients (30.4%) remained stable. At 48 weeks of PEG-IFNα pegylated interferon (Peg-IFN)-based antiviral therapy in chronic
treatment, 18 (17.6%) patients achieved HBsAg seroclearance, and hepatitis B (CHB) patients remains controversial and requires further
23/35 (65.7%) of patients achieved HBeAg loss. Logistic multivariate investigation.
regression analysis indicated that GGT (OR = 1.020; 95% CI: 1.005- Method: This study included 319 CHB patients who received Peg-IFN-
1.035; P = 0.010), PLT (OR = 0.974; 95% CI: 0.950-0.999; P = 0.044), based antiviral therapy at the Hepatology Department of Tianjin Second
GPR (OR = 15.56; 95% CI: 2.237-112.801; P = 0.006) at 24 weeks People’s Hospital between July 2020 and June 2024. The baseline was
of PEG-IFNα treatment were independent predictive factors for liver defined as the start of Peg-IFN antiviral therapy, and patients were
fibrosis progression. followed up every 3–6 months. Antiviral efficacy, biochemical markers,
Conclusion: Nearly 23% of NAs-treated CHB patients with advanced and lipid metabolism data were compared between the two groups
liver fibrosis in combination with PEG-IFN α treatment experienced at baseline and at each follow-up visit. Factors influencing complete
progression of liver fibrosis. GGT to PLT ratio could predict progression virological response (CVR) were identified, and a prediction model
of liver fibrosis at 24 weeks of PEG-IFN α treatment. for HBsAg clearance was constructed using LASSO-COX regression
Table and Figure:Figure 1.The patients flowchart. analysis.
Figure 2.ROC curves for using the PLT,GGT and GPR index in Result: After propensity score matching (1:1) based on sex and pre-
predicting hepatic fibrosis progression. treatment cirrhosis status, both groups consisted of 132 patients.
During the Peg-IFN antiviral therapy, at the 3, 6, 12 months, end of
PP0169 treatment, and end of follow-up, patients with MASLD showed lower
reductions in HBV DNA, HBsAg, and CVR rates compared to the CHB
A Model to Estimate Survival in Hepatitis B Virus-Related Acute-
group at all follow-up points. The median time to first achieving CVR
on-Chronic Liver Failure Based on Dynamic Changes in Objective
was significantly longer in the MASLD group (5.7 vs 4.4 months, P =
Parameters
0.010), though there was no significant difference in the median time
RUI ZHOU1 to HBsAg clearance between the two groups (20.9 vs 23.0 months,
1
Meng Chao Hepatobiliary Hospital, Fujian Medical University P = 0.928). Multivariate regression analysis revealed that male sex
Background: We aimed to develop a survival model for patients (HR: 0.377, 95% CI: 0.202–0.703, P = 0.002), MASLD comorbidity
with HBV-related ACLF based on dynamic changes in the values of (HR: 0.609, 95% CI: 0.395–0.937, P = 0.024), high HBsAg levels at 3
objective parameters. months of treatment (HR: 0.738, 95% CI: 0.621–0.877, P < 0.001), and
Method: This analysis was based on 714 patients (derivation cohort high baseline HBV DNA levels (HR: 0.610, 95% CI: 0.481–0.773, P <
and validation cohort) with HBV-related ACLF who were hospitalized 0.001) significantly hindered the occurrence of CVR. A LASSO-COX
for more than 7 days in Mengchao Hepatobiliary Hospital of Fujian regression model for predicting HBsAg clearance in non-responding
Medical University. Multivariable proportional hazards models and populations was established, including baseline HBsAg levels,
corresponding risk scores were created based on demographic HBsAg decline at 3 months, baseline AST levels, and HBeAg status
characteristics and dynamic changes in the values of objective at 3 months. In both the training and validation sets, the C-index (both
parameters. The validity of the new model was compared with the >0.8) and time-dependent AUC (both >0.8) demonstrated strong
Model for End-stage Liver Disease (MELD). discriminatory power. Calibration curves and decision curve analysis
Result: The survival model incorporated age, international normalized showed that the model had good consistency and clinical applicability.
ratio (INR), Δ INR, Δ platelet (PLT) count, and levels of serum albumin At the end of the follow-up, three patients with MASLD progressed to
(ALB), ΔALB, serum total bilirubin (TBIL), serum natrium (Na+), serum cirrhosis, while only one patient in the CHB group did; however, no
alpha-fetoprotein (AFP), and Δ serum creatinine (Cr). The area under patient in either group progressed to hepatocellular carcinoma.
the curve (AUC) for the new model (0.791) was superior to that for Conclusion: The presence of MASLD significantly prolonged the
MELD (0.579). The optimal cutoff for the new model was −4.98, with a median time for CHB patients to achieve CVR during Peg-IFN-based
sensitivity of 80.6% and specificity of 72.4%. antiviral therapy. The predictive nomogram for HBsAg clearance
Conclusion: The new model for predicting the survival of patients demonstrated high efficacy and stability.
with HBV-related ACLF based on dynamic changes in the values of Table and Figure:Figure 1.Virological and serological responses in
objective parameters was valid and superior to the MELD scoring the MASLD-CHB group and CHB group, and the construction of a
system. predictive model for HBsAg clearance in non-responding populations.
Table and Figure:Figure 1.Figure 1. The survival rate curve of the
 PP0171 Result: Among the 117 patients with HBsAg / anti-HBs double
From Guidelines to Practice: Assessing the 2022 CHB Guidelines positive, the proportions of males and females were 61.54 % and
in Clinical Use 38.46 %, respectively. The positive rate of HBV DNA and HBeAg in 125
positive patients were significantly higher than those in 25 positive and
Xiao Zhong1,2, Ruochan Chen1,2, Zebing Huang1,2, Jun Chen1,2, Yan
15 positive patients, and the liver fibrosis-related indexes PIIIP and LN
Huang1,2
were significantly higher than those in 15 positive patients. In addition,
1
Department of Infectious Diseases, Hunan Key Laboratory of Viral after grouping the double-positive patients according to different
Hepatitis, Xiangya Hospital, Central South University, 2National Clinical
indicators, the serum liver fibrosis-related indicators in 125 positive
Research Center for Geriatric Disorders, Xiangya Hospital, Central
patients with abnormal liver enzyme ALT or AST were significantly
South University
higher than those in patients with normal liver enzyme, and the content
Background: To align with the WHO’s goal of eliminating viral hepatitis of HBeAg was also significantly increased. In the serum of HBV DNA
by 2030 and enhance the management of chronic hepatitis B (CHB) positive 125 positive patients, the content of HBsAg and HBeAg was
in China, the Guidelines for the Prevention and Treatment of CHB were significantly higher than that of HBV DNA negative group. And the
updated in 2022. This study aimed to assess the familiarity of clinical platelet count and HBV DNA positive rate of 125 positive patients with
physicians with the updated guidelines, evaluate their implementation HBsAg ≥ 1000 IU / ml were significantly higher than those in the control
in clinical practice, and identify unresolved clinical issues. group. The serum fibrosis index PIIIP and positive rate of HBV DNA
Method: A survey was conducted among attending and senior doctors in HBeAg positive 125 positive patients were significantly higher than
working in outpatient clinics across 49 hospitals in Hunan Province. those in HBeAg negative patients, while the age was significantly lower
The questionnaire gathered basic demographic information about the than that in HBeAg negative patients. Finally, after correlation analysis
respondents and their clinical practices based on the 2022 edition of of serum indexes in 125 positive patients, it was found that HBsAb
the Chinese Guidelines for CHB. in the serum of 125 positive patients was positively correlated with
Result: By November 16, 2024, a total of 225 valid questionnaires other liver fibrosis indexes except for PIIIP, and the significance was
were collected. Among the respondents, 95.56% were over 30 years statistically significant.
old and 40.89% had more than 20 years of clinical experience. 57.33% Conclusion: The liver fibrosis indexes of chronic hepatitis B patients
of clinicians received more than 50 outpatient visits per week. 53.33% with the coexistence of HBsAg / anti-HBs are significantly higher than
of them had over half their patients diagnosed with hepatitis B and those of the control group, suggesting that the continuous development
73.78% saw more than 5 newly diagnosed or untreated patients of the serotype model may indicate the poor prognosis of the disease.
weekly. Most respondents had reviewed the updated guidelines and Attention should be paid to the clinical treatment and management of
understood the differences in antiviral treatment indications between such group.
the 2019 and 2022 editions. However, 58.22% reported not fully
adhering to the 2022 guidelines for antiviral treatment indications.
Reasons for non-adherence included patient refusal to initiate PP0173
treatment, comprehensive assessment of liver fibrosis, family history Safety and efficacy profiles of Tenofovir amibufenamide fumarate
and other clinical factors, economic constraints, and concerns about and Entecavir in treatment-naïve patients with chronic hepatitis B:
patient compliance. Furthermore, approximately 50% of physicians A comparative assessment
stated that fewer than half of newly diagnosed or previously untreated Shipeng MA1, Liang Wang1, Yuliang Zhang1, Xin Wan1, Qian Liu1,
patients meeting treatment indications began therapy within three YUlun Tang1, Shanfei Ge1
months. Additionally, 54.22% indicated that it usually required two or 1
The First Affiliated Hospital of Nanchang University
more visits to effectively communicate with patients and recommend
Background: Hepatitis B virus (HBV) infection is prevalent worldwide,
initiating antiviral therapy. A significant barrier identified by 90.22% of
with the risk of long-term HBV infection progressing to cirrhosis, liver
physicians was patients’ reluctance to initiate long-term medication,
failure, and hepatocellular carcinoma. Early antiviral treatment is
which was seen as the primary factor influencing treatment decisions.
particularly crucial. As the indications for antiviral therapy expand, the
Notably, there was no consensus on the ALT threshold for initiating
population of patients with chronic hepatitis B undergoing long-term
antiviral therapy, and 15.11% of respondents expressed confusion or
antiviral treatment continues to grow, making the selection of a safe
raised questions about the guidelines during clinical practice.
and effective antiviral regimen essential. Tenofovir amibufenamide
Conclusion: Nearly two years after the release of the 2022 edition of
(TMF) is an original research drug in China, but it lacks real-world
the Guidelines, the survey demonstrates a high level of acceptance
studies on safety and efficacy.
among clinicians. However, adherence to the guidelines remains
Method: A retrospective analysis was conducted on the clinical data of
suboptimal. Moving forward, efforts should prioritize clarifying the
187 treatment-naïve CHB patients who received TMF or ETV for at least
ALT treatment threshold, improving patient communication strategies,
48 weeks from June 2021 to October 2024 at the Infectious Disease
and expanding access to timely antiviral therapy to enhance clinical
Outpatient Department. Patients were divided into the TMF group
outcomes and contribute to achieving hepatitis B elimination goals.
(n=48) and the ETV group (n=139) based on their antiviral medication.
Propensity Score Matching (PSM) was applied at a 2:1 ratio to balance
PP0172 baseline clinical characteristics. Changes in estimated Glomerular
Analysis of the Correlation between HBsAg and HBsAb Double Filtration Rate (eGFR), blood lipids, liver function, and virological
Positive and Liver Fibrosis in Patients with Chronic Hepatitis B markers at 48 weeks were observed and compared between the two
Futing Liu1 groups. Continuous variables were compared using independent
samples t-tests or Mann-Whitney U tests, while categorical variables
1
The Second Affiliated Hospital of Anhui Medical University
were assessed using chi-square tests or Fisher’s exact tests.
Background: Hepatitis B virus ( HBV ) is a hepatotropic DNA virus, Result: After PSM matching, 48 patients in the TMF group and 96 in
which is the main cause of chronic hepatitis B, cirrhosis, and liver the ETV group were included. At baseline, there were no statistically
cancer. At present, about 254 million people worldwide suffer from significant differences in clinical characteristics between the TMF and
hepatitis B. HBV infection affects more than 290 million people ETV groups (P>0.05). The baseline eGFR values were 111.83 ml/
worldwide, and there are 1.5 million new infections every year. The min/1.73 m2 for the TMF group and 112.50 ml/min/1.73 m2 for the ETV
lifetime risk of cirrhosis in HBV carriers is 15 % to 40 %, which poses a group (t=-0.370, P=0.712). At 48 weeks, both groups experienced
great burden on global public health. a decrease in eGFR from baseline, with the ETV group showing a
Method: The clinical serum samples and medical records of 117 significantly lower eGFR than the TMF group (106.10 ml/min/1.73
patients with HBsAg / anti-HBs double-positive chronic hepatitis B m2 vs 111.01 ml/min/1.73 m2), which was statistically significant
were collected from November 2022 to February 2024 in the Second (t=-2.367, P=0.019). In terms of blood lipids, at 48 weeks, the TMF
Affiliated Hospital of Anhui Medical University, Shushan District, Hefei group showed an increase in triglycerides and total cholesterol from
City, and their clinical data and characteristics were analyzed. baseline, while the ETV group had an increase in triglycerides and a
decrease in cholesterol, with no significant differences between the and osteoporosis should consider switching to entecavir (ETV) or
groups at 48 weeks (P>0.05). Regarding liver function, both groups tenofovir alafenamide fumarate (TAF) for antiviral therapy. However,
had a decrease in ALT and AST levels from baseline, with no significant regarding the two medications ETV and TAF, whether there is a
differences between groups at 48 weeks (P>0.05). Similarly, there significant difference in the risk of renal injury remains undetermined.
were no significant differences in HBV-DNA negativity rates and Method: A retrospective analysis was performed for the clinical data
HBeAg negativity rates at 48 weeks between the two groups (P>0.05). of 167 previously untreated CHB patients who received ETV or TAF
No patients in either group had HBsAg seroconversion by 48 weeks. treatment for at least 48 weeks, they were divided into ETV group
Conclusion: In treatment-naïve CHB patients, ETV treatment was with 117 patients and TAF group with 50 patients. In order to balance
associated with a higher risk of renal impairment at 48 weeks compared baseline clinical data, propensity score matching (PSM) was used
to TMF, with no significant differences in blood lipids or therapeutic for matching and analysis at a ratio of 2:1, and the two groups were
efficacy. compared in terms of estimated glomerular filtration rate (eGFR) and
Table and Figure:Figure 1.Table 1 Comparison of baseline clinical data the incidence rate of abnormal renal function at week 48. According to
and characteristics before and after propensity score matching in eGFR at week 48, the patients were divided into normal renal function
patients with chronic hepatitis B in the two groups group and abnormal renal function group. The multivariate Logistic
Figure 2.Table 2 Comparison of 48-week clinical data between the two regression analysis was used to investigate the influencing factors
groups of patients with chronic hepatitis B for abnormal renal function, and the receiver operating characteristic
(ROC) curve was used to assess the performance of each indicator in
predicting abnormal renal function.
PP0174
Result: After PSM matching, there were 100 patients in the ETV group
Characteristics and factors affecting serum HBV RNA in chronic and 50 patients in the TAF group. There were no significant differences
hepatitis B patients achieving complete virological response after in baseline clinical data between the ETV group and the TAF group.
nucleoside analogues therapy. There was a reduction in eGFR from baseline to week 48 in both
Juanli Wu1, Yushuang Zhang1, Han Gao1, Yiheng Zhang1, Lei Wang1, groups, and compared with the TAF group at week 48, the ETV group
Yundong Qu1, Tao Li1 had a significantly lower eGFR and a significantly higher incidence rate
1
the second hospital of shandong university of abnormal renal function. After the patients were divided into normal
Background: The study demonstrates that hepatitis B virus renal function group with 131 patients and abnormal renal function
pregenomic RNA( HBV RNA) indicates the replication activity of group with 19 patients, the multivariate Logistic regression analysis
covalently closed circular DNA ( cccDNA) in hepatocytes. We aimed to showed that baseline eGFR and treatment drug were independent
examine the factors and characteristics correlated with the persistence influencing factors for abnormal renal function. Baseline eGFR had
of (HBV RNA) despite achieving complete virologic response in an area under the ROC curve of 0.781 in predicting abnormal renal
chronic hepatitis B(CHB) and HBV-related cirrhotic patients treated function in CHB patients, with a cut-off value of 105.24 mL/min/1.73
with nucleos(t)ide analogues (NAs). m2.
Method: The study was cross-sectional and involved 360 patients Conclusion: For CHB patients initially treated with ETV or TAF, ETV
with CHB and 149 patients with CHB ralated cirrhosis. Simultaneous antiviral therapy has a higher risk of renal injury than TAF therapy at
amplification and testing(SAT) was used to detect serum HBV RNA week 48.
levels. Multivariable logistic regression analysis was employed to Table and Figure:Figure 1.Table 1 Comparison of baseline clinical data
ascertain factors associated with detectable serum HBV RNA. and characteristics before and after propensity score matching in
Result: In 509 patients treated with nucleos(t)ide analogs (NAs), patients with chronic hepatitis B in the two groups
serum HBV RNA was detectable in 335 individuals. Among these, the Figure 2.Table 2 Comparison of 48-week clinical data between patients
positivity rate for serum HBV RNA was significantly higher in HBeAg- in the ETV and TAF groups
positive patients, at 94.6% (157 out of 166), compared to 51.9% (178
out of 343) in HBeAg-negative patients (p <0.001). Additionally, HBV PP0176
RNA-positive patients exhibited elevated HBsAg levels, with a mean of
Functional Cure of Hepatitis B in Recipients with Chronic Hepatitis
3.1 (2.6, 3.6) log10 IU/mL (p <0.001). Multivariable logistic regression
B Following Allogeneic Hematopoietic Stem Cell Transplantation
analysis showed cirrhosis (OR=2.21, 95% CI: 1.37~3.59, p =0.001),
Therapy
HBeAg positivity (OR=14.49, 95% CI: 7.04~29.81, p <0.001) as well
as serum HBsAg >2.56log10IU/mL (OR=2.58, 95% CI: 1.62 to 4.13, p Qiannan Wang1, Yushan Liu1, Qijuan Zang1, Qiao Zhang1, Pan
<0.001) were associated with measurable serum HBV RNA. Huang1, Yamin Wang1, Yingli He1,2,3
Conclusion: In patients achieving a complete virologic response after
1
Department of Infectious Diseases, the First Affiliated Hospital of
NAs therapy, cirrhosis, HBeAg positivity, and elevated HBsAg levels Xi’an Jiaotong University, 2Institution of Hepatology, The First Affiliated
are associated with detectable HBV RNA. Detecting HBV RNA in these Hospital of Xi‘an Jiaotong University, 3Shaanxi Clinical Research
Center for Infectious Diseases
patients helps assess intrahepatic viral transcriptional activity and
replication status. Background: Allogeneic haematopoietic stem cell transplantation
Table and Figure:Figure 1.Figure1 (allo-HSCT) has the potential to modify hepatitis B virus (HBV)
Figure 2.Table1-2 reservoirs among patients with chronic HBV infection. However,
data regarding the mechanisms underlying this alteration have only
been partially reported. In this study, our objective was to delineate
PP0175
the hepatitis B virus surface antigen (HBsAg) seroclearance and the
Changes in renal function in chronic hepatitis B patients treated dynamics of HBsAg, which is a virological marker of HBV persistence,
initially with entecavir versus tenofovir alafenamide fumarate and following allo-HSCT.
related influencing factors Method: A retrospective study was meticulously conducted,
Shipeng MA1, Liang Wang1, Yuliang Zhang1, Xin Wan1, Qian Liu1, incorporating a decade - long dataset of allo - HSCT patients from
Yulun Tang1, Shanfei Ge1 our medical centers. Patients presenting with positive HBsAg were
1
The First Affiliated Hospital of Nanchang University carefully screened. During the follow-up period, the quantitative
Background: Hepatitis B virus (HBV) infection continues to be a outcomes of serum HBsAg were tested every 3 months or on demand
significant global public health challenge. The nucleos(t)ide analogues to identify the occurrence of HBsAg seroclearance.
(NAs) widely used in clinical practice, particularly tenofovir disoproxil Result: Ultimately, a total of 15 recipients with hematological
fumarate (TDF), have been associated with the risks of osteoporosis malignancies and positive HBsAg who had undergone allo-HSCT
and renal impairment. Consequently, guidelines recommend that were included in the study, with a median follow-up period of 48.9
patients with chronic hepatitis B (CHB) who are at risk of renal damage months. Twelve patients received prophylactic antiviral therapy prior
to allo-HSCT. The cumulative incidence of HBsAg seroclearance was
found to be 13.3% (2 out of 15), with HBsAg clearance achieved at with histological severity (e.g., G stage, r = 0.757 and 0.688,
6 months and 12 months post-allo-HSCT. Additionally, three patients respectively; both p < 0.0001) and retained diagnostic performance
exhibited a decline in HBsAg levels greater than 1 log. Among the independent of ALT. ROC curve analysis identified CK18-M65 (AUC:
three patients who did not receive prophylactic antiviral therapy, one 0.933) and CK18-M30 (AUC: 0.872) as the most effective standalone
experienced HBV reactivation nine months following the procedure. biomarkers for detecting significant liver pathology in “IT” patients.
Furthermore, one patient developed liver cancer at the 24-month mark. In the “IC” group, 46% (116/253) exhibited significant liver pathology,
No significant differences were observed between patients receiving with CK18-M65, CK18-M30, and GP73 levels elevated in the G and/
prophylactic antiviral therapy and those who did not regarding the or S ≥ 2 group compared to “True IC” patients. However, weaker
incidence of HBsAg loss during the observation period (16.67% vs. correlations with disease severity and lower diagnostic performance
0%, p > 0.05). Moreover, we meticulously illustrated the dynamics of precluded further IC-specific analysis. Machine learning models for
quantitative results for HBV DNA and HBsAg levels in patients with IT patients incorporating CK18-M65 and CK18-M30 combinations
positive HBsAg following allo-HSCT. achieved superior diagnostic performance (AUC: 0.884–0.956)
Conclusion: Patients with hematological malignancies and HBV compared to APRI (AUC: 0.807) and FIB-4 (AUC: 0.796), with all
infection, who are subjected to treatment regimens based on allo - p-values < 0.0001. Decision curve analysis reinforced the clinical utility
HSCT, may potentially exhibit HBsAg loss. It is of utmost importance of these biomarker-based models over conventional methods.
to conduct close and continuous monitoring of the dynamics of HBV Conclusion: Novel biomarkers, especially CK18-M65 and M30,
markers. demonstrated robust potential for rapid, non-invasive diagnosis of
Table and Figure:Figure 1.Quantitative HBsAg in blood. (A) The detailed significant liver pathology among “IT” CHB infected patients with
quantitative HBsAg; The grey vertical line represents the allo-HSCT normal liver function indicators. These biomarkers closely aligned with
date. (B) Pairwise comparison of quantitative HBsAg for patients with liver biopsy results and could serve as promising auxiliary diagnostic
from before allo-HSCT to the last follow-up date. allo-HSCT, allogeneic tools for early risk stratification and intervention in CHB management.
haematopoietic stem-cell transplantation. Table and Figure:Figure 1.Figure 1. Flowchart of patient recruitment and
Figure 2.Fig. 2 The detailed quantitative HBsAg of 15 patients; The study design. From multiple centers, 3258 CHB case were screened,
grey vertical line represents the allo-HSCT date. A-O present the of which 137 “Presumed IT” and 253 “Presumed IC” treatment-naïve
quantitative HBsAg in patients No. 1-15, respectively. HBsAg, hepatitis patients were included for novel biomarker investigation.
B virus surface antigen; allo-HSCT, Allogeneic haematopoietic stem Figure 2.Figure 2. Distribution patterns and diagnostic performance
cell transplantation; ETV, entecavir; TDF, tenofovir disoproxil fumarate; of novel biomarkers for significant liver pathology in “Presumed IT
TAF, tenofovir alafenamide fumarate; LdT, telbivudine. Phase” CHB patients. (A) Boxplots and correlations of CK18-M30,
CK18-M65, GP73, IL-10, and IL-2R with liver pathology stages. ROC
curves indicate the diagnostic performance of standalone biomarkers.
PP0177
(B) ROC curves comparing CK18-M65+M30-based machine learning
Novel Biomarkers for Non-Invasive Diagnosis of Significant Liver models with conventional non-invasive parameters for diagnosing
Pathology in Immune-Tolerant Chronic Hepatitis B Infection significant liver pathology. (C) Decision curve analysis (DCA)
Xinjie Li1, Meijie Shi2, Feng Guo3, YingJie Qi4, Ming Lin2, Xiaoling Liu5, demonstrating the net benefit of different diagnostic approaches
Pengyuan Kang1, Yuqi Zhang1, Shanshan Ji6, Yizhong Hu6, Jinbao across threshold probabilities.
Huang6, Hui Zhuang1, Xihong Wang6, Xiaozhong Wang3, Xiaoling
Chi2, Tao Shen1
PP0178
1
Department of Microbiology and Infectious Disease Center, School
of Basic Medical Sciences, Peking University, 2Department of Functional Cure of Hepatitis B in Recipients with Chronic Hepatitis
Hepatology, The Second Affiliated Hospital of Guangzhou University B Following Allogeneic Hematopoietic Stem Cell Transplantation
of Chinese Medicine, Guangdong Provincial Hospital of Chinese Therapy
Medicine, 3Department of Liver Disease, Traditional Chinese Medicine Qiannan Wang1, Yushan Liu1, Qijuan Zang1, Qiao Zhang1, Pan
Hospital Affiliated to Xinjiang Medical University, 4Department of Huang1, Yamin Wang1, Chengbin Zhu1, Yingli He1,2,3
Laboratory Medicine, Infection Hospital Area of the First Affiliated 1
Department of Infectious Diseases, the First Affiliated Hospital of
Hospital of University of Science and Technology of China (Hefei Xi’an Jiaotong University, 2Institution of Hepatology, The First Affiliated
Infectious Disease Hospital), 5Department of infectious diseases, Hospital of Xi‘an Jiaotong, 3Shaanxi Clinical Research Center for
People’s Hospital of Chizhou, 6Department of Laboratory Medicine, Infectious Diseases
People’s Hospital of Chizhou
Introduction:
Background: Chronic hepatitis B (CHB) poses a persistent global Allogeneic haematopoietic stem - cell transplantation (allo - HSCT) has
health challenge. Patients in the immune-tolerant (IT, HBeAg+) the potential to modify hepatitis B virus (HBV) reservoirs among patients
and inactive carrier (IC, HBeAg-) phases, despite normal alanine with chronic HBV infection. However, data regarding the mechanisms
aminotransferase (ALT) levels, harbor a risk of significant but hidden underlying this alteration have only been partially reported. In this
liver pathology. This study investigated CK18-M30, CK18-M65, GP73, study, our objective was to delineate the hepatitis B virus surface
IL-10, and IL-2R as potential non-invasive biomarkers for identifying antigen (HBsAg) seroclearance and the dynamics of HBsAg, which is
significant liver pathology (G and/or S ≥ 2) among these populations. a virological marker of HBV persistence, following allo - HSCT.
Method: This multi-center cohort study enrolled 3,258 CHB cases from Case presentation:
four hospitals (2013–2023), stratified in accordance with the 2024 WHO A retrospective study was meticulously conducted, incorporating a
and 2017 EASL guidelines. A total of 137 patients in the “Presumed decade - long dataset of allo - HSCT patients from our medical centers.
IT Phase” and 253 in the “Presumed IC Phase”, all treatment-naïve, Patients presenting with positive HBsAg were carefully screened.
were included for analysis. Liver biopsy served as the gold standard During the follow-up period, the quantitative outcomes of serum HBsAg
for pathology, and multiple serum biomarkers were quantitatively were tested every 3 months or on demand to identify the occurrence
assessed. For “IT” patients, 16 biomarker combinations centered on of HBsAg seroclearance. Ultimately, a total of 15 recipients with
CK18-M65 were developed and validated using 9 machine learning hematological malignancies and positive HBsAg who had undergone
models for non-invasive detection of significant liver injury. allo-HSCT were included in the study, with a median follow-up period
Result: Among “IT” patients, approximately 45% (62/137) demonstrated of 48.9 months. Twelve patients received prophylactic antiviral therapy
significant liver pathology (G and/or S ≥ 2). Compared with “True IT” prior to allo-HSCT. The cumulative incidence of HBsAg seroclearance
patients (G and S < 2), those with significant pathology were older, was found to be 13.3% (2 out of 15), with HBsAg clearance achieved
had higher BMI, near-upper-normal ALT/AST levels, elevated HBsAg, at 6 months and 12 months post-allo-HSCT. Additionally, three patients
and lower HBV DNA levels. Novel biomarkers including CK18-M65, exhibited a decline in HBsAg levels greater than 1 log. Among the
CK18-M30, GP73, IL-10, and IL-2R were substantially elevated. Among three patients who did not receive prophylactic antiviral therapy, one
these, CK18-M65 and CK18-M30 exhibited the strongest correlations experienced HBV reactivation nine months following the procedure.
Furthermore, one patient developed liver cancer at the 24-month mark. No Causal Relationship Between Chronic Hepatitis B and Anxiety
No significant differences were observed between patients receiving or Depression: A Mendelian Randomization Study
prophylactic antiviral therapy and those who did not regarding the Cunliang Deng 1, Xiaozhou Mao2, Xiaoling Liu1
incidence of HBsAg loss during the observation period (16.67% vs. 1
Department of Infectious Diseases, The Affiliated Hospital, Southwest
0%, p > 0.05). Moreover, we meticulously illustrated the dynamics of Medical University,, 2Department of Infectious Diseases, The Affiliated
quantitative results for HBV DNA and HBsAg levels in patients with Hospital, Southwest Medical University
positive HBsAg following allo-HSCT. Patients with hematological
Background: Previous research suggests a potential link between
malignancies and HBV infection, who are subjected to treatment
chronic hepatitis B (CHB) and anxiety or depression, but the causal
regimens based on allo - HSCT, may potentially exhibit HBsAg loss. It
relationship remains uncertain. This study aims to clarify the causal
is of utmost importance to conduct close and continuous monitoring of
relationship between CHB and anxiety or depression using Mendelian
the dynamics of HBV markers.
randomization (MR) analysis.
Method: This study utilizes publicly available GWAS summary data to
PP0179 assess the causal relationship between CHB and anxiety or depression
Does metabolic-related fatty liver disease speed up the progress using MR analysis. Additionally, MR-PRESSO was employed to detect
of liver fibrosis in patients with chronic hepatitis B ? outliers, MR-Egger for intercept testing, and Cochran’s Q test to
Li Ying Guo1, Quan Wei Xu2, Hui Sun1, Ao Chen2, Jia Wen Shang2, Xi evaluate the heterogeneity among instrumental variable SNPs.
Liang Wu1, Jie Zhao1, Jing Miao1 Result: This study selected three SNPs (rs114077552, rs114351943,
rs499606) as instrumental variables to assess the causal association
1
Tianjin Second People‘s Hospital, 2Tianjin University of TCM
between CHB and anxiety, and four SNPs (rs114077552, rs114351943,
Background: This study aims to analyze the liver fibrosis in patients rs499606, rs28826696) to evaluate the causal relationship between
with chronic hepatitis B (CHB) who also have metabolic related fatty CHB and depression. Furthermore, the results indicate that the causal
liver disease (MAFLD). association between CHB and anxiety is not statistically significant.
Method: A retrospective study was conducted on 192 individuals The odds ratios (OR) with 95% confidence intervals (CI) for various MR
diagnosed with CHB and CHB combined with MAFLD through liver methods were as follows: MR Egger (OR: 0.997152, 95%CI: 0.99371-
biopsy and puncture at the Second People’s Hospital of Tianjin from 1.000606), Weighted Median (OR: 0.999842, 95%CI: 0.998908-
2018 to 2023.After screening, 157 patients were enrolled, including 95 1.000777), Inverse Variance Weighted (IVW) (OR: 0.999852, 95%CI:
CHB patients (referred to as the CHB group) and 62 CHB combined with 0.998881-1.000824), Simple Mode (OR: 0.999726, 95%CI: 0.998515-
MAFLD patients (referred to as CHB-MA group ).Collect clinical data 1.000937), and Weighted Mode (OR: 0.999821, 95%CI: 0.998757-
including alanine aminotransferase ( ALT ), aspartate aminotransferase 1.000885), all P >0.05.The analysis of the causal association between
( AST ), glutamyl transpeptidase ( GGT ), alkaline phosphatase ( ALP ) CHB and depression also did not yield statistically significant results.
, total cholesterol ( TC ), triglyceride ( TG );blood glucose , hyaluronic The OR with 95% CI for the various MR methods were as follows:
acid ( HA ), III procollagen ( PIIIP ), IV collagen ( IV ), laminin ( LN ) . MR Egger (OR: 1.004656, 95%CI: 0.995291-1.01411), Weighted
Result: The age of CHB group was 36.46 ± 9.66 years old, and the Median (OR: 1.000958, 95%CI: 0.999191-1.002729), Inverse Variance
age of CHB- MA group was 38.58 ± 8.66 years old, the difference Weighted (IVW) (OR: 1.000904, 95%CI: 0.999305-1.002506), Simple
was not statistically significant. There was no significant difference in Mode (OR: 0.998824, 95% CI: 0.995419-1.002241), and Weighted
ALT, AST and TBIL between the two groups.There were 37 males and Mode (OR: 1.001688, 95% CI: 0.999881-1.003499), all P >0.05.
58 females in the CHB group;There were 40 males and 22 females in Conclusion: in this MR study, we found no direct causal relationship
the CHB - MA group, and the difference between the two groups was between CHB and anxiety or depression.
statistically significant ( p=0.01).The difference of ALP between the two Table and Figure:Figure 1.The three assumptions of the MR analysis of
groups ( 69.27 ± 30.40U / L vs 74.62 ± 24.39U / L ) was statistically CHB and its association with anxiety or depression.
significant ( p = 0.033 ). There was no significant difference in GGT ( Figure 2.Forest Plot of Causal Relationships Between CHB and Anxiety
38.41 ± 46.21U / L vs 44.50 ± 80.58U / L ) between the two groups( or Depression
p = 0.225).There were significant differences in TC ( 4.61 ± 0.97mmol
/ L vs 5.16 ± 1.23mmol / L ) and TG ( 0.88 ± 0.33mmol / L vs 1.50 ±
1.00mmol / L ) between the two groups ( p = 0.001,0.000 ). There PP0181
was no significant difference in GLU ( 5.39 ± 1.59mmol / L vs 5.31 ± Comparative Effectiveness and Safety of Tenofovir Alafenamide
0.87mmol / L ) between the two groups ( p = 0.888 ).The PIIIP of the Versus Tenofovir Disoproxil Fumarate in Patients with HBV-
two groups ( 9.43 ± 7.85ng / ml vs 11.69 ± 4.99ng / ml ) was statistically Associated Decompensated Cirrhosis: Insights from a
significant ( p = 0.000 ). There was no significant difference in HA ( Retrospective Real-World Analysis
61.11 ± 63.57ng / ml vs 77.45 ± 104.5ng / ml ), LN ( 81.89 ± 34.11ng Lu Chen1, Mingqin Lu1
/ ml vs 87.50 ± 86.52ng / ml ) and IV ( 51.19 ± 49.87ng / ml vs 46.29 1
The First Affiliated Hospital of Wenzhou Medical University
± 35.61ng / ml ) between the two groups ( p = 0.076,0.285,0.936 ).
Background: Hepatitis B virus (HBV) infection is a pervasive and
According to liver pathology,the inflammation grading1≥ G≥0,2≥G>1,
devastating global health issue. Given the severity of decompensated
4≥G>2, was classified as G1, G2, G3 group; the liver fibrosis grading1≥
cirrhosis, selecting the most appropriate first-line antiviral medication
S≥0,2≥S>1, 4≥S>2, was classified as S1, S2, S3 group.There were
is crucial for optimizing treatment outcomes and providing the best
significant differences in liver fibrosis and inflammation between the
possible disease control. This retrospective real-world study aimed to
two groups (p=0.021,0.034). With liver pathological fibrosis as the
evaluate the comparative effectiveness and safety profiles of tenofovir
dependent variable ,the ordinal logistic regression analysis showed
alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in
that MAFLD was an independent risk factor for the aggravation of liver
patients with hepatitis B virus (HBV)-related decompensated cirrhosis.
fibrosis in CHB ( OR = 0.261, P = 0.001 ).
Method: Patients receiving TAF or TDF were categorized into
Conclusion: The degree of liver fibrosis in CHB patients with MAFLD
respective groups based on their treatment regimen. The study
was 10.3 times higher than CHB alone. Clinical attention should be
spanned 48 weeks, during which the impact on HBV replication, liver
paid to the impact of MAFLD on the CHB population.
enzyme levels, and renal function was assessed. Propensity score
Table and Figure:Figure 1.Does metabolic-related fatty liver disease
matching (PSM) was utilized to minimize disparities between TAF and
speed up the progress of liver fibrosis in patients with chronic hepatitis
TDF cohorts, considering factors such as age, gender, HBeAg status,
B?
baseline HBV DNA, and ALT levels.
Result: After 48-week treatment, the percentage of patients with
PP0180 detectable HBV DNA significantly decreased from 27.9% to 13.1%
(p=0.044). HBeAg positivity remained stable, increasing slightly from
27.9% to 31.15% (p=0.887). Mean ALT levels decreased slightly from
26 U/L to 25 U/L, with 85.25% of patients achieving normal ALT levels Table and Figure:Figure 1.Changes in lipid profiles after 96 weeks in
by week 48. TAF was well-tolerated with no significant impact on renal the TDF and TAF groups of the PSM cohort
function, as indicated by stable serum creatinine and eGFR levels. Figure 2.Changes in ASCVD Risk in TDF and TAF Groups During
TAF treatment showed improvements in liver fibrosis and function, Treatment
with stable APRI, FIB-4, and Child-Pugh scores. After PSM (propensity
score matching), both TAF and TDF groups showed improvements
PP0183
in virologic response and liver function. TAF demonstrated a better
renal safety profile with no significant change in serum creatinine or Efficacy and Safety of Tenofovir Amibufenamide in Chronic
eGFR, while TDF showed a significant increase in serum creatinine Hepatitis B: A Real-World Analysis of Monotherapy and
and decrease in eGFR. Both groups showed a trend towards improved Combination Therapy with Pegylated Interferon Alpha
liver function and ALT normalization, with TAF achieving a higher rate of Jingjing Li1, Jiaquan Huang1
ALT normalization. The TAF group showed a non-significant increase 1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical
in APRI scores, while the TDF group had a significant decrease. FIB- College, Huazhong University of Science and Technology
4 scores in the TAF group slightly increased, while the TDF group Background: Tenofovir amibufenamide (TMF) is a widely used
showed a non-significant decrease. Changes in Child-Pugh scores treatment for chronic hepatitis B (CHB), demonstrating strong antiviral
were minimal for both groups. efficacy in clinical studies. This study aimed to evaluate the real-
Conclusion: TAF appears to offer similar virologic response rates to world effectiveness and safety of TMF, with comparisons to entecavir
TDF, with potentially superior renal safety. This study provides valuable (ETV) and tenofovir disoproxil fumarate (TDF) in monotherapy and
insights into the management of HBV-related decompensated combination therapy with pegylated interferon alpha (Peg-IFNα).
cirrhosis, advocating for TAF’s consideration in treatment protocols. Method: This observational study included 505 CHB patients
However, the retrospective design and limited sample size constrain categorized into four groups based on treatment regimens: TMF
the generalizability of these findings. Future prospective studies with monotherapy (Group 1, n=121), ETV/TDF monotherapy (Group 2,
larger cohorts are warranted to substantiate these preliminary results n=102), TMF combined with Peg-IFNα (Group 3, n=128), and ETV/TDF
and explore long-term outcomes associated with TAF versus TDF combined with Peg-IFNα (Group 4, n=154). Propensity score matching
treatment. (PSM) was applied to minimize baseline differences, resulting in 102
Table and Figure:Figure 1. matched pairs for Groups 1 and 2 and 53 matched pairs for Groups
Figure 2. 3 and 4. The primary outcomes were HBsAg clearance and HBeAg
seroconversion rates at 12, 24, 36, and 48 weeks. Secondary outcomes
PP0182 included changes in renal function, glucose levels, and lipid profiles.
Result: At Week 48, HBsAg clearance rates in the TMF monotherapy
Lipid Profile and Cardiovascular Risk in Treating Hepatitis B
group (Group 1) were 19.0%, significantly higher than the 4.0%
with Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide: A
observed in the ETV/TDF monotherapy group (Group 2) (p = 0.004).
Propensity Score-Matched Cohort Study
This difference was also significant at earlier time points: Week 24
Tingdan Ye1, Lin Zhu2, Ke Mi1, Calvin Q Pan1,3 (11.6% vs. 3.9%, p = 0.037) and Week 36 (15.7% vs. 3.9%, p =
1
Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical 0.004). HBeAg seroconversion rates at Week 48 were 7.0% in Group 1
University, 2Department of Infectious Disease and Clinical compared to 4.9% in Group 2, with no significant difference observed
Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, (p > 0.05).
3
Division of Gastroenterology and Hepatology, Department of In the combination therapy groups, HBsAg clearance rates at Week
Medicine, NYU Langone Health, New York University Grossman
48 were 47.2% in the TMF + Peg-IFNα group (Group 3) and 41.5%
School of Medicine
in the ETV/TDF + Peg-IFNα group (Group 4) (p = 0.558). HBeAg
Background: Randomized clinical studies suggested that tenofovir seroconversion rates were 53.8% in Group 3 and 61.5% in Group 4 (p
disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) had = 0.691). At Week 36, HBsAg clearance rates in Group 3 were slightly
different effects on lipid profiles in treating chronic hepatitis B (CHB). higher than in Group 4 (41.5% vs. 35.8%), but the difference was not
We aimed to assess if changes of lipid profiles from these regimens statistically significant (p = 0.550).
affected atherosclerotic cardiovascular disease (ASCVD) risk in a real- Renal function remained stable during TMF treatment, with no
world practice. significant changes in serum creatinine or Blood urea nitrogen (BUN)
Method: We retrospectively enrolled CHB patients who initiated TDF levels. Blood glucose and total cholesterol showed minor fluctuations
or TAF between January 2019 and February 2022. The propensity but no significant differences.
score-matched (PSM) cohorts (TDF:TAF in 1:1 ratio) were generated Conclusion: TMF demonstrates potential in achieving HBsAg
from enrollees. The primary outcome was changes in overall 10- clearance, and TMF combined with Peg-IFNα presents an effective
year ASCVD risk scores or in ASCVD-risk categories during 96-week option for achieving a functional cure for chronic hepatitis B. These
therapy. The secondary outcomes included the incidence of ASCVD findings support TMF as a safe and effective treatment option for
events, changes in lipid profiles in 96 weeks in each group and CHB, offering a foundation for further studies to optimize treatment
between groups. strategies.
Result: Among 446 patients (223 in each regimen) selected from 644
enrollees through the PSM, the median age was 41, 71% male, and
76% treatment-naïve. At week 96, TDF therapy did not significantly
PP0184
change fasting lipid profiles except reduced median [IQR] total Development of a nomogram to predict 5 years mortality in patients
cholesterol levels compared to baseline (4.3 [3.8, 4.9] vs 4.2 [3.5, with hepatitis B-related cirrhosis of Portal vein thrombosis: A
4.8]; p=0.049); whereas TAF regimen increased fasting levels of all retrospective study
lipids except the low-density lipoprotein cholesterol (LDL) levels were Yang Zhou1, Feixiang Xiong1, Jialiang Chen2, Xiaoli Liu1, Peipei
similar to baseline. Additionally, both groups had a median decrease Meng1, Tong Wu1, Xiaomin Ji1, Yuyong Jiang1, Yixin Hou1
in high-density lipoprotein cholesterol (HDL) levels. The overall 10-year 1
Beijing Ditan Hospital, Capital Medical University, 2 Beijing Ditan
ASCVD risk and ASCVD-risk categories at 96 weeks were similar to Hospital, Capital Medical University
those at baseline in each treatment group. In addition, the frequency of Background: To establish a nomogram model to predict the long-
ASCVD events were comparable between the TAF-treated group and term mortality in patients with hepatitis B-related cirrhosis of Portal vein
the TDF-treated group (1.3% vs 2.3%; p = 0.34). thrombosis (PVT).
Conclusion: CHB patients treated with TDF or TAF for 96 weeks had Method: 685 patients were enrolled from January 2015 to August
not increase the 10-year ASCVD risk despite their effects on fasting 2020 to December 2023 as the validation cohort .The independent risk
lipid profiles. The frequency of clinical ASCVD events were similar factors of five-year mortality were analyzed by COX regression and we
between regimens.
established a nomogram. The receiver operating characteristic ( ROC) Beijing Youan Hospital, Capital Medical University, Beijing, China,
curve, C-index, calibration curves and decision curve analysis(DCA ) 7
Department of Infectious Diseases, Shengjing Hospital of China
were utilized to evaluate the value of the nomogram. Medical University, Shenyang, China, 8Xiamen Amoytop Biotech Co.,
Result: Age(HR = 1.09, 95%CI:1.06–1.11;P <0.001), leukocyte(HR = Ltd, Xiamen, China, 9Department of Epidemiology and Biostatistics,
1.09, 95%CI:1.03–1.17; P = 0.002) ,NLR(HR = 1.29, 95%CI:1.22–1.35; School of Public Health, Tongji Medical College, Huazhong University
P <0.001), serum sodium (HR = 0.94, 95% CI:0.90–0.98; P=0.005) of Science and Technology, Wuhan, China
were independent prognostic factors in patients with hepatitis-B Background: Functional cure is considered the advanced treatment
Cirrhosis complicated with PTV. The AUROC of the nomogram in goal for patients with chronic hepatitis B (CHB). We aimed to evaluate
training cohort and validation cohort were 0.906(95% CI: 0.891–0.921) hepatitis B surface antigen (HBsAg) loss rates after combination
and 0.910 (95% CI: 0.885–0.927) respectively. The performance and treatment of entecavir (ETV), peginterferon alfa-2b (Peg-IFN) with or
discriminative ability were better than the current model, such as CTP without granulocyte-macrophage colony stimulating factor (GM-CSF).
scores, and MELD scores. Method: In this multicenter randomized controlled trial, 257 virally-
Conclusion: Age, leukocyte, NLR and serum sodium were suppressed patients undergoing nucleos(t)ide analogues treatment
independent risk factors affecting the 5-year prognosis of patients who had HBsAg <3000 IU/mL were randomized (1:1:1) to receive
with hepatitis-B cirrhosis complicated with PVT. The established in this either ETV for 96 weeks (E group), or 48 weeks of Peg-IFN+ETV,
study has certain application value in predicting the 5-year prognosis followed by 48-week Peg-IFN alone (EP group), or 48 weeks of Peg-
of such patients. IFN+ETV+GM-CSF, followed by 48-week Peg-IFN alone (EPG group).
Table and Figure:Figure 1.A nomogram for predicting 1, 3 and 5 years The primary outcome is HBsAg loss at week 96.
mortality in patients with hepatitis-B related cirrhosis. Result: Among 249 patients (81 in E group, 83 in EP group and
Figure 2. The ROC of 5-year mortality in training cohort 85 in EPG group) receiving at least one dose of the study drug, EP
group (30.12%, 35.53%) and EPG group (22.35%, 34.67%) achieved
PP0185 significantly higher HBsAg loss and hepatitis B surface antibody
(HBsAb) positivity rates than E group (0.00%, 0.00%; p<.0001,
The relationship between HBV DNA levels and liver fibrosis scores p<.0001) at week 96. Multivariate analysis showed that age, HBsAg
Mengyu Tao1, Xincheng Wu2, Xiaoping WU1 level at baseline and HBsAg decline at week 24 correlated with HBsAg
1
The First Affiliated Hospital of Nanchang University, 2The First loss or HBsAb positivity at the end of Peg-IFN-based treatment. HBV
People‘s Hospital of Fuzhou RNA decline at week 24 correlated with HBsAg loss. The HBsAg
Background: Serum hepatitis B virus (HBV) DNA levels and non- longitudinal trajectory could predict HBsAg loss with an AUROC of
invasive liver fibrosis scores are significantly associated with 0.944. More patients in EP group and EPG group experienced adverse
hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) events than E group. Peg-IFN-based therapy was generally well
patients. tolerated.
Method: We enrolled 265 patients who diagnosed with chronic Conclusion: In virally-suppressed patients with CHB, combination of
hepatitis B between June 2022 and December 2023. Inclusion of ETV and Peg-IFN with or without GM-CSF improved the rates of HBsAg
HBsAg positive for more than 6 months and ALT less than twice the loss and HBsAb positivity. HBsAg trajectory may accurately predict
upper limit normal. Comparison of correlations between HBV DNA and HBsAg loss under Peg-IFN-based therapy.
indicators of non-invasive liver fibrosis, include platelet count, CHI3L1,
APRI, FIB-4, GPR, LSM. The association of HBV DNA levels with the PP0187
aspartate aminotransferase to platelet ratio index (APRI) and fibrosis
Safety and Effectiveness of Tenofovir Amibufenamide for Pregnant
(FIB)-4 score at baseline was analyzed using general linear models.
Women with Chronic Hepatitis B
Result: In HBeAg-negative patients, HBV DNA levels were inversely
correlated with APRI and FIB-4 scores and had a nonlinear parabolic Ruyue Chen1, Yanqin Ai2, Xueyan Lv1, Yuehang Wang1, Yajie Pan1,
relationship with CHI3L1 levels. In contrast, in HBeAg-positive patients, Qinglei Zeng1
HBV DNA levels were nonlinearly parabolic with APRI and FIB-4 scores
1
Department of Infectious Diseases, The First Affiliated Hospital of
and linearly correlated with CHI3L1 levels. In the entire cohort, there Zhengzhou University, China, 2Department of Infectious Diseases,
was a significant nonlinear parabolic relationship between HBV DNA Xuchang Central Hospital, China
levels and fibrosis scores. Notably, moderate viral loads corresponded Background: Data on tenofovir amibufenamide (TMF) for the pregnant
with the highest APRI and FIB-4 scores (p<0.001). women with chronic hepatitis B (CHB) are lacking. This study aims to
Conclusion: HBV viral load correlated significantly with APRI and FIB- investigate the safety and effectiveness of TMF for the treatment of CHB
4 scores. Our findings suggest that HBV DNA levels are associated pregnant women and the prevention of mother-to-child transmission of
with hepatocarcinogenesis through direct and indirect pathways. hepatitis B virus (HBV-MTCT).
Method: The clinical data of a total of 13 women of childbearing age
PP0186 who took TMF tablet (25mg per day, orally after meals) and became
pregnant were retrospectively collected in The First Affiliated Hospital
Combination therapy of entecavir, peginterferon alpha and of Zhengzhou University and Xuchang Central Hospital from January
granulocyte-macrophage colony stimulating factor enhanced 2022 to September 2024. The changes of HBV markers, biochemistry,
HBsAg loss and HBsAb response blood routine and other parameters and adverse events were analyzed
Wu Di1, Da Huang1, Shifang Peng2, Yongping Chen3, Fengchun at baseline, during pregnancy, and within 7 months after delivery, and
Yang1, Xiaoyun Zhang1, Lei Fu2, Lanman Xu4, Jiaji Jiang5, Qi Zheng5, the infants’ growth indexes at birth and 7 months of age and the effect
Xinyue Chen6, Yali Liu6, Xiaoguang Dou7, Ke Ma1, Xi Dong1, Peng of hepatitis B immunization were also analyzed.
Wang1, Li Sun8, Ruoyi He8, Yuchen Tian9, Ping Yin9, Weiming Yan1, Result: (1) At baseline (16.2±7.4 weeks before pregnancy), 10 of
Meifang Han1, Qin Ning1 the 13 women of childbearing age were positive for hepatitis B e
1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical antigen (HBeAg), with an age of 29.4±4.1 years and HBV DNA level
College and State Key Laboratory for Diagnosis and Treatment of of 5.6±3.3 log10 IU/mL. The level of alanine aminotransferase (ALT)
Severe Zoonotic Infectious Disease, Huazhong University of Science was 127.2±77.3 U/L, and the parameters of blood routine and renal
and Technology, Wuhan, China;, 2Department of Infectious Diseases, function were normal. (2) During pregnancy, the HBV DNA and ALT
Xiangya Hospital, Central South University, Changsha, China, levels in pregnant women gradually decreased to 0.5±1.2 log10 IU/mL
3
Hepatology Diagnosis and Treatment Center, The First Affiliated and 20.9±14.3 U/L at delivery, respectively. In addition, hemoglobin
Hospital of Wenzhou Medical University, Wenzhou, China, 4The First and creatinine levels were progressively reduced and estimated
Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, glomerular filtration rate (eGFR) was progressively increased. (3)
5
Liver Research Center, First Affiliated Hospital of Fujian Medical
At 7 months postpartum, a total of 1 woman (7.7% [1/13]) achieved
University, Fuzhou, China, 6International Medical Department,
HBeAg seroconversion, and all the women’s HBV DNA levels were
lower than the lower limit of quantitation (LLOQ, <25 IU/mL), ALT cure.
level was 18.5±8.0 U/L, and hemoglobin, serum creatinine, eGFR Table and Figure:Figure 1.Changes in HBsAg Levels Over Time in
levels returned to baseline levels. (4) The main adverse events during HBsAg Responder and Non-Responder Groups. Total Patients (A);
treatment were nausea (84.6% [11/13]), anorexia (69.2% [9/13]) and HBeAg Positive (B); HBeAg Negative (C).
fatigue (53.8% [7/13]), and the main complication was premature Figure 2.HBsAg Seroclearance Rate. Total Patients (A); Gender (B);
rupture of membranes (15.4% [2/13]). (5) The gestational age of the 13 HBeAg Status (C); Baseline HBsAg Quantification (D).
infants at birth was 38.9±1.2 weeks, 7 of them were male, there were
no premature or overdue births, and no birth defects or malformation.
PP0189
The Apgar score at 1 minute after birth was 9.4±0.7, and the growth
indexes at birth (height, weight, head circumference, the same below) A real-world study of the efficacy of tenofovir amibufenamide
were normal. All infants received standard hepatitis B immunization (TMF) in the treatment of patients with chronic hepatitis B and its
prophylaxis. Eight cases were breastfed. (6) When the infants were 7 effect on blood glucose and lipid levels
months old, the growth indexes were normal, and the HBV-MTCT was JUN LI1, Baixin Qian1, QING YE1
successfully prevented in all 13 infants, and the hepatitis B surface 1
Tianjin The Third Central Hospital
antibody level was 502.4±292.0 mIU/mL. Background: To observe the efficacy of Tenofovir amibufenamide
Conclusion: This study is the first to prove that TMF has favorable (TMF) treatment and its impact on blood glucose and lipids levels in
maternal and infant safety and effectiveness in the treatment of CHB patients with chronic hepatitis B (CHB) in the real world.
pregnant women; meanwhile, combined with standard hepatitis B Method: Patients with CHB who received TMF antiviral therapy
immunization, TMF can successfully prevent the HBV-MTCT. from July 2022 to July 2024 at our center were included. General
Table and Figure:Figure 1.Figure 1. Study Design and Overview. information, biochemical indicators, and virological indicators were
collected at baseline, 24 weeks, and 48 weeks of treatment. These
PP0188 included alanine transaminase (ALT), aspartate aminotransferase
(AST), fasting blood sugar (FBS), total cholesterol (TC), triglyceride
HBsAg Clearance in Chronic Hepatitis B Patients Treated with
(TG), hepatitis B virus deoxyribonucleic acid (HBV DNA), and hepatitis
Interferon: A Large-Scale Observational Study
B surface antigen (HBsAg). The efficacy of TMF treatment in the real
Daqiong Zhou1, Jianru Jia2, Feng Zhao2, Wei Qin2, Jiangyu Liu1, world and its impact on blood glucose and lipid levels in CHB patients
Zichen Zhang1, Zhenhuan Cao1 were observed. Utilize SPSS 23.0 to perform paired T-tests on follow-
1
Beijing Youan Hospital, 2Baoding People‘s Hospital up and baseline data.
Background: HBsAg clearance signifies a functional cure for hepatitis Result: Out of 165 CHB patients treated with TMF, 80 patients with
B and is the primary goal of antiviral therapy. Interferon-α (IFNα), used complete virological and biochemical follow-up data were included.
alone or with nucleos(t)ide analogs (NAs), is an option for achieving There were 45 males and 35 females, aged from 26 to 71 years, with
this goal. However, due to its adverse effects, interferon is less an average age of 45.98 ± 10.61 years. Seventy-six cases met the
commonly used than nucleos(t)ide analogs, leading to smaller sample diagnosis of chronic hepatitis B, and four cases met the diagnosis of
sizes in past studies. This research seeks to assess the clinical cure compensated hepatitis B cirrhosis. 69 patients(69/80,86.25%) were
rate of hepatitis B in a large cohort receiving interferon therapy and treatment-naïve, and 11 patients(11/80,13.75%) were treatment-
explore the relationship between baseline characteristics and HBsAg experienced. Among the 80 patients, 53 completed 24-week follow-
clearance to enhance personalized treatment strategies. up, and 52 completed 48-week follow-up. No significant adverse
Method: This study analyzed chronic hepatitis B patients at Beijing reactions were observed.
You’an Hospital from February 2008 to January 2023. All patients had After 24 and 48 weeks of TMF treatment, the number of patients with
HBsAg positivity persist for over six months before receiving treatment HBV DNA below the lower limit of detection were 42 (42/53, 79.25%)
and more than 24 weeks of interferon (IFNα) treatment. Patients with and 50 (50/52, 96.15%), respectively. The virological complete
cirrhosis or liver cancer were excluded from the study. Based on response rate gradually increased with extended treatment duration.
HBsAg seroclearance during follow-up, the patients were divided into Compared to baseline, the levels of fasting blood sugar and lipids
the HBsAg responder group (R) and the non-responder group (NR). at 24 and 48 weeks after TMF treatment showed only minor and
The study assessed the HBsAg seroclearance rate and associated statistically significant changes in HDL at 24 weeks (t(52) = -2.16, p
factors using logistic regression and Kaplan-Meier methods. = 0.035) and 48 weeks (t(52) = -3.271, p = 0.002). The differences in
Result: A total of 5,288 patients with chronic hepatitis B (CHB) were blood sugar and lipid components at other follow-up time points were
included in this study, out of which 887 patients (16.8%) achieved not statistically significant.
HBsAg seroclearance during the follow-up period. Kaplan-Meier Conclusion: TMF treatment in CHB patients showed significant
analysis revealed that the cumulative HBsAg clearance rates at 48, efficacy up to 48 weeks, with no obvious impact on patients’ glycemic
96, and 144 weeks of treatment were 10.6%, 25.7%, and 39.9%, and lipid levels, and overall safety was relatively good.
respectively. Patients with a baseline HBsAg level of less than 100 IU/ Table and Figure:Figure 1.Table 1 Paired T-test of blood glucose and
mL demonstrated a cumulative clearance rate of up to 58.8% within lipid levels compared to baseline at 24 weeks of follow-up with oral
96 weeks, whereas those with baseline HBsAg levels exceeding TMF
1,500 IU/mL showed only an 11.1% clearance rate during the same Figure 2.Table 2. Paired T-test of blood glucose and lipid levels
timeframe (P<0.001). In comparison to the non-responder group, the compared to baseline at 48 weeks of follow-up with oral TMF
responder group exhibited lower baseline HBeAg positivity rates (38%
vs. 63.5%, P<0.001), reduced HBsAg levels (2.27 vs. 3.38 log10 IU/
PP0190
mL, P<0.001), and lower HBV DNA levels (0 vs. 2.75 log10 IU/mL,
P<0.001). Furthermore, thyroid function markers, including FT3 and ALT/(qHBsAg×age) ratio at week 12 predicts HBsAg seroclearance
FT4 levels, were slightly elevated but remained within the normal and seroconversion in nucleos(t)ide analogue-experienced
range in the responder group compared to the non-responder group. chronic hepatitis B patients receiving Peg-IFNα add-on therapy
Multivariate logistic regression analysis identified several factors JIAYI WANG1,2, Ning Han1,2, Huan Liu1,2, Juan Liao1,2, Xuebing Chen3,
significantly associated with HBsAg seroclearance: male gender Yilan Zeng4, Lang Bai1,2, Hong Li1,2, Lingyao Du1,2, Mengya Liu1,2,
(OR=0.744, P<0.001), baseline HBsAg level (OR=0.451, P<0.001), Chen Zhou1,2, Libo Yan1,2, Hong Tang1,2
GGT (OR=0.997, P=0.025), FT3 (OR=1.148, P=0.021), and FT4 1
Center of Infectious Diseases, West China Hospital of Sichuan
(OR=1.028, P=0.033). University, Chengdu 610041, China, 2Laboratory of Infectious and
Conclusion: In patients with chronic hepatitis B receiving interferon Liver Diseases, Institution of Infectious Diseases, West China Hospital
therapy, lower baseline HBsAg levels, female gender, and improved of Sichuan University, Chengdu 610041, China, 3Department of
thyroid function are strongly associated with HBsAg seroclearance. Infectious Diseases, the People‘s Hospital of Deyang City, Sichuan
These factors indicate that this population will likely achieve a functional Province 618000, China, 4Public Health Clinical Center of Chengdu,
Chengdu, Sichuan 610041, China 48 weeks, and then withdraw the antiviral therapy. All patients were
Background: Chronic hepatitis B (CHB) involves complex interactions followed up every 24 weeks after the discontinuation of anti-virus
between the hepatitis B virus (HBV) and the host immune system, therapy, and HBV related indicators were tested. Finally, a total of
which are particularly critical during Peg-IFNα therapy. Dynamic 114 patients completed the 96 weeks follow up after discontinuation
changes in certain indicators during treatment may influence the of medication. The indicators predicting HBsAg loss at follow up 96
final therapeutic outcome. Identifying predictors that reflect both weeks (FU 96 weeks) were identified by univariate and multivariate
host immune responses and viral activity during therapy is essential analysis, then the nomogram model was constructed and internally
for optimizing the use of Peg-IFNα. This study aims to evaluate and validated. The primary endpoint analyzed in the study was HBsAg
integrate host and viral factors to predict Peg-IFNα-induced HBsAg loss at the end of follow up (EOF), defined as serum HBsAg loss and
seroclearance and seroconversion in CHB patients previously treated HBV DNA undetected up to 96 weeks after withdrawal, with or without
with nucleos(t)ide analogues (NUCs). seroconversion to HBsAb.
Method: This multicenter prospective observational study enrolled Result: After 96 weeks of discontinuing antiviral therapy, there
CHB patients who had been treated with NUCs for ≥1 year, with negative were 28.07% (32/114) patients with HBsAg negative. The univariate
HBeAg, quantitative HBsAg (qHBsAg) ≤1500 IU/mL and undetectable and multivariate analysis showed that the serum quantification of
HBV DNA. Patients received Peg-IFNα add-on therapy for 48 weeks. HBcrAg≤4.25 log10U/mL, HBsAb>20 IU/L at EOT and HBsAg decline
Blood tests for HBV DNA, qHBsAg and HBsAb, liver biochemistry (ALT, more than 630 IU/mL from baseline to week 24 during treatment
AST, and albumin) and complete blood cell counts were monitored could predict HBsAg loss at 96 weeks after discontinuation. The
every 12 weeks. Logistic regression analysis was performed to identify nomogram model was developed based on the risk factors, and
predictors of both HBsAg seroclearance and seroconversion after 48 the internal validation was conducted using Bootstrap method, with
weeks of Peg-IFN therapy. Identified predictors were then combined a concordance index (C-index) of 0.829. Meanwhile, the calibration
and further evaluated as independent factors using Cox regression. curve and decision curve of the nomogram model also performed well.
The area under the receiver-operating characteristic curve (AUROC) The joint indicators could predict HBsAg loss at FU 96 weeks with the
was calculated to assess the predictive accuracy of the combined areas under the ROC curves (AUROC)=0.834 (p<0.0001).
predictor for HBsAg seroclearance and seroconversion. A p-value Conclusion: Serum HBsAg decline more than 630 IU/mL from
of < 0.05 was considered statistically significant. baseline to week 24 combined with the quantification of HBcrAg and
Result: A total of 758 patients (73.4% male) were recruited; 309 HBsAb at the EOT of Peg-IFN predict HBsAg loss at FU 96 weeks after
(40.8%) and 203 (26.8%) patients achieved HBsAg seroclearance and withdrawal for CHB patients. We provide novel and effective predictive
seroconversion at the week 48 of Peg-IFNα therapy, respectively. Age, factors to predict functional cure at follow up 96 weeks after Peg-IFN
ALT levels at week 12, and qHBsAg were associated with both HBsAg withdrawal.
seroclearance and seroconversion. By combining the three variants,
we found the ALT/(qHBsAg×age) ratio at week 12 independently PP0192
predicted both HBsAg seroclearance and seroconversion outcomes
Comparative efficacy and safety of tenofovir amibufenamide
(all p<0.05). This ratio outperformed baseline qHBsAg in predicting
vs tenofovir alafenamide and entecavir in the hepatitis B virus
both HBsAg seroclearance and seroconversion, with AUROCs of 0.802
related acute-on-chronic liver failure patients: A single-centre
(cut-off 0.07) and 0.787 (cut-off 0.12) respectively. Patients with a week-
retrospective study
12-ALT/(qHBsAg×age) ratio above cut-off values had significantly
Xiao Chuan Diao1, Qian Jun Wu1, Mi Si Gu1, Fei Huang1, Yue Chen1,
higher cumulative probabilities of HBsAg seroclearance (63.4% vs.
Yi Xuan Zhang1, Qin Ning1, Mei Fang Han1
17.8%, Log-rank test p<0.001) or seroconversion (47.3% vs. 11.0%,
Log-rank test p<0.001). A higher week 12 ALT/(qHBsAg×age) ratio
1
The Department of Infectious Diseases, Tongji Hospital, Tongji
(β=0.206, p=0.006) was also independently associated with elevated Medical College and State Key Laboratory for Diagnosis and
Treatment of Severe Zoonotic Infectious Diseases, Huazhong
HBsAb levels at week 48 of Peg-IFNα therapy.
University of Science and Technology
Conclusion: The ALT/(qHBsAg×age) at week 12 effectively predicts
both HBsAg seroclearance and seroconversion during Peg-IFNα add- Background: There is a scarcity of clinical studies on the use of
on therapy in NUC-experienced CHB patients. Patients with higher tenofovir amibufenamide (TMF) for Hepatitis B Virus-Associated
ALT/(qHBsAg×age) ratios at week 12 are more likely to exhibit elevated Acute-on-Chronic Liver Failure (HBV-ACLF) patients. The aim of this
HBsAb levels by week 48. research is to investigate the efficacy and safety between entecavir
Table and Figure:Figure 1.Figure 1. Patient deposition (ETV), tenofovir alafenamide fumarate (TAF), and TMF in the treatment
of HBV-ACLF.
Method: We selected patients diagnosed with HBV-ACLF, in
PP0191 accordance with the APASL 2019 guidelines. Admitted between May
Serum HBsAg decline combined with the quantification of HBcrAg 2022 and January 2024 to the department of infectious diseases ward
and HBsAb at the end of treatment of Peg-IFN predict HBsAg loss were the aforementioned patients, from whom we collected multiple
at 96 weeks after withdrawal for CHB patients clinical indicators and outcomes at the time of their admission and
QianJun Wu1,2, Jie You1,2, Wenyu Wu1,2, Misi Gu1,2, Wu Di1,2, Weiming after two weeks and 60 days of their treatment. We then analyzed the
Yan1,2, Peng Wang1,2, Qin Ning1,2, Meifang Han1,2 differences in clinical indicators between and within ETV, TAF, and TMF.
1
Institute of infectious diseases, Tongji Hospital Affiliated to Tongji Concurrently, we conducted a survival analysis to assess the efficacy
Medical College of Huazhong University of Science and Technolog, and safety profiles of these three medications. The research was
2
Tongji Medical College and State Key Laboratory for Diagnosis approved by the Ethics Committee of Tongji Hospital, Tongji Medical
and Treatment of Severe Zoonotic Infectious Disease, Huazhong College, Huazhong University of Science and Technology.
University of Science and Technology Result: A total of 235 patients were included in the study: 41 in the
Background: Functional cure is the ideal goal recommended by TMF group, 60 in the TAF group, and 117 in the ETV group. The 60-
chronic hepatitis B (CHB) management guideline. Pegylated interferon day overall survival rates for three groups were 71.11%, 73.77%, and
alpha (Peg-IFNα) therapy could help CHB patients achieve HBsAg loss. 73.65%, respectively (P>0.05). After two weeks of treatment, all the
This study aims to explore the predictive factors involved in predicting three groups of patients showed significant improvements in alanine
HBsAg loss at follow up 96 weeks after 96 weeks of nucleos(t)ide aminotransferase (ALT) and aspartate aminotransferase (AST) levels
analogues (NUCs) and Peg-IFNα combination and sequential therapy. (P<0.05), and there were no significant differences between the three
Method: This is a multicenter prospective study named of OCEAN groups in above indicators. None of the groups experienced worsening
study(NCT03358108), in which 170 NUCs experienced patients deteriation of renal function after treatment, and the estimated
received a combination treatment of NUCs(ETV or TDF) and Peg- glomerular filtration rate (eGFR) levels at two weeks post-treatment
IFNα for 48 weeks, followed by Peg-IFNα monotherapy for another were significantly improved in the TAF and TMF groups compared to
the ETV group (P<0.05). There were no significant changes in total
cholesterol levels in any of the groups compared to baseline. short-term mortality, and high incidence in areas with a large number
Conclusion: TMF, TAF, and ETV exhibited no differences in the 60-day of patients with chronic hepatitis B. However, few study have analyzed
overall survival rate among patients with HBV-ACLF. However, TMF and the treatment outcome of this disease. The purpose of this study is to
TAF showed a greater improvement in renal function compared to ETV. investigate the prognosis of patients with HBV-ACLF in Qingdao over
the past decade.
Method: Methods: Based on inclusion and exclusion criteria, we
PP0193
collected data on the clinical outcomes of 146 patients diagnosed
Prediction and Validation of HBsAg Clearance with Extended with HBV-ACLF at the Affiliated Hospital of Qingdao University from
Interferon Therapy: A Multicenter Study November 2014 to November 2024. The clinical outcomes included
Fei Yan1, Xiulan Xue2,3, Ying Guo4, Fei Tang5, Jing Chen1, Yicheng liver transplantation, improvement after medical and artificial liver
Lin1, Xinyu Chen1, Qin Du6, Xiaoyan Wang4, Jianyong Zeng2,7, Weili treatment, death, and voluntary discharge. Descriptive statistical
Yin5, Jing Liang5, Lei Liu5, Fang Wang5, Baiguo Xu5, Qing Ye5, Huiling methods were used to analyze the data.
Xiang5 Result: Results: The mean age of the patients was 49.6 years, with
1
The Third Central Clinical College of Tianjin Medical University, 80.95% (119 patients) being male and 19.05% (28 patients) being
2
Department of Infectious Diseases of the First Affiliated Hospital of female. Among the 146 patients with HBV-ACLF, the majority (45.21%,
Xiamen University, 3The School of Clinical Medicine of Fujian Medical 66 patients) showed improvement after non-liver transplantation
University, 4The third people‘s Hospital of Taiyuan, 5Department of treatment, followed by those who underwent liver transplantation
Gastroenterology and Hepatology , Tianjin Third Central Hospital, (26.03%, 38 patients). In-hospital mortality accounted for 9.59% (14
6
Nankai University Affiliated Third Center Hospital, 7Xiamen Quality patients), with one death occurring after liver transplantation. Among
Control Center of Infectious Diseases the 28 patients (19.18%) who were voluntarily discharged, 2 continued
Background: Studies have shown that long-term interferon therapy treatment at another hospital due to personal circumstances after
may increase clinical cure rates and enhance prognosis, yet no ideal stabilizing their condition, while the remaining 27 abandoned further
predictor exists for a long course. This study aimed to identify chronic treatment. Of the 38 patients who underwent liver transplantation, 31
hepatitis B(CHB) patients likely to require extended interferon therapy received entecavir for anti-HBV therapy postoperatively, 3 received
(≥52 weeks) for achieving clinical cure. tenofovir, and the antiviral treatment regimen for the remaining 4
Method: Patients with CHB, receiving PEG-IFN α-2b monotherapy patients was unknown. There was no statistically significant difference
or combined with NAs (Nucleoside Analogs), were recruited from in gender and age distribution among the different outcomes (p<0.05).
January 2018 to March 2024 in Tianjin, Xiamen, and Taiyuan, China. Conclusion: Conclusion: The prognosis of patients with HBV-ACLF
All patients achieved HBsAg clearance post-treatment. The study’s is mainly characterized by improvement and liver transplantation,
baseline was the start of Peg-IFNα-2b therapy, with the endpoint being However, a significant proportion of patients still experience mortality
HBsAg clearance (<0.05 IU/mL). or abandon treatment. How to promote liver transplantation and
Result: A total of 276 patients with CHB were enrolled, with a mean improve treatment regimens remains an urgent issue to improve the
age of 41.56 ± 8.62 years. 14.13% of patients had cirrhosis at survival rate of patients with liver failure.
baseline, and the mean IFN treatment course was 31.20 ± 24.04 Table and Figure:Figure 1.Clinical outcome and antiviral drug use
weeks. The training cohort comprised 178 patients, and the validation
cohort 98; the training cohort was stratified based on IFN treatment
PP0195
duration of ≥52 weeks for HBsAg clearance. 19.66% of patients
required IFN treatment >52 weeks, with a baseline HBsAg of 2.53 ± Development and validation of a predictive model for HBsAg
1.11 log IU/ml, and a 12-week HBsAg level of 1.45 ± 1.61 log IU/ml. seroclearance after Peg-IFN-based therapy in patients with
Logistic regression analysis showed that baseline HBsAg, 12-week HBeAg-negative chronic hepatitis B: a multicentre study
HBsAg, and cirrhosis were factors significantly affecting the duration Shuai Gao1,2, Xuemei Jiang3, Jing Zhao4, Juan Xu5, Sikui Wang6,
of interferon therapy (β=2.23,1.48,3.78; P<0.05). Subgroup analysis Yanping Yin7, Jun Shi8, Xiao Wang9, Lijun Yu10, Cheng Xu11, Zhenghua
confirmed the influence of these factors on IFN course in most patients Zhao12, Yanqing Xing13, Kai Wang1,2
and identified that cirrhotic patients with baseline HBsAg >2.54 log IU/ 1
Department of Hepatology, Qilu Hospital of Shandong University,
ml and 12-week HBsAg >0.89 log IU/mL were likely to need extended 2
Hepatology Institute of Shandong University, 3Department of
treatment (≥52 weeks). A predictive model incorporating these factors Hepatology, Shandong Public Health Clinical Center, 4Department
had a training cohort AUC of 0.847 (95% CI: 0.79-0.96) and an external of infectious disease, Weifang People‘s Hospital, Shandong Second
validation cohort AUC of 0.846 (95% CI: 0.63-0.82), indicating good Medical University, 5Department of Infectious Disease, Shengli Oilfield
calibration and potential as a preclinical treatment planning tool. Central Hospital, 6Department of Infectious Disease, Liaocheng
Conclusion: Baseline HBsAg, 12-week HBsAg, and baseline cirrhosis People‘s Hospital, 7Department of Gastroenterology, Yantai City
in chronic hepatitis B (CHB) patients significantly are significant factors Yantai Mountain Hospital, 8Department of Hepatology, Shandong
influencing the duration of interferon therapy. Ultimately, predictive Provincial Hospital Affiliated to Shandong First Medical University,
9
Liver Disease Center, Digestive Diseases Hospital of Shandong
modeling to quantify these criteria aids clinical decision-making.
First Medical University, 10Department of Epidemiology, The First
Table and Figure:Figure 1.Figure 1. Kinetics of Hepatitis B Surface
Affiliated Hospital of Shandong First Medical University & Shandong
Antigen (HBsAg) Levels in Patients Achieving HBsAg Clearance Within
Provincial Qianfoshan Hospital, 11Department of Infectious Disease,
and After 52 Weeks. Patients who achieved HBsAg clearance within 52
Linyi People‘s Hospital, 12Department of Infectious Disease, Taian City
weeks of treatment had lower baseline HBsAg levels and at 12 weeks Central Hospital, 13Department of Infectious Disease, Zibo Central
had a dramatic decrease, which was statistically significant (P < 0.05) Hospital
compared to those who required extended treatment for clearance.
Figure 2.Figure 2. ROC Curves for Risk Modeling in Training and Background: Early prediction of HBsAg seroclearance prior to
Validation Cohorts on IFN Treatment Longer than 52 Weeks. the application of Peg-IFN-based therapy has important clinical
implications. In this study, we aim to construct a predictive model with
baseline parameters for HBsAg seroclearance after Peg-IFN-based
PP0194 therapy in patients with HBeAg-negative chronic hepatitis B (CHB).
Outcome analysis of hepatitis B related chronic acute liver failure Method: From January 1, 2018 to May 1, 2023, we retrospectively
patients in Qingdao area in recent 10 years enrolled 377 nucleos(t)ide analogue-suppressed patients with HBeAg-
Zhao Hanwen1, Ren Lili1, Niu Qinghui2 negative CHB who received a 48-week Peg-IFN-based therapy from 11
1
Qingdao University, 2 Liver Disease Center , Affiliated Hospital of centres in China. A multivariate cox regression model was developed
Qingdao University for predicting HBsAg seroclearance in a development cohort with 229
patients recruited from 5 centres, then validated in an independent
Background: Background: Hepatitis B virus-associated chronic
validation cohort with 148 patients recruited from another 6 certres.
acute liver failure (HBV-ACLF) has poor prognosis, high cost, high
This study is registered with ClinicalTrials.gov, number NCT06196632. control group for TG, TC and HDL-C levels.
Result: In the development and validation cohorts, 17.9% (41/229) Conclusion: Both TMF and TAF can effectively inhibit HBV replication
and 20.27% (30/148) of patients achieved HBsAg seroclearance and promote liver function recovery without significantly impacting
respectively. The best performing model was constructed by age renal function. However, TAF may affect lipid metabolism, whereas the
(HR 0.962, 95%CI 0.928-0.997), baseline HBsAg (HR 0.998, 95%CI effect of TMF on lipid metabolism is not as pronounced.
0.997-0.999) and baseline alanine aminotransferase (HR 1.008, 95%CI Table and Figure:Figure 1.Table 1. Changes in blood lipid levels before
1.003-1.012). It showed good predictive performance in predicting and after treatment in two groups of patients
HBsAg seroclearance in both the development [area under the Figure 2.Figure 1 . Changes in lipid expression after drug interventions
receiver operating characteristic curve (AUC) 0.842] and validation in HepG2 cells or C57/BL6J mice
cohorts (AUC 0.852). Using cut-off points of -2.7 and -1.3, it can
identify HBeAg-negative CHB patients with high, intermediate and low
PP0197
incidence rate of HBsAg seroclearance.
Conclusion: A model was constructed with baseline parameters Efficacy of Zhenqifuzheng capsule combined with Tenofovir
for predicting HBsAg seroclearance after Peg-IFN-based therapy in Amibufenamide in treating chronic hepatitis B
patients with HBeAg-negative CHB. It showed good predictive value Zhong Hua1
and can provide guidence for the clinical application of Peg-IFN- 1
Department of Liver Diseases ,Wuxi Fifth People’s Hospital Wuxi
based therapy. Background: To evaluate the efficacy of Tenofovir Amibufenamide
Table and Figure:Figure 1.The ROC curves of the FC-48w score in (TMF)combined with Zhenqifuzheng capsule for the treatment of
predicting HBsAg seroclearance after Peg-IFN-based therapy in the chronic hepati tis B(CHB)patients in cellular immune function and
development and validation cohort inhibit viral replication.
Figure 2.Algorithm for application of FC-48w score in predicting HBsAg Method: 70 patients of CHB on the basis of treating liver were
seroclearance after Peg-IFN-based therapy in patients with HBeAg- divided into two groups randomly. There were 36 patients in treatment
negative CHB group and 34 patients in control group. The treatment group used
Zhenqifuzheng capsule 1.4g tid combined with TMF 25mg qd, and the
PP0196 control group used TMF 25mg qd alone, both treatment course were
48 weeks treatment.
The effect of tenofovir amibufenamide on lipid metabolism in
Result: The peripheral blood immune function: after 48 weeks treatment,
patients with chronic hepatitis B is less than that of tenofovir
the CD4+, CD4+/CD8+, NK cell values in treatment group were higher
alafenamide
than those in control group(all, P<0.05). HBeAg seroconvertion rate:
Jishen Zhang1, Xiaoxiong Hu1 after 48 weeks, the rate in treatment group (50.0%)was higher than
1
Yichun People’s Hospital affiliated to Yichun University in control group(26.3%)(χ2=6.98, P<0.05). HBV DNA load: after 24
Background: This study aimed to compare the efficacy and safety of weeks treatment and 48 weeks treatment, the decrease of HBV DNA
tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) in the load in the two groups was statistically significant compared with the
treatment of chronic hepatitis B (CHB), with a particular focus on their baseline HBV DNA value (P < 0.05).
impact on lipid metabolism. Conclusion: Zhenqifuzheng capsule combined with TMF in the
Method: We conducted a retrospective real-world study involving 159 treatment of CHB was superior to TMF alone in regulating immune
CHB patients, comprising 72 patients treated with TMF and 87 patients function, and also superior to TMF alone in reducing HBVDNA load
treated with TAF. The study assessed virological and biochemical and enhancing HBeAg seroconversion rate.
response rates, renal function, and blood lipid levels after 48 weeks
of antiviral treatment. Additionally, in vitro and in vivo studies were
PP0198
performed to further investigate the effects of the two drugs on lipid
metabolism. Diagnostic accuracy of FibroScan-AST (FAST) score, non-
Result: Baseline characteristics, including age, gender ratio, viral alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver
loads, transaminase levels, renal function, and blood lipid levels, were fibrosis index (FIB-4) for identifying fibrotic non-alcoholic
similar between the two groups. After 48 weeks of treatment, the levels steatohepatitis in patients with chronic hepatitis B with non-
of HBV DNA and transaminase significantly decreased in both groups, alcoholic f
and there was no significant difference in the virological response rate Youwen Tan1
(84.2% vs 75.8%, p=0.392) and biochemical response rate (86.1% vs 1
The Third Hospital of Zhenjiang Affiliated Jiangsu University
85.1%, p=0.851). There was no significant change in renal function Background: To evaluate the diagnostic value of the FibroScan-AST
levels before and after treatment both in the two groups. There were (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan,
no significant changes in triglyceride(TG), total cholesterol(TC), and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic
high density lipoprotein cholesterol(HDL-C), Low density lipoprotein steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with
cholesterol(LDL-C), and TC/HDL-C before and after treatment in the non-alcoholic fatty liver disease (NAFLD).
TMF group. After TAF treatment, TG (1.24 vs 1.42, p=0.004), TC (4.44 Methods: All patients with CHB and NAFLD who underwent liver
vs 4.68, p=0.005), LDL-C (2.74 vs 2.87, p=0.016), TC/HDL-C (3.89 biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University
vs 4.39, p<0.001) significantly increased, while HDL-C significantly between January 2006 and December 2022 were included in the
decreased (1.19 vs 1.04, p=0.002). After 72 hours of intervention analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4
with TMF or TAF at a concentration of 10μg/mL respectively, HepG2 for diagnosing NASH and liver fibrosis were evaluated based on the
cells were harvested and stained with Oil Red O. The number of area under the receiver-operating characteristic curve (AUC).
intracellular lipid droplets in the TMF group (12196 vs 4029, p<0.001) Method: All patients with CHB and NAFLD who underwent liver
and TAF group (12483 vs 4029, p<0.001) was significantly higher biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University
than that in the control group. Male C57/BL6J mice aged 10 weeks between January 2006 and December 2022 were included in the
were gavage administered with 3.8mg/kg body weight TMF or TAF for analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4
12 weeks. Liver tissue was stained with Oil Red O, and the number for diagnosing NASH and liver fibrosis were evaluated based on the
of lipid droplets in the TAF group was significantly higher than that area under the receiver-operating characteristic curve (AUC).
in the control group (30647 vs 27614, p=0.011). After administration, Result: A total of 156 patients with CHB combined with NAFLD were
the serum TG (1.17 vs 1.06 p=0.039) and TC (2.58 vs 2.33, p=0.037) included, including 69 with NASH and fibrosis stage 2 or higher
of TAF group mice were significantly higher than those of the control (NASH+F≥2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of
group, while HDL-C was significantly lower than those of the control FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing
group (1.14 vs 1.29, p=0.021) and TMF group (1.14 vs 1.30, p=0.005). NASH+F≥2 was 0.739 (P<0.001), 0.643 (P=0.006), 0.754 (P<0.001),
There was no significant difference between the TMF group and the
and 0.665 (P=0.003), respectively. The specificity of FAST, NFS, LSM, potential use of ESPL1 as a biomarker and therapeutic target, with
and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and significant clinical implications.
the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No Table and Figure:Figure 1.Low methylation levels in the promoter
significant differences were found between groups. The AUC of FAST, region of the ESPL1 gene enhance transcriptional activity of ESPL1
NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (P=0.038), Figure 2.ESPL1 heterozygous cells have no significant effect on cell
0.725 (P=0.001), 0.851 (P<0.001), and 0.560 (P=0.533), respectively. apoptosis
The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%,
71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%,
PP0200
100%, and 50.0%, respectively. The differences between AUCs of FIB-
4 and FAST compared with LSM were 0.291 and 0.201, respectively Efficacy and safety of BLV monotherapy for chronic hepatitis
(P<0.05). delta: post treatment results through 48 weeks after the end of
Conclusion: In patients with CHB combined with NAFLD, FAST did treatment from an interim analysis of a randomized Phase 3 study
not have better accuracy than NFS and FIB-4 for predicting fibrotic MYR301
NASH, whereas LSM had better accuracy than FAST and FIB-4. Soo Aleman1, Maurizia Brunetto2,3, Antje Blank4, Pietro Andreone5,
Table and Figure:Figure 1.Receiver-operating characteristic curves Pavel Bogomolov6, Vladimir Chulanov7, Nina Mamonova7, Natalia
showing the diagnostic value of four non-invasive scores for predicting Geyvandova8, Viacheslav Morozov9, Olga Sagalova10, Tatyana
non-alcoholic steatohepatitis with advanced liver fibrosis (NASH+F≥2) Stepanova11, Grace M Chee12, Dmitry Manuilov12, Sarah Arterburn12,
in patients with chronic hepatitis B and non-alcoholic fatty liver disease. Audrey H Lau12, Anu Osinusi12, Florence Christian-Cox12, Frank Duff12,
Figure 2.Receiver-operating characteristic curves showing the Julian Schulze zur Wiesch13, Markus Cornberg14, Stefan Zeuzem15,
diagnostic value of four non-invasive scores for predicting non- Heinerr Wedemeye16, Pietro Lampertico17,18
alcoholic steatohepatitis and cirrhosis (NASH+F4) in patients with 1
Karolinska University Hospital/Karolinska Institutet, Department of
chronic hepatitis B and non-alcoholic fatty liver disease. Infectious Diseases, Stockholm, Sweden, Division of Gastroenterology
and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore,
2
University Hospital of Pisa, Hepatology Unit, Reference Center of
PP0199 the Tuscany Region for Chronic Liver Disease and Cancer, Pisa, Italy,
ESPL1 as a Potential Biomarker and Therapeutic Target in 3
University of Pisa, Department of Clinical and Experimental Medicine,
Hepatocellular Carcinoma Associated with Hepatitis B Virus: A Pisa, Italy, 4Heidelberg University, Medical Faculty Heidelberg,
Study of Expression Regulation and Biological Impact Heidelberg University Hospital, Department of Clinical Pharmacology
Bobin Hu1, Hang Wang1, Long Huang1, Hongqian Liang1, Yanfei and Pharmacoepidemiology, Heidelberg, Germany, 5University of
Feng1, Rongming Wang1, Huan Liang1, Minghua Su1, Jianning Jiang1 Modena and Reggio Emilia, Internal Medicine, Baggiovara Hospital,
Modena, Italy, 6State Budgetary Institution of Health Care of Moscow
1
The First Affiliated Hospital of Guangxi Medical University
Region “Moscow Regional Research Clinical Institute Named
Background: Despite advancements in biomarkers for hepatitis B After M.F. Vladimirsky“, Moscow, Russian Federation, 7Sechenov
virus-related hepatocellular carcinoma (HBV-HCC), reliable markers for University, Moscow, Russian Federation, 8Stavropol Regional
early diagnosis and screening of high-risk populations remain scarce. Hospital, Stavropol, Russian Federation, 9LLC Medical Company
Studies suggest the ESPL1 gene has potential as an early warning “Hepatolog“, Samara, Russian Federation, 10Federal State-Funded
biomarker for liver cancer, but its role and regulatory mechanisms in Institution of Higher Education “South Ural State Medical University
tumorigenesis need further elucidation. This study aims to investigate of Ministry of Health of the Russian Federation“, Chelyabinsk,
the expression regulation of the ESPL1 gene in HBV-HCC, analyze how Russian Federation, 11Limited Liability Company “Clinic of Modern
its promoter methylation status affects gene transcription levels, and Medicine”, Moscow, Russian Federation, 12Gilead Sciences,
evaluate the biological effects of ESPL1 on liver cancer cells, revealing Inc., Foster City, United States, 13Universitätsklinikum Hamburg-
its role in liver cancer development. Eppendorf, Medizinische Klinik Studienambulanz Hepatologie,
Method: Cancer tissues and corresponding adjacent non-tumor Hannover, Germany, 14Medizinische Hochschule Hannover, Klinik
tissues from 20 HBV-HCC patients were selected. Methylation levels für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie,
of the ESPL1 promoter were analyzed using Multiplex PCR Bisulfite Hannover, Germany, 15Department of Medicine, University Hospital,
Sequencing, and RNA-seq was performed for relative quantification Goethe-University, Frankfurt, Germany, 16Medizinische Hochschule
of ESPL1 mRNA transcription levels. CRISPR/Cas9 gene editing Hannover, Klinik für Gastroenterologie, Hepatologie, Infektiologie
established an ESPL1 knockout model in HepG2 2.2.15 cells, with real- und Endokrinologie, Hannover, Germany, RESIST, DZIF and D-Solve,
1
7Division of Gastroenterology and Hepatology, Foundation IRCCS
time quantitative PCR (Q-PCR) validating the relative expression levels
Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, 18CRC “A.
of the ESPL1 gene. Proliferation, migration, invasion capacities, and
M. and A. Migliavacca” Center for Liver Disease, Department of
apoptosis were assessed. Statistical analyses employed t-tests and
Pathophysiology and Transplantation, University of Milan, Milan, Italy
chi-square tests, with p-values < 0.05 considered significant.
Result: The methylation level of the ESPL1 promoter in HBV-HCC Background: Bulevirtide (BLV, Hepcludex®) is a first-in-class entry
tissues was significantly lower than in adjacent tissues (0.241 vs. inhibitor approved in Europe for chronic hepatitis delta (CHD). Results
0.352, p < 0.05), while ESPL1 transcript mRNA expression was from MYR301 (NCT03852719), a phase 3 randomized study, showed
higher in cancer tissues (3.0 vs. 0.1, p < 0.05). Treatment with the monotherapy with BLV 2 mg/day (d) or 10 mg/d was found to be
methyltransferase inhibitor 5-Azacytidine in HepG2 2.1.25 cells efficacious and safe through 144 weeks (w) of treatment. Here we
significantly reduced ESPL1 promoter methylation (0.350 vs. 0.255, present results from MYR301 through 48 weeks after end of treatment
p < 0.05) and increased ESPL1 transcription levels (3.5 vs. 10.5, p (FU48).
< 0.05). In gene knockout experiments, 159 monoclonal cells were Method: 150 CHD patients were randomized (stratification by
screened, identifying 64 as ESPL1 knockout heterozygotes (40.25% presence/absence of compensated cirrhosis) in a 1:1:1 ratio to Arm A:
heterozygosity). No homozygous cells were found, and the ESPL1 no active anti-HDV treatment for 48 weeks followed by BLV 10 mg/d for
mRNA level in heterozygous cells decreased by 50%, with no 96 weeks (n=51), Arm B: BLV 2 mg/d (n=49) or Arm C: BLV 10 mg/d
significant changes in proliferation, migration, invasion, or apoptosis. (n=50) for 144W. Patients will continue to be followed for 96 weeks after
Conclusion: This study highlights the critical role of ESPL1 in HBV- the end of treatment (EOT). Endpoints include: combined response
HCC, showing that low methylation of the ESPL1 promoter enhances (CR) defined as virologic response (VR; undetectable HDV RNA or a
transcriptional activity, suggesting its importance in liver cancer decrease by ≥2 log10 IU/mL from baseline) and ALT normalization,
development. Knockout of ESPL1 homozygotes may lead to cell death, VR, ALT normalization, undetectable HDV RNA, liver stiffness (LS), and
emphasizing its essential function in proliferation. Although ESPL1 liver related outcomes.
heterozygous cells did not significantly affect proliferation, migration, Result: Demographic and baseline (BL) characteristics were similar
invasion, or apoptosis, liver cancer cells may maintain biological across groups and included: mean (SD) age 42 (8.4) years, 57%
characteristics through alternative pathways. Findings support the males, 83% White, 47% with compensated cirrhosis, mean (SD)
HDV RNA 5.04 (1.34) log10 IU/mL, ALT 111 (69.0) U/L, LS 14.7 (8.8) (300 vs 126 weeks, respectively; P = .02; Figure). Seventy percent
kPa and 61% were on concomitant nucleos(t)ide analogues (NA) (7/10; Study 108) and 83% (24/29; Study 110) of patients experiencing
therapy. 72% of participants remained in the study at FU48. Efficacy HBsAg loss also achieved anti-HBs seroconversion during the study.
and safety results are summarized below (figure). All response rates The median duration of the rapid phase of HBsAg loss was 96 weeks
decreased after treatment was stopped due to viral relapses or for both groups. HBV genotype (GT) affected HBsAg loss rates, with
rebounds, which mainly occurred over the first 24 weeks after EOT. the highest in GT F (2/5; 40%), followed by GT A (9/85; 11%; Figure).
CR and ALT normalization rates were similar regardless of dose and Despite GT C being the most common (48%), its HBsAg loss rate was
duration. Viral response and undetectable HDV RNA rates post EOT 2% (11/618), and GTs B and D had 2% (6/248) and 3% (11/330) loss
were numerically higher with BLV 10 mg compared to BLV 2 mg or DT. rates, respectively.
Only 2 liver related events were reported after EOT: ascites (Arm A) Conclusion: Long-term tenofovir-based treatment resulted in low
and esophageal variceal bleed (Arm B), both in patients with cirrhosis rates of HBsAg loss, consistent with prior long-term studies. Although
at BL. Two patients first experienced HBsAg loss during the post proportions of HBsAg loss were similar for HBeAg-negative/-positive
treatment period, not associated with increase in ALT. Safety during the patients, HBeAg-positive patients required less time to achieve HBsAg
post treatment period was similar between Arms B and C, with slightly loss. GTs A and F had higher rates of HBsAg loss.
higher rates of patients with reported SAEs and grade > 3 AE in Arm A. Table and Figure:Figure 1.HBsAg Decline in Relation to HBeAg Status
Previously reported death in Arm A due to plasma cell myeloma after and Viral Genotype
patient discontinued study drug, unrelated to BLV. Of the 13 patients
who reported an SAE that started after EOT, 9/13 had post treatment
PP0202
flare with increases in ALT and HDV RNA, 4/9 were noncirrhotic, 5/9
were cirrhotic, at least 4/9 started commercial BLV with no reports of Characterization of Changes in Noninvasive Fibrosis Markers
liver failure. Over 8 Years of Tenofovir-based Treatment in Patients With
Conclusion: A subset of patients treated with BLV monotherapy for 2-3 Chronic Hepatitis B Enrolled in Two Phase 3 Trials
years maintained virological and biochemical responses one year after Jinlin Hou1, Laurent Castera2, Ming Lung Yu3, Maria Buti4,5, Frida
stopping BLV. Rates of liver related events one year after completing Abramov6, Hongyuan Wang6, Hongyuan Wang6, Ben L Da6, Dana
BLV monotherapy were low. Assessment of durability of response at 96 Tedesco6, Leland J Yee6, John F Flaherty6, Harry Janssen7,8, Milan J
weeks after EOT is planned. Sonneveld9
Table and Figure:Figure 1.Efficacy and Safety From EOT to FU48 1
Department of Infectious Diseases, State Key Laboratory of Organ
Failure Research, Nanfang Hospital, Southern Medical University,
Guangzhou, 2Department of Hepatology, Hôpital Beaujon, Université
PP0201 de Paris, Paris , 3Hepatobiliary Division, Department of Internal
Kinetics of Hepatitis B Surface Antigen Loss Following 8 Years of Medicine, Kaohsiung Medical University Hospital, Kaohsiung
Tenofovir-based Treatment in Hepatitis B e Antigen-negative and Medical University, Kaohsiung, 4Hospital Universitario Vall d’Hebron,
Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B Barcelona, 5CIBEREHD del Instituto Carlos III, Madrid, 6Gilead
Jeong Heo1, Scott K Fung2, Maria Buti3,4, Roberto Mateo5, Tahmineh Sciences, Inc., Foster City, 7Toronto Centre for Liver Disease,
Yazdi5, Frida Abramov5, John F Flaherty5, Thomas Aeschbacher5, Yu Toronto General Hospital Research Institute, University Health
Hu5, Silvia Chang5, Hongyuan Wang5, Hongmei Mo5, Young Suk Lim6, Network, Toronto, 8Department of Gastroenterology and Hepatology,
Edward J Gane7, Kosh Agarwal8 Erasmus University Medical Center, Rotterdam, 9Department of
Gastroenterology and Hepatology, Erasmus MC University Medical
1
Department of Internal Medicine, Pusan National University
Center, Rotterdam
and Biomedical Research Institute, Busan, Republic of Korea,
2
Department of Medicine, University of Toronto, Toronto, Canada, Background: Blood-based noninvasive tests (NITs) are frequently
3
Hospital Universitario Vall d’Hebron, Barcelona, Spain, 4CIBEREHD used to assess liver fibrosis severity or monitor fibrosis progression.
del Instituto Carlos III, Madrid, Spain, 5Gilead Sciences, Inc., Foster However, limited data exist on the evolution of these markers in the
City, CA, USA, 6Asan Medical Center, University of Ulsan College context of patients with chronic hepatitis B (CHB) receiving long-term
of Medicine, Seoul, Republic of Korea, 7Auckland Clinical Studies, nucleos(t)ide analogue therapy. We serially evaluated 3 blood-based
Auckland, New Zealand, 8Institute of Liver Studies, King’s College NITs to characterize changes in fibrosis over 8 years in patients with
Hospital NHS Foundation Trust, London, UK CHB receiving tenofovir-based therapy.
Background: Sustained hepatitis B surface antigen (HBsAg) loss is a Method: In 2 similarly designed Phase 3 studies (GS-
marker of hepatitis B virus (HBV) functional cure and remains the goal US-320-0108/0110) evaluating tenofovir alafenamide (TAF), HBeAg-
of antiviral treatment for patients with chronic HBV infection (CHB). We positive and -negative patients were randomized 2:1 to double-blind
sought to characterize patients with CHB achieving HBsAg loss after treatment with TAF 25 mg once daily (QD) or tenofovir disoproxil
long-term antiviral treatment enrolled in 2 large, recently completed, fumarate (TDF) 300 mg QD for up to 144 weeks followed by open-
Phase 3 studies of tenofovir alafenamide (TAF). label TAF (i.e., TAF and TDF®TAF groups). Patients were assessed
Method: In 2 studies (GS-US-320-0108/0110), hepatitis B e antigen through 384 weeks (8 years). Three blood-based NITs were evaluated:
(HBeAg)-negative (Study 108; n=425) and -positive (Study 110; FibroTest (BioPredictive SAS), aspartate aminotransferase–to-platelet
n=873) patients with CHB were treated with TAF or tenofovir disoproxil ratio index (APRI), and fibrosis index based on 4 factors (FIB-4), all
fumarate followed by TAF for up to 8 years. HBsAg levels were performed at baseline (BL) and annually thereafter. The FibroTest
measured using the Abbott Architect assay (quantification limit ≤0.05 cutoff for no to mild fibrosis was <0.49; moderate to severe, 0.49–0.74;
IU/mL); HBsAg loss was defined as a change from HBsAg positive and cirrhosis, >0.74. Respective cutoffs to rule out or rule in advanced
at baseline (BL) to negative at a post-BL visit with anti-HBs negative/ fibrosis or cirrhosis were FIB-4 ≤0.7 and >3.25 or APRI ≤0.45 and >2.
missing at BL. HBsAg seroconversion was defined as HBsAg loss plus Differences in blood-based NITs were evaluated using descriptive
a change from anti-HBs negative/missing at BL to positive at a post-BL statistics of absolute values and change from BL through year 8.
visit. The rapid-phase kinetics of HBsAg loss were calculated as the Result: Overall, 1632 patients were included in this pooled analysis.
time required for a negative HBsAg result, starting from a constant rate The mean (SD) absolute values for FibroTest, APRI, and FIB-4 at
of decline of at least 0.12 log10 IU/mL/month. BL and changes from BL through year 8 were comparable across
Result: Median (IQR) BL HBsAg levels were 3.51 (3.14, 3.85) and treatment groups, with the greatest mean declines observed at week
4.22 log10 IU/mL (3.68, 4.64) for Studies 108 and 110, respectively. 48 (Table). At year 8, 95% of TAF- and 88% of TDF®TAF–treated
At year 8, the median (IQR) decline in HBsAg level was 0.60 (−1.16, patients with available FibroTest data with a BL fibrosis category of no
−0.19) log10 IU/mL from BL, with 2%–3% of patients experiencing or minimal fibrosis remained in that fibrosis category (Table). Similar
HBsAg loss. Both HBeAg-negative (10/425; 2%) and -positive patients trends were observed for APRI and FIB-4. For patients with FibroTest
(29/873; 3%) had similar HBsAg loss rates, with longer median values suggestive of cirrhosis at BL, 75% showed improvement at year
duration in HBeAg-negative patients than HBeAg-positive patients 8. Similarly, 99% and 83% of patients with advanced fibrosis/cirrhosis
at BL by APRI and FIB-4, respectively, improved by year 8. Overall, few Prognostic Value of Combined HBV pgRNA and MELD Score for
low/intermediate-category patients moved to a higher fibrosis category Mortality in HBV-Related Acute-on-Chronic Liver Failure
at year 8. Chen Fenlan1, Zhang Xiongle 1, Cheng Jilin2,3, Liping Chen4,5
Conclusion: Improvements in FibroTest, FIB-4, and APRI scores were 1
Department of infectious Diseases, Fuqing City Hospital Affiliated
observed over 8 years of tenofovir-based treatment. Early declines to Fujian Medical University, Fuqing, Fuzhou, China, 2Shanghai YiDa
may be due to reduced necroinflammation. The significance of these Hospital, 3Shanghai Public Health Clinical Center, 4Shanghai Geriatric
dynamic long-term changes in fibrosis markers requires further Medical Center, Shanghai, China , 5Zhongshan Hospital, Fudan
investigation. University, Shanghai, China
Table and Figure:Figure 1.Changes From Baseline in FibroTest, APRI, Background: Rapid prognostic assessment of individuals suffering
and FIB-4 Scores by Treatment Group from HBV-related acute-on-chronic liver failure (HBV-ACLF) is crucial
for optimizing clinical intervention. The aim of the study is to explore the
PP0203 clinical value of combining Hepatitis B Virus (HBV) pregenomic RNA
Tenofovir-based antiviral therapy reduces long-term incidence of (pgRNA) with the Model for End-stage Liver Disease (MELD) score in
hepatocellular carcinoma in chronic hepatitis B patients assessing the short-term prognosis of patients with HBV-ACLF.
Method: This retrospective study included 220 patients with HBV-
W Ray Kim1, Young Suk Lim2, Harry LA Janssen3,4, Sang Hoon Ahn5,
ACLF hospitalized at Fuqing Hospital in Fujian Province from July
Ira Jacobson6, Masashi Mizokami7, Grace Wong8, Frida Abramov9,
2016 to July 2024. Basic information of the patients was recorded
Leland J Yee9, Hongyuan Wang9, Carrie Frenette9,10, John F Flaherty9,
and the clinical data within 24 hours after the diagnosis of HBV-ACLF
Scott K Fung11, Patrick Marcellin12, Wai Kay Seto13, Kosh Agarwal14,
at our hospital was analyzed, including HBV pgRNA, blood routine,
Jinlin Hou15, Seng Gee Lim16, Jia Horng Kao17, Maria Buti18
C-reactive protein, biochemical profile, coagulation function, and
1
Mayo Clinic College of Medicine, Rochester, 2Asan Medical Center,
MELD score. Patients were divided into survival and death groups
Seoul, 3Erasmus MC University Hospital, Rotterdam, 4Toronto Centre
based on the follow-up results within 90 days after the diagnosis of
for Liver Disease, Toronto, 5Yonsei University College of Medicine,
HBV-ACLF. Binary logistic regression analysis was applied to identify
Seoul, 6NYU Langone Health, New York, 7National Center for
Global Health and Medicine, Ichikawa, 8The Chinese University of independent risk factors affecting the 90-day prognosis of HBV-
Hong Kong, Hong Kong 9Gilead Sciences, Foster City, 10Scripps ACLF patients. The predictive value of HBV pgRNA, MELD, and the
Clinic, La Jolla, 11University of Toronto, Toronto, 12Hôpital Beaujon, combined HBV pgRNA and MELD score models was assessed using
Clichy, 13The University of Hong Kong, Hong Kong14Kings College receiver operating characteristic (ROC) curves and MedCalc 18.2.1
Hospital, London, 15Nanfang Hospital of Southern Medical University, software.
Guangzhou, 16National University Hospital, Singapore, 17National Result: During the 90-day follow-up after hospitalization and
Taiwan University Hospital, Taipei, 18Hospital General Universitari Vall discharge, 90 patients died, and 130 survived. The survival group
d‘Hebron, Ciberehd del Instituto Carlos III, Barcelona had lower HBV pgRNA levels [4.120 (3.8050, 5.0625) lgIU/ml vs. 6.07
Background:Chronic hepatitis B (CHB) is a leading cause of (5.6175, 6.7100) lgIU/ml, Z=-10.144,P<0.05], and lower MELD score
hepatocellular carcinoma (HCC). Antiviral therapy with nucleot(s)ide [21.2711 (18.5006, 23.1394)vs.31.8807 (27.8187, 34.6558) Z=-12.033,
analogues (NAs) has been shown to reduce HCC risk. This pooled P<0.05],than that of the death group. Multivariate logistic regression
analysis of four phase 3 studies (GS-US-174-0102 [Study 102], GS- analysis showed that HBV pgRNA and MELD score are independent
US-174-0103 [Study 103], GS-US-320-0108 [Study 108], and GS- factors affecting the short-term mortality of HBV-ACLF patients [Odds
US-320-0110 [Study 110]) aimed to assess impact of tenofovir (TFV)- ratio (OR)=12.378, 95% Confidence interval (CI) 2.676~57.246;
based NAs on long term HCC risk in CHB patients, utilizing three OR=3.205, 95%CI 1.334~7.702; both P<0.01]. The areas under the
validated risk prediction algorithms. ROC curve for the three scoring models were 0.902, 0.977, and 0.988
Method:Studies 102 and 103 randomized patients 2:1 to double-blind for HBV pgRNA, MELD score, and the combination of HBV pgRNA and
(DB) treatment with tenofovir disoproxil fumarate (TDF) or adefovir MELD score,respectively. The combined HBV pgRNA and MELD score
dipivoxil (ADV) for 48 weeks, then open-label (OL) TDF, whereas model outperformed both individual scores, with statistically significant
Studies 108 and 110 randomized patients 2:1 to DB treatment with differences (Z=4.487, 2.012, both P<0.05).The optimal cutoff value
tenofovir alafenamide (TAF) or TDF for up to 144 weeks, then OL for the combination of HBV pgRNA and MELD score with a Youden
TAF. All patients were assessed over 384 weeks (8 years). HCC risk index of 0.967 was determined to be 0.301679. Based on this, our
was estimated using the following models: Risk Estimation for HCC new predictive model score is: -42.253+2.516×lgRNA+1.165×MELD,
in Chronic Hepatitis B (REACH-B); modified Platelet Age Gender- which we name the pgRNA-MELD. So patients with pgRNA-MELD
HBV (mPAGE-B); and age–Male–ALBI– Platelets (aMAP). Primary score ≥0.301679 exhibits significantly lower survival rates compared
outcomes included: HCC incidence (via standardized incidence ratios to those scoring <0.301679 (χ²=253.087, P<0.01).
[SIRs] of HCC based on ratio of observed vs. model-predicted cases Conclusion: A new prognostic score based on combining HBV
[REACH-B]); and the proportions of patients who shifted from baseline pgRNA and MELD score models can effectively predict the short-term
risk categories (aMAP and mPAGE-B). prognosis of HBV-ACLF patients, showing higher clinical assessment
Result:In total, 1,939 (n = 641 from 102/103 and n = 1,298 from 108/110) value.
patients were included in the pooled analysis. By Year 8, 41 (2.1%)
patients had developed HCC. By multivariate analysis, older age, male PP0205
sex, and cirrhosis at baseline were associated with HCC development. Study on the Differences in Gut Microbiota and Metabolites
By REACH-B, the SIR was 0.39 (95% confidence interval: 0.29, 0.53; Between Relapsed and Non-relapsed CHB Patients After Drug
p < 0.0001), indicating the observed incidence to be 61% lower than Discontinuation
the predicted incidence; for patients with cirrhosis, the SIR was 46%
Xiaoke Li1,2, Xin Sun1, Shuo Li3, Tingyu Zhang1, Yizi Ao1, Shuying Hu1,
lower. By aMAP and mPAGE-B models, most patients were at low- or
Jinyu Li1, Hongbo Du1,2, Yongan Ye4,2
medium-risk for HCC development at baseline, and either stayed the 1
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing
same or shifted to a lower risk category at Year 8, while most high-risk
100700, China, 2Institute of Liver Diseases, Dongzhimen Hospital,
patients had shifted to at least medium-risk by Year 8.
Beijing University of Chinese Medicine, Beijing 100700, China,
Conclusion:In this large dataset of prospectively followed CHB 3
Department of Traditional Chinese Medicine, Peking University
patients, HCC risk was significantly impacted with long-term TFV- Shougang Hospital, Beijing, China, 4Academy of Liver disease,
based treatment in CHB patients with and without cirrhosis. Dongzhimen Hospital, Beijing Unversity of Chinese Medicine
Background: Hepatitis B virus (HBV) infection poses a global health
threat, with issues like drug resistance and high relapse rates. This
PP0204 study explores gut microbiota and metabolite differences between
relapsed and non-relapsed CHB patients after drug discontinuation, (HBsAg) clearance rate between CHB patients with and without
offering insights for safe withdrawal. MAFLD treated with PegIFNα-2b combined with NAs, and to provide a
Method: A multi-center study included 100 CHB patients who tested reference for clinical treatment.
negative for HBeAg and were treated between January and September Method: This is a prospective, multicenter, real-world clinical study.
2019. The cohort was divided into two groups: relapse (CHB_R) and CHB patients with or without MAFLD treated with NAs for more than
non-relapse (CHB_N) based on whether they experienced relapse after 6 months, HBeAg negative, HBsAg ≤ 1500 IU/mL, HBV DNA positive
treatment discontinuation. A healthy control group of 50 individuals was or negative, ALT < 5 × ULN were included. All patients were treated
also included. Participants were stratified based on traditional Chinese with PegIFNα-2b combined with NAs for 48 weeks. The primary
medicine intervention and relapse status, and plasma and stool outcome was the difference in HBsAg clearance rate between CHB
samples were collected for metagenomic, metabolomic, and lipidomic patients with and without MAFLD at 48 weeks. Secondary outcome
analyses. Correlation and redundancy analyses were conducted to was the proportion of participants with HBsAg decline > 1 lg IU/mL.
associate gut microbiota, metabolites, and clinical indicators. Other outcomes included the proportion of participants with HBV
Result: Compared to the non-relapse group (CHB_N), the relapse DNA undetectable, changes in body mass index (BMI), liver function
group (CHB_R) showed a significant reduction in gut microbiota biomarkers and blood routine. Safety was also assessed.
diversity, primarily characterized by a decrease in microbiota involved Result: A total of 354 CHB patients with or without MAFLD from
in short-chain fatty acid production and amino acid metabolism. 10 centers were included in this study from December 1, 2022 to
Functional analysis revealed increased expression of lipid metabolism- November 20, 2024. Of these, 93 patients (45 with MAFLD and 48
related genes and decreased expression of genes associated without MAFLD) had completed 48 weeks of treatment. The HBsAg
with amino acid metabolism, signal recognition, and transporter clearance rates at 24 and 48 weeks were 26.67% (12/45) and 33.33%
pathways (all P < 0.05). Four plasma differential metabolites were (15/45) in CHB patients with MAFLD, and 37.50% (18/4) and 41.67%
identified, mainly phosphatidylinositol and amino acids, while ten stool (15/45) in CHB patients without MAFLD. The differences between the
differential metabolites included amino acids, fatty acids, steroids, two groups were not statistically significant (all P values > 0.05). Both
and lipids (all P < 0.05). The differential metabolic pathways involved groups showed significant reductions in HBsAg levels from baseline to
arginine biosynthesis, glutathione metabolism, and amino acid 24 and 48 weeks (all P values < 0.01), but the differences between the
metabolism. Correlation analysis showed that plasma metabolites two groups were not significant (all P values > 0.05). By week 48, the
such as PI(22:6/0:0), PI(18:1/0:0), Glutamate, and 1-Methyl-L-Histidine proportions of CHB patients with MAFLD and without MAFLD achieving
significantly influenced gut microbiota species abundance (all P < an HBsAg decline > 1 lg IU/mL were 44.44% and 47.92%, respectively
0.05). 1-Methyl-L-Histidine was positively correlated with AST, CHE, (P > 0.05). After 48 weeks of treatment, the proportion of patients with
and GGT, and PI(22:6/0:0) with AST (P < 0.05). In stool, metabolites HBV DNA undetectable reached 100% in both groups. CHB patients
like Arctiol, Cholic acid, Sodium deoxycholate, and Prolylproline with MAFLD had a higher baseline BMI compared to those without
significantly affected microbiota composition (all P < 0.05). ALT was MAFLD, and BMI decreased significantly with prolonged treatment in
negatively correlated with Sodium deoxycholate and other metabolites both groups. ALT and AST in the two groups were significantly higher
(all P < 0.05), and TBIL showed a negative correlation with Prolylproline than baseline at 24 weeks (P > 0.05), and decreased at 48 weeks.
(P < 0.05). Conclusion: MAFLD has no impact on HBsAg clearance in CHB
Conclusion: CHB relapse patients after drug withdrawal show patients treated with NAs combined with PegIFNα-2b.
reduced gut microbiota linked to short-chain fatty acid and amino acid Table and Figure:Figure 1.Table:Efficacy of NAs Combined With
metabolism, along with changes in amino acid and lipid metabolism. PegIFNα-2b in Chronic Hepatitis B Patients With / Without Metabolic-
These alterations may indirectly impact liver function, providing related Fatty Liver Disease
evidence for microbiota-based interventions to improve relapse Figure 2.Clearance Rate of HBsAg and changes of HBsAg
outcomes.
Table and Figure:Figure 1.Species structure and functional
PP0207
characteristics of gut microbiota in patients with recurrent CHB after
discontinuation Current Status of HBV Infection in Infertility Patients: A Preliminary
Figure 2.Metabolite and related functional pathway characteristics of Survey Report
recurrent patients with CHB after discontinuation Wei Xue1, Jiexiao Wang1, Yingren Zhao1, Jinfeng Liu1
1
The First Affiliated Hospital of Xi’an Jiaotong University
PP0206 Background: The infertility rate in China has risen from 11.9% in
2007 to 17.6% in 2020, exceeding the global prevalence (8-12%).
Efficacy of NAs Combined With PegIFNα-2b in Chronic Hepatitis
The impact of Hepatitis B virus (HBV) infection on infertility remains
B Patients With / Without Metabolic-related Fatty Liver Disease: A
controversial. This survey aims to assess the status of infertility in China
Multicenter, Prospective Real-world Study
and related HBV infection issues, providing a theoretical foundation
Huxibaiheti 1, Dou Jing1, Zeng Sheng Tao2, Da Xin3, Lu Xiao Bo4, for strategies to prevent mother-to-child transmission (MTCT) in this
Wu Yan Qin5, Maimaitiaili ·Tuerxun6, Zhang Yong Ping7, Wang population.
Zhuan Guo1, Maimaitijiang ·Wubuliaishan8, Wang Jun9, Yue Yong Method: The design and optimization of the questionnaire were
Hong1, Wang Xiao Bo1, Chen Min10, Ma Yan1, Sayilaxi ·Jieensinue1, performed by experts in infection, hepatology, and fertility. It covered
Ning Zhong Hui1, Xu Qiang1, Wang Hong Feng1, Ni Ka1, Ailifeire topics including situation of assisted reproductive technology (ART),
·Abulajiang1, Zhang Rong1, Guo Feng1, Wu Xu11, Wang Xiao Zhong1 HBV prevention and control measures, and challenges in eliminating
1
Traditional Chinese Medical Hospital Affiliated to Xinjiang Medical HBV transmission. Participants included healthcare professionals
University, 2Yili Prefecture Xinhua Hospital, 3Kelamayi Center Hospital, (HCPs) such as doctors, nurses, and laboratory technicians from
4
The First Affiliated Hospital of Xinjiang Medical University, 5Bazhou various fertility clinics.
People‘s Hospital, 6The First People‘s Hospital of Kashgar, 7People‘s
Result: A total of 156 questionnaires were collected from fertility
Hospital of Xinjiang Uygur Autonomous Region, 8Hotan Infectious
clinics across 12 provinces in China. Most clinics reported an annual
Diseases Hospital, 9The First People‘s Hospital of Aksu Prefecture,
number of intrauterine insemination cycles ranging from 1,000 to
1
0Changji Branch Hospital, First Affiliated Hospital of Xinjiang Medical
2,000 (34.62%) or over 10,000 cycles (23.72%). Approximately
University, 11The Fourth Clinical Medical College of Xinjiang Medical
University 75.64% of clinics had ART fertilization rates above 50%, with around
73.07% achieving an average cleavage rate of more than 5 embryos.
Background: Functional cure is now an achievable and ideal goal Additionally, 66.03% of clinics reported clinical pregnancy rates
of hepatitis B virus (HBV) treatment. However, the antiviral efficacy in exceeding 50%. Regarding HBV management, over 80% of HCPs
chronic hepatitis B (CHB) patients with and without metabolic-related recognized patterns of HBV infection. About half estimated that the
fatty liver disease (MAFLD) remains controversial. The purpose of this HBV infection rate among infertility patients exceeded 5%, with
study was to evaluate the difference in hepatitis B surface antigen 13.46% suggesting it could surpass 10%. Notably, approximately
70.51% of HCPs encountered HBV-infected infertility patients in the effects on fetal development or infant growth before 36 months,
past 3 months. However, over 30% were either unaware of antiviral suggesting TDF’s safety in preventing HBV MTCT and during
treatment or did not recommend it, indicating a need for enhanced breastfeeding.
education on HBV management. In terms of HBV screening, 90.38% of Table and Figure:Figure 1.The effects of intrauterine TFV-exposed at
HCPs routinely conducted testing, however, 51.28% did not follow up different gestational weeks on intrauterine growth and development
regularly with HBV-infected patients. Many HCPs expressed a desire to and Apgar score of newborns.
understand the psychological support needs of HBV-infected infertility Figure 2.Effects of TFV intrauterine and extrauterine exposed on growth
patients, with 25% believing these patients required professional and development of infants aged 0-36 months.
counseling and approximately 46.15% feeling these patients needed
more support and understanding. Only 22.44% of HCPs thought that
PP0209
the psychological state of HBV-infected infertility patients was similar
to that of other infertility patients. High-risk factors associated with significant liver damage in
Conclusion: This survey highlights the potential impact of HBV chronic hepatitis B patients with “immune tolerance” phase
infection on ART and reveals gaps in HCPs’ knowledge regarding Xuyang Li1, Mengwen He1, Chunyan Wang2, DONG JI2, Fusheng
HBV management. There is also a notable deficiency in understanding Wang2
the psychological support needs of HBV-infected infertility patients. 1
Peking University 302 Clinical Medical School, 2The Fifth Medical
Improving awareness of HBV infection among ART HCPs is crucial for Center of PLA General Hospital
enhancing patient care and reducing transmission risks. Background: Whether patients with chronic hepatitis B (CHB) in the
“immune tolerance (IT)” phase need treatment is still under discussion
PP0208 without the assistance of liver biopsy. The present study was to
investigate histologic characteristics and identify the high-risk factors
Impact of In Utero and Postnatal Tenofovir Exposure on Growth
for significant liver damage (SLD) in the specific patients.
and Development in Infants Born to Pregnant Women with
Method: The “IT-CHB” patients (HBsAg>104 IU/ml, HBeAg-positive,
Hepatitis B Virus Infection
HBVDNA >2ⅹ107 IU/ml, normal ALT, defined by 2022 China CHB
HUAN LIANG1, BOBIN HU1, RONGMING WANG1, HENGKAI LIANG1, guidelines) who underwent liver biopsy, were retrospectively
LU WEI1, QINGMEI LI1, TUMEI SU1, QIANBIN Yin1, JIANNING analyzed, and were divided into two groups with or without SLD
JIANG1 (≥G2 [inflammation] or S2 [fibrosis]), assessed using Scheuer’s
1
The First Affiliated Hospital of Guangxi Medical University classification. Univariate and multivariable logistic regression analyses
Background: Mother-to-child transmission (MTCT) is the predominant were employed to identify high-risk factors.
route for Hepatitis B virus (HBV) spread, and international guidelines Result: A total of 251 “IT-CHB” patients were included, of whom
endorse tenofovir disoproxil fumarate (TDF) for pregnant women to 14.3% (36 of 251) had SLD. The study population had a median age
prevent MTCT. However, the impact of tenofovir (TFV) exposure on of 30.9 years (range:17‐60 yr), with a male-to-female ratio of 2.7:1.
growth and development in newborns and infants from HBV-infected The multivariable logistic regression analysis showed that stiffness
mothers treated with TDF merits further study. measurements (LSM, OR=1.308, 95% CI:1.053-1.625, P=0.003)
Method: The study included pregnant women infected with HBV who and aspartate aminotransferase (AST, OR=1.157, 95% CI:1.029-
received TDF treatment and delivered at our hospital from January 1.300, P<0.001) were high-risk factor for SLD, while neither HBV
1, 2022, to December 31, 2022, as well as their newborns and DNA (OR=0.490, 95% CI:0.239-1.005, P=0.052) nor platelet count
infants aged 0-3 years. Ultra-performance liquid chromatography- (OR=0.967, 95% CI:0.983-0.997, P=0.006) were identified as risk
tandem mass spectrometry (UPLC-MS) was utilized to quantify TFV factors.
concentrations in peripheral blood, umbilical cord blood, and breast Conclusion: A minor proportion of “IT-CHB” patients exhibits
milk. TFV exposure intensity in utero was analyzed using Spearman’s significant liver damage, patients with high-risk factors associated with
correlation in 8 newborns. The 24-hour pharmacokinetics of TFV in SLD should be treated timely to prevent further liver inflammation or
serum and breast milk postpartum was evaluated in 14 women using fibrosis progression.
repeated measures ANOVA, with TDF administration at 0, 1.5, 12, and
24 hours. Non-parametric tests compared TFV levels in serum and PP0210
breast milk at 0 and 1.5 hours post-TDF in 57 women during various
lactation stages. TFV concentrations in 20 breastfed infants aged The Impact of Hepatic Steatosis on the Efficacy of Pegylated
7-12 months were assessed by comparing peripheral blood levels Interferon Therapy in Chronic HBV Infection
with concurrent breast milk concentrations. A total of 157 newborns Pengxuan Wu1, Shan Ren2, Dacheng Sheng1, Jianxia Dong1, Jing
and 235 infants exposed to TDF both in utero and postnatally were Zhao1, Sujun Zheng1
compared with 75 unexposed controls to evaluate the impact of TFV 1
First Department of Hepatology, Beijing YouAn Hospital, Beijing,
exposure on growth and nutritional status at different ages. China, 2Beijing You‘an Hospital, Capital Medical University
Result: 1. The cord blood TFV concentrations in 8 newborns were Background: Non-alcoholic fatty liver disease (NAFLD) and chronic
positively correlated with maternal peripheral blood concentrations hepatitis B (CHB) are common liver diseases. The coexistence of
at delivery (r2=0.734, P<0.05), with newborns exposed to 81.85% of NAFLD may affect the antiviral treatment effect in CHB patients. This
maternal blood exposure levels in utero. 2. The trough concentration study aimed to investigate the effect of hepatic steatosis on the efficacy
occurred at 0 hours , and the peak concentration at 1.5 hours post- of pegylated interferon in patients with CHB, providing evidence for
TDF administration, Serum TFV concentrations in women taking TDF individualized antiviral treatment strategies.
varied with time of administration and were not affected by the duration Method: This single-center, retrospective cohort study included 282
of lactation, while relatively stable TFV concentrations in breast milk HBeAg-negative CHB patients with baseline HBsAg < 1500 IU/mL who
over 24 hours,but declined rapidly with prolonged lactation.3. No TFV received interferon treatment during the treatment period at Beijing
was detected in the peripheral blood of 20 infants aged 7-12 months YouAn Hospital from 2019 to 2023. Clinical data at baseline, week 12,
whose mothers used TDF during pregnancy and Lactation period. 4. 24, 36, 48 were collected. Controlled attenuation parameter (CAP) and
No statistical differences were observed in gender ratio, gestational liver stiffness measure (LSM) were evaluated at baseline, and patients
age, birth weight, length, chest circumference, head circumference, or were divided into no steatosis, mild steatosis, moderate steatosis, and
Apgar scores at birth between 157 TFV-exposed and 75 unexposed severe steatosis according to CAP values. The primary endpoint of the
newborns (P>0.05). 5. No differences in growth and development study was HBsAg loss after treatment.
were found between 144 infants with both in utero and postnatal TFV- Result: A total of 282 patients were enrolled, including 139 patients
exposed, 16 with in utero-exposed, and 75 unexposed infants aged in the hepatic steatosis group (HS group) and 143 patients in the non-
1-3 years (P>0.05). hepatic steatosis group (non-HS group). The cumulative incidence
Conclusion: TFV exposed in utero and postnatal show no significant
of HBsAg loss were 25.90% (n=36/139) in HS group and 26.57% Table and Figure:Figure 1.Virological response after NAs antiviral
(38/143) in non-HS group at Week 48 (p>0.05); After Propensity Score therapy
Matching (PSM), The HBsAg loss rates was 26.96% (31/115), 27.78% Figure 2.Changes of liver function after NAs antiviral treatment and
(10/36), 47.37% (9/19) and 20.69% (12/58) in CHBs without and with analysis of factors affecting CVR
mild, moderate, severe hepatic steatosis. HBsAg clearance was
significantly higher in patients with moderate hepatic steatosis than
PP0212
those with severe hepatic steatosis (47.37% vs 20.69%, p = 0.014). At
24 weeks, patients with mild, moderate, and severe hepatic steatosis High-risk factors associated with significant liver damage in young
exhibited significantly higher levels of alanine aminotransferase chronic hepatitis B patients with normal alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) compared to patients in Yifan Guo1, Chunyan Wang2, Dong Ji2, Fusheng Wang2
the non-HS group (p<0.05). Patients with mild to moderate hepatic 1
Peking University 302 Clinical Medical School, 2The Fifth Medical
steatosis showed a faster decline in HBsAg during treatment; however, Center of PLA General Hospital
this difference was not statistically significant. Background: To determine whether young patients (<30 years) with
Conclusion: Hepatic steatosis may affect the efficacy of pegylated chronic Hepatitis B (CHB) and normal alanine aminotransferase (ALT)
interferon in CHB patients. CHBs with mild and moderate hepatic (< 40 U/L) require antiviral therapy.
steatosis are more sensitive for the treatment, while patients with Method: Clinical data of the above specific group of patients were
severe hepatic steatosis may have adverse effect to the therapy. analyzed in this retrospective cross-sectional study. Hepatic fibrosis
Table and Figure:Figure 1.Table 1 Demographic and clinical (S0-4) and inflammation (G0-4) were evaluated according to Scheuer
characteristics of participants at baseline scoring system. Liver inflammation ≥G2 and/or liver fibrosis≥S2 was
Figure 2.Figure 1 The cumulative incidence of HBsAg clearance in HS defined as significant liver damage (SLD). The patients were divided
group and non-HS group. into two groups (with or without SLD) according to the pathological
(inflammation or fibrosis) score ≥2. Multivariate logistic regression
PP0211 analysis was used to analyze the independent risk factors.
Result: Totally, of 883 patients, 62.1% were male, with a median age
Effect of type 2 diabetes on the efficacy of nucleoside (acid)
of 25.4 years (IQR 22.4–28.0). Among them, 28.5% of patients had
analogues in chronic hepatitis B
SLD. HBV DNA levels were <2000 IU/mL in 176 (19.9%) patients,
Minghui Zeng1,2, Liang Xu2,3, Yuqiang MI2,3 2000–2×107 IU/mL in 322 (36.5%) and ≥2×107 IU/mL in 385(43.6%).
1
Tianjin Medical University, 2Clinical School of the Second People’s The proportion of the patients in the high-normal AST group (≥ 20U/L)
Hospital, 3Tianjin Research Institute of Liver Diseases was 67.5%. The percentages of patients in the PLT ≤ 100×10⁹/L group
Background: Nucleoside (acid) analogs (NAs) have become the main were 1.6%. Logistic regression analysis showed that risk factors for
method for treating chronic hepatitis B (CHB), but the impact of type 2 SLD were AST≥ 20U/L (OR=1.841, 95% CI: 1.225–2.766, P =0.003),
diabetes mellitus (T2DM) on their efficacy remains unclear.This study PLT ≤ 100×10⁹/L (OR=4.059, 95% CI: 1.287–12.799, P =0.017) and
aims to explore this issue and provide a scientific basis for developing HBV DNA 2000–2×107 IU/mL (OR=1.601, 95% CI: 1.008–2.543,
a more optimized treatment strategy for CHB patients with T2DM. P=0.046). Whereas, patients with HBV DNA≥2×107 IU/mL (OR=0.424,
Method: Patients with CHB who underwent liver biopsy in Tianjin 95% CI: 0.239 ~ 0.752, P=0.003) had relatively lower likelihood of SLD.
Second People’s Hospital from January 2015 to June 2021 and were Whereas, the status of HBeAg had no impact on SLD.
newly treated by NAs were included (n=350).According to their Conclusion: Significant liver damage is still present in a significant
medical history, the patients were divided into T2DM-CHB group and proportion of young CHB patients with normal ALT, antiviral treatment
CHB group. And after propensity matching according to gender, age, should be initiated in a timely manner for such patients with high-risk
Lg (HBV DNA) level, HBeAg status, ALT and AST levels, a total of factors regardless of HBeAg status.
238 patients were included (T2DM-CHB group: n=70; CHB group: Table and Figure:Figure 1.Factors significantly associated with
n=168).A 5-year retrospective follow-up study was conducted to significant liver damage based on multivariable logistic regression
collect patients’ medication status, liver and kidney function indicators, analysis in young CHB patients with normal ALT.
virological indicators to compare the differences between the two
groups.
PP0213
Result: During the 5-year follow-up, the levels of Lg(HBV DNA) and
HBsAg in T2DM-CHB group were significantly higher than those in Tenofovir Alafenamide Therapy Throughout Pregnancy in Mothers
CHB group (P < 0.05) at 1 st, 3 rd, 6 th and 18 th, 36 th, 48 th ,60 with Hepatitis B
th after NAs antiviral treatment,respectively.CHB patients with T2DM Xingfei Pan1,2,3, Liyang Zhou1,2,3, Jing Hu4,2,3, Panpan Zhai1,2,3, Xueting
had a longer time to first reach cumulative virological response (CVR) Ou1,2,3, Fang He5,2,3, Calvin Pan6,7
than CHB patients (25.58 months vs. 14.84 months, P < 0.001), and 1
The Third Affiliated Hospital of Guangzhou Medical University,
had a lower cumulative CVR rate at all follow-up periods (1st: 1.43% Department of Infectious Diseases, 2Guangdong Provincial Key
vs.13.10%; 3rd: 4.29% vs. 19.64%; 6th: 14.29% vs. 45.24%; 12th: Laboratory of Major Obstetric Diseases, 3Guangdong Provincial
22.86% vs. 64.29%;18 th: 32.86% vs. 70.83%; 24 th: 38.57% vs. Clinical Research Center for Obstetrics and Gynecology, 4The Third
77.98%;30 th: 42.86% vs. 79.76%; 36 th: 45.71% vs. 82.14%; 42 th: Affiliated Hospital of Guangzhou Medical University, Department of
47.14% vs.83.92%; 48 th: 50% vs. 85.12%; 54 th: 52.86% vs. 85.71%; Obstetrics and Gynecology, Department of Obstetrics, 5The Third
60 th: 54.86% vs. 86.31%) (all P < 0.05).The HBeAg cumulative Affiliated Hospital of Guangzhou Medical University, Department
clearance rate and seroconversion rate of patients in the T2DM-CHB of Obstetrics and Gynecology, 6Division of Gastroenterology and
group were significantly lower than those in the CHB group from 6th to Hepatology, Department of Medicine, NYU Langone Health, 7NYU
Grossman School of Medicine
30th of follow-up (P < 0.05).The liver function of patients in CHB group
recovered to normal within 2 years, and the cumulative normalization Background: Mothers with active chronic hepatitis B (CHB) or
rate in each follow-up time was higher than that in T2DM-CHB group advanced fibrosis may require antiviral therapy throughout pregnancy.
(1st: 33.93% vs.12.86%; 3rd: 48.81% vs.28.57%; 6th: 76.19% vs. However, current guidelines recommend tenofovir disoproxil fumarate
47.14%; 12th: 86.90% vs.51.43%; 18th: 89.29% vs.57.14%; 24th: (TDF), which is unsuitable for mothers at risk of renal dysfunction or
92.26% vs. 62.86% (all P < 0.05).Cox regression showed that T2DM decreased bone mineral density. This study aimed to evaluate the
and high Lg (HBV DNA) levels were positively correlated with the time safety of tenofovir alafenamide (TAF) therapy throughout pregnancy.
to CVR (HR: 0.706, P < 0.001 and 0.624, P < 0.001), while eGFR was Method: Mothers with CHB treated with TAF or no therapy were
negatively correlated (HR: 1.197, P < 0.031). retrospectively enrolled at a university hospital. Participants were
Conclusion: The presence of T2DM reduces the virological response divided into: (A) TAF-first trimester, (B) TAF-late trimester, and (C)
of CHB patients to NAs treatment, prolongs the time to achieve CVR no treatment groups. Propensity score matching (PSM) was used to
and liver function recovery. create comparable groups. Primary assessments included serious
adverse events, and secondary assessments were predictors of such the immune response of hepatitis B to develop targeted drugs and
events and vertical transmission rates. improve the cure rate of hepatitis B patients.T cells are important
Result: Of 284 mothers, 160 were selected via PSM (17 in group A, immune cells. However, the transcriptional differences and related
68 in group B, and 75 in group C), with a mean age of 32.4 years. molecular mechanisms of T cells between individuals with good and
Baseline characteristics were balanced, except for elevated ALT, poor antiviral treatment response have not been fully elucidated.This
HBeAg positivity, and higher HBV DNA levels in the TAF-first trimester study aims to explore the transcriptomic characteristics of T cells in
group. No significant differences were observed in fetal loss, low birth pediatric patients with chronic hepatitis B (CHB) who exhibit poor
weight, preterm delivery, or congenital abnormalities between groups antiviral treatment response.
A and B, or groups A and C (Table 1). Other adverse events were Method: The selected pediatric patients with CHB undergoing
similar across groups, except for a higher frequency of gestational treatment with nucleoside analogues (NAs) and interferon-α (IFN-α) 48
diabetes in the TAF-first trimester group. Independent predictors of weeks. By extracting peripheral blood mononuclear cells (PBMCs) and
serious events were identified, and no infants were reported with HBV performing single-cell RNA sequencing, the immune characteristics of
infection at 28 weeks. patients with and without HBsAg loss were comprehensively analyzed.
Conclusion: This study suggests that TAF therapy throughout Through expression matrix filtering, statistical analysis of cell and
pregnancy is safe for mothers with CHB and their infants, with no gene expression, cell cluster identification, and functional enrichment
increased risk of serious adverse events or fetal abnormalities. TAF analysis, to systematically study the differences among various T cell
therapy is a viable option for these mothers. subsets.
Table and Figure:Figure 1. Result: 11 types of T cell subsets were identified, including CD4+
effector memory T cells, CD4+ Naive T cells, CD4+ regulatory T cells,
CD8+ cytotoxic T cells, and CD8+ Naïve T cells. The proportions of
PP0214
CD4+ effector memory T cells and CD8+ T cells were higher in the
Association of AFP Elevation with HBsAg Loss During IFN-Based HBsAg loss group at week 48. Among these 11 T cell subsets, 14
Therapy in Chronic Hepatitis B differential genes were highly expressed in the HBsAg loss group.
Mezuo Nian1, Haishi Wu1, Na Gao1, Zhiliang Gao1 These genes were significantly enriched in pathways related to viral
1
The Third Affiliated Hospital of Sun Yat-sen University response, defense reactions, and type I interferon response.
Background: Functional cure is the ideal goal in HBV infection Conclusion: T cells with memory and effector functions were
treatment, but predicting its achievement remains challenging. Alpha- significantly expanded in the HBsAg loss group, with differential genes
fetoprotein (AFP), a well-established marker for liver cancer, is also highly enriched in virus response-related pathways.
associated with liver damage, regeneration, and immune modulation.
This study aims to explore the relationship between AFP elevation PP0216
during IFN-based therapy and functional cure, as well as to evaluate
Interferon-α induces robust neutralizing anti-HBs production by
AFP as a potential predictive biomarker for treatment outcomes.
restoring the HBsAg-specific B cell immune response in nucleos(t)
Method: We conducted a post hoc analysis of a multicenter, real-
ide analogues experienced chronic hepatitis B patients
world study in China (http://www.chictr.org.cn, registration number:
ChiCTR1800020369) and included 260 chronic hepatitis B (CHB) Zhize Yuan1, Da Huang1, Di Wu1, Yuying Chen1, Jiang Chang1, Yizhi
cases with measurable AFP elevation during PegIFNα-2b therapy, Wu1, Ran Zhao1, Weiming Yan1, Qin Ning1
with or without nucleos(t)ide analogs (NAs), over a 48-week treatment
1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical
period. Inclusion criteria were age 18–65 years and HBeAg negative College and State Key Laboratory for Diagnosis and Treatment of
status. Exclusion criteria included other viral infections, hepatocellular Severe Zoonostic Infectious Disease, Huazhong University of Science
and Technology, Wuhan, China
carcinoma (HCC), and cirrhosis. On-treatment AFP elevation was
defined as an AFP level greater than the upper limit of normal (ULN) at Background: Anti-HBs play an important role in HBsAg clearance and
weeks 12, 24, 36, or 48. The primary outcome was the rate of HBsAg functional cure of chronic hepatitis B (CHB). In this study, we aimed to
loss at 48 weeks, defined as HBsAg <0.05 IU/ml. Logistic regression determine the biological function of anti-HBs appeared in CHB patients
analysis was used to identify predictive factors for the study endpoints. undergoing Pegylated-Interferon-α (Peg-IFN-α)-based treatment, and
Result: Of the 260 patients, 63 (24%) experienced on-treatment explore the underlying mechanisms by which IFN-α improves anti-HBs
AFP elevation, and 68 (26%) achieved HBsAg loss at 48 weeks. No production by B cell.
significant differences in baseline characteristics were observed Method: A total of 171 nucleos(t)ide analoges (NAs) experienced CHB
between the AFP elevation group and the non-elevation group. The patients undergoing a clinical trial (ANCHOR study, NCT02327416)
rate of HBsAg loss was significantly higher in the elevation group were included and randomized to receive either Peg-IFN-α-based
(38.1%) compared to the non-elevation group (22.3%) (p = 0.013). therapy (IFN group) or entacvir (ETV) therapy (ETV group) for 96
Multivariate analysis identified on-treatment AFP elevation as an weeks. The neutralization activity (NAT) determined by blocking
independent predictor of HBsAg loss at 48 weeks (OR = 4.200, 95% HBV infection in HepG2 cells expressing sodium taurocholate co-
CI: 1.110-15.890, p = 0.035). transporting polypeptide (NTCP) and Fc effector functions assessed
Conclusion: AFP elevation during IFN-based treatment is associated by FcγRIIIa dimer binding assay, antibody dependent cell-mediated
with higher rates of HBsAg loss at 48 weeks and may serve as a phagocytosis (ADCP) assay, and complement-mediated cytotoxicity
potential predictive biomarker for treatment outcomes in chronic (CDC) assay were performed on serum anti-HBs in CHB patients.In-
hepatitis B. vivo and ex-vivo regulation of phenotypic and functional characteristics
of peripheral B cell subsets by IFN-α were evaluated by flow cytometry
and The Elispot assay was employed to quantify the frequency of
PP0215
HBsAg-secreting B cells.
Transcriptional characteristics of T cells in children with chronic Result: The IFN group exhibited significantly higher cumulative anti-
hepatitis B and poor antiviral efficacy HBs positive rate and quantitative anti-HBs (qAnti-HBs) than the ETV
Yanwei Zhong1, Min Zhang1, Ce Shi1, Ruiyang Yuan1,2, Jia Liu1, Yanbo group, obviously increased NAT but decreased Fc effector function
Yu1, Fang Chu1, Wenling Wang1, Xiuchang Zhang2 compared to qAnti-HBs-matched healthy individuals who received
1
the Fifth Medical Center of chinesePLA General Hospital, 2Hebei vaccine immunization. IFN-α therapy and external stimulation resulted
North University in more aboundant expression of activation markers CD86/CD95 on
Background: The World Health Organization has proposed the goal of memory B cells and higher level of plasma cell, especially for patients
eliminating viral hepatitis by 2030, but there are still some children with with qAnti-HBs above 10 log10IU/mL at the end of treatment (EOT), as
chronic hepatitis B who have poor antiviral treatment effect.Therefore, well as a close correlation between the increased proportion of plasma
it is very important to explore the key cells and targets that regulate cell and the decreased proportion of memory B cell at week 48 and
72. Importantly, in the ex vivo culture system containing overlapping
peptide pools derived from HBsAg, IFN-α was confirmed to be capable antiviral efficacy in randomized clinical studies for chronic hepatits B
of promoting the generation of activated memory B cells, plasma cell, (CHB). However, its efficacy and safety profile in patients with hepatitis
HBsAg-specific B cell and Anti-HBs (IgM/IgG) production. B virus (HBV)-related cirrhosis is not well-established. This study aimed
Conclusion: IFN-a treatment could successfully reinvigorate to assess the effectiveness and safety of TMF in the real world and
HBsAg-specific B cells to produce robust neutralizing anti-HBs, thus compared compare its outcomes with those of tenofovir alafenamide
contributing to functional cure of CHB. (TAF).
Method: In this retro-prospective study, TMF-treated patients with
hepatitis B cirrhosis were divided into treatment-naive (TN) and
PP0217
treatment experienced (TE) groups with low-level viremia. Using the
Research on the Regulation of Intestinal Microbiota in Chronic propensity score matching method (PSM), TAF-treated patients were
Hepatitis B(CHB) Patients by Tiaogan Buxu Jiedu formula(TGBXJD) enrolled. A total of 606 subjects meeting the inclusion criteria were
Xiaoke LI1,2, YIzi Ao1, Shuo Li3, Shuying Hu1, Tingyu Zhang1, Xin Sun1, divided into two groups: TMF group (n = 304) and TAF group (n =
Jinyu Li1, Hongbo Du1,2, Yongan YE1,2 302). The virologic response (VR, HBV DNA < 10 IU/mL) rate, alanine
1
Dongzhimen Hospital, Beijing University of Chinese Medicine, transaminase (ALT) normalization rate, liver stiffness measurement
Beijing, China, 2Beijing University of Chinese Medicine, Liver (LSM), renal function parameters and blood lipid profiles during 48
Diseases Academy of Traditional Chinese Medicine, Beijing, China, weeks of treatment were evaluated. The fibrosis 4 score was also
3
Department of Traditional Chinese Medicine, Peking University calculated in both groups.
Shougang Hospital, Beijing, China. Result: At week 24 and week 48, the VR rates in the TMF group were
Background: Hepatitis B Virus (HBV) infection is a global prevalent. 63.2% and 85.7% respectively, compared to 59.3% and 82.4% in the
Western medical treatment primarily focuses on inhibiting the replication TAF group (P > 0.05). Similar VR rates were observed in both groups
and spread of HBV.Interferon and nucleoside analogues (NAs) were among TN and TE patients with low-level viremia. ALT normalization
the main antiviral drugs.However, interferon therapy has issues such rates were 86.8% (264/304) in the TMF group and 84.1% (254/302) in
as resistance mutations and high relapse rates after discontinuation. the TAF group (P = 0.26). In the TAF group, total cholesterol and low-
The potential function of the intestinal microbiota and its metabolites density lipoprotein cholesterol (LDL-C) levels showed a slight increase
in CHB patients has drawn attention.Traditional Chinese medicine (P = 0.15), which was not observed in the TMF group. Renal function
(TCM) has accumulated experience in regulating intestinal function, parameters, including serum creatinine and estimated glomerular
balancing the body’s microecology and improving liver function. This filtration rate, were no significant changes from baseline to week 48
research will analyze the regulatory effects of a liver-regulating,spleen- in the two groups. LSM and fibrosis 4 score reduced significantly in
invigorating,and detoxifying(TGJDBX)formula on the structure and both groups.
function of the intestinal microbiota in CHB patients. Conclusion: Both TMF and TAF have profound antiviral effectiveness
Method: It included a total of 100 patients with CHB who had and improvement of liver fibrosis among patients with hepatitis B
undergone clinical treatment and achieved HBeAg seroconversion cirrhosis. The effects on blood lipids are mild and regular monitoring of
within one year. These patients receive the antiviral drug entecavir blood lipid profiles is recommended.
(ETV) alongside either TGBXJD formula or a placebo. After 96 weeks
of treatment, both the TCM and ETV were discontinued.Then observe PP0219
any relapse after discontinuation.Fecal samples were collected from
the subjects at specific times,for macrogenomic testing of the intestinal Prognostic Evaluation and Clinical Classification of Hepatitis
microbiota. Then the test results were statistically analyzed. B-Related Acute-on-Chronic Liver Failure
Result: 1, After ETV treatment alone, the alpha diversity of the Cai Xianghao1, Xiao Xiaolong1, Liao Yingying1, You Lijie1, Zhang
intestinal microbiota in CHB patients showed an increasing trend, Yibo1, Gong Jiao1, Chong Yutian1, Li Xinhua1
but the change in beta diversity was not significant.After treatment 1
Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
with the TGBXJD formula combined with ETV, there were significant Background: This study analyzes the characteristics of intrahepatic
differences in both alpha and beta diversity.2, ETV treatment alone and extrahepatic organ failure at the onset of HBV-related acute-on-
had little effect on the species.Treatment with the TGBXJD formula chronic liver failure (HBV-ACLF), explores features of a novel ACLF
combined with ETV,there were prominent changes in the composition clinical classification, compares scoring systems, and provides a basis
of the intestinal microbiota, mainly in microbiota involved in the for diagnosis, treatment, and prognosis.
production of short-chain fatty acids and amino acid metabolism.3, Method: Clinical data of HBV-ACLF patients hospitalized at the
The functional differences before and after ETV treatment were mainly Third Affiliated Hospital of Sun Yat-sen University from May 2019 to
reflected in sugar, amino acid, nucleic acid and vitamin metabolism. December 2020 were retrospectively collected. Based on the new
After the treatment with the TGBXJD formula combined with ETV, the ACLF classification by YouAn Hospital (Capital Medical University) ,
main changes were in sugar metabolism, protein decomposition and patients were divided into type I (liver failure on chronic liver disease)
translation, and lipid metabolism. and type II (acute decompensation of chronic liver disease with
Conclusion: TGBXJD Formula can significantly increase the multiple organ failure). Clinical characteristics were analyzed, and
species diversity of the intestinal microbiota in CHB patients,regulate ROC curves were used to evaluate the predictive value of MELD,
microbiota involved in the production of short-chain fatty acids and MELD-Na, MELD-cys, COSSH II, and CLIF-C ACLF scores for 28- and
amino acid metabolism,optimize the structure.It increases the number 90-day prognoses. MELD-cys replaces Cr with Cys in the MELD score.
of microbiota that produce short-chain fatty acids and regulates the Result: Among 663 HBV-ACLF patients, 566 were type I, and 97 were
lipid metabolism,protein decomposition,and translation functions of the type II. Median MELD, MELD-Na, MELD-cys, COSSH II, and CLIF-C
intestinal microbiota. ACLF scores were significantly higher in type II than type I (all P <
Granted by NSFC No.82174341 0.05). The 28- and 90-day mortality rates in type II were 69.07% and
75.26%, significantly higher than 13.88% and 20.91% in type I (both P
PP0218 < 0.05). In type I ACLF, the AUCs for 28-day prognosis using MELD,
MELD-Na, MELD-cys, COSSH II, and CLIF-C ACLF were 0.708, 0.716,
Efficacy and Safety of Tenofovir Amibufenamide and Tenofovir
0.743, 0.744, and 0.706, with no significant differences (all P > 0.05).
Alafenamide in Patients with Hepatitis B Cirrhosis: A Retro-
For 90-day prognosis, MELD-cys had an AUC of 0.741, higher than
Prospective Observational Study
MELD (AUC = 0.684) and MELD-Na (AUC = 0.683) (both P < 0.05)
Jun Chen1, Lihua Duan1, Xueyao Yang1, Xuexuan Li1, Shang Gao1, but not significantly different from COSSH II (AUC = 0.732) and CLIF-C
Zebing Huang1, Yan Huang1 ACLF (AUC = 0.691) (both P > 0.05). In type II ACLF, COSSH II had
1
Department of Infectious Diseases, Xiangya Hospital Central South the highest AUC for 28-day prognosis at 0.598, while MELD-cys had
University the highest AUC for 90-day prognosis at 0.619, with no statistical
Background: Tenofovir amibufenamide (TMF) has shown potent significance compared to other scores. Logistic regression showed that
NLR is an important prognostic factor in ACLF. Replacing neutrophil from a total of 4 Asia-Pacific-based societies and 6 other national and
count with NLR in COSSH II produced the COSSH-NLR model. For 28- international societies were included in the scoping review. Guideline
day prognosis, COSSH-NLR had an AUC of 0.790, higher than MELD- coverage of identified topics relating to management is summarised in
based and CLIF-C ACLF scores (all P < 0.05). For 90-day prognosis, the Table. Compared with guidelines from other regions, Asia-Pacific
COSSH-NLR had an AUC of 0.783, higher than MELD-based, CLIF-C guidelines were more likely to have been updated since 2020, more
ACLF, and COSSH II scores (all P < 0.05). likely to include guidance on the role of qHBsAg in predicting HBsAg
Conclusion: Type II HBV-ACLF patients have more severe organ loss, and more likely to include guidance on the role of qHBsAg in
failure and higher mortality than type I. COSSH-NLR provides monitoring treated patients, particularly for those receiving antiviral
better prognostic accuracy, highlighting the value of incorporating therapy.
inflammatory markers in ACLF models. Conclusion: Compared with other regions, Asia-Pacific guidelines
Table and Figure:Figure 1.90-day prognosis provide greater guidance on using qHBsAg in predicting HBsAg
Figure 2.28-day prognosis loss and on the role of qHBsAg in monitoring treated patients.
Consensus is needed to harmonise recommendations globally and
would help support the most appropriate use of qHBsAg testing in the
PP0220
management of patients with CHB.
A review of published data and comparison of Asia-Pacific and Table and Figure:Figure 1.
international guidelines on the use of quantitative HBsAg in the
management of chronic hepatitis B
Hong You1, Norah Terrault2, Kosh Agarwal3, Tarik Asselah4, Carla
PP0221
Coffin5, Chari Cohen6, Markus Cornberg7, Robert G Gish8, Cary Impact of Antiviral Treatments on Male Sexual Function in Chronic
James9, Harry LA Janssen10, Pietro Lampertico11, Jeffrey Lazarus12,13, Hepatitis B Patients: A Cross-Sectional Study
Sabela Lens Garcia14, Mark S Sulkowski15, Yasuhito Tanaka16, Chengrun Song1, Yujing Li1, Yonghong Wang1, Wei Jiang1, Menglan
Thomas Tu17, Grace Wong18, Shayon Salehi19, Patrick Kennedy20 Wang1, Yachao Tao1, Taoyou Zhou1, Fang He1, Jiajie Lu1, Xuezhong
1
Beijing Friendship Hospital, Capital Medical University, Beijing, Lei1, Hong Tang1, Enqiang Chen1
China, 2Keck School of Medicine, University of Southern California, 1
Center of Infectious Diseases, West China Hospital, Sichuan
Los Angeles, USA, 3King‘s College Hospital, London, UK, 4Hôpital University
Beaujon APHP, Paris, France, 5Cumming School of Medicine, The Background: In the management of chronic hepatitis B (CHB),
University of Calgary, Calgary, Canada, 6Baruch S. Blumberg Institute,
sexual dysfunction is a significant concern due to its potential to
Hepatitis B Foundation, Doylestown, USA, 7Hannover Medical School,
affect patients’ quality of life. However, the precise impact of various
Hannover, Germany, 8Hepatitis B Foundation, California/Pennsylvania,
antiviral treatments on male sexual function in CHB patients remains
USA, 9World Hepatitis Alliance, London, UK, 10Erasmus University
incompletely understood, necessitating further comprehensive
Medical Center, Rotterdam, Netherlands, 11Fondazione IRCCS Ca’
Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, exploration.
Italy, 12Barcelona Institute for Global Health (ISGlobal), Barcelona, Method: A cross-sectional study was carried out from December 2023
Spain, 13CUNY Graduate School of Public Health and Health Policy, to July 2024. CHB patients aged 18 - 60 years were recruited from liver
Barcelona, Spain, 14Hospital Clinic de Barcelona, Barcelona, Spain, disease clinics in multiple regions. Exclusions included those without
1
5Johns Hopkins University School of Medicine, Baltimore, Maryland, sexual activity, with incomplete questionnaires, or having comorbidities
USA, 16Kumamoto University, Kumamoto, Japan, 17Westmead Clinical that could cause sexual dysfunction. Male sexual function was
School and Westmead Institute for Medical Research, The University evaluated using the Erection Hardness Score (EHS), the International
of Sydney, Sydney, Australia, 18The Chinese University of Hong Kong, Index of Erectile Function - 5 (IIEF - 5), and the Premature Ejaculation
Hong Kong, China, 19GSK, London, UK, 20Barts Health NHS Trust, Diagnostic Tool (PEDT). Data analysis compared multiple parameters
London, UK among three groups: the Peg IFNα - 2b group (302 patients), the NAs
Background: Chronic hepatitis B (CHB) infection is typically group (166 patients), and a control group (83 patients), including age,
diagnosed and monitored in China using quantitative hepatitis B virus BMI, and various lifestyle and clinical factors. Appropriate statistical
(HBV) surface antigen (qHBsAg) measurement. However, the value of tests were used.
qHBsAg in monitoring untreated patients and predicting clinical and Result: Among the three groups, significant differences were found
treatment-related outcomes remains to be established. We conducted in age (P = 0.022), education level (P < 0.001), drinking habits (P <
a systematic literature search to summarise and evaluate evidence on 0.001), and PHQ - 9 score (P = 0.030). For male sexual function, in
the use of qHBsAg in CHB, as well as a scoping review of existing the EHS, grade Ⅱ was 32.1% in the interferon group, 22.9% in the NAs
clinical guidelines and recommendations. group, and 14.5% in the control group; grade Ⅳ was 22.8%, 33.1%,
Method: A systematic literature search was conducted using ProQuest and 49.4% respectively, and the prevalence of ED (EHS < Ⅲ) differed
(31 October 2024) to search Embase and Medline, supplemented by (χ2 = 21.459, P < 0.05). For IIEF - 5, median scores were 20.00(16, 22)
manual searches (October 2024) of published congress abstracts from in the interferon group, 21.00(19, 23) in the NAs group, and 23.00(20,
international society meetings (AASLD 2022-2023, EASL 2024-2024, 24) in the control group, with overall distribution differences (H =
and APASL 2022-2024). Eligible publications were any clinical trials 52.008, P < 0.001). The ED prevalence was 70.9% in the interferon
or cohort studies conducted in people aged ≥16 years with CHB that group (mild 66.3%, moderate 3.3%, severe 1.3%), 51.8% in the NAs
reported (in English) qHBsAg measurements. Studies were excluded group (47.0%, 3.6%, and 1.2%), and 37.3% in the control group (all
if they focused on HBV prevention/vaccination or on people with HIV, mild), with significant overall composition ratio differences (P < 0.001),
HCV or HDV coinfection. Identified studies were screened by two and the mild ED prevalence in the interferon group differed from the
independent reviewers. For guidelines, systematic literature reviews others (P < 0.05). For PEDT, median scores had no overall distribution
and meta-analyses, methodology, findings and recommendations differences (H = 2.132, P > 0.05). Correlation analysis showed age
were summarised. was inversely related to EHS and IIEF - 5 scores, education level was
Result: In total, 2477 publications were identified, and 348 were positively related, and PHQ - 9 and GAD - 7 scores were negatively
found to be relevant. After screening, the proportion of studies that related.
included data relevant to topics of interest from the Asia-Pacific region Conclusion: This study has shown that interferon and NAs likely
were: prediction of HBsAg-loss (spontaneous, following pegylated influence erectile function rather than premature ejaculation, and that
interferon therapy, and as part of nucleos(t)ide cessation strategies), age along with psychological elements, such as those gauged by
59% (n=79/133); monitoring during management, 50% (n=114/227); PHQ - 9 and GAD - 7 scores, are associated with male sexual function,
prediction of clinical outcomes in treated patients, 53% (n=39/73). thereby furnishing valuable perspectives and hinting at prospective
In addition, 58% (n=18/31) of studies reported the use of qHBsAg research pathways.
in people with untreated CHB (disease natural history). Guidelines
 PP0222 were assessed using Scheuer’s classification. Multivariable logistic
Characteristics of monocytes with different clinical outcomes of regression identified risk factors for significant inflammation (G ≥ 2)
antiviral therapy in children with hepatitis B and fibrosis (F ≥ 2).
Result: Of the 748 patients, 61.8% were male, with a median age of
Yanwei Zhong1, Yuxi Ning1,2, Min Zhang1, Xiuchang Zhang2, Ce Shi1,
38.0 years (IQR 31.0–45.5). HBV DNA levels were <500 IU/mL in 312
Ruiyang Yuan1,2, Wenling Wang1
(41.7%) patients. ALT levels were < ULN in 484 (64.7%) patients. HBeAg
1
the Fifth Medical Center of chinesePLA General Hospital, 2Hebei was tested positive in 125 (17.1%) patients. Significant inflammation (G
North University
≥ 2) was present in 129 (17.2%) patients, while significant fibrosis (F
Background: As an important component of the innate immune system, ≥ 2) was identified in 218 (29.1%) patients. Independent risk factors
monocytes are activated after HBV infection to produce and secrete for inflammation included ALT ≥ ULN (OR 1.84, 95% CI: 1.22–2.77),
large amounts of inflammatory and chemokines, recruit inflammatory HBeAg positivity (OR 2.82, 1.79–4.45), and platelet count < ULN (OR
cells as well as clear target cells. simultaneously participating in 2.90, 1.90–4.40). Significant fibrosis was associated with platelet count
antigen presentation, activating and proliferating T cells, enhancing < ULN (OR 4.62, 3.18–6.72), HBeAg positivity (OR 2.34, 1.52–3.61),
antiviral response. Exploring the changes of monocyte subsets after and HBV DNA 20–500 IU/mL (OR 1.82, 1.29–2.58).
antiviral therapy can provide a new strategy for the research of antiviral Conclusion: A substantial proportion of CHB patients with LLV exhibit
therapy against hepatitis B. This study aims to explore transcriptional significant liver inflammation and fibrosis. HBeAg positivity, decreased
characteristics of monocyte subpopulations and key genes in the PLT, and lower HBV DNA levels are risk factors, underscoring the need
peripheral blood in children with chronic hepatitis B (CHB) and provide for careful monitoring and timely intervention in this subgroup.
new therapeutic targets for children with CHB. Table and Figure:Figure 1.Factors significantly associated with
Method: A total of 8 CHB children who received 48 weeks of antiviral liver histology based on multivariable logistic regression analysis in
treatment were included. Peripheral blood mononuclear cells treatment-naïve CHB patients with LLV.
(PBMCs) were extracted and subjected to 10 × genomics single-
cell sequencing to analyze changes in monocyte subpopulations in
PP0224
children with different clinical outcomes. Meanwhile, Olink analysis was
performed on plasma inflammatory proteins in 64 children with CHB. Peginterferon alpha-2b retreatment promotes HBsAg loss in
Combining single-cell sequencing and Olink data, screen monocyte chronic hepatitis B patients with low HBsAg levels: Report at 48
subpopulations and target genes. ELISA further validated the target weeks follow-up after a phase 3 trial
gene. Fengqin Hou1, Jia Shang2, Qing Xie3, Chunliang Lei4, Jianmei Lin5,
Result: Single cell RNA sequencing showed that the differentially Guoxin Hu6, Zhiliang Gao7, Yilan Zeng8, Jiabin Li9, Qianguo Mao10,
expressed genes between groups mainly involved antiviral response Liying Zhu11, Jun Chen12, Xiaozhong Wang13, Zuxiong Huang14, Jiming
and interferon related signaling pathways, with the top 10 differentially Zhang15, Ping An16, Xiulan Xue17, Yan Huang18, Tianyan Chen19, Jianqi
expressed genes mainly expressed in monocytes. Receptor ligand Lian20, Yueyong Zhu21, Huiling Xiang22, Xinyue Chen23, Hui Guo24,
analysis identified four key subgroups associated with HBsAg loss. Ruoyi He25, Yalin Yin25, Li Sun25, Guiqiang Wang1,26
These subgroups exhibit significant differences in cell proportions 1
Peking University First Hospital, Beijing, 100034, China, 2Henan
and gene expression between groups. Interferon induced monocytes Provincial People‘s Hospital, Zhengzhou, 450000, China, 3Ruijin
exhibit strong interferon responses, while cytotoxic monocytes reduce Hospital, Shanghai Jiaotong University School of Medicine, Shanghai,
adaptive responses to prevent excessive immunity in HBsAg loss 2
00000, China, 4Guangzhou Eighth People‘s Hospital, Guangzhou
group. Inflammatory monocytes exhibit strong inflammatory responses. Medical University, Guangzhou, 510000, China, 5Sichuan Provincial
In addition, the IFITM3 expression of all monocyte subpopulations in People‘s Hospital·Sichuan Academy of Medical Sciences, Chengdu,
the HBsAg loss group was significantly upregulated. The ELISA results
6
10000, China, 6Peking University Shenzhen Hospital, Shenzhen,
showed that baseline IFITM3 levels have a good prediction for HBsAg
5
18000, China, 7The Third Affiliated Hospital, Sum Yat-Sen University,
loss. Guangzhou, 510000, China, 8Public Health Clinical Center of
Conclusion: The decrease of cytotoxic monocytes, interferon induced Chengdu, Chengdu, 610000, China, 9The First Affiliated Hospital of
monocytes, and inflammatory monocytes is closely related to HBsAg Anhui Medical University, Hefei, 230000, China, 10Xiamen Hospital of
loss. Traditional Chinese Medicine, Xiamen, 361000, China, 11The Fourth
Affiliated Hospital of Harbin Medical University, Harbin, 150001, China,
1
2Shenzhen Third People‘s Hospital, Shenzhen, 518000, China,
PP0223 1
3Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese
Significant Liver Inflammation and Fibrosis in Chronic Hepatitis Medicine, Urumqi, 830000, China, 14Mengchao Hepatobiliary Hospital
B Patients with Low-Level Viremia: A Liver Biopsy-Based Cross- of Fujian Medical University, Fuzhou, 350000, China, 15Huashan
Sectional Study Hospital, Fudan University, Shanghai, 200040, China, 16The Sixth
People‘s Hospital of Shenyang, Shenyang, 110000, China, 17The
Mengwen He1,2, Jie Zhou3, Le Li4, Yan Liu4, Wucai Yang2, Jing Chen5,
First Affiliated Hospital of Xiamen University, Xiamen, 361000, China,
Yudong Wang6, George Lau6,7, DONG JI2,1 1
8Xiangya Hospital Central South University, Changsha, 410000,
1
Peking University 302 Clinical Medical School, Beijing 100191, China, 19The First Affiliated Hospital of Xi‘an Jiaotong University,
China, 2Senior Department of Hepatology, the Fifth Medical Center Xi‘an, 710061, China, 20The Second Affiliated Hospital of the Air Force
of PLA General Hospital, Beijing 100039, China , 3Department of Military Medical University of CPLA, Xi‘an, 710038, China, 21The First
Infectious Diseases, Xinjiang Uygur Autonomous Region Infectious Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, China,
Disease Hospital, Xinjiang, China, 4Senior Department of Infectious 2
2Tianjin Third Central Hospital, Tianjin, 300170, China, 23Beijing
Disease, the Fifth Medical Center of PLA General Hospital, Beijing Youan Hospital, Capital Medical University, Beijing, 100000, China,
100039, China, 5JC School of Public Health and Primary Care, 2
4First Teaching Hospital of Tianjin University of Traditional Chinese
Chinese University of Hong Kong, Hong Kong SAR, China, 6Humanity Medicine, Tianjin, 300170, China, 25Xiamen Amoytop Biotech Co. Ltd,
and Health Clinical Trial Center, Humanity and Health Medical Group, Xiamen, 361028, China, 26Peking University International Hospital,
Hong Kong SAR, China, 7Zhongshan Hospital, Fudan University, Beijing, 102206, China
Shanghai, China
Background: Patients with chronic hepatitis B (CHB) can achieve high
Background: Although low-level viremia (LLV; HBV DNA 20–2000 IU/ hepatitis B surface antigen (HBsAg) loss rates through the treatment
mL) in chronic hepatitis B (CHB) is often considered low-risk, it can still with peginterferon alpha (PegIFNα). However, there are few studies
cause significant liver inflammation and fibrosis. This study aimed to exploring the efficacy of PegIFNα retreatment in patients who had
identify factors influencing inflammation and fibrosis in treatment-naïve good responses to PegIFNα therapy but did not achieve functional
CHB patients with LLV. cure. This study investigated the efficacy of retreatment with PegIFNα
Method: This cross-sectional study analyzed liver biopsies from in patients who initially responded well in a phase 3 clinical trial.
748 treatment-naïve CHB patients. Liver inflammation and fibrosis Method: This is a long-term follow-up study (NCT06707922) of a
randomized controlled phase 3 trial (NCT04846491). At the end of the not be reached due to incorrect phone numbers, disconnection,
phase 3 trial, nucleos(t)ide analogue (NA)-experienced patients with or unavailable phone lines; 721 patients (40.2%) did not answer or
HBsAg decline ≥ 1 log10 IU/mL and HBsAg level < 100 IU/mL, as declined to take calls; and 805 patients (44.8%) successfully received
well as treatment-naïve patients with HBsAg decline ≥ 1.5 log10 IU/mL calls.
and HBsAg level < 1500 IU/mL were enrolled in cohort 2. All patients Of the patients reached, 103 (12.8%) reported the death of the
initially received treatment with PegIFNα-2b 180 μg/week combined index patient. Family members of 208 patients (25.8%) disclosed
with tenofovir disoproxil fumarate (TDF) for 72 weeks, after which all the presence of HBV infection among relatives, while 373 patients
drugs were discontinued and patients were followed up to 5 years. (46.3%) reported no HBV infection within their families. Among the
PegIFNα-2b was given intermittently in cycles (8 weeks of treatment successfully contacted individuals, 3 patients were unexamined, 90
+ 4 weeks of interval, repeating every 12 weeks). Here, we report the (11.2%) vafrefused to provide answers, and 28 (3.5%) were uncertain
results of the 48-week analysis in cohort 2. about family members’ HBV status. Notably, 81 patients (38.9%) with
Result: A total of 47 NA-experienced patients and 15 treatment- confirmed HBV-affected family members reported that relatives were
naïve patients were included in cohort 2. The average ages of the two receiving antiviral treatment.
populations were 42.5 and 34.5 years, and 85.1% and 66.7% were Conclusion: The recall program for first-degree relatives of HBV-HCC
male. The mean baseline HBsAg level of NA-experienced patients was patients is ongoing. The results indicate low treatment and recall rates,
13.04 IU/mL, and HBeAg and HBV DNA were negative in all patients. highlighting the need for enhanced medical education for patients’
Treatment-naïve patients had mean baseline HBsAg and HBeAg levels families and the optimization of the recall process. Further efforts are
of 269.56 IU/mL and 2.24 COI, respectively, with 73.3% were HBeAg required to ensure timely diagnosis and standardized follow-up care
negative and 100% were HBV DNA undetectable. Significant HBsAg for at-risk relatives.
declines were noted in both patients as the duration of treatment Table and Figure:Figure 1.
progressed (Figure 1). By week 48, reductions in HBsAg from baseline
were 1.25 log10 IU/mL in NA-experienced patients and 1.01 log10 IU/
PP0226
mL in treatment-naïve patients, with 42.6% (20/47) and 26.7% (4/15)
achieving HBsAg loss, respectively (Figure 2). 30% of NA-experienced Impact of Nucleos(t)ide Analogues on the Serum Lipids in Patients
patients also achieved HBsAg seroconversion. Additionally, 42.6% with Chronic Hepatitis B: a Prospective Cohort Study in China
(20/47) of NA-experienced patients and 20.0% (3/15) of treatment- Xun Qi1, Xiongyue Cao1, Xinyan Li1, Yuxian Huang1,2, Jiming Zhang2,
naïve patients achieved both HBsAg loss and HBV DNA undetectable Liang Chen1
at week 48. Among four treatment-naïve patients with HBeAg positive, 1
the department of hepatology, shanghai public health clinical center,
one achieved HBeAg loss and seroconversion. 2
the department of infetion, Huashan hospital
Conclusion: A significant proportion of CHB patients with low HBsAg Background: Due to the easy administration and potential antiviral
level can still achieved HBsAg loss after retreatment with PegIFNα-2b, effect, nucleos(t)ide analogues (NAs) were approved to treat with
including 42.6% of NA-experienced patients and 26.7% of treatment- chronic hepatis B. However, NAs cannot eradicate cccDNA, the
naïve patients. Patients with good initial responses to PegIFNα have duration for CHB patients may last for a long time. Therefore, long-
great chance to pursure functional cure by retreatment with PegIFNα. term safety is a concern. It was reported that the lipid may elevate
Table and Figure:Figure 1.Figure 1. Mean HBsAg change over time. treated with tenofovir alafenamide (TAF). Up to now, there has not been
Figure 2.Figure 2. HBsAg loss rate over time. a head-to-head controlled study to assess serum liplid in nucleos(t)
ide-treated CHB patients.
PP0225 Method: A prospective controlled study involving 417 patients with
chronic hepatitis B and 100 healthy individuals was conducted. Among
HBV screening, diagnosis and treatment model for family
them, 137 patients were treated with ETV TDF and TAF respectively.
members of HBV-related HCC patients
Physical examination data of 100 healthy people were collected as
Peng Wang1, Tiaojiao Luo1, Min Zhou1, Huabang Zhou1, Heping Hu1 control group. The serum lipids data of patients during treatment and
1
Department of Hepatobiliary Medicine, Eastern Hepatobiliary follow-up were collected and the factors affecting the changes of
Surgery Hospital, Navy Medical University, Shanghai, 200438 China. serum lipids were analyzed.
Background: HBV infection represents a major risk factor for HCC Result: In the TDF group, serum TC, TG, HDL and LDL were
in China. 2022 China HBV guidelines recommend HBsAg screening decreased compared with baseline during the follow-up. In the TAF
among family members or close contacts of HBV-infected individuals. group, TC, TG, LDL were increased compared with baseline. In the
In China, MTCT is the main route of chronic HBV infection, accounting ETV group, there were no significant changes in serum lipids during
for 40–50% of new infections. A study found 65.88% HBsAg positivity the follow-up. Multivariate logistic regression analysis showed that TDF
rate among relatives of HBV-HCC patients, and the treatment rate was was an independent risk factor for TC decrease >20% (OR = 4.294,
33.98%. Hence, screening and linkage to care for HBV among relatives P = 0.002), and TAF was an independent risk factor for TC increase
of HBV-HCC patients is essential. Notably, a family history of HBV-HCC >20% (OR = 2.287, P = 0.043). Although TDF and TAF has different
is an independent risk factor for disease progression. According to influence on serum lipids, there were no
the 2022 China HBV guidelines, antiviral therapy is recommended for significant differences of numbers of adverse reactions associated
patients with detectable HBV DNA, regardless of ALT levels, if with with the serum lipids above level 2 between groups on the basis of
family history of HBV-HCC. Following the 2024 WHO HBV guidelines, common terminology criteria for adverse events(CTCAE) classification.
physicians should treat all with family history of HBV-HCC regardless of Conclusion: TDF can lead to the reduction of serum lipids in patients
HBV DNA or ALT levels. Therefore, optimizing HBV screening among with CHB, TAF can lead to the increase of serum lipids, and ETV has
HBV-HCC family members and promptly initiating antiviral therapy for no significant effect on serum lipids in patients with CHB. In addition,
those meeting guideline criteria can reduce the progression of HBV- there was no significant difference in the proportion of patients with
related diseases, including the long-term risk of developing HCC. dyslipidemia requiring additional clinical intervention.
Method: A retrospective telephone follow-up study was conducted Table and Figure:Figure 1.The change of serum lipid during the
involving HBV-HCC patients who were treated at our hospital between treatment
January 2020 and Dec 2023. The objective was to assess the HBV Figure 2.The adverse effect during the study
infection status and treatment history of their first-degree relatives.
Relatives with HBsAg positivity were encouraged to visit the hospital
PP0227
for HBV DNA testing. For those who tested positive for HBV DNA,
antiviral therapy was recommended. The renal safety of tenofovir alafenamide fumarate for the long-
Result: A total of 1,795 HBV-HCC patients were identified between term treatment of chronic hepatitis B liver fibrosis/cirrhosis
January 2020 and December 2023, comprising 1,515 males (84.4%) confirmed by histological
and 280 females (15.6%). Among them, 269 patients (15.0%) could Jialing Zhou1, Xiaoning Wu1, Chuanwu Zhu2, Jiming Zhang3, Ping
Li4, Tao Han5, Huiguo Ding6, Chenghai Liu7, Wen Xie8, Qing Xie9, Yali The study encompassed an analysis of HDV prevalence, HDV RNA
Zong10, Jidong Jia1 detection, and clinical features. Patients were stratified into HBV+HDV
1
Being Friendship Hospital, Capital Medical University, National and HBV+HDV+HCV groups based on the absence or presence of
Clinical Research Center of Digestive Diseases, 2The Fifth People‘s HCV coinfection, with subsequent comparative analysis of their clinical
Hospital of Suzhou, 3Shanghai Fudan University HuaShan Hospital, characteristics .
4
Tianjin Second People‘s Hospital, 5Tianjin Third Central Hospital Result: A total of 179 patients were enrolled in this study,with ages
, 6Beijing Youan Hospital, Capital Medical University, 7Shuguang spanning from 4 to 78 years, mainly concentrating in the age of 50
Hospital Affiliated to Shanghai University of Traditional Chinese to 60 (27.84%, 49/176), followed by the 40-50 age group (21.59%,
MedicineShanghai Key Laboratory of Traditional Chinese Clinical 38/176), 60-70 age group (17.61%, 31/176)(detail see Fig.1A).
Medicine, 8Beijing Ditan Hospital, Capital Medical University, 9Ruijin Geographically, cases predominantly originated from the Guangdong
Hospital, Shanghai Jiaotong University School of Medicine, 10The region, with a concentration in the Pearl River Delta. Specifically, there
Ninth Hospital of Nanchang were 88 cases from the Pearl River Delta (50.00%), 31 from Northern
Background: We all know that long-term antiviral therapy has some Guangdong (17.61%)(detail see Fig.1B). In this study, 55.31% (99/179)
effect on renal function. The study was to evaluate the changes renal were predominantly positive for HDV Ag(detail see Fig.1C). A total of
function of tenofovir alafenamide fumarate (TAF) for long-term antiviral 16 cases were tested for HDV RNA, with a positivity rate of HDV RNA
therapy patients with hepatitis B liver fibrosis/cirrhosis. reaching 37.50% (6/16)(detail see Fig.1D).Further analysis of HBV
Method: A total of 100 treatment-naïve CHB patients with liver fibrosis serological markers revealed a predominance of positivity for HBsAg,
and cirrhosis diagnosed by liver biopsy were enrolled and followed HBeAb, and HBcAb(detail see Fig.1E). Among these, 114 cases were
up for 2 years. Clinical data, blood renal function test (eGFR (by CKD- complicated by cirrhosis, 38 by esophageal and gastric varices, 34 by
EPI), serum creatinine (Scr), urea, urinary creatinine (Ucr)) and the splenomegaly with hypersplenism, 31 by hepatic malignancies, 25 by
urine test (micro-albuminuria (mAlb), Urinary microalbumin/creatinine hepatitis C, 25 by alcoholic liver disease(detail see Fig.1F).In patients
ratio (UACR), β2-microglobulin (β2-MG), and retinol-binding protein with hypersplenism, a reduction in two cell lines was the predominant
(RBP)) were collected at baseline, 48 and 96 weeks during treatment. manifestation, accounting for 44.12% (15/34) of the cases. Notably,
Result: At baseline, the median age of the cohort was 42.2±10.3 years the concurrent decrease in red blood cells and platelets was the
and 59% of the subjects were male. About 61% of the patients were most prevalent hematological feature. Comparative analysis of clinical
HBeAg positive, 23% were cirrhosis patients, and 3% with diabetes. characteristics between the HBV+HDV and HBV+HDV+HCV groups
After 1 and 2 years of treatment, the median eGFR slightly decreased revealed significantly lower levels of HBV DNA in the HBV+HDV+HCV
from baseline of 125.2 to 123.3 and 122.1 mL/min/1.73ml, respectively group (p<0.001) (detail see table 1).
(p=0.006). The median Scr slightly increased by 2.8% after 2 years Conclusion: Over the past decade, the rate of hepatitis delta screening
of treatment, with the values of 64, 65, and 65.8 mmol/l at baseline, has decreased annually, with a low positivity rate. There is a critical
year 1 and year 2 (p=0.009). Three patients were persistently abnomal need to enhance HDV screening, particularly among the 50-60 age.
from baseline, and 12 patients returned to normal at year 2. The urea This study also observed that in patients with HBV/HDV coinfection, the
slightly increased by 6.3%, with medians of 4.6, 4.9 and 4.89 mmol/l at presence of HCV further reduces the levels of HBV DNA.
baseline, year 1 and year 2, respectively (p=0.002). Only 1 patient was Table and Figure:Figure 1.figure1.The clinical characteristics of HDV
abnormal and 10 patients returned to normal at year 2. In the urine test, Figure 2.figure1.The clinical characteristics of HDV
UACR as an indicator of early kidney injury, was relatively stable, with
medians of 4.4, 5.8, and 5.2 mg/g, respectively (p=0.102). At baseline, PP0229
6 patients had UACR more than 30 mg/g, and 5 patients sustained
more than 24 weeks. After 2 years of treatment, two patients improved, Epidemiological and clinical profiles of patients with chronic
and three additional patients were still abnormal. The median Ucr hepatitis B with different serum hepatitis B surface antigen levels
slightly increased after treatment, with medians of 1.05, 1.29, and 1.31 Tao Fan1, Li Zhu2, Ye Xiong1, Chao Jiang3, Shaoqiu Zhang4, Jian
mmol/L, respectively (p=0.032). The median mAlb slightly increased Wang4,5, Yuxin Chen6, Shengxia Yin4, Jie Li1,4,5, Chuanwu Zhu2,
from 3.0 to 5.78 and 6.79 mg/L, with a statistically significant difference Xingxiang Liu7, Chao Wu1,4,5, Rui Huang1,4,5
at year 2 (p=0.046). The median β2-MG slightly decreased from 0.175 1
Department of Infectious Diseases, Nanjing Drum Tower Hospital
to 0.157 mg/L after treatment, but no significant difference was found Clinical College of Nanjing University of Chinese Medicine, Nanjing,
(p=0.651). Most patients had normal BRP levels, only two patients Jiangsu, China, 2Department of Infectious Diseases, The Affiliated
(2/91) showing a slight increase at 2 years. There was no statistically Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu,
significant difference with the fibrosis and cirrhosis patients in the China, 3Department of Infectious Diseases, Nanjing Drum Tower
changes of eGFR, Scr, Ucr, mAlb, β2-MG and BRP (all p>0.05). Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu,
Conclusion: TAF has good renal safety in patients with hepatitis B liver China, 4Department of Infectious Diseases, Nanjing Drum Tower
fibrosis/cirrhosis. Hospital, Affiliated Hospital of Medical School, Nanjing University,
Nanjing, Jiangsu, China, 5Institute of Viruses and Infectious Diseases,
Nanjing University, Nanjing, Jiangsu, China, 6Department of
PP0228 Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital
Prevalence and clinical characteristics of hepatitis D of Medical School, Nanjing University, Nanjing, Jiangsu, China,
7
Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital,
Lihua Lin1, Xiuhan Yang1, Yaping Wang1, Xiaowen Jiang2, Pei Zhou1,
Huai’an, Jiangsu, China
Aiqi Lu1, Chujing Li1, Calvin Pan1, Yujuan Guan1
1
Guangzhou Medical Research Institute of Infectious Diseases, Background: Quantitative hepatitis B surface antigen (qHBsAg) is an
Center for Liver Disease, Guangzhou Eighth People’s important biomarker for the management of chronic hepatitis B (CHB).
Hospital,Guangzhou Medical University, Guangzhou, Guangdong We investigated the prevalence of CHB patients with different HBsAg
Province, 520440, P.R. China, 2Department of Clinical Laboratory, levels, with a particular focus on specific levels of qHBsAg.
Guangzhou Eighth People‘s Hospital, Guangzhou Medical University, Method: Treatment-naïve patients with CHB were included from three
Guangzhou, Guangdong Province, 520440, P.R. China medical institutions between 2016 and 2023. The prevalence of CHB
Background: Hepatitis D virus (HDV) infection, also known as patients with different qHBsAg levels was explored.
hepatitis delta, can lead to the exacerbation of chronic hepatitis B, Result: Of a total 8,392 treatment-naïve patients, the median age was
representing a significant global public health challenge. This study 37 years and 28.4% of patients were HBeAg positive. The median
aims to delineate the prevalence and clinical characteristics of patients level of HBsAg was 3.25 log10 IU/ml and decreased with the increase
afflicted with hepatitis delta. of age. The qHBsAg was highest in the immune-tolerant phase (4.70
Method: A retrospective analysis was performed on 179 cases log10 IU/ml) and lowest in the immune inactive phase (2.77 log10 IU/
diagnosed with hepatitis delta at Guangzhou Eighth People’s Hospital, ml), while patients in the indeterminate phase had moderate qHBsAg
Guangzhou Medical University from January 1, 2010, to July 31, 2024. levels (3.06 log10 IU/ml). The proportions of patients with HBeAg-
negative, normal ALT and qHBsAg <100 IU/ml was 12.2% in overall PP0231
patients. 20.4% of overall patients had HBeAg-negativity, normal ALT, Anti-HBc IgM associates with acute flare and HBeAg/HBsAg loss
HBV DNA <2,000 IU/ml and qHBsAg <1,000 IU/ml. 37.0% of overall in chronic hepatitis B patients with acute exacerbation
patients were HBeAg-negative and qHBsAg <1,000 IU/ml, while the
Ying Zhang1, Ying Zhu1, Yi Zhou1, Zhaoxia Tan1, Yunjie Dan1,2, Xin
proportion of patients with qHBsAg ≥1,000 IU/ml was 59.9% in overall
Zou1, Guohong Deng1,2,3, Wenting Tan1,2
patients.
Conclusion: Serum qHBsAg levels varied significantly in CHB patients
1
Department of Infectious Diseases, Southwest Hospital, Third Military
Medical University, Chongqing, China, 2Chongqing Key Laboratory
with different phases and decreased with the increase of age. 12.2% of
for Research of Viral Infectious Diseases, Chongqing, China, 3Yu-Yue
CHB patients have HBeAg negativity, normal ALT and qHBsAg <100
Center for Pathology Research, Chongqing, China
IU/ml, while 59.9% of overall patients have qHBsAg ≥1,000 IU/ml.
Strategies of different therapies for CHB patients with different qHBsAg Background: Acute exacerbation (AE) is common for patients with
are needed in future drug discovery and development. chronic hepatitis B (CHB), yet pinpointing their underlying causes
frequently poses a significant challenge. The aim of the study is to
investigate the values of immunoglobulin M antibodies against hepatitis
PP0230 B core antigen (anti-HBc IgM) for indicating hepatitis B virus (HBV)-
\Evolution and Challenges in Antiviral Therapy for Chronic related acute flares and its clinical significance in CHB-AE.
Hepatitis B: Trends in Nucleoside/nucleotide analogues (NAs), Method: Patients were screened from a prospective cohort. A total of
Resistance Mutations, and Genotypic Characteristics 419 CHB patients with AE were enrolled and divided into four groups
Guo Luyao1,2, Wei Feili2, Guo Shan2, Liu Fang2, Ma Lina1, Hu according to antiviral treatment and withdrawal history, treatment naïve
Zhongjie1,2 (n=205), withdrawal above (n=71) or within (n=34) 6 months, and on-
1
Beijing Youan Hospital, Capital Medical University, 2Beijing Institute of treatment (n=109). The prevalence, clinical characteristics of anti-HBc
Hepatology IgM, and its influence on the outcome of CHB were assessed.
Background: Nucleoside/nucleotide analogues (NAs) remain the Result: Totally, 157 patients (37.5%) were tested positive for anti-HBc
primary antiviral therapy for chronic hepatitis B (CHB). However, IgM, of which patients with interruption of antiviral therapy more than
studies on the trends in NA usage, virological characteristics, and 6 months had the highest prevalence (49.3%). Significantly higher
genotype-associated resistance mutations among Chinese CHB prevalence and serum level of anti-HBc IgM were observed in patients
patients are relatively scarce. with positive HBV DNA or abnormal alanine transaminase (ALT)
Method: A retrospective analysis was conducted on 2,307 CHB (P<0.001), meanwhile, serum level of anti-HBc IgM was positively
patients treated at Beijing You’an Hospital from 2020 to 2023. correlated with HBV DNA and ALT in total and HBeAg-negative CHB
Sanger sequencing was performed to analyze the HBV reverse patients. Furthermore, serum anti-HBc IgM values varied in different
transcriptase (RT) gene (positions 143-180). A total of 1,844 samples phases of CHB, of which immune active and HBeAg-negative chronic
were successfully sequenced (detection limit: ≥500 IU/mL), yielding a hepatitis phases were significantly higher than that in inactive carriers.
positivity rate of 79.93%. The area under the curve (AUC) of anti-HBc IgM for differentiation
Result: Trends in NA Usage between hepatitis and inactive infection phases in HBeAg-negative
The use of high-resistance-barrier NAs significantly increased. TAF patients was 0.841 (sensitivity 68.9%, specificity 85.7%). A significantly
(tenofovir alafenamide fumarate) usage rose from 16.31% in 2020 higher anti-HBc IgM level was found in subgroup who developed acute-
to 34.11% in 2023, gradually replacing TDF (tenofovir disoproxil on-chronic liver failure (ACLF) regardless of HBeAg status (P<0.05),
fumarate), which declined from 28.25% to 16.44%. Entecavir (ETV) but no effect on short-term mortality. Finally, anti-HBc IgM seropositivity
usage showed a gradual decrease from 38% to 30%, while the use of was the only predictor of HBeAg seroclearance (OR: 3.18, 95% CI:
low-resistance-barrier NAs markedly declined. 1.30-7.73) and all patients who achieved HBsAg seroclearance within
Virological Characteristics 1-year had a markedly elevated pretreatment anti-HBc IgM level in
The overall resistance detection rate was 11.3% (208/1,844), with this cohort.
multidrug resistance accounting for 62.5%. Resistance detection rates Conclusion: Our study shows anti-HBc IgM is highly prevalent in CHB
increased significantly with higher HBV DNA levels (e.g., 8.8%-12.4% patients with AE and would be a new predictor of HBeAg and HBsAg
for lamivudine [LAM] and 3.3%-8.1% for ETV). loss in this population.
Resistance Mutations
A total of 25 resistance mutation sites were identified (e.g., M204V/I, PP0232
L180M, and A181T/V), with M204V/I and L180M+M204V/I being the The Predicting Value of Plasma Soluble Programmed Death-1
predominant resistance patterns. The ETV resistance mutation rate on HBV Virological Response after Antiviral Therapy of Chronic
increased annually, reaching 19.76% in 2023. Potential resistance Hepatitis B Patients
mutations, including V191I, S213T, and V214A, were detected.
Hu Hao1, Huaping Xie1, Yanhua Bi1, Yurong Gu1
Notably, multiple mutations were found in one TAF-treated patient with 1
The Third Affiliated Hospital, Sun Yat-sen University
suboptimal response, suggesting possible TAF resistance.
Genotypic Characteristics Background: Soluble programmed death-1(sPD-1) plays a critical role
Genotype C (77.2%) and genotype B (21.6%) were the predominant in immune regulation during chronic hepatitis B virus (HBV) infection.
HBV genotypes. Genotype C patients were more prone to resistance This study aims to investigate further the clinical value of sPD-1 levels
mutations, with significantly higher rates of L180M+M204V/I (8.7% vs. in antiviral treatment efficacy prediction among chronic hepatitis B
5%, P=0.02), ETV resistance (6.7% vs. 3.5%, P=0.02), and multidrug (CHB) patients.
resistance (9.1% vs. 5%, P=0.01) compared to genotype B. Method: The study included two cohorts. The entecavir therapy
Conclusion: High-resistance-barrier NAs are emerging as the cohort (n=40) consisted of HBeAg-positive patients who initially
mainstay treatment for CHB. The dynamic changes in HBV genotypes received entecavir therapy for at least 48 weeks. The peginterferon-α
and resistance mutations underscore the need for enhanced (Peg-IFNα) therapy cohort (n=40) consisted of CHB patients who
individualized treatment strategies and resistance monitoring, with had completed at least one year of nucleoside/nucleotide analogues
particular attention to the clinical implications of potential resistance (NAs) monotherapy and then subsequently Peg-IFNα treatment. We
mutations. collected their clinical data and measured sPD-1 levels by ELISA at
Table and Figure:Figure 1.NAs drug use among chronic hepatitis B baseline and all follow-up time points.
patients treated with anti-HBV NAs at Beijing You’an Hospital from Result: The sPD-1 level significantly decreased with entecavir
2020 to 2023. treatment time. Patients in HBeAg seroconversion group decreased
Figure 2.Dynamics of the proportion of six major drug resistance more in sPD-1 levels at all the time points. Patients with quantifiable
mutations in chronic hepatitis B patients treated with anti-HBV NAs at HBV DNA (>20IU/ml) at week 48 exhibited higher sPD-1 levels at both
Beijing You’an Hospital from 2020 to 2023. weeks 24 and 48 compared to those with unquantifiable HBV DNA. The
sPD-1 level significantly increased with Peg-IFNα sequential therapy PP0234
time, but no significant differences were observed between patients THE VALUE OF THE MELD SCORE AND THE AE MODEL IN
with and without HBsAg loss. sPD-1 level showed a positive correlation PREDICTING ACUTE-ON-CHRONIC LIVER FAILURE IN PATIENTS
with various clinical parameters, but the strength of this correlation WITH SEVERE ACUTE EXACERBATION OF CHRONIC HEPATITIS
weakened and eventually disappeared over the course of NAs B VIRUS INFECTION
treatment. Additionally, the difference in sPD-1 between the baseline
Hai ThiThu Nguyen1, Van Huy Vo2, Hoang Huu Bui2
and the following time-point (Δ0wsPD1) at week 12 can be applied to
predict HBeAg conversion at week 48(AUC=0.742, p=0.008).
1
Nguyen Trai Hospital, Ho Chi Minh City, Vietnam, 2University Medical
Center, Ho Chi Minh City, Vietnam
Conclusion: Our study revealed that sPD-1 levels decreased with
ETV treatment but increased with sequential Peg-IFNα treatment. Background: Severe acute exacerbation of chronic hepatitis B virus
sPD-1 showed the potential to be an indicator in predicting HBeAg infection can lead to the development of acute-on-chronic liver failure
seroconversion and virological response in the duration of NAs (ACLF). Early diagnosis and timely treatment are crucial for preventing
treatment. disease progression and lowering mortality rates in ACLF patients.
In Vietnam, there is a limited number of studies on ACLF and a lack
of standardized predictive models for identifying the risk of ACLF in
PP0233
patients with severe acute exacerbation of chronic hepatitis B virus
Analysis of liver pathological characteristics and influencing infection.
factors in patients with an inactive HBsAg carrier status Method: A cross-sectional descriptive study with analysis and
Shan Ren1, Xin Yang Zhang2, Su Jun Zheng2, Rong Shan Fan3, Qing longitudinal follow-up was conducted on patients with severe acute
Fa Ruan3, Wen Qi Huang4, Hai Bing Gao5, Xiu Lan Xue6, Fang Yang7, exacerbation of chronic hepatitis B. The study took place at the
Xin Yue Chen1 Department of Gastroenterology, University Medical Center Ho Chi
1
Beijing You‘an Hospital, Capital Medical University, 2Beijing You‘an Minh City, from January 1, 2019, to March 30, 2024. Patients were
Hospital, Capital Medical University, 3Shenzhen Hospital of Integrated monitored for 28 days after hospital admission to record the outcome
Traditional Chinese and Western Medicine, 4Xiamen Humanity of acute-on-chronic liver failure (ACLF). The study aimed to evaluate
Hospital, 5Mengchao Hepatobiliary Hospital of Fujian Medical the predictive value of the MELD score, MELD-Na score, and AE
University, 6the First Affiliated Hospital of Xiamen University, 7Shenyang (Acute exacerbation) model in predicting ACLF in these patients.
Sixth People‘s Hospital Result: Among 120 patients experiencing severe acute exacerbation,
Background: The purpose of this study was to analyze the liver 58 progressed to ACLF within 28 days of admission. The AE model
pathological characteristics and influencing factors in patients with an demonstrated superior predictive performance for acute-on-chronic
inactive hepatitis B surface antigen (HBsAg) carrier status (IHCs) and liver failure progression in these patients, with an AUROC of 0.734
to explore the need for antiviral treatment in newly defined IHC patients (95% CI: 0.642–0.825; p < 0.001), compared to the MELD score
according to liver tissue inflammation and fibrosis. (AUROC = 0.605; 95% CI: 0.503–0.706; p < 0.05) and the MELD-Na
Method: This multicenter, retrospective and cross-sectional score (AUROC = 0.656; 95% CI: 0.558–0.755; p < 0.05)
study included 231 IHC patients who underwent histopathological Conclusion: Our study demonstrated that the AE model is effective
examination via liver biopsy at eight hospitals, from January 2018 to in predicting the progression to ACLF in patients experiencing severe
December 2023. Patient general information, biochemical indicators, acute exacerbation of chronic hepatitis B virus infection. This indicates
HBV DNA and HBsAg levels, liver ultrasound findings, FibroScan that the AE model can be utilized in clinical practice to facilitate the
results, and other examination results were collected. IHC patients early identification of ACLF in these patients, enabling proactive and
were grouped on the basis of HBV DNA negativity. Differences in liver targeted treatment strategies.
pathological inflammation activity (G) and liver fibrosis stage (S) of Table and Figure:Figure 1.Basic Characteristics of Patients With and
the patients in the two groups were analyzed. Factors affecting the Without Acute-on-Chronic Liver Failure Progression
degree of inflammation and fibrosis in the patients were identified Figure 2.Predictive Value of MELD, MELD-Na Scores, and AE Model
with univariable and multivariable analyses, and the subsequently for ACLF Progression (N=120)
established multivariable prediction model was evaluated via receiver
operating characteristic (ROC) curve analysis. The significance level PP0235
was set to α=0.05.
The impact of long‐term nucleos(t)ide analogs treatment on
Result: The median age of the 231 chronic hepatitis B patients was
metabolism of chronic hepatitis B patients
43 years, among 95.2% (220/231) were aged ≥30 years, and men
accounted for 95.2% (220/231). The median HBV DNA concentration Yan Li1, Huichun Xing1
was 94 IU/ml; a total of 35.9% (83) of the patients were negative
1
Center of Liver Diseases Division 3, Beijing Ditan Hospital,
for HBV DNA (<20 IU/ml). Patients with G≥2 accounted for 16.5% CapitalMedical University Beijing China
(38 patients) of the cohort, those with S≥2 accounted for 29% (67 Background: The impact of long-term treatment with nucleos(t)ide
patients), and those with evident hepatic injury (EHI), that is, those analogs (NAs) on host metabolism in CHB patients has always been
with G≥2 and/or S≥2, accounted for 35.9% (83 patients). In HBV DNA- a concern. Currently, few studies have reported the effects of NAs on
negative IHC patients, the percentage of liver tissues with S≥2 was metabolic parameter levels in patients with CHB, and related studies
42.2%, significantly greater than that in DNA-negative IHC patients are limited. Thus, we conducted this study to compare the effects of
(21.6%; χ 2 =10.9, P < 0.001). This significant difference occurred TAF, TDF and ETV on various metabolic indicators among patients with
mainly in the population over 30 years of age (44.9% vs. 31%, χ 2 CHB.
=4.22, P=0.04), whereas in the population under 30 years of age. Method: We reviewed CHB patients receiving antiviral treatment (TAF,
Multivariable analysis indicated that sex, HBV DNA, and the LSM were TDF, or ETV) at Beijing Ditan Hospital, Capital Medical University,
independent predictors of the liver tissue S value among IHC patients between April 2020 and January 2022. Clinical data were collected
over 30 years of age.. The area under the ROC curve (AUC) of the at baseline and 12, 24, and 48 months after treatment to compare
prediction model established from the independent factors was 0.855. the dynamic changes in fasting metabolic indicators(TCHO(mmol/L),
Conclusion: Despite presenting with HBV DNA negativity, 42.2% TG(mmol/L), HDL(mmol/L), LDL(mmol/L), Urca(umol/L)and
of patients exhibited significant liver fibrosis, and the percentage of Glu(mmol/L)) and their differences among groups. All statistical
patients with S ≥ 2 gradually increased with age. Male IHC patients analyses were performed using R (version 4.3.3), and a P-value <0.01
over 30 years of age with negative HBV DNA should undergo was considered statistically significant.
comprehensive assessments including LSMs and platelet counts, as Result: A total of 460 eligible patients were enrolled in the study and
well as liver biopsy as appropriate. Selection of appropriate antiviral were divided into 3 groups according to medication, including 231 in
treatment can improve the chance of clinical cure and minimize the risk the TAF group, 110 in the TDF group, and 119 in the ETV group. There
of long-term adverse outcomes. were no statistically significant differences in the metabolic indicator at
baseline among groups (Fig. 2). TCHO showed significant differences carcinoma (HCC) cases. Antiviral therapy with nucleo(s/t)ide analogs
at all follow-up time points among groups, and the differences were (NAs) reduces HCC risk in CHB patients and may be most effective
mainly characterized by the TDF group being significantly lower than when prescribed earlier in the disease course and for significant
the other two groups. For TG, the TDF group was significantly lower duration. A systematic literature review (SLR) and meta-analysis (MA)
than the TAF group at 6 months. HDL was significantly lower in the TDF were conducted to estimate HCC risk reduction for non-cirrhotic CHB
group than the others at 12 months. LDL differences were significant patients who were treated with NAs vs untreated patients.
at 6, 12, and 24 months, with the TDF group significantly lower than Method: An SLR conducted in February 2023 identified studies
others at 6/12 months and lower than TAF at 24 months. Urca showed reporting on HCC incidence in CHB patients who were non-cirrhotic
no significant differences across groups at any time point. For Glu, and treatment-naïve at baseline, in which treated patients were treated
a significant difference at 12 months was noted; the ETV group was for ≥three years on average. Following a heterogeneity assessment
higher than the others (with relaxed criteria at P<0.05). The trends of of patient and study characteristics, an MA generated an unadjusted
different metabolic markers in the 3 groups were observed over time estimate of the incidence rate ratio (IRR) of HCC between treated and
(Fig. 1 p-values indicate the comparison of data at that follow-up point untreated patients among papers reporting on both groups.
with baseline). Result: Among 50 studies identified in the SLR, four cohort studies
Conclusion: Long-term use of nucleos(t)ide analogs may significantly reporting on both treated and untreated patients were included in
impact metabolism, with notable differences observed among groups. analyses. These studies included a total of 5,546 patients in Asian
The TDF group showed significantly lower levels of TCHO and LDL countries, with average follow-up ≥five years in both groups. There
compared to the others at multiple time points. Uric acid levels was moderate between-study heterogeneity in sample size, NAs
increased significantly in all three groups, with the most pronounced used, baseline patient age, HBV DNA levels, and HBeAg positivity.
changes at 24 months. For Glu, levels were significantly elevated in Two studies employed propensity score matching and had relatively
the short term (6,12 months) in all groups, but no consistent long-term balanced patient characteristics between untreated and treated
differences from baseline were observed. cohorts, while two studies did not and had substantial differences
Table and Figure:Figure 1.Group Comparisons of Metabolic Indicators between arms. A random effects MA found an IRR of 0.59 (95% CI:
(P < 0.01) 0.37, 0.96), indicating that treated populations experienced a 41%
Figure 2.Trends of Variables over Time (P < 0.01) reduction in HCC risk compared to untreated populations (Figure 1a).
The I2 value of 36% indicates moderate between-study heterogeneity.
Further analysis identified Hosaka 2013 as a potential outlier; re-
PP0236
analyzing the data without this study increased risk reduction to 51%
The distribution and risk factors of serum HBV RNA (+) in HBV (IRR 0.49, 95% CI: 0.33, 0.73) and reduced heterogeneity (I2= 0%)
related post-liver transplantation recipients (Figure 1b).
Lijun Wang1, Qiuju Tian2, Qun Zhang2, Fengchao Liu2, Chuanshen Conclusion: This MA suggests that long-term treatment with NAs
Xu2, Jinzhen Cai2, Wei Rao2 in non-cirrhotic CHB patients reduces HCC risk compared to no
1
Qingdao University, 2Affiliated Hospital of Qingdao University treatment. In the context of exclusively non-cirrhotic and treatment-
Background: HBV RNA is a direct transcription product of HBV naïve patients, who are likely to be earlier in the CHB disease course
cccDNA, which can be used to evaluate the transcriptional activity of and have lower cumulative HBV DNA exposure, these findings support
the intrahepatic viral reservoir. However, the distribution of HBV RNA earlier treatment initiation. This study adds to a growing body of
levels and associated influencing factors in the liver transplantation research on the cumulative effects of HBV DNA exposure on HCC risk.
(LT) population are unknown. Table and Figure:Figure 1.Unadjusted comparative meta-analysis of
Method: At the 43 months post-LT follow-up, eighty-three HBV related HCC incidence in treated vs. untreated populations
LT recipients were tested for HBV RNA, the clinical information including
HBV DNA, HBsAg, HBsAb, HBeAg, and hepatic and renal functions at PP0238
the time of LT and HBV RNA testing were collected. The distribution of
Characteristics and risk factors of anti-tuberculosis drug-induced
HBV RNA levels and related influencing factors were analyzed.
liver injury in patients with HBV infection and tuberculosis
Result: A total of 5 (6.02%) of 83 HBV related LT recipients showed
HBsAg serological conversion, 10 (12.05%) recipients were detected Huiqin Huang1, Bin Gu1, Jiancai Chen1
as positive for HBV RNA, of which 3 recipients were positive for HBsAg,
1
Chenzhou Second People‘s Hospital
and 3(3/6) recipients were HCC recurrence. HBsAg, HCC recurrence, Background: To analyze the distribution characteristics of hepatitis
bilirubin correlated with HBV RNA positivity in HBV-related LT recipients B virus surface antigen (HBsAg) positivity among tuberculosis (TB)
(p<0.05). patients in our hospital, to explore the clinical characteristics and risk
Conclusion: HBV RNA may assist in the diagnosis of HBV relapse in factors of anti-tuberculosis drug-induced liver injury (ATB-DILI) in this
HBV-related LT recipients. group of patients, and to provide references for the rational use of
Table and Figure:Figure 1.Flow chart of the patient selection. drugs in the clinic.
Figure 2.Comparison of HBV RNA-positive and HBV RNA-negative Method: This is a retrospective study enrolled patients with anti-
recipients tuberculosis treatment in the tuberculosis department of Chenzhou
Second People’s Hospital, Hunan province, from January 2016 to
December 2020. Population demographics and clinical data were
PP0237
collected by reviewing the electronic medical records. One-way
Hepatocellular Carcinoma Risk Reduction Associated with logistic regression and multifactorial logistic regression analyses
Antiviral Treatment in Non-Cirrhotic Chronic Hepatitis B Patients: were performed on the relevant independent variables to screen for
A Comparative Meta-Analysis independent risk factors for ATB-DILI reassortment (ALF).
Alice Stead1, Arpan Mohanty2, Laura Telep1, Amanda Singer1, Result: Of all 11260 inpatients in the TB unit, 1683 (14.9%) were
Tristan Curteis3, Zarena Jafry4, Anna Zolotor4, Carrie Frenette1, Kyle screened for hepatitis B surface (HBsAg)-positive TB. ATB-DILI was
Hammond1, Dona Khoshabafard1, Tom McQuaid1, Robin K Kelley5 present in 125 (7.4%) cases, of which 47 (37.6%) had mild liver injury,
1
Gilead Sciences, Inc., Foster City, California, USA, 2Boston University 38 (30.4%) had moderate liver injury, 26 (20.8%) had severe liver injury,
Chobanian & Avedisian School of Medicine & Boston Medical Center, and 17 (13.6%) had hepatic failure (ALF), of which 9 (7.2%) died.
Boston, Massachusetts, USA, 3Costello Medical, Ltd., Manchester, There were 7 cases (5.6%) of HBV reactivation in those patients with
UK, 4Costello Medical, Inc., Boston, Massachusetts, USA, 5Helen ATB-DILI. Multifactorial logistic regression analysis was performed,
Diller Family Comprehensive Cancer Center, University of California, and the results suggested that the underlying liver disease (such as
San Francisco, California, USA alcoholic hepatitis, fatty liver hepatitis, etc.), the level of HBV DNA(>6
Background: Chronic hepatitis B (CHB) affects nearly 300 million log10IU/mL) and prophylactic antiviral treatment were independent
people globally and is responsible for over half of hepatocellular influencing factors for the development of ALF in HBsAg-positive TB
patients (P<0.05). PP0240
Conclusion: The prevalence of HBV infection is higher in TB patients A prospective study of the efficacy and safety of lifestyle
than in the general population, and such patients are more susceptible intervention in patients with chronic hepatitis B and non-alcoholic
to drug-induced liver injury. Individualized anti-tuberculosis regimens fatty liver disease
should be developed, especially for patients with high HBVDNA loads,
Lufeng Li1, Jing Wang1, Jiaqi Wang1, Jie Xia1, Guohong Deng1, Qing
and interventions such as prophylactic antiviral should be carried out
Mao1
to reduce the incidence of liver injury, and anti-tuberculosis drugs
should be vigilant for HBV reactivation.
1
The First Affiliated Hospital of PLA Army Medical University
Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver
disease (NAFLD) are both threats to human health worldwide. The
PP0239
combination of the two diseases is not uncommon, which can promote
Therapeutic effect and influencing factors analysis of TMF and the progression of liver disease to severe liver diseases such as
other nucleoside (acid) analogues combined with Peg-IFN-α-2b in cirrhosis and liver cancer. Antiviral therapy and lifestyle intervention
treatment of CHB such as diet and exercise were the main treatment measures for
Xiaoxia Geng1, Xianbo Wang2, Jingyu Yang1, Yao Cao3, Yiheng Yang2, these patients respectively. However, in addition to antiviral therapy,
Ting Feng1, Hengjian Du1 the efficacy of dietary intervention for chronic hepatitis B patients with
1
Sichuan Provincial People‘s Hospital, Chengdu, China, 2North fatty liver needs to be further studied. Some researchers even worry
Sichuan Medical College, Nanchong, China, 3The People‘s Hospital of about the possibility of hepatitis B virus activation while controlling fatty
Wenchuan liver. The purpose of this study was to study the efficacy and safety
Background: To investigate the efficacy and influencing factors of of lifestyle interventions such as diet, exercise, and behavior in these
tenofovir amibufenamide (TMF) and other nucleoside (acid) analogues patients.
(NAs) combined with Peg-IFN-α-2b in treatment of chronic hepatitis Method: Patients with CHB combined NAFLD were enrolled in this
B(CHB) patients. study. The inclusion criteria were patients who had received nucleos
Method: A total of 108 CHB patients treated with TMF combined (t) ide analogues antiviral therapy for more than 1 year and were
with Peg-IFN-α-2b (n=64) and other NAs combined with Peg-IFN- diagnosed with fatty liver by ultrasound. Strict exclusion criteria were
α-2b (n=44) in Sichuan Provincial People’s Hospital from May 2021 used to exclude patients with fatty liver disease other than alcoholic
to December 2024 were analyzed. The therapeutic effects were fatty liver disease, cirrhosis, liver cancer, pregnant women, plans
analyzed, and the related factors affecting the significant early HBsAg for pregnancy, and renal insufficiency. All participants were given a
decline achieved by TMF combined with Peg-IFN-α-2b were explored. balanced low-energy diet, which paid attention to the balanced intake
Result: 1.In terms of biochemistry, ALT, AST and GGT levels were of nutrients such as protein, fat, carbohydrates, vitamins, minerals and
significantly increased in all patients after treatment of 12 weeks (p dietary fiber, while reducing 30%-50% of their normal discretionary
< 0.05), but there were no significant changes during subsequent energy intake. Weight and diet were recorded by using wechat group
treatment (p > 0.05). There were no significant changes in Crea and and Tencent questionnaire.
eGFR in all patients after treatment of 24 weeks and 36 weeks (p > Result: Forty-six patients with CHB combined NAFLD were all from
0.05). In terms of virology, TMF combined with Peg-IFN-α-2b group the outpatient department of Infectious Diseases of the First Affiliated
achieved rapid HBV-DNA decline after 12 weeks of treatment (P<0.05), Hospital of Army Medical University. The ratio of male to female was
while other NAs combined with Peg-IFN-α-2b group had no significant 38/8, the ratio of HBeAg positive and negative was 7/39, and the
decrease in 12 weeks (p > 0.05). All patients achieved a sustained average age, BMI value and CAP value were 42.3 years, 26.57Kg/
and significant decrease in HBsAg at 12w and 24w (p<0.05). In TMF m2 and 291dB/m, respectively (Table 1). One month later, 89.1% of
combined with Peg-IFN-α-2b group, 7 patients were HBeAg positive the patients had a weight loss, with an average weight loss of 2.46Kg,
at baseline, and 14.2%(1/7) of patients had HBeAg negative after 12 and 21.7% of the patients had a weight loss of 3%-5%. At the same
weeks treatment, without HBeAg seroconversion. After treatment of time, the mean value of the controlled attenuation parameter (CAP) of
12 weeks, 24 weeks and 36 weeks, the serological conversion rate of fatty liver decreased from 291dB/m to 270dB/m. In addition, Alanine
HBsAg was 1.56% (1/64), 3.13% (2/64) and 1.56% (1/64), respectively aminotransferase (ALT) normalization rate and the rate of complete
(Figure1) . virological inhibition of HBV DNA (HBV DNA<20IU/ml) were increased
2, After baseline matching, TMF combined with Peg-IFN-α-2b group (58.7% vs 76.1%; 78.3%VS82.6%), while the proportion of patients
and other NAs combined with Peg-IFN-α-2b group were compared, with hyperuricemia, hyperlipidemia and elevated fasting blood glucose
and there were no significant differences in the quantitative changes of decreased (38.4%VS23.9%; 41.3% vs 34.8%; 6.5% vs 4.3%) (Figure
HBsAg, ALT, GGT, crea and eGFR between the two groups (p > 0.05). 1).
3, Multiple linear regression analysis was used to predict the quantitative Conclusion: Lifestyle intervention has a positive effect on CHB
decline in HBsAg after TMF combined with Peg-IFN-α-2b treatment for combined NAFLD patients, which can reduce body weight, improve
24 weeks based on sex, age, baseline ALB, PLT, GGT, and ALT levels. fatty liver and liver function, increase the virological suppression rate
The regression model was statistically significant (F= 2.458, P<0.05). and reduce the risk of metabolic abnormalities.
The two independent variables included in the model (baseline ALT Table and Figure:Figure 1.Table 1. Sociodemographic and biochemical
and GGT) had a statistically significant impact on the decline of the characteristics of Hepatitis B combined with fatty liver Patients.
quantitative level of HBsAg (P<0.05). The higher the baseline ALT level Figure 2.Figure 1. Changes in Efficacy Measures Before and after
and the lower the GGT level, the more likely the quantitative level of Treatment
HBsAg to decline after treatment (Figure 2) .
Conclusion: Treatment of TMF combined with Peg-IFN-α-2b can PP0241
rapidly achieve a significant decline in HBsAg at the early stage (12w)
Effectiveness and Safety of 48-Week Tenofovir Amibufenamide in
and continue to 24w, which is similar to the clinical efficacy of other
Patients with Hepatitis B Virus-Related Cirrhosis: A Retrospective
NAs combined with PEG-IFN-α2b in the treatment of CHB. High ALT
Real-World Study
level and low GGT level at baseline were associated with significant
HBsAg decline after early TMF combined with Peg-IFN-α-2b treatment. Xueyan Lv1, Rueyue Chen1, Zhuangzhuang Zhai1, Yuehang Wang1,
Table and Figure:Figure 1.Figure 1: Therapeutic effect of TMf combined Xuejing Yu1, Yajie Pan1, Qinglei Zeng1
with Peg-IFN-α-2b group and other NAs combined with Peg-IFN-α-2b
1
Department of Infectious Diseases, The First Affiliated Hospital of
group Zhengzhou University
Figure 2.Figure 2 : Multiple linear regression analysis of TMF combined Background: Few data are existed on the effectiveness and safety
with Peg-IFN-α-2b therapy resulted in significant early (24w) HBsAg of tenofovir amibufenamide (TMF) for patients with chronic hepatitis B
decline (CHB)-related cirrhosis in real-world settings. The aim of this study was
to evaluate the 48-week effectiveness and safety profiles of TMF for
patients with CHB-related cirrhosis. between HBV infection and CKD. Older age and elevated BUN levels
Method: This retrospective single-arm study recruited patients with were significant CKD predictors, while higher education reduced risk.
CHB-related cirrhosis who undergone TMF or TAF therapy at 25 mg These findings highlight the need for individualized monitoring and
daily at The First Affiliated Hospital of Zhengzhou University, China, management of at-risk HBV-infected patients when offering antiviral
from January 2021 to August 2023. The primary endpoint was HBV therapy.
DNA undetectable (less than 20 IU/mL) rate at week 48. The secondary Table and Figure:Figure 1.Figure 1: Multivariate logistic analysis of
endpoints included the rate of alanine aminotransferase (ALT) factors associated with CKD in participants with HBV infection.
normalization, as well as changes in renal function and lipid profile Figure 2.Table 2: Association between HBV infection and CKD
dynamics at week 48, with comparisons between the two groups.
Result: A total of 212 patients were enrolled, with 104 patients in the
PP0243
TMF group and 108 in the TAF group (Table 1). Baseline characteristics
were as follows: the age, HBV DNA, ALT, and LSM levels of the Efficacy of antiviral treatment for CHB patients younger than 30
patients in the TMF and the TAF group were 45 (38, 55) vs 44 (40, 51) years old
years, 4.72 ± 2.09 vs 3.92 ± 1.27 log10 IU/mL, 38.0 (24.3, 76.5) vs Senlin You1, Xiaoqiong Tang1, Hong Tang1, Hong Li1
35.1 (22.0, 89.5) U/L, and 14.7 (10.4, 25.0) vs 12.6 (9.55, 17.8) kPa, 1
Laboratory of Infectious and Liver Diseases, Institute of Infectious
respectively, while no significant differences were observed between Diseases, West China Hospital of Sichuan University, Chengdu, China
the two groups (all P> 0. 05). At 48 weeks of treatment, the HBV DNA Background: Chronic hepatitis B (CHB) is a leading cause of
undetectable rates were 96.2% in the TMF group versus 96.3% in hepatocellular carcinoma (HCC) in China, highlighting the importance
the TAF group (P = 0.618). Meanwhile, the ALT normalization rates of timely antiviral therapy in reducing cirrhosis and HCC risk. While the
were 77.3% (34/44) in the TMF group and 75.0% (36/48) in the TAF 2022 Chinese CHB guidelines expanded antiviral treatment indications
group (P = 0.823). Regarding renal safety, after 48 weeks of treatment, to include patients over 30 years of age with detectable HBV DNA
there were no significant differences between the groups in estimated regardless of ALT levels, the optimal treatment strategy for younger
glomerular filtration rate [106.5 (99.1, 113.4) vs 108.8 (101.5, 114.6) patients (≤30 years) with HBV DNA positive remains unclear. This
mL/min/1.73m², P = 0.134] or serum creatinine levels (68.3 ± 12.3 vs study assessed the efficacy of nucleos(t)ide analogues (NAs) therapy
67.8 ± 10.4 μmol/L, P =0.323) in TMF and TAF groups, respectively. among CHB patients younger than 30 years old.
Moreover, the patients’ lipid profiles maintained stable, while no Method: This retrospective study analyzed data from HBeAg-positive
significant differences were observed between the two groups (all P treatment-naïve CHB patients who were younger than 30 years and
> 0.05). Meanwhile, no severe adverse events were occurred and no received NAs therapy (either ETV, TDF, or TAF alone, or the combination
one discontinued therapy due to adverse events during therapy in the of ETV plus TDF or ETV plus TAF) for at least one year at West China
two groups. Hospital of Sichuan University between January 2015 and July 2023.
Conclusion: TMF and TAF exhibited similar 48-week effectiveness Patients were stratified into ALT normal (< 40 U/L) and ALT abnormal
and safety profiles for patients with CHB-related cirrhosis in real- (≥ 40 U/L) groups. All patients had a baseline HBV DNA level > 10⁷
world settings. Future prospective, long-term validation studies are IU/mL. Virological response (VR) was defined as HBV DNA < 100 IU/
warranted. mL and analyzed using intention-to-treat (ITT) and per-protocol (PP)
Table and Figure:Figure 1.Table 1. Laboratory parameters at baseline approaches.
and 48 weeks for patients with HBV-related cirrhosis with TMF or TAF Result: A total of 176 HBeAg-positive treatment-naïve CHB young
Figure 2.Table 1. Laboratory parameters at baseline and 48 weeks for patients were enrolled, including 86 in ALT normal group and 90 in ALT
patients with HBV-related cirrhosis with TMF or TAF abnormal group. After 12 months’ antiviral treatment, part of patients
achieved VR. And VR rates in the ALT normal group (24.4%, 21/86)
PP0242 were significantly lower than ALT abnormal group (43.3%, 39/90; P <
0.05). However, at 24 and 36 months, ITT analysis showed VR rates
Chronic Kidney Disease in Hepatitis B Patients: Risk Analysis
increased to 62.8% (54/86) and 75.6% (65/86) in the ALT normal
from NHANES 2017–2020 Study.
group, also 77.8% (70/90) and 88.9% (80/90) in ALT abnormal group,
Ke Mi1, Tingdan Ye1, Calvin Q Pan1,2 respectively. PP analysis yielded similar trends, with VR rates of 68.4%
1
Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical (54/79) and 90.3% (65/72) in the ALT normal group, and 82.4% (70/85)
University, Beijing, China., 2Division of Gastroenterology and and 98.8% (80/81) in ALT abnormal group, respectively. Notably, for
Hepatology, Department of Medicine, NYU Langone Health, New patients who did not achieve VR at 12 months, those initially treated
York University Grossman School of Medicine, New York, USA. with ETV monotherapy achieved VR at 24- or 36-months following add-
Background: The association between HBV infection and chronic on therapy of TDF or TAF. Similarly, patients initially treated with TDF or
kidney disease (CKD) remains debated. While some studies suggest TAF monotherapy who failed to achieve VR at 12 months subsequently
HBV infection increases CKD risk, others report inconclusive findings. achieved VR at 24 or 36 months with the addition of ETV.
This study evaluated the relationship between HBV infection and CKD Conclusion: Antiviral treatment might be beneficial for HBeAg-positive
in the U.S. population. CHB patients younger than 30 years old, regardless of ALT levels. For
Method: Data from adult participants in the NHANES 2017–2020 patients who did not achieve viral response after 1-year monotherapy
pre-pandemic cycle were analyzed based on prespecified eligibility with NAs, add-on therapy could be considered as an alternative.
criteria. Participants were categorized into HBV-infected and non- Table and Figure:Figure 1.Table1. Basic characteristics of CHB patients
infected groups. Weighted means and percentages described younger than 30 years old & Figure 1. Viral response rate of ALT normal
participant characteristics, while logistic regression models evaluated and ALT abnormal groups
the association between HBV infection and CKD. Multivariate logistic
regression identified CKD risk factors among HBV-infected individuals.
PP0244
Result: Among 7,613 participants (7072 non-HBV and 541 HBV-
infected), CKD prevalence was higher in HBV-infected individuals Hepatic Fat Attenuation Changes During IFN Therapy Linked to
(7.6% vs. 5.2%, P = 0.023). Unadjusted analyses showed HBV CHB Treatment Outcomes
infection increased CKD risk (OR = 1.23, 95% CI: 1.03–1.47, P = HAISHI WU1, NA GAO1, MEZUO NIAN1, ZHILIANG GAO1
0.025). However, adjusted analyses revealed an inverse association 1
No. 600 Tianhe Road, Tianhe District, Guangzhou, Sun Yat-sen
(OR = 0.75, 95% CI: 0.57–0.97, P = 0.034). In HBV-infected individuals, University Third Affiliated Hospital.
older age (OR = 1.06, P = 0.017) and serum urea nitrogen (BUN) Background: In chronic hepatitis B (CHB) patients undergoing
elevation (OR = 1.20, P = 0.001) were independent CKD risk factors, interferon (IFN) therapy, fluctuations in liver stiffness and hepatic fat
while higher education reduced risk (OR = 0.28, P = 0.030). attenuation have been observed. However, the association between
Conclusion: Although CKD prevalence was 7.6% in HBV-infected these fluctuations and treatment outcomes has not been previously
patients, adjusted analyses showed no independent association
explored. to 100%) in the TMF group versus 94.1% (95% CI, 86.2% to 100%) in
Method: We conducted a study involving 162 CHB patients who the ETV group (P = 0.651). However, the ALT normalization rate was
received IFN therapy for more than 48 weeks. Hepatic fat attenuation significantly higher in the TMF group than that in the ETV group (89.7%
and liver stiffness were measured at baseline, 24 weeks, and 48 weeks. [95% CI, 78.6% to 100%] vs. 64.7% [95% CI, 48.6% to 80.8%], P =
Multivariate logistic regression analysis was performed to identify 0.020). Regarding renal safety, after 48 weeks of treatment, there were
factors associated with HBsAg seroclearance following IFN therapy. no significant differences between the groups in estimated glomerular
Result: In this study, 162 chronic hepatitis B (CHB) patients filtration rate (106.19 ± 11.80 vs. 104.31 ± 8.39 mL/min/1.73m², P
receiving interferon (IFN) therapy for over 48 weeks were included. = 0.738) or serum creatinine levels (65.68 ± 11.88 vs. 63.82 ± 9.65
Measurements of hepatic fat attenuation and liver stiffness were taken μmol/L, P = 0.688) in TMF and ETV groups, respectively. In terms of
at baseline, 24 weeks, and 48 weeks. No significant differences were lipid profile, the serum triglyceride levels were significantly lower in the
observed between the HBsAg seroclearance and non-seroclearance TMF group compared to the ETV group (TMF: 3.21 [2.88, 3.52] mmol/L
groups in terms of age, sex, presence of non-alcoholic fatty liver vs. ETV: 3.71 [3.16, 3.93] mmol/L, P = 0.002], while no significant
disease (NAFLD), or baseline liver stiffness measurement (LSM). differences were observed for other lipid parameters between the two
Compared to the seroclearance group, the non-seroclearance group groups (all P > 0.05).
had higher baseline HBsAg (hepatitis B surface antigen) levels (5.56 Conclusion: This study is the first to demonstrate that TMF exhibits
log IU/mL vs. 6.02 log IU/mL, P < 0.001). Multivariate analysis showed favorable effectiveness and safety in the treatment of HBV-related
that higher baseline HBsAg levels were associated with a lower HCC patients; notably, TMF showed a significantly higher rate of ALT
likelihood of HBsAg seroclearance (OR: 0.619, 95% CI: 0.465–0.801, normalization and a better lipid profile compared to ETV, with similar
P = 0.001). renal safety. Further large-scale studies are needed to confirm these
Regarding hepatic fat attenuation, the Δ 24 LFAI (hepatic fat attenuation findings.
index) was significantly different between groups (6.45 dB/m vs. 15.68 Table and Figure:Figure 1.Table 1 Laboratory parameters at baseline
dB/m, P = 0.027), with smaller changes linked to higher seroclearance and 48 weeks in patients with hepatitis B virus-related hepatocellular
probability (OR: 0.987, 95% CI: 0.973–0.999, P = 0.047). Changes in carcinoma treated with TMF or ETV
LFAI from baseline to 48 weeks were not significantly different (P =
0.202). LSM did not differ significantly between groups at either 0-24
PP0246
or 0-48 weeks (P = 0.351 and P = 0.172, respectively).
Multivariate analysis indicated that higher baseline HBsAg levels Development and Validation of a Novel Scoring System for
and smaller Δ 24 LFAI were independent predictors of HBsAg Determining Treatment Eligibility for Patients with Chronic
seroclearance. These findings suggest that early changes in hepatic Hepatitis B
fat attenuation can predict treatment outcomes in CHB patients. Shaoqiu Zhang1, Jian Wang1,2, Chao Jiang3, Li Zhu4, Tao Fan5, Ye
Conclusion: Fluctuations in hepatic fat attenuation during the first Xiong5, Renling Yao1, Juan Xia1, Xiaomin Yan1, Yuanwang Qiu6,
24 weeks of IFN therapy are linked to treatment outcomes in CHB Xingxiang Liu7, Chuanwu Zhu4, Rui Huang1,2,3, Chao Wu1,2
patients. Smaller variations in hepatic fat attenuation are associated 1
Department of Infectious Diseases, Nanjing Drum Tower Hospital,
with a higher likelihood of achieving HBsAg seroclearance, suggesting Affiliated Hospital of Medical School, Nanjing University, Nanjing,
the potential importance of monitoring these parameters for predicting Jiangsu, China, 2Institute of Viruses and Infectious Diseases, Nanjing
treatment response. University, Nanjing, Jiangsu, China, 3Department of Infectious
Table and Figure:Figure 1.Table 1. Multivariable logistic analysis for Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu
predictors of HBsAg seroclearance University, Nanjing, Jiangsu, China, 4Department of Infectious
Diseases, The Affiliated Infectious Diseases Hospital of Soochow
University, Suzhou, Jiangsu, China, 5Department of Infectious
PP0245 Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing
Effectiveness and Safety of 48-Week Tenofovir Amibufenamide in University of Chinese Medicine, Nanjing, Jiangsu, China, 6Department
Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: of Infectious Diseases, The Fifth People‘s Hospital of Wuxi, Wuxi,
A Retrospective Real-World Study Jiangsu, China, 7Department of Clinical Laboratory, Huai’an No. 4
Yuehang Wang1, Ruyue Chen1, Xueyan Lv1, Zhuangzhuang Zhai1, People’s Hospital, Huai’an, Jiangsu, China
Xuejing Yu1, Yajie Pan1, Qinglei Zeng1 Background: Antiviral treatment can significantly decrease the risk of
1
Department of Infectious Diseases, The First Affiliated Hospital of cirrhosis, liver failure, and hepatocellular carcinoma in patients with
Zhengzhou University, China chronic hepatitis B (CHB). This study aimed to develop and validate a
novel predictive score based on easily accessible clinical parameters
Background: Currently, there is a lack of data on the effectiveness
to identify eligibility for antiviral therapy of CHB patients in resource-
and safety of tenofovir amibufenamide (TMF) for patients with hepatitis
limited regions.
B virus (HBV)-related hepatocellular carcinoma (HCC) in real-world
Method: Treatment-naïve CHB patients were included from four
settings. The aim of this study was to evaluate the 48-week real-life
medical centers and randomly divided into a training set and a
effectiveness and safety profiles of TMF in patients with HBV-related
validation set with a ratio of 7:3. Stepwise logistics regression analysis
HCC.
was conducted in the training set to derive the novel score model for
Method: This retrospective study enrolled HBV-related HCC patients
antiviral therapy eligibility according to the 2017 European Association
who underwent antiviral treatment with TMF (25 mg/day) or entecavir
for the Study of the Liver (EASL) guidelines and validated in the
(ETV) (0.5 mg/day) following HCC surgery, at The First Affiliated
validation set. The performance of the model was evaluated using area
Hospital of Zhengzhou University, China, from August 2018 to August
under the receiver operating characteristic curve (AUROC), sensitivity,
2024. The primary endpoint was HBV DNA undetectable (less than 20
and specificity.
IU/mL) rate at week 48. The secondary endpoints included the rate of
Result: A scoring model (HAP) incorporated alanine aminotransferase
alanine aminotransferase (ALT) normalization, as well as changes in
(<20 U/L: 0 point; 20-40 U/L: 1 point; 40-60 U/L: 2 points; 60-80 U/L: 3
renal function and lipid profile dynamics at week 48, with comparisons
points; ≥80 U/L: 12 points), platelet count (≥150×109/L: 0 point; 100-
between the two groups.
150×109/L: 5 points; <100×109/L: 7 points), and hepatitis B e antigen
Result: A total of 63 patients were enrolled, with 29 patients in the
(negative: 0 point, positive 12 points), with the optimal cutoff value
TMF group and 34 in the ETV group (Table 1). Baseline characteristics
of 7 points. In the training set, HAP score demonstrated an AUROC
were as follows: the mean age was 51.93 ± 10.94 years in the TMF
of 0.843 (95% CI: 0.826-0.860), sensitivity of 78.3%, and specificity
group and 54.91 ± 8.35 years in the ETV group (P = 0.225); the HBV
of 77.6%. In the validation set, HAP score also achieved similar high
DNA levels were 1.10 ± 1.66 log10 IU/mL vs. 1.41 ± 2.03 log10 IU/mL
accuracy, with an AUROC of 0.846 (95% CI: 0.821-0.870), sensitivity
(P = 0.516); and ALT levels were 26.00 (18.50, 42.50) U/L vs. 30.00
of 80.3%, and specificity of 73.8%. Compared to existing models for
(20.75, 52.25) U/L (P = 0.440). At 48 weeks of treatment, the HBV DNA
predicting treatment eligibility, the HAP score outperformed TREAT-B
undetectable rates were 96.6% (95% confidence interval [CI], 89.9%
scores (AUROC 0.821, P<0.001; 0.816, P<0.001), and HEPSANET donor HBsAb levels (≥157.88 IU/L) were associated with improved
scores (AUROC 0.755, P P<0.001; 0.750, P<0.001) both in the training seroclearance rates. Additionally, lower baseline HBsAg levels (<250
and validation sets. IU/mL) in recipients correlated with higher cumulative seroclearance
Conclusion: The novel HAP scoring system is a promising and ease- rates. No significant difference was found between entecavir and
to-use practical tool with high diagnostic accuracy for selecting CHB tenofovir-based antiviral therapies in achieving HBsAg seroclearance.
patients who are eligible for antiviral treatment in resource-limited Conclusion: These findings suggest that HBsAg seroclearance after
regions. allo-HSCT is influenced by pre-transplant HBsAg and donor HBsAb
levels, with functional cure being more likely in patients with favorable
baseline characteristics.
PP0247
Table and Figure:Figure 1.Kaplan-Meier curves for overall cumulative
Expression of CD161+CD8+ T Cells in Patients with Hepatitis B incidence ofHBsAg loss for leukemia patientswith chronic HBV
Virus-Associated Hepatocellular Carcinoma infection after allogeneic stem cell transplantation.
Chenrui Liu1, Na Huang1, Yaping Li1 Figure 2.The ROC analysis of baseline HBsAb levels in donors for
1
Department of Infectious Diseases, Second Affiliated Hospital of prediction of HBsAg loss in leukemia patientsundergoing HSCT.
Xi‘an Jiaotong University
Background: This study aims to examine the expression profiles of PP0249
three immune molecules including CD161, CD8, and programmed
The combination of PegIFNα2b and nucleos(t)ide analogues may
death receptor 1 (PD-1) in patients with hepatitis B virus (HBV)-
impact the renal tubular reabsorption function
associated chronic liver disease and hepatocellular carcinoma (HCC)
and to evaluate the impact of PD-1 inhibitors on the expressions of Yujing Li1, Chengrun Song1, Jing Zhou1, Yonghong Wang1, Taoyou
these molecules in the peripheral blood of HCC patients. Zhou1, Fang He1, Yachao Tao1, Jiajie Lu2, Wei Jiang1, Menglan
Method: The expression levels of CD161, CD8, and PD-1 in the Wang1, Xuezhong Lei1, Hong Tang1, Enqiang Chen2
peripheral blood of individuals in the healthy control group as well
1
Center of Infectious Diseases, West China Hospital, Sichuan
as patients with chronic hepatitis B (CHB), decompensated cirrhosis University, 2West China Hospital of Sichuan University
(DCC), and HCC and in the liver cancer tissues obtained from the Background: Interferon-based regimens are crucial for achieving
HCC group were analyzed using bioinformatics, flow cytometry, and clinical remission in chronic hepatitis B (CHB). Although interferon’s
immunohistochemistry. adverse events have been widely studied, the impairment of renal
Result: The proportion of CD161+CD8+ T cells was significantly tubular reabsorption remains under-reported. This study aimed to
elevated in the peripheral blood of CHB patients, suggesting a potential evaluate the incidence of renal tubular reabsorption dysfunction, its
correlation between T cell exhaustion and chronic inflammation. In HCC effect on treatment efficacy, and the predictive factors in CHB patients
patients, the proportion of CD161+CD8+ T cells significantly dropped undergoing nucleos(t)ide analogues (NAs) combined with PegIFNα2b
in the peripheral blood; however, CD8+ T cells with high expression therapy.
of PD-1 and CD161 showed significant infiltration. PD-1 inhibitors Method: A prospective observational study was conducted, enrolling
effectively lowered the proportion of PD-1+ cells in the peripheral CHB patients who received NAs plus PegIFNα2b treatment at West
blood but had no significant effects on the expression of CD161. The China Hospital from February 2023 to January 2024. Patients were
elevated expression of CD161 within the immune microenvironment divided into three subgroups based on the NAs subtype: Nucleotide
of HCC was associated with immunosuppressive mechanisms, with analogue plus PegIFNα2b (Group A), Nucleoside analogue plus
the protein level of CD161 in HCC tissues exceeding that observed in PegIFNα2b (Group B), and a combination of nucleotide and nucleoside
paracancerous tissues. analogues plus PegIFNα2b (Group C). The incidences of elevated
Conclusion: CD161 may serve as a crucial immunosuppressive urinary β2 microglobulin (β2-MG), decreased blood phosphorus
molecule and a potential therapeutic target for immunotherapy in HBV- levels, elevated serum creatinine (sCr), and changes in HBsAg during
associated HCC. When used in combination with PD-1 inhibitors, it may the treatment were carefully analyzed.
further improve the prognosis of patients with HBV-associated HCC. Result: A total of 217 eligible patients participated, including 163
males and 54 females, with a median age of 41 years (ranging from
22 to 65 years). After 4 to 48 weeks of treatment, 90.3% (196/217)
PP0248
showed an increase in urinary β2-MG, 42.9% (93/217) had a decrease
Incidence and Determinants of Functional Cure in Chronic in blood phosphorus, and 38.7% (84/217) had elevated serum
Hepatitis B Virus-Infected Leukemia Patients Following Allogeneic creatinine levels. However, only 5 patients had sCr above the upper
Hematopoietic Stem Cell Transplantation limit of normal, and only 2 patients had sCr exceeding 20% above the
Xiong Dan Ping1, Lin Jing1, Wei Feng Zhao1 baseline. There were no significant differences in the proportion and
1
Department of Infection Diseases, The First Affiliated Hospital of degree of urinary β2-MG elevation and blood phosphorus decrease
Soochow University, among the three subgroups. Overall, a significant downward trend
Background: This study aimed to investigate the incidence in HBsAg levels was observed after adding PegIFNα2b treatment.
and influencing factors of Hepatitis B surface antigen (HBsAg) Among the 87 patients with concurrent urinary β2-MG elevation and
seroclearance in chronic Hepatitis B virus (HBV)-infected leukemia blood phosphorus decrease, the reduction in HBsAg levels was less
patients undergoing allogeneic hematopoietic stem cell transplantation than that in other patients, indicating that the efficacy of PegIFNα2b
(allo-HSCT). was lower in patients with renal tubular reabsorption dysfunction.
Method: A retrospective analysis was conducted on clinical data However, the efficacy of patients with normal blood phosphorus and
from 84 patients (≥18 years old) who underwent allo-HSCT at the First urinary β2-MG elevation > 10ULN was significantly better than that of
Affiliated Hospital of Soochow University from January 1, 2017, to other patients at 24, 36, and 48 weeks (P = 0.0006, P = 0.0062, P =
December 31, 2022. 0.0328). Univariate analysis revealed that females had a lower risk of
Result: 14 patients (16.67%) achieved HBsAg seroclearance within renal tubular reabsorption function impairment compared to males (OR
a median time of 17.5 months (range: 7–45 months). The cumulative = 0.077, 95%CI: 0.027 - 0.223, P < 0.001). Renal tubule reabsorption
1-year, 3-year, and 5-year HBsAg seroclearance rates were 3.6%, function impairment might potentially be restored by switching the NAs
15.7%, and 31.3%, respectively. Significant differences were observed subtype or discontinuing PegIFNα2b.
in pre-transplant baseline HBsAg levels and donor Hepatitis B Conclusion: The incidence of renal tubular reabsorption dysfunction is
surface antibody (HBsAb) levels between the seroclearance and relatively high in patients receiving NAs plus PegIFNα2b combination
non-seroclearance groups (P < 0.05). Both univariate and multivariate therapy, warranting close attention. Modifying the NAs subtype or
Cox regression analyses identified baseline HBsAg and donor HBsAb discontinuing PegIFNα2b may be beneficial for improving renal tubule
levels as independent predictors of HBsAg seroclearance. Higher reabsorption function.
 PP0250 HBV infection were 97.3% (549/564), 61.3% (1208/1972), and 13.0%
The diagnostic value of serum CHI3L1 in the progression of (331/2540), respectively, while those on antiviral treatment were 64.1%
chronic liver disease and prognosis of liver cancer (352/549), 22.7% (274/1208), and 9.4% (31/331), respectively (P <
0.05). Compared to the control group, patients with a family history of
Haiying Zhang1, Yuyuan Jia1, Runling Zhang1, Huiying Rao1
unfavorable prognosis were diagnosed and initiated treatment at older
1
Peking University People‘s Hospital, Peking University Hepatology ages (27.79±13.89 vs. 22.70±12.80, 40.68±11.22 vs. 34.22±10.37).
Institute, Infectious Disease and Hepatology Center of Peking
Among the untreated patients, the natural history was similar in both
University People‘s Hospital, Beijing Key Laboratory of Hepatitis
groups, and the proportion of patients in the indeterminate phase was
C and Immunotherapy for Liver Diseases, Beijing International
45.5% (51/112) and 50.0% (19/38). Among the treated patients, the
Cooperation Base for Science and Technology on NAFLD Diagnosis,
average duration of treatment was 3.61±4.18 and 3.19±3.97 years in
Beijing 100044, China.
patients from clustering of HBV infection in families with unfavorable
Background: The diagnostic and prognostic significance of serum prognosis and the control group, respectively, with no statistically
CHI3L1 in hepatocellular carcinoma (HCC) remains unclear. To significant difference in the incidence of low-level viremia (LLV) after
investigate the diagnostic value of chitosinase 3-like protein 1 (CHI3L1) treatment (49/273, 17.9% vs. 17/70, 24.3%).
in patients with chronic liver diseases such as viral hepatitis, cirrhosis Conclusion: The delayed diagnosis and treatment of clustering
and hepatocellular carcinoma. families with HBV infection and unfavorable prognosis may be an
Method: Serum CHI3L1 levels in 55 cases of viral hepatitis, 85 cases important factor affecting prognosis.
of non-viral hepatitis, 102 cases of cirrhosis, 138 cases of HCC, 93 Table and Figure:Figure 1.The diagnosis and treatment rates of
cases of HCC after radical hepatectomy, 26 cases of HCC recurrence probands, first-degree relatives, and second-degree relatives
were detected by electrochemiluminescence method, and 52 healthy
subjects were used as controls.
Result: The levels of CHI3L1 in liver cirrhosis group, HCC group, PP0252
HCC radical hepatectomy group and HCC recurrence group were Influencing factors of liver biopsy for patients with chronic
significantly higher than those in healthy control group (P < 0.001, P hepatitis B in the indeterminate phase
< 0.001, P < 0.05, P < 0.001). Serum CHI3L1 levels in liver cirrhosis Ye Xiong1, Tao Fan1, Li Zhu2, Jian Wang3,4, Shaoqiu Zhang3, Juan
group were significantly higher than those in viral hepatitis group/non- Xia3, Renling Yao3, Yue Yang3, Bei Jia3, Jie Li3, Yuanwang Qiu5,
viral hepatitis group (P < 0.01, P < 0.001). Serum CHI3L1 levels in Xingxiang Liu6, Chuanwu Zhu2, Chao Wu1,3,4, Rui Huang1,3,4
HCC group were significantly higher than those in HCC group after 1
Department of Infectious Diseases, Nanjing Drum Tower Hospital
radical hepatectomy (P < 0.001). There were no significant differences Clinical College of Nanjing University of Chinese Medicine, Nanjing,
in serum CHI3L1 levels between viral hepatitis group and healthy Jiangsu, China, 2Department of Infectious Diseases, The Affiliated
physical examination group, non-viral hepatitis group and healthy Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu,
physical examination group, HCC group and cirrhosis group, HCC China, 3Department of Infectious Diseases, Nanjing Drum Tower
relapse group and HCC group after radical hepatectomy (P > 0.05). Hospital, Affiliated Hospital of Medical School, Nanjing University,
Conclusion: The level of CHI3L1 in patients with chronic hepatitis Nanjing, Jiangsu, China, 4Institute of Viruses and Infectious Diseases,
increased to cirrhosis and HCC, but decreased from HCC to HCC Nanjing University, Nanjing, Jiangsu, China, 5Department of Infectious
after radical hepatectomy. Serum CHI3L1 can be used as a predictor Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China,
of progression of chronic liver disease and prognosis of patients with 6
Department of Clinical Laboratory, Huai‘an No. 4 People‘s Hospital,
liver cancer. Huai‘an, Jiangsu, China
Background: A substantial proportion of significant liver injury
PP0251 has been reported in patients with chronic hepatitis B (CHB) in the
indeterminate phase (IDP), while only a small proportion patients with
The clinical characteristics of clustering families with HBV
IDP received liver biopsy. We aimed to assess the influencing factors
infection and unfavorable prognosis
of liver biopsy decision of patients with CHB in the IDP.
Ze Zhang1,2, Taotao Yan1,2, Danfeng Ren1,2, Tianzhi Ni1,3, Shan Fu1,3, Method: A total of 2,928 consecutive untreated patients with CHB in
Yingli He1,2,3, Jinfeng Liu1,2,3, Yuan Yang1,2,3, Yingren Zhao1,2,3 the IDP were retrospectively included. IDP was classified based on
1
Department of Infectious Diseases, First Affiliated Teaching Hospital, AASLD 2018 guidance.
School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, Result: The median age of patients was 40.0 and male sex accounted
China, 2Institution of Hepatology, First Affiliated Teaching Hospital, for 65.0%. Only two hundred eighty-eight (9.8%) CHB patients with IDP
School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, underwent liver biopsy. Patients with liver biopsies (vs. non-liver biopsy)
China, 3Shaanxi Clinical Research Center of Infectious Diseases, were much older (41.5 years vs. 39.0 years, P = 0.001), and had higher
Xi’an, Shaanxi 710061, China HBV DNA levels (3.3 log10 IU/ml vs. 2.8 log10 IU/ml, P = 0.013), and
Background: Hepatitis B virus (HBV) infection is primarily transmitted higher APRI scores (0.42 vs. 0.31, P =0.001), fibrosis-4 scores (1.56
from mother to child in China, and chronic hepatitis B as well as vs. 0.87, P <0.001), and liver stiffness measurement values (9.9 kPa
HBV associated cirrhosis and hepatocellular carcinoma (HCC) vs. 6.6 Pa, P <0.001) than those without liver biopsy. Patients with age
exhibit characteristics of familial clustering. However, the clinical > 30 years (odds ratio [OR] 2.095, 95% confidence interval [CI] 1.467-
characteristics of clustering families with HBV infection and unfavorable 2.993, P < 0.001), low PLT (OR 0.996, 95% CI 0.994-0.998, P < 0.001),
prognosis are not yet fully understood, and there is an urgent need for and high HBV DNA (OR 1.251, 95% CI 1.109-1.412, P < 0.001) were
investigation. more likely to receive liver biopsy in CHB patients with IDP.
Method: Patients with HBV infection featuring familial clustering Conclusion: Only 9.8% of CHB patients with IDP underwent liver
were recruited from December 2021 to September 2024 and signed biopsy. Over 30 years, low PLT levels, and high HBV DNA levels were
informed consents. Basic information of the enrolled patients, as well associated with receiving liver biopsy in CHB patients with IDP.
as baseline serological, immunological, and radiological data were
collected, and inquiries were made about the HBV infection, treatment,
PP0253
and prognosis of their first- and second-degree relatives. Additionally,
blood samples were taken at each follow-up visit to facilitate the Research on the Regulation of Metabolites in CHB Patients by
study of long-term prognosis. Patients were divided into two groups Tiaogan Buxu Jiedu Formula(TGBXJD)
based on the presence or absence of a family history of unfavorable Xiaoke Li1,2, Shuying Hu1, Shuo Li3, Yizi Ao1, Tingyu Zhang1, Xin Sun1,
prognosis and compared. Jinyu Li1, Hongbo Do1,2, Yongan Ye1,2
Result: A total of 715 serum samples from 564 families with clustering 1
Dongzhimen Hospital, Beijing University of Chinese Medicine,
of HBV infection were collected. In the probands, first-degree blood Beijing, China, 2Beijing University of Chinese Medicine, Liver
relatives, and second-degree blood relatives, patients diagnosed with Diseases Academy of Traditional Chinese Medicine, Beijing, China,
3
Department of Traditional Chinese Medicine, Peking University and gastric varices, but continued to experience recurrent bleeding
Shougang Hospital, Beijing, China. and hospitalizations.
Background: Chronic Hepatitis B (CHB) was one of the most common One month before admission, the patient developed hematemesis
chronic infectious diseases in the world, which seriously endangers and worsening abdominal pain. At an external hospital, endoscopy
people’s health. Interferons and nucleoside analogues (NAs) are revealed gastric varices, and tissue adhesive injection therapy was
currently the main antiviral treatments. Interferon has problems such performed. Initial hemostasis was achieved, but she developed fever,
as large side effects and low serum response rate of the virus, so left upper abdominal pain, and leukocytosis one week later.
it is often difficult for CHB patients to obtain functional cure. In this Upon admission to our hospital, her condition had deteriorated further,
study, we analyzed the effect of the Liver Regulating Deficiency and with scleral icterus, ascites, and left upper abdominal tenderness.
Detoxification Formula on metabolites in CHB patients, and combined Laboratory findings indicated systemic inflammation and worsening
with the identification and analysis of metabolites, the mechanism of liver dysfunction. Contrast-enhanced CT confirmed a perisplenic
the formula to reduce the recurrence rate after drug discontinuation abscess and gastric perforation near the injection site. The patient was
was discussed. treated conservatively with percutaneous abscess drainage, broad-
Method: This study was Granted by NSFC No.82174341. It included spectrum antibiotics, intravenous albumin, and nutritional support. No
a total of 100 patients with CHB who had undergone clinical treatment surgical intervention was required.
and achieved HBeAg seroconversion between January 2019 and Over two weeks, her condition improved with resolution of the abscess
September 2019. These patients had previously undergone drug on imaging and normalization of inflammatory markers. She was
interventions as part of earlier studies, receiving the antiviral drug discharged on November 19, 2024, in stable condition, with follow-up
entecavir (ETV) alongside either Tiaogan Buxu Jiedu formula (TGBXJD) arranged for ongoing liver disease management.
or a placebo. After 96 weeks of treatment, both the traditional Chinese This case underscores the potential for rare but severe complications
medicine and ETV were discontinued. The patients were then followed of tissue adhesive injection for gastric varices and highlights the
up every 4 weeks for a total of 24 weeks to observe any relapse after importance of timely diagnosis and non-surgical management in such
discontinuation. Additionally, based on relapse status, the CHB cohort complex scenarios.
was divided into relapse (CHB_R) and non-relapse (CHB_N) groups.
Fifty healthy individuals undergoing regular health check-ups during PP0255
the same period were included as controls. Following grouping based
Research on the Correlation between Single Nucleotide
on traditional Chinese medicine intervention and relapse status, blood
Polymorphism in the NTCP Gene and Liver Diseases
plasma and fecal samples were collected from the participants for
Zhuandi Niu1, Yuxing Ma1, Wenli Du1, Junzhe Jiao1, Ruijuan Yan1,
inter-group analysis of metagenomics, metabolomics, and lipidomics.
Zhanjie Chang1, Haibo Zhang2, Jingtao Li1
Result: Metabolomics showed that phospholipids and fatty acid
metabolites were significantly increased after ETV treatment, while most
1
Hepatology Hospital affiliated Hospital of Shaanxi University of
of the amino acids and their derivatives were significantly reduced, Chinese Medicine, 2Basic medicine college of Shaanxi University of
and a total of 9 differential metabolites were obtained in plasma, of Chinese Medicine
which 8 were up-regulated and 1 was down-regulated. Background: NTCP, encoded by SLC10A1, is highly expressed on
Metabolomics revealed that the combination treatment significantly hepatocyte basolateral membranes. It’s key for bile acid enterohepatic
reduced lipid metabolites such as triglycerides while significantly circulation and homeostasis, and serves as a receptor for HBV and
increasing amino acid and fatty acid metabolites. Eleven differential HDV. NTCP SNPs are linked to viral hepatitis and cholestasis risks. This
metabolites were identified in plasma, primarily lipids, amino acids, article analyzes the association between NTCP SNPs and HBV/HDV
and their derivatives. Differential metabolites were mainly involved infection, bile acid metabolism, and liver injury risks, aiming to provide
in arginine and proline metabolism, glycine, serine and threonine a basis for interventions targeting NTCP polymorphisms to reduce liver
metabolism, arginine biosynthesis, and alpha-linolenic acid injury risks.
metabolism, with the highest enrichment factor in the alpha-linolenic Method: We systematically reviewed studies on NTCP SNPs and liver
acid metabolism pathway (0.333). disease risk, including HBV/HDV infections and bile acid metabolism.
Conclusion: Therefore, the Liver Regulating Deficiency and We investigated the correlation between specific NTCP SNP loci
Detoxification Formula can regulate the elevation of metabolites such like rs2296651, rs61745930, rs4646287, etc., and the risk of these
as fatty acids, amino acids and their derivatives, and significantly diseases.
regulate the pathways of fatty acid and amino acid metabolism. Result: NTCP is the receptor for HBV and HDV to enter hepatocytes.
The NTCP rs2296651 (c.800C>T, p.S267F) variant is linked to reduced
HBV infection risk and lower cirrhosis and HCC risks in CHB patients.
PP0254
Yet, some homozygous patients with this variant can still be infected
Gastric Perforation and Perisplenic Abscess: A Rare Complication with HBV, indicating complex infection mechanisms. In the Han Chinese
of Tissue Adhesive Treatment for Gastric Varices population, individuals with the NTCP rs7154439-AA genotype are
Qiongjie Li1, Bin Niu1,2, Rong Wang1,2, Liaoyun Zhang1 more likely to clear HBV, while those with the rs4646287 AA genotype
1
Department of infectious Diseases, The First Hospital of Shanxi have a higher HCC incidence. Moreover, rs2296651 can significantly
Medical University, 2Graduate School, Shanxi Medical University reduce susceptibility to HBV and HDV infections and slow liver disease
Gastric varices (GVs) are a potentially life-threatening complication progression. NTCP mainly transports bile acids in hepatocytes, and
of portal hypertension, often seen in patients with advanced liver its mutations can cause hyperbile acidemia, triggering hepatocyte
disease. Endoscopic injection of tissue adhesives is a widely inflammation and necrosis. The rs2296651 (c.800C>T, p.S267F)
accepted therapeutic approach for controlling variceal bleeding. mutation leads to complete NTCP dysfunction, causing high serum
Despite its effectiveness, this technique is associated with rare but bile acid levels and jaundice. Other NTCP variants like rs147226818
severe complications, including embolism, perforation, and abscess (c.755G>A, p.A252H), rs148467625 (c.263T>C, p.Ile88Thr), and
formation. We present a rare and complex case of gastric perforation (c.615_618del, p.Ser206Profs*12) are being actively studied for their
and subsequent perisplenic abscess after tissue adhesive injection for roles in cholestasis. NTCP mutations change hepatocyte susceptibility
gastric varices, managed through a combination of surgical, medical, to HBV/HDV infections and bile uptake function, closely related to the
and supportive measures. prognosis and pathological progression of HBV/HDV and cholestatic
A 39-year-old female presented to our hospital with progressive liver diseases such as liver fibrosis, cirrhosis, liver cancer precursors,
abdominal discomfort, jaundice, fatigue, and recurrent hematemesis hepatocellular carcinoma, and liver cancer.
over the past two years. Diagnosed with decompensated cirrhosis Conclusion: The single nucleotide polymorphisms (SNPs) of the
secondary to hepatitis B at an external hospital, she had undergone NTCP gene play a crucial role in the occurrence and progression
multiple treatments, including endoscopic therapies for esophageal of liver diseases. Through association analysis between NTCP
SNPs and the incidence of liver diseases, we have uncovered
the complex mechanisms of NTCP SNPs in HBV/HDV infections, Table and Figure:Figure 1.Changes in HBsAg Over Time in CHB
bile acid metabolism, and liver injury. These findings provide a patients with HT-101 Post 48 Weeks
theoretical basis for early diagnosis of liver diseases, the formulation Figure 2.HBsAg distribution post HT-101 dosed
of individualized treatment strategies, and the discovery of new drug
targets. Individualized treatment strategies developed based on NTCP
PP0257
SNPs as targets may represent a new direction and challenge in the
treatment of liver diseases. Mechanisms Underlying Delayed loss of HBeAg and HBV DNA
Table and Figure:Figure 1.Table1. NTCP single nucleotide Following HBsAg Seroclearance in PEG-IFNα Treated Patients of
polymorphisms (SNPs) and liver disease chronic hepatitis B
Bei Jiang1, Xiangmei Chen2, Fengmin Lu2
1
Tianjin Second People‘s Hospital Department of Gastroenterology,
PP0256 2
Xueyuan Road 38 Haidi Beijing Peking university
Robust and sustained hepatitis B surface antigen reduction after
Background: A notable proportion of CHB patients undergoing PEG-
HT-101 dosed twice in chronic hepatitis B patients: results from a
IFNα based therapy experience lagged serum HBeAg and/or HBV
phaseⅠstudy including extension follow-up data
DNA disappearance in patients achieving HBsAg loss. In this study, we
Wen XIE1, Yanbin Wang1, Liang Chen2, Xun Qi2, Jinlin Hou3, explored the molecular mechanisms behind this clinical phenomenon,
Xuebing Yan4, Junqi Niu5, Hongxin Piao6, Dong Wang7, Yanqin Ma7, offering novel insights into the sustainability of chronic HBV infection.
Shanzhong Zhang7, Zhipeng Zhang7, Lijuan Ding7, Hong Ma8, Jidong Method: Two independent clinical cohorts were enrolled to validate
Jia8 this phenomenon. Then comprehensive analysis was performed
1
Beijing Ditan Hospital Capital Medical University, 2Shanghai Public using public datasets, coupled with a series of molecular biology
Health Clinical Center, 3Nanfang Hospital Southern Medical University, experiments.
4
The Affiliated Hospital Of Xuzhou Medical University, 5The First Result: Approximately 17-20 % CHB patients underwent PEG-IFNα
Bethune Hospital of Jilin University, 6The Affiliated Hospital of Yanbian based therapy experienced seroclearance of HBsAg, while serum
University, 7Hepa thera, 8Liver Research Center, Beijing Friendship
HBeAg and/or HBV DNA remained positive. These patients are more
Hospital
prone to serum HBsAg reappearance compared to those achieving
Background: HT-101 is N-acetylgalactosamine (GalNAc)–conjugated complete virological response. Analysis of public datasets revealed
small interfering ribonucleic acid (siRNA) targeting the HBV genome that compared to the PC/BCP, the SP1/SP2 promoter displayed more
S-region. Preclinical studies exhibited a promising potential for the pronounced inhibitory epigenetic modifications in HBeAg-negative
treatment of chronic HBV infection. Here we reported the phase 1b&1c patients and SP1/SP2 in-frame mutation peaked in immune active
study results to evaluate the safety, tolerability, pharmacokinetics and patients. In vitro experiments demonstrated that introduced SP1/SP2
antiviral activity of HT-101 in HBV-infected patients on nucleos(t)ide inactive mutations would enhance PC/BCP transcriptional activity
analogue(NA) therapy (CTR2022854/ChiCTR2200066547). by a mechanism known as adjacent transcriptional interference.
Method: The phase 1b study was a randomized, double-blind, Furthermore, the deletion of L-HBsAg facilitated intracellular cccDNA
placebo-controlled, multiple ascending doses study of HT-101 replenishment.
administered via subcutaneous (SC) injection to HBV-infected patients Conclusion: This study elucidates that under IFNα treatment and low
who received continuous NA therapy for ≥ 6months. Participants with viral load, transcriptional suppression of SP1/SP2 promoters through
non-cirrhosis (<F3) were restricted with HBsAg 200-5,000IU/mL at mutations and/or epigenetic changes would favor the maintenance of
screening. Participants received two SC HT-101 injections, 4 weeks sustain chronic HBV infection, via enhancing the transcription activity
apart, of 50, 100, 200 or 400mg. At each dose level, eight participants of BCP to promote cccDNA replenishment.
were randomly assigned to HT-101 or placebo (6:2 ratio). Follow-up Table and Figure:Figure 1.
was carried out for 24 weeks post first dose. The participants after the Figure 2.
final follow-up visit (w24) could enter an optional 6-month extension
follow-up period (1c).
Result: The multiple SC doses of HT-101 up to 400mg in HBV-infected
PP0258
subjects demonstrated a favorable safety profile and well tolerated. Evaluating the diagnostic value of different field strengths MRI
No subjects discontinued due to AE. No SAE nor death were reported. diffusion‑weighted imaging in liver inflammation grading in
No concerning ALT elevations were observed. Reductions in HBsAg chronic hepatitis B patients
with time were observed across all HT-101 groups regardless of Yuan Liu1, Jinghui Dong1, Hongwei Ren1, Yanan Zhang2, Huiyi Ye3,
baseline HBeAg status or HBsAg level. Higher doses associated with Jianming Cai1
greater reduction and greatest mean reduction reached 3.29log in 1
Fifth medical centre of Chinese PLA general hospital, 2Third medical
400mg group. All 6 subjects achieved <10IU/ml from w16 to w24 and centre of Chinese PLA general hospital, 3First medical centre of
maintained<100 IU/ml till w48, including 3 subjects reached<10IU/ Chinese PLA general hospital
ml, notably 1 subject achieved below LLOQ at w48. In 100&200mg Background: According to WHO, The number of People are living with
group, most subjects (11/12) achieved<100IU/ml from w12 to w24. hepatitis B worldwide is 296 million. Hepatitis B(HBV) also has a high
At w48, 3 in 4 subjects remained below 100 IU/ml in 200mg group. prevalence in China. There are about 86 million HBV infected patients,
In 50mg group most subjects (5/6) remained over 1log reduction which means about 1 in 15 Chinese carries HBV and there are about
at w24 and 3 in 6 subjects sustained over 1 log reduction at w48. 20-30 million chronic hepatitis B (Chronic Hepatitis B, CHB) patients.
Other viral parameters (HBV DNA, RNA, HBcrAg, HBeAg) above “Guidelines for the Prevention and Treatment of Chronic Hepatitis B”
LLOQ at baseline also improved. Plasma PK parameters (AUC, pointed out that when the liver inflammation grade greater than or
Cmax,Tmax,T1/2) was consistent in CHB patients with healthy equal to G2 can be used as indication for antiviral treatment.
volunteers. Urine PK parameters were similar between healthy and Biopsy is the gold standard for liver inflammation, but it has the following
CHB subjects in 50-400mg. The mean percentage excreted in urine disadvantages, such as late reporting, Potential complications and so
up to 48 hours was 13.3% ~30.9%. The recovery rate reached the on. Based on former studies, we found that Field strength affected
plateau at 24h after dose. apparent diffusion coefficient (ADC) values in patients with CHB, ADC
Conclusion: Two monthly SC doses of HT-101 were general safe and value of 3.0 T < ADC value of 1.5 T for the same patient.So we can
well tolerated with a favourable PK profile in HBV-infected patients. explore the clinical value of diffusion‑weighted imaging (DWI) derived
Dose-dependent significant reductions from baseline in HBsAg levels from 3.0 T and 1.5 T MRI in assessing liver inflammation grades in
were observed through up to 44weeks post last dose, including CHB.
1subject achieved HBsAg seroclearance at w48. These data support Method: The research was designed by the method of diagnostic test
the continued development of HT-101 for treatment of chronic HBV and self-matching. Since August 2020-May 2024,we prospectively
infection.
recruited 140 consecutive patients with CHB who underwent both Cell Diagnostics Pte. Ltd.
1.5 T and 3.0 T DWI MRI (b = 800s / mm2) at random order within 6 Background: The technical complexity of characterizing HBV-specific
hours before liver biopsy, the interval between two scans was within T cells has limited their routine assessment in clinical trials aimed at
15 minutes, the protocol was respiratory-triggered DWI(RT-DWI).The HBV cure. We developed a simplified, point-of-care immunological
apparent diffusion coefficient (ADC )values near the liver puncture site test—the Whole Blood HBV Cytokine Release Assay (WB-HBV-CRA)—
of the same patient were measured at both field strengths by using the to profile the complex heterogeneity of HBV-specific T cells in chronic
delineation region of interest (ROI) method. With the pathological liver hepatitis B (CHB) patients. Here, we applied this assay to longitudinal
inflammation grade as the gold standard, the patients were divided samples from CHB patients participating in a trial of siRNA/therapeutic
into the case group (N=70,inflammation stage≥G2) and the control vaccine combination therapy to assess its utility in monitoring therapy-
group (N=70,inflammation stage≤G1), ROC was used to predict induced dynamic changes in HBV-specific T cell responses.
the diagnostic power for liver inflammation stages≥G2 of different Method: Six CHB patients received an HBV-targeted siRNA
strengths DWI MRI for the same CHB patient. (elebsiran), either alone (n=1) or in combination with a VLP-based
Result: The area under curve(AUC) of 3.0 T DWI MRI in predicting liver therapeutic vaccine (BRII-179) containing Pre-S1, Pre-S2, and S
inflammation stages≥G2 was 0.913 in CHB patients, the sensitivity and antigens (n=5). Samples were collected at multiple time points (weeks
specificity was 85.7 % and 80 %, the cutoff value of ADC = 1.16×10- 0, 8, 24, 28, 36, and 44) to measure anti-HBs titers, HBsAg levels, and
3 mm2/s, meanwhile the AUC of 1.5 T DWI MRI in predicting liver HBV-specific T cell responses. T cell responses to Pre-S1/Pre-S2 and
inflammation stages≥G2 was 0.880,the sensitivity and specificity was S antigens were assessed in parallel via direct ex vivo and in vitro-
78.6 % and 88.6 %, the cutoff value of ADC = 1.19×10-3 mm2/s . expanded ELISpot assays and the WB-HBV-CRA. For the latter, 1 mL
Conclusion: When using DWI to evaluate the liver inflammation stage of whole blood was aliquoted and stimulated with customized peptide
non-invasively, if the measured ADC values of 3.0 T DWI MRI ≤ 1.16×10- pools covering Pre-S1/Pre-S2, S, and core HBV antigens, followed by
3 mm2/s or the measured ADC values of 1.5 T DWI MRI ≤ 1.19×10-3 cytokine quantification (IFN-γ, IL-2, granzyme B, TNF-α, IL-5, IL-4) after
mm2/s, the accuracy of predicting liver inflammation stage≥G2 in CHB 16 hours.
patients is high, and antiviral therapy should be actively performed. Result: Among all three CHB patients who developed anti-HBs
following combination therapy and showed Pre-S1/Pre-S2 T cells by
PP0259 in vitro expansion ELISpot, we detected significant IL-2 production
in response to Pre-S1/Pre-S2 peptide pools, with minimal IFN-γ and
Spontaneous Mobilization of Bone Marrow-Derived Stem Cells
TNF-α. This IL-2 response was observed only in post-vaccine samples
and Prognosis of Patients with Acute-on-Chronic Hepatitis B Liver
(weeks 24, 28, 36, 44) and was absent at baseline (weeks 0 and 8).
Failure
In contrast, no IL-2 secretion was observed in the non-responders
RUI ZHOU1
(n=2) and non-vaccinated control (n=1). S-peptide stimulation elicited
1
Meng Chao Hepatobiliary Hospital, Fujian Medical University minimal cytokine response post-vaccination, consistent with the lack of
Background: The aim of the study was to assess spontaneous detectable S-specific T cells by ELISpot. Additionally, selected whole
mobilization of BMSC expressing the antigen CD34+ in acute-on- blood samples exhibited a Th2-skewed cytokine profile (high IL-2, IL-
chronic hepatitis B liver failure (ACHBLF) and its relation to the 4, IL-5, minimal IFN-γ) in response to Pre-S1/Pre-S2, which was not
prognosis. observed in in vitro-expanded T cell lines.
Method: By analyzing clinical data, blood biochemistry, hepatitis B Conclusion: The WB-HBV-CRA, requiring only a small blood volume,
virology index and peripheral blood CD34+ cell counts of patients effectively quantifies and profiles the functional dynamics of HBV-
with ACHBLF, chronic hepatitis B, and carriers with chronic HBV, specific T cell responses in clinical samples of CHB patients.
the difference of CD34+ cell counts among the three groups was Table and Figure:Figure 1.Whole-Blood HBV Cytokine Release Assay
discussed. The influencing factors of CD34+ cell counts of patients
with ACHBLF were analyzed.
PP0261
Result: The results showed that the influences of ALT, ALT/AST, AFP,
AMY, TG, CHE, INR and WBC on mobilization of bone marrow-derived The Effects of Granulocyte Colony-stimulating Factor on the
stem cells and prognosis of patients with ACHBLF were statistically Marrow-derived Stem Cells Mobilization and Prognosis in Patients
significant. 30 deaths (45.5%) were among patients with ACHBLF. The with HBV-Related Acute-on-Chronic Liver Failure
average CD34+ cell count of the death group was 0.36(1.63)/μl which RUI ZHOU1
was lower than 2.71(3.17)/μl in the survival group, and the differences 1
Meng Chao Hepatobiliary Hospital, Fujian Medical University
were of statistically significance. Grouping median of CD34+ cell Background: To investigate the effects of granulocyte colony-
counts, survival analysis showed that the survival rate of the group stimulating factor (G-CSF) on the marrow-derived stem cells
which CD34+ cell counts were higher than 1.855/μl was higher than mobilization and prognosis in patients with hepatitis B virus related
the group which CD34+ cell counts were lower than 1.855/μl. acute-on-chronic liver failure (HBV-ACLF) by random control.
Conclusion: The control group of liver failure was more active than Method: First, 140 patients with HBV-ACLF were divided into a
chronic hepatitis B group and chronic HBV group in spontaneous control group and a treatment group randomly. Patients in the control
mobilization of bone marrow-derived stem cells. ALT, ALT/AST, group received the comprehensive physical treatment; patients in
AFP, INR, AMY, TG, CHE and WBC were the influencing factors in the treatment group received the comprehensive physical treatment
spontaneous mobilization of bone marrow-derived stem cells. Levels and G-CSF. Next, compare the differences of maximum CD34+ cell
of spontaneous mobilization of bone marrow-derived stem cells were count and prognosis between two groups. Then adopt t test or non-
related with prognosis. parametric test, Chi-square test or Fisher exact test to examine results
Table and Figure:Figure 1.Figure 2 The results of survival analysis of and use Survival Analysis on prognostic difference according to
all patients with liver failure grouped by CD34+ cell count of 1.855/μl different data.
Result: The study was completed with 66 patients of the control group
PP0260 and 60 patients of the treatment group. The maximum CD34+ cell
count of the treatment group [3.0(1.45)/μl] was higher than the control
A Novel Point-of-Care Assay for Profiling HBV-Specific T Cell
group [1.86(2.58)], and the difference was statistically significant (Z=-
Dynamics in Clinical Samples
2.385, P=0.017). The results of Survival Analysis showed that the area
Nina Le Bert1, Yun Ji2, Anthony T Tan1, Rajneesh Kumar3, Shou Kit
under the curve (AUC ) was larger than the control group with a higher
Hang4, Alessandro Sidoli4, Wan Cheng Chow3, Qing Zhu2, Antonio
survival rate, and the difference was equally statistically significant
Bertoletti1
(Log Rank =4.101, P=0.043).
1
Signature Research Program in Emerging Infectious Diseases, Conclusion: G-CSF can enhance the marrow-derived stem cells
Duke-NUS Medical School, 2Brii Biosciences Inc., 3Department of mobilization in HBV-ACLF patients and improve survival rate.
Gastroenterology and Hepatology, Singapore General Hospital, 4T
Table and Figure:Figure 1.Fig 7 Survival analysis of the treatment group Clinical Medicine, The University of Hong Kong, Hong Kong, China
and the control group Background: Combination therapies using siRNA to reduce viral
antigen production alongside therapeutic vaccines are thought to
PP0262 impact the humoral and cellular immunity profiles of chronic HBV (CHB)
participants, which may contribute to HBsAg seroclearance. To test
Identification of RAD51AP1 as a Key Gene in Hepatitis B Virus-
this hypothesis, we characterized HBV-specific humoral and cellular
Associated Hepatocellular Carcinoma
immune responses and their potential correlation with virological
Xiaoling Liu1,2, Yonghong Wang1,2, Qiaoli Zhao1,2, Meiling Wan1,2,
outcomes in a subset of participants from a phase 2 study previously
Changfeng Sun1,2, Cunliang Deng1,2
receiving 9 doses of HBV-targeted siRNA elebsiran, either alone or in
1
Department of Infectious Diseases, The Affiliated Hospital, Southwest combination with a therapeutic vaccine BRII-179 containing Pre-S1,
Medical University, 2Laboratory of Infection and Immunity, The Pre-S2, and S antigens, with or without IFNα co-adjuvant.
Affiliated Hospital, Southwest Medical University
Method: Serum HBsAg and anti-HBs in clinical samples from the
Background: Background: Hepatocellular carcinoma (HCC) is a previous phase 2 study were quantified with Elecsys HBsAg II quant II
significant global health concern, with chronic hepatitis B virus (HBV) kit and Elecsys Anti-HBs II kit/Cobas e601 according to manufacturer’s
infection being a major contributor. Understanding the mechanisms instructions. The neutralizing activity of representative sera was
of HBV-associated HCC is crucial to improving the prognosis and assessed using HepG2-NTCP cells infected with HBV virions. HBV-
developing effective treatments. specific T cell response was analyzed both directly ex vivo (cytokine
Method: Methods: HBV-associated HCC datasets (GSE19665, assay upon HBV-specific peptides stimulation of whole blood) or after
GSE121248, GSE55092, GSE94660, and TCGA-LIHC) acquired in vitro expansion of PBMCs (ELISpot assays, intracellular cytokine
from public databases were mined to identify key driver genes staining).
by differentially expressed gene analysis, weighted gene co- Result: Both anti-HBs and HBsAg-specific T cell responses were
expression network analysis (WGCNA), followed by protein-protein significantly enhanced in the BRII-179 and elebsiran combination
interaction network analysis, Lasso-Cox regression analysis, and groups compared to elebsiran alone group. Anti-HBs production was
randomforestSRC algorithm. Then, in vitro experiments including preferentially associated with the presence of Pre-S1/S2-specific T
CCK8 assay, wound healing, and Transwell assay were performed to cells, but rarely associated with S-specific T cells. Co-existence of
explore the functions and mechanisms. HBsAg with anti-HBs was observed, however, HBsAg levels were
Result: Results: RAD51AP1 was identified as a specific key gene inversely associated with neutralizing ability in representative sera.
linked to the progression of HBV-associated HCC. High expression Notably, two participants, who received the combination treatment
of RAD51AP1 was associated with worse overall survival (OS) in and achieved HBsAg seroclearance, exhibited immune profiles
patients with HBV-associated HCC, but not in patients with non- characterized by high anti-HBs titers, strong neutralization activity, and
HBV-associated HCC. Mechanistically, RAD51AP1 forms a potential IL-2-producing Pre-S1/S2-specific T cells.
ceRNA axis with LINC01419 and miR-8070, where LINC01419 acts Conclusion: BRII-179, in combination with elebsiran, induced
as a molecular sponge for miR-8070 to upregulate RAD51AP1. HBV substantial HBV-specific B and T responses in a subset of CHB
infection can enhance the LINC01419/miR-8070/RAD51AP1 axis, and participants. Anti-HBs induction is correlated with vaccine-induced
LINC01419 overexpression conversely promotes HBV replication. The Pre-S1/S2-specific T cell responses. Furthermore, the neutralizing
ceRNA axis and HBV synergistically promote the proliferation and activity in representative sera was inversely associated with HBsAg
metastasis of HBV-associated HCC cells. Furthermore, LINC01419 or levels, suggesting immune response induced by BRII-179 may play a
RAD51AP1 knockdown, and miR-8070 overexpression in HepG2.2.15 role in reducing HBsAg and controlling HBV.
cells significantly attenuated the Wnt/β-catenin signaling.
Conclusion: Conclusions: The LINC01419/miR-8070/RAD51AP1
axis promotes the HBV-associated HCC progression through an
PP0264
HBV-boosted positive feedback loop and Wnt/β-catenin signaling. The safety and efficacy of PD-1 antibody combined with pegylated
These findings provide novel insights into the underlying mechanisms interferon-α therapy to promote the clinical cure in nucleoside
and may offer potential diagnostic and therapeutic targets in HBV- (acid) analogues-suppressed chronic hepatitis B patients
associated HCC. Hongmin Wang1,2, Xiaoying Li3, Fusheng Wang1, Junliang Fu1
Table and Figure:Figure 1.Correlation between the expression of 1
Department of lnfectious Diseases, the Fifth Medical Center of
LINC01419/miR-8070/RAD51AP1 axis and HBV infection. Chinese PLA, 2The First Affiliated Hospital of USTC, University of
Figure 2.Model of LINC01419/miR-8070/RAD51AP1 axis promotes the Science and Technology of China, 3Shandong Public Health Clinical
HBV-associated HCC progression through an HBV-boosted positive Center
feedback loop and Wnt/β-catenin signaling. Background: The clinical cure of chronic hepatitis B (CHB) is an ideal
goal of therapy, which is associated with improved long-term outcome.
PP0263 Studies have shown that PD1 antibody therapy can reduce HBsAg in
patients with CHB. This study was used to evaluate the efficacy and
Combination treatment with siRNA (elebsiran) and therapeutic
safety of a novel strategy, PD-1 antibody combined with pegylated
vaccine (BRII-179) induced anti-HBs associated with Pre-S1/S2-
interferon-α, in nucleoside (acid) analogues-treated CHB patients.
specific T cell responses and HBsAg reduction in a subset of
Method: This study was designed as two cohorts. Cohort 1 was a
chronic hepatitis B participants
prospective, multicenter, open-labled, randomized controlled study.
Ying Tan1, Bing Wang2, Nina Le Bert3, Grace Lai-Hung Wong4, Mark
Viral suppressed CHB patients with NAs treatment (HBeAg nagetive,
W Douglas5, Ariel Lee6, Chong Zhu1, Jianxiang Lv1, Dong Li1, Haiyan
HBV DNA nagetive, HBsAg ranged from 200 to 1000IU/mL) were
Ma6, Xiaofei Chen1, Yun Ji7, Man Fung Yuen8, Jieliang Chen2, Antonio
enrolled and randomized into Peg-IFNα-2b group, PD-1 antibody
Bertoletti3, Qing Zhu7
group and Combined group (Figure 1). Cohort 2 was a prospective,
1
Brii Biosciences (Beijing) Co. Ltd., Beijing, China, 2Key Laboratory multicenter, single group assignment study. Patients with HBsAg
of Medical Molecular Virology (MOE&NHC), Shanghai Medical < 200IU/ml were treated with PD-1 antibody for 12 weeks and then
College Fudan University, Shanghai, China, 3Programme in Emerging efficacy was evaluated. If the HBsAg reduction of patients was less
Infectious Diseases, Duke-NUS Medical School, Singapore, 4Medical
than 0.5log, Peg-IFNα-2b therapy was added, otherwise, the original
Data Analytics Centre, State Key Laboratory of Digestive Disease, Li
treatment regimen was continued (Figure 2). The primary endpoint
Ka Shing Institute of Health Sciences, The Chinese University of Hong
was rate of HBsAg loss at 24 weeks and 48 weeks, while safety was
Kong, Hong Kong, China, 5Westmead Institute for Medical Research,
evaluated by the adverse events (AEs) profile.
The University of Sydney and Westmead Hospital, Sydney, Australia,
6
TCD/Hyris Pte. Ltd., Singapore, 7Brii Biosciences, Inc., Durham, Result: In cohort 1, 12 eligible CHB patients randomized to Peg-IFNα
NC, USA, 8Department of Medicine, Queen Mary Hospital, School of group (n=3), PD-1 antibody group (n=5) or Combined group (n=4).
And 10 patients were enrolled in cohort 2. Safety population included types might serve as an effective indicator for predicting non-
all 22 patients. In total, 51 AEs were reported in 100% (3/3), 20% (1/5) responsiveness of antiviral therapy.
and 75% (3/4) patients in Peg-IFNα group, PD-1 antibody group and
Combined group of cohort 1, respectively. In cohort 2, 17 AEs were
PP0266
reported in 30% (3/10) patients during firsts 12weeks PD-1 antibody
therapy. Peg-IFNα was added to 3 patients at the 12-week evaluation, ORC1 Protein as a Serum Marker of HBV-associated Hepatocellular
and 10 AEs were reported in all these 3 patients. There was no study Carcinoma
drug-related serious adverse event (SAE). Su Tumei1, Jiang Jianning1
Conclusion: PD-1 antibody or combined with Peg-IFNα was shown to 1
The First Affiliated Hospital of Guangxi Medical University
be safe and well-tolerated in CHB patients according to our preliminary Background: HBV catalyzes the transformation of hepatocytes to
data. And more comprehensive data in our study later will provide malignancy by integrating its DNA into the host genome and affecting
evidence to verify the safety and efficacy of this strategy in promoting cell proliferation. Our team’s previous study showed that cancer tissues
clinical cure. from 15 cases of HBV-HCC were sequenced, and showed that patients
Table and Figure:Figure 1.Figure 1: The design of cohort 1. with HBV-HCC not only had the HBV S-ESPL1 integration gene, but
Figure 2.Figure 2: The design of cohort 2. also had a high frequency of gene integration of HBV in the vicinity
of ORC1, and it is possible that ORC1 may be an integration site of
PP0265 HBV.Whether ORC1 is related to the HBV-asHCC.Is ORC1 related to
HBV-HCC, and can ORC1 protein be used as a serologic marker for
High levels of HBV DNA integration by high-throughput viral
HBV-HCC? It is worth further investigation.
integration detection method predict non-responsiveness of
Method: Based on the screening of inclusion and exclusion criteria,
antiviral treatment
552 patients were included in the study, which were categorized into
Misi Gu1, Wenyu Wu1, Jie You1, Fei Huang1, Qianjun Wu1, Yixuan HBV-HCC(n=96), HBV-associated cirrhosis(n=154 ), CHB(n=162),
Zhang1, Peng Wang1, Dong Xi1, Weiming Yan1, Xiaojing Wang1, Tao HBV-infected S-gene-integrated(n=20), and HBV-infected non-S-
Chen1, Di Wu1, Qin Ning1, Meifang Han1 gene-integrated(n=47); and the healthy(n=44) and non-HBV-HCC
1
Department of Infectious Diseases, Tongji Hospital, Tongji Medical (n=29). Detection of ORC1, ESPL1, and AFP levels of each group; the
College and State Key Laboratory for Diagnosis and Treatment of correlation between ORC1 and ESPL1 was compared between the
Severe Zoonotic Infectious Disease, Huazhong University of Science HBV infection-related groups, and the diagnostic efficacies of ORC1,
and Technology, Wuhan, 430030, Hubei, China.
ESPL1, AFP, and the combined diagnosis of HBV-HCC were compared
Background: Hepatitis B virus (HBV) integration into host genome Result: 1.Serum ORC1 were higher in the HBV infection-related
serves as a crucial mechanism influencing antiviral responses. Our group than in the non-HBV infection group (1199.82 vs. 945.19ng/L,
objective was to analyze the features of HBV integration in chronic P<0.05).2. ORC1 were higher in the HBV infection S gene integration
hepatitis B (CHB) patients and identify integration parameters group than in non-S gene integration group (1842.16vs.1191.98ng/L,
predicting antiviral response. P<0.05).3. The expression level of ORC1 increased in the order
Method: A total of 257 nucleos(t)ide analogues (NUCs) experienced of CHB , HBV-related cirrhosis, HBV-HCC group in the following
CHB patients were recruited in Anchor study, then were randomized order:(1046.74<1214.11<1305.25)ng/L 4. The levels of ORC1 and
(1:1:1) into ETV monotherapy group (Group I), pegylated interferon ESPL1 were positively correlated (r=0.241, P<0.05).5. The area under
alpha-2b (Peg-IFN) & ETV combination therapy group (Group II), and the ROC1 curve was in the following order from highest to lowest:
Peg-IFN & ETV & Granulocyte-macrophage Colony Stimulating Factor ORC1+ESPL1+AFP(0.887) > AFP(0.844) > ESPL1+AFP(0.838)
(GM-CSF) combination therapy group (Group III), and 249 participants > ORC1+AFP(0.816) > ORC1+ESPL1(0.776),ESPL1(0.776)
completed the entire 96-week antiviral treatment regimen. The patients > ORC1(0.587).6.Youden’s index in descending order
who obtained HBsAg loss at week 96 were named as responders, was:ESPL1+AFP(0.693) > ORC1+ESPL1+AFP(0.686)
otherwise named as non-responders. Respectively,13 and 17 cases > ESPL1(0.579),ORC1+ESPL1(0.579) > AFP(0.566) >
were randomly selected from responders and non-responders in Group ORC1+AFP(0.509) > ORC1(0.204).7.The sensitivity, in descending
II, as well as additional 15 cases from Group I for high-throughput Viral order, was ORC1+ESPL1+AFP (84.44%) > ESPL1 + AFP(78.89%) >
Integration Detection (HIVID) with pairs of liver samples (at baseline ORC1 + AFP(76.67%) > ORC1 + ESPL1 (71.11%),ESPL1(71.11%) >
and week 48). ORC1(65.56%) > AFP(21.17%).
Result: The KEGG pathway analysis of these recurrent host genes at Conclusion: The integration of HBV and ORC1 genes after HBV
baseline revealed a series of significant human pathways, including infection may promote the expression of ORC1.2.ORC1 protein level
Pathway in cancer, Ferroptosis, Arrhythmogenic right ventricular increases with the progression of HBV infection-related liver disease.3
cardiomyopathy, Axon guidance, Cell adhesion molecules, MAPK Significantly elevated ORC1 protein level is closely related to HBV-
signaling pathway and so on. The majority of HBV DNA integration HCC.4 ORC1 protein as a diagnostic marker for HCC does not have
breakpoints (57.23%) were found within the range of HBV nucleotide an advantage over ESPL1 and AFP. Compared with ESPL1 and AFP,
positions 1560-1900nt including basic core promoter (BCP) and ORC1 protein as a diagnostic marker for HCC is not yet advantageous,
enhancer II. HBV X gene occupied the highest number of integration and further research is needed
breakpoints into host genes. At baseline, the levels of integration
were positively correlated with the duration of CHB, and the levels
PP0267
of alanine aminotransferase (ALT) and aspartate aminotransferase
(AST), but not with the levels of HBsAg, HBcrAg, HBV RNA and Impact of Peg-IFNα on Peripheral Blood PD-1 Levels in Patients
HBV cccDNA quantification. Totally, the non-responders of antiviral with Chronic Hepatitis B: A Non-Randomized Controlled Study
therapy demonstrated greater elevated numbers of breakpoint Chenrui Liu1, Yaping Li1, Yikai Wang1, Jia Li1, Shuangsuo Dang1
types of integration at both baseline and week 48 when compared to 1
Department of Infectious Diseases, Second Affiliated Hospital of
responders. Especially, the non-responders in Peg-IFN group (Group Xi‘an Jiaotong University
II) displayed much higher numbers of recurrent integrations and Background: To investigate the differences in peripheral blood PD-1
clonal integrations than responders at week 48. A baseline number levels between CHB patients and healthy controls, and to further
of breakpoint types exceeding 28 might serve as an indicator for evaluate the impact of pegylated interferon (Peg-IFN) treatment on
predicting non-response at week 96 of antiviral therapy totally. peripheral blood PD-1 levels in CHB patients.
Conclusion: HIVID displays that the family history of CHB, duration Method: CHB patients with HBsAg < 1500 IU/ml, HBeAg-negative,
of CHB, ALT and AST levels were associated with the integration and HBV DNA < 20 IU/ml were recruited from the Second Affiliated
levels of NUCs experienced CHB patients. The higher numbers of Hospital of Xi’an Jiaotong University between May and August 2023.
recurrent integrations and clonal integrations contribute to the non- Based on treatment preference, 50 patients were assigned to the Peg-
responsiveness of Peg-IFN treatment and the number of breakpoint
IFN combined with nucleos(t)ide analogues (NAs) group, and 43 to the 48 and 72.
NAs monotherapy group. Nineteen healthy controls were also included. Result: The HBsAg loss rate in the treatment group and the control
Peripheral blood CD3+PD-1+, CD4+PD-1+, and CD8+PD-1+ T-cell group was 32.05% (25/78) and 0% (0/80) at week 72, respectively.
levels were measured at baseline using flow cytometry. CHB patients The rate of HBsAg seroconversion in the treatment group was 29.49%
underwent further PD-1 level assessments at baseline, 12 weeks, 24 (23/78) at week 72, while no patients achieved HBsAg seroconversion
weeks, and 48 weeks. Changes in PD-1 levels over 48 weeks were in the control group. The HBsAg loss and seroconversion rates in the
analyzed in both treatment groups. treatment group were significantly higher than in the control group
Result: At baseline, no significant differences were observed in at week 72 (P < 0.001). Multivariate regression analysis showed
CD3+PD-1+, CD4+PD-1+, or CD8+PD-1+ T-cell levels between baseline HBsAg level and frequency of enhanced IFN therapy were
the Peg-IFN+NAs group and the NAs monotherapy group (all P > both independently associated with HBsAg clearance rate. No severe
0.05). Both treatment groups showed higher levels of CD3+PD-1+, adverse events occurred.
CD4+PD-1+, and CD8+PD-1+ T cells compared to healthy controls. Conclusion: The pulsed enhanced immunomodulatory/ antiviral
During the 48-week observation period, no significant changes in PD-1 therapy can improve the clinical cure rate (HBsAg loss rate) and
levels were observed in the NAs monotherapy group (all P > 0.05). HBsAg seroconversion rates in CHB patients. Meanwhile, this pulsed
In the Peg-IFN+NAs group, CD3+PD-1+ T-cell levels significantly enhanced therapy can be guided by baseline HBsAg levels.
increased at 24 weeks compared to baseline (38.95 ± 5.66% vs. 34.41
± 8.44%, P < 0.001) and further increased at 48 weeks (44.21 ± 6.70%
PP0269
vs. 34.41 ± 8.44%, P < 0.001). CD4+PD-1+ T-cell levels significantly
increased at 12 weeks (37.40 ± 5.02% vs. 35.38 ± 4.85%, P = 0.044), Artificial Liver Support System Improves One-year Prognosis of
with further increases at 24 weeks (39.91 ± 5.61% vs. 35.38 ± 4.85%, P Patients with Hepatitis B virus-associated Acute-on-Chronic Liver
< 0.001) and 48 weeks (54.43 ± 6.73% vs. 35.38 ± 4.85%, P < 0.001). Failure
CD8+PD-1+ T-cell levels in the Peg-IFN+NAs group also significantly Xiaoqin Lan1, Changze Hong1, Jinjun Chen1
increased at 48 weeks compared to baseline (40.14 ± 4.45% vs. 34.85 1
Hepatology Unit, Department of Infectious diseases, Nanfang
± 4.53%, P < 0.001). Hospital, Southern Medical University, Guangzhou, China
Conclusion: Peripheral blood PD-1 levels in CHB patients were Background: Acute-on-chronic liver failure (ACLF) is a complex
elevated compared to healthy controls. During NAs monotherapy, syndrome with limited treatment options. This study aims to investigate
PD-1 levels remained unchanged, potentially due to the inclusion the impact of artificial liver support system (ALSS) on the one-year
of treatment-experienced patients. However, Peg-IFN treatment prognosis of Hepatitis B virus (HBV)-associated ACLF patients.
significantly increased peripheral blood PD-1 levels, with CD4+PD-1+ Method: A retrospective study was conducted on 239 patients with
T-cell levels showing the earliest and greatest elevation. HBV-ACLF in Nanfang Hospital from January 2016 to June 2021.
Patients were divided into the ALSS group (n=103) and the Standard
PP0268 Medical Therapy (SMT group, n=136). Demographic, clinical and
laboratory data were collected before the first ALSS treatment for
Pulsed Enhanced Immunomodulatory/Antiviral Therapy Improved
patients in ALSS group, while baseline data were collected in SMT
Clinical Cure Rate of Chronic Hepatitis B: a Multicenter and
group. According to receiving different ALSS modes, patients in ALSS
Prospective Study
group were divided into plasma exchange (PE) group and non-PE
Lisha Yang1,2, Siqi Sun1, Huan Cai1, Heng Liu1, Shanyan Zhang1, group.
Xiaoli Zhang1, Guodong Yu1, Yida Yang1, Hongyu Jia3 Result: The 12-week and 1-year liver transplant (LT) free survival rates
1
State Key Laboratory for Diagnosis and Treatment of Infectious in the ALSS group were significantly higher than that in the SMT group
Diseases, National Clinical Research Center for Infectious Diseases, (65.05% vs, 52.21%, p=0.0011; 63.11% vs. 48.53%, p=0.0006). ALSS
National Medical Center for Infectious Diseases, Collaborative therapy was the independent predictive factors associated with 12-
Innovation Center for Diagnosis and Treatment of Infectious week and 1-year mortality (hazard ratio, HR: 0.59, p=0.04, and HR:
Diseases, The First Affiliated Hospital, Zhejiang University School of
0.54, p=0.01). Comparatively more ALSS related complications were
Medicine, Research Units of Infectious disease and Microecology,
observed in PE group. After Propensity Score Matching, the 12-week
Chinese Academy of Medical Sciences, 2Department of Infectious
and 1-year LT-free survival rates between PE and non-PE group were
Diseases, The First Affiliated Hospital of Ningbo University, 3State
similar (88% vs. 80%, p=0.227, 88% vs. 80%, p=0.227).
Key Laboratory for Diagnosis and Treatment of Infectious Diseases,
National Clinical Research Center for Infectious Diseases, National Conclusion: ALSS therapy is a safe and effective treatment for HBV-
Medical Center for Infectious Diseases, Collaborative Innovation ACLF. ALSS improves 1-year prognosis of patients with HBV-ACLF.
Center for Diagnosis and Treatment of Infectious Diseases, The First Table and Figure:Figure 1.Graphical Abstract
Affiliated Hospital, Zhejiang University School of Medicine, Research
Units of Infectious disease and Microecology, Chinese Academy of PP0270
Medical Sciences, Branch of the First Affiliated Hospital of Zhejiang
The clinical features of patients with Porto-Sinusoidal Vascular
University
Disease (PSVD) accompanied by chronic HBV infection: a
Background: Nucleos(t)ide analogs (NAs) or Peginterferon alpha retrospective study in China
(PegIFN-α) monotherapy have limited effect on the clinical cure of
Jinyu Wang1, Tiantian Hu1, Xiangyu Chi1, Hao Wang1, Jiming Zhang1
hepatitis B virus surface antigen (HBsAg) loss in chronic hepatitis 1
Fudan University affiliated Huashan Hospital
B(CHB) patients, while the optimized regimen of sequential or
combined treatment with NAs and PegIFN-α showed good efficacy Background: Porto-Sinusoidal Vascular Disease (PSVD) is a non-
for part of advantage population.To explore the efficacy and safety of cirrhotic vascular liver disorder defined by distinctive histopathological
pulsed enhanced immunomodulatory/ antiviral therapy on improving and clinical features of portal hypertension (PH). Chronic hepatitis
the clinical cure rate in patients with CHB. B virus (HBV) infection, a well-established cause of liver disease,
Method: A total of 160 CHB patients whose HBsAg level significantly frequently coexists with PSVD; however, its contribution to the
decreased compared to baseline after initial interferon (IFN) pathogenesis and clinical manifestations of PSVD remains poorly
monotherapy /combined with NA therapy (1-2 courses) and followed understood. This study aims to elucidate the clinical characteristics
by NA therapy were enrolled and randomly divided into two groups: and delineate the differences between PSVD patients with and without
treatment group, PegIFN α-2b combined with Tenofovir disoproxil HBV infection in a Chinese cohort.
fumarate (TDF) therapy; control group, TDF monotherapy. The total Method: A retrospective cohort of 2007 patients who underwent liver
therapy duration of PegIFN α-2b was 48 weeks. All patients were biopsy from 2017 to 2024 at Huashan Hospital was reviewed, identifying
followed up to week 72. The primary endpoint was the proportion of 73 cases of PSVD, of which 31 were assessed with concurrent chronic
patients with HBsAg clearance and HBsAg seroconversion at weeks HBV infection. Comprehensive analyses were conducted, including
laboratory parameters, imaging studies, histopathological evaluations, WB experiments. (8) Co-transfection of HA-RNF2 and FH-USP43 in
comorbid conditions, genetic mutations, and treatment strategies. To cells explored how USP43 regulates RNF2’s ubiquitination type via
minimize potential confounding factors, a matched analysis by age immunoprecipitation and WB analyses.
and gender was performed. Result: This study builds on previous findings that USP4 regulates the
Result: Among PSVD patients, HBV infection prevalence was IFN signaling pathway and antiviral function. We further discovered
significantly higher compared to the general population (43.1% that USP43 inhibits the antiviral effects of IFN. For the first time, we
vs. 6.1%, p < 0.0001). HBV-positive patients displayed distinct identified that USP43 regulates STAT1 K33-linked ubiquitination, which
histological patterns, including a lower prevalence of nodular is modulated by RNF2. By removing K48-linked ubiquitination from
regenerative hyperplasia (p = 0.008) and a higher prevalence of RNF2, its stability increases, promoting K33-linked ubiquitination. When
nonzonal sinusoidal dilation (p = 0.068) compared to HBV-negative STAT1 undergoes K33-linked ubiquitination, it reduces p-STAT1 levels,
patients. Interestingly, median BMI was significantly higher in HBV- down-regulates ISRE transcriptional activity and ISG expression,
negative group, which showed more severe PH manifestations, ultimately negatively impacting the antiviral function of IFN.
such as varices and portosystemic collaterals (p < 0.0001). Clinical Conclusion: USP43 promotes the ubiquitination of STAT1 protein K33
parameters including ALP, GGT, ALB and PT were found significantly by stabilizing RNF2 and negatively regulates the antiviral function of
differ between HBV-positive and negative patients (p < 0.05). Genetic IFN.
analysis revealed mutations in genes like UGT1A1 and JAK2 in parts Table and Figure:Figure 1.Diagram of USP43 inhibiting IFN response
of PSVD patients, suggesting potential genetic contributions.During
the follow-up period, three patients achieved HBV functional cure.
PP0272
In additionm HBV-negative PSVD patients underwent more surgical
interventions, including transjugular intrahepatic portosystemic shunt Angiopoietin-like protein 3: a promising prognostic biomarker for
(TIPS), partial splenic embolization and splenectomy. patients with acute-on-chronic liver failure caused by hepatitis B
Conclusion: PSVD patients with chronic HBV infection exhibit milder virus
PH and distinct histopathological features compared to HBV-negative Xueying Zhang1, Yasi Tu1, Qunfang Rao1, Daxian Wu1,2
patients. HBV may influence vascular remodeling independently of 1
The First Affiliated Hospital of Nanchang University, 2National Clinical
cirrhosis, complicating differentiation from HBV-related liver diseases. Research Center for Infectious Diseases, The First Affiliated Hospital,
Routine PSVD screening in long-term HBV follow-up is recommended Zhejiang University School of Medicine, Hangzhou, China.
for early detection and management. Background: Acute-on-chronic liver failure (ACLF) is a life-threatening
Table and Figure:Figure 1. disease with a high mortality rate, particularly in patients with chronic
liver disease (CLD) who experience an acute hepatic insult. This study
PP0271 aimed to evaluate the potential of ANGPTL3, a hepatocyte-specific
protein, as a prognostic biomarker in patients with HBV-ACLF.
USP43-mediated regulation of STAT1 K33-linked ubiquitination
Method: A cross-sectional survey involving 72 subjects, including
inhibits interferon antiviral function
negative controls, Chronic Hepatitis B (CHB) patients, patients
Chuanwu Zhu1, Jin Liu2, Feng Qian1, Li Zhu, Ming Li, Yuanmei Chen, with liver cirrhosis (LC), LC-AD, and ACLF was performed. And a
Yinling Wang, Yujuan Yan prospective longitudinal cohort study was conducted at the First
1
Department of Infectious Diseases, The Affiliated Infectious Diseases Affiliated Hospital of Zhejiang University and the First Affiliated Hospital
Hospital of Soochow University; The Fifth People‘s Hospital of of Nanchang University involving 219 patients with HBV-ACLF to
Suzhou, Suzhou, Jiangsu, China., 2Department of Infectious Diseases, assess the prognostic capacity of ANGPTL3. ANGPTL3 levels were
The Affiliated Infectious Diseases Hospital of Soochow University; The measured using a commercial ELISA kit, and statistical analyses were
Fifth People‘s Hospital of Suzhou, Suzhou, Jiangsu, China. conducted using SPSS and Medcalc software.
Background: Antiviral immunity is essential for combating viral Result: The results showed that the ANGPTL3 levels in the ACLF
infections, with interferons (IFNs) serving as key antiviral cytokines. group were significantly lower compared to the CHB group (P=0.001).
Recent studies have emphasized the importance of protein Moreover, the ANGPTL3 levels in non-survivors were lower than those
ubiquitination in the antiviral response to IFNs, highlighting a significant in survivors (P<0.001). Multivariate Cox regression analysis revealed
research area. More investigation is needed to understand how that ANGPTL3 was an independent prognostic factor for HBV-ACLF.
deubiquitin enzymes regulate IFN’s antiviral functions. This study aims Patients with lower ANGPTL3 levels had a higher mortality rate of
to examine how USP43 regulates STAT1 deubiquitination and its impact 71.26%, while those with higher ANGPTL3 levels had a mortality rate
on activating the IFN signaling pathway, ultimately clarifying USP43’s of almost zero. When patients were stratified based on their cirrhosis
role in enhancing the antiviral function of IFNs through substrate status, ANGPTL3 remained an independent prognostic factor,
protein regulation. regardless of whether they had cirrhosis. As the number of failing
Method: (1)Expression of FH-USP43 plasmid was analyzed after organs increased, the ANGPTL3 levels decreased correspondingly
transfecting USP43 knockdown plasmid into cells and infecting them (P<0.001), which was closely associated with coagulation dysfunction.
with VSV. Immunofluorescence assessed GFP intensity, while Western The AUC of ANGPTL3 levels for predicting 30-day mortality was 0.790,
Blot (WB) and RT-qPCR detected VSV protein and mRNA levels. (2) with a sensitivity of 0.647 and a specificity of 0.810 at the optimal cut-
Following shUSP43 transfection, cells were co-transfected with ISRE- off value of 51.18 ng/mL. The cumulative survival rate was significantly
Luc and Renilla plasmids, then stimulated with IFNα. Dual-luciferase lower in the low ANGPTL3 group than in the high ANGPTL3 group
reporter gene technology evaluated the impact of USP43 on ISRE (P<0.0001). At the end of the assessment period (14th day after
transcriptional activity. (3) Cells transfected with FH-USP43 or control admission or discharge), the ANGPTL3 levels increased significantly
plasmids underwent immunoprecipitation using Flag, followed by LC- in the improvement group (70.54[55.40-89.36] vs. 73.99[52.14-145.10]
MS to identify targets interacting with USP43 in the IFNα signaling ng/mL, P=0.044).
pathway. (4) In cells co-transfected with FH-USP43 and Myc-STAT1, Conclusion: In conclusion, ANGPTL3 demonstrates promising
the interaction between USP43 and STAT1 was examined through potential as an independent prognostic biomarker for HBV-ACLF.
immunoprecipitation and WB experiments. (5) Cells co-transfected Sequential monitoring of circulating ANGPTL3 levels may hbe
with FH-USP43 or shUSP43 along with Myc-STAT1 and HA-Ub (and valuable for tracking disease progression. It is expected to improve
their ubiquitin mutants) were analyzed for the effect of USP43 on STAT1 current commonly used ACLF prognostic models. Further studies are
ubiquitination via immunoprecipitation and WB. (6) The influence of needed to explore the potential mechanisms underlying organ failure
USP43 on RNF2-STAT1 interaction was studied in cells co-transfected associated with decreased ANGPTL3 levels, particularly in relation to
with HA-RNF2, Myc-STAT1, and FH-USP43 using immunoprecipitation coagulation function.
and WB techniques. (7) In cells gradually overexpressing FH-USP43 Table and Figure:Figure 1.Correlation of ANGPTL3 levels with HBV-
or shUSP43 alongside HA-RNF2 plasmid, the effect of USP43 on ACLF patients at admission.
RNF2 protein levels was assessed through immunoprecipitation and Figure 2.Correlation of ANGPTL3 and the number of organ failures
 PP0273 A novel mechanistic viral dynamics modeling (MVDM) framework
FIND HDV AND DETERMINE ITS STATUS IN TURKEY “SITU(HD) to characterize the effect of combination therapies in chronic
VATION TURKEY” hepatitis B and evaluate the influence of individual characteristics
in the Piranga phase 2 platform study
Mustafa Kemal CELEN1, Cigdem MERMUTLUOGLU1, Yesim
TASOVA2, Ismail YILDIZ3, Yakup DEMIR4, Pinar CAKMAK5, Tuba Annabelle Lemenuel-Diot1, Selma El Messaoudi2, Jeremie Guedj2,
DAMAR CAKIRCA6, Ulkiye YETIM7, Yasar BAYINDIR8 Sylvie Retout1, Franziska Schaedeli-Stark1, Amine Ait-Ali1, Nelson
Guerreiro1, Sijie Lu3, Farouk Chughlay1, Claire McGeown1, Remi
1
Dicle University, Faculty of Medicine, Department of Infectious
Kazma1, for the Piranga Study Group
Diseases and Clinical Microbiology, 2Çukurova University, Faculty
of Medicine, Department of Infectious Diseases and Clinical
1
F. Hoffmann-La Roche Ltd, Basel, Switzerland, 2Université Paris Cité,
Microbiology, 3Dicle University, Faculty of Medicine, Department of INSERM, Infection, Antimicrobials, Modelling, Evolution, Paris, France,
Biostatistics, 4Antakya Defne Hospital, Clinic of Infectious Diseases
3
Roche R&D Center (China) Ltd, Shanghai, China
and Clinical Microbiology, 5Mardin Training and Research Hospital, Background: In platform clinical trials, aiming to evaluate regimens
Clinic of Infectious Diseases and Clinical Microbiology, 6Sanlıurfa to achieve functional cure in chronic hepatitis B (CHB), individual
Training and Research Hospital, Clinic of Infectious Diseases and characteristics are randomized but often not controlled. The variability
Clinical Microbiology, 7Batman Training and Research Hospital, Clinic of such characteristics can influence efficacy results. To describe
of Infectious Diseases and Clinical Microbiology,, 8Ankara Güven the various modes of action of new therapeutics for CHB, a novel
Hospital, Department of Infectious Diseases and Clinical Microbiology mechanistic viral dynamics modeling (MVDM) framework has been
Background: Hepatitis D virus (HDV) is associated with hepatitis B developed. Using this model, the source of response variability due
virus (HBV) infection. Therefore, it is recommended that all HBsAg to different individual characteristics was evaluated and simulations
positive patients should be screened for HDV. If HDV serology is showed their influence on model parameters and ultimately on efficacy
positive, HDV replication should be screened. The prevalence of HDV estimation.
in Turkey is not clear and fibrosis evaluation is recommended in HDV- Method: Leveraging the Piranga Phase 2 platform study
infected patients. In developed countries, sexual contact has replaced (NCT04225715), the MVDM framework (see figure) was developed
intravenous drug use (IVDU) as the main route of transmission of HDV to fit jointly the dynamics of the full pharmacokinetic and biomarker
among HIV-infected individuals. The aim of this study was to determine datasets. Data originated from 188 nucleos(t)ide analogue-treated
the prevalence of HDV. participants randomized into one of 6 arms with different combination
Method: Firstly, 250 Family Physicians from four different cities regimens of xalnesiran, a GalNAc-conjugated small interfering RNA
(Diyarbakır, Batman, Mardin, and Şanlıurfa), were trained on HBV/HDV targeting HBsAg transcripts, with or without an immunomodulator
infections and prognosis. Between March 2024 and October 2024, we (ruzotolimod, pegylated interferon α, or PD-L1 LNA). This MVDM
tested 20,000 chronic HBs-Ag-positive patients for HDV antibodies. framework included a pool of infected hepatocytes producing
All HDV-infected patients were tested for HIV, and for HDV replication. viral transcripts at different rates, either from cccDNA (ps1), or
All HDV-Ab positive patients underwent Fibroscan®. The Ethical from integrated HBV sequences (ps2). The death rate of infected
Committee approval was obtained from Dicle University. IBM SPSS hepatocytes (δ) was modelled primarily using ALT data. A model
21.0 for Windows statistical package program was used for statistical selection process estimated the effect of each molecule and the
evaluation of our research data. (Our research was registered in influence of individual characteristics, such as ethnicity or the HBV
ClinicalTrials.gov ID: NCT06248580) genotype, on the observed differences in efficacy. Using the MVDM
Result: In 20,000 HBs Ag-positive patients. 1,019 (5.1%) patients framework, simulations predicted the in silico performance of different
were positive for HDV. HDV-infected patients were referred to a combination regimens tested in Piranga in populations with different
gastroenterology/infectious diseases specialist for diagnosis and distributions of these individual characteristics.
follow-up. HDV-RNA was detected in 367 (36%) of the patients. Liver Result: The effect of xalnesiran was estimated as an inhibition
stiffness measurement (LSM) and controlled attenuation parameter of HBsAg production from both origins (ps1 and ps2) and an
(CAP) levels were evaluated by performing vibration controlled acceleration of hepatocytes death rate (δ). Furthermore, the model
transient elastography (VCTE) by using Fibroscan® M530 in 992 HDV estimated the add-on effect of each immunomodulator mainly through
positive patients. Liver cirrhosis was detected in 5.5% of the patients. an enhancement of the δ parameter and, specifically for pegylated
Hepatocellular carcinoma (HCC) was not detected in any of these interferon α, an increase in anti-HBs.The investigation of individual
patients. While the mean LSM value of all HDV-infected patients was characteristics influencing the effect of xalnesiran revealed that the
found to be 8.7 kPa, the mean LSM value was found to be significantly HBV genotype plays a role in modulating its effect. Using the MVDM
higher (17.2 kPa, P=0.019) in cirrhotic HDV infected patients. In framework, simulations of different combination regimens tested
1,019 HDV infected patients, 18 patients (1.8%) were positive for in Piranga showed how variations of the HBV genotype impacted
Anti-HIV. All Anti-HIV positive patients were treated by a specialist efficacy estimations depending on the potential underlying geographic
physician. CAP value was found to be significantly higher in patients distribution.
with HBV+HDV+HIV co-infection (p=0.012). Spelling-increased HIV Conclusion: This novel MVDM framework improves the characterization
positivity was found to be associated with the risk of IVDU (38.8%) of the complex long-term dynamics of viral parameters during and
in this patient group. MASLD (Metabolic Dysfunction-Associated after treatment with different combination regimens. Furthermore, it
Steatotic Liver Disease) rate was detected as 72.2% in this group. allowed the detection and evaluation of the influence of the individual
Conclusion: Screening for HDV in HBsAg-positive individuals revealed characteristics on the efficacy of the different combinations.
that the prevalence of HDV in our region was 5.1%. Evaluation of Table and Figure:Figure 1.
HDV patients using VCTE showed that it was extremely important for
the detection of liver cirrhosis (5.5%). This study demonstrated the PP0275
importance of screening all HBsAg patients for HDV and HDV-positive
patients for HIV. NTCP Inhibitors: A New Frontier in Acute and Chronic Liver Injury
Table and Figure:Figure 1.Table-1. Demographic characteristics of all Management
subjects. Liang Shi1, Miaomiao Liang1, Xiaojia Liu1, Junzhe Jiao1, Ruijuan Yan1,
Figure 2.Table-2. Characteristics of HDV positive patients Zhanjie Chang1, Haibo Zhang2, Jingtao Li1
1
Hepatology Hospital, Affiliated Hospital of Shaanxi University of
Chinese Medicine, 2Basic medicine college of Shaanxi University of
PP0274 Chinese Medicine
Background: Sodium taurocholate transport polypeptide (NTCP),
encoded by the SLC10A1 gene, is a transmembrane protein that is
highly expressed on the hepatocyte basement membrane, crucial
for maintaining bile acid homeostasis in hepatocytes. Moreover, much lower in the group with anti-HBs levels above 100 IU/L (10.48%).
NTCP serves as a receptor for hepatitis B virus (HBV) and hepatitis The group with anti-HBs levels below 100 IU/L had a higher proportion
D virus (HDV), aiding their invasion into hepatocytes. Recognizing its of men and a significantly higher body mass index (BMI) (P <0.05). No
significance in liver physiology and pathology, NTCP has emerged as significant differences were noted in age, qHBsAg, aminotransferase,
a promising target for liver disease intervention and treatment, with or white blood cell counts between the groups. Multivariate analysis
NTCP inhibitors garnering significant research interest. This paper showed that gender, age, and baseline qHBsAg had no significant
reviews recent findings on NTCP inhibitors and their therapeutic effect on the HBsAg relapse rate.
potential in liver disease, providing a foundation for the development Conclusion: HBsAg relapse is least likely when anti-HBs levels
of novel NTCP inhibitors and the exploration of combination therapies. progressively rise above 1000 IU/L. A level of anti-HBs above 100
Method: This article comprehensively assesses the pathophysiological IU/L also significantly decreases the rate of HBsAg relapse, indicating
role of NTCP in liver diseases, detailing the evolution and current restored antiviral B-cell function. In addition, men and elevated body
landscape of NTCP-targeted inhibitors, and scrutinizing their impact mass index (BMI) are unfavorable for antibody production.
and mechanisms in both acute and chronic liver conditions. Table and Figure:Figure 1.Demographic and laboratory characteristics
Result: NTCP inhibitors inhibit hepatic bile acid uptake, mitigating of the patients in six groups based on anti-HBs dynamic fluctuations
cholangiocarcinoma. They reduce intracellular bile acid levels and patterns & Demographic and laboratory baseline characteristics of the
dampen the inflammatory response of hepatocytes, modulating patients in two groups based on anti-HBs levels.
intracellular bile acid circulation to alleviate the bile acid burden and Figure 2.Anti-HBs fluctuation patterns & HBsAg relapse percentage &
injury. Anti-HBs level & HBsAg relapse percentage
NTCP inhibitors thwart HBV/HDV hepatocyte entry and viral
spread. By targeting HBV’s key hepatocyte receptors, these inhibitors
PP0277
block viral entry, curbing infection and cytopathic effects. The synergy
between NTCP inhibitors and other antiviral therapies enhances HBV Prognostic Value of Inflammatory Markers Including Neutrophil
treatment efficacy. to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, Mean
NTCP inhibitors mitigate liver fibrosis progression. They Platelet Volume, Platelet Distribution Width, and Red Blood Cell
impede HBV/HDV infection, modulate bile acid metabolism, and Distribution Width in Viral Hepatitis: A Systematic Review and
suppress the activation and expression of TGF-β, PI3K, and Akt Meta-Anal
signaling pathways, thereby inhibiting hepatic stellate cell activation Hanieh Radkhah1
and extracellular matrix accumulation. They can also prevent various 1
Departement of internal medicine sina hospital
liver diseases from escalating into hepatocellular carcinoma. Background: Hematological markers offer valuable and cost-effective
Conclusion: NTCP inhibitors mitigate cholangiocarcinoma by tools for hepatitis prognosis and treatment customization due to their
reducing bile acid uptake, prevent HBV and HDV hepatocellular role in inflammatory responses.Hence, this study seeks to explore the
invasion and replication, ameliorate liver fibrosis, and show preventive prognostic potential of inflammatory markers including neutrophil-
and therapeutic effects against liver cancer. As a new therapeutic to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean
target for liver diseases, NTCP inhibitors require further research to platelet volume (MPV), platelet distribution width (PDW), and red blood
elucidate their long-term effects and potential risks. cell distribution width (RDW) in viral hepatitis patients.
Table and Figure:Figure 1.Table1. Mechanism of NTCP inhibitors and Method: We conducted a systematic search in online databases of
liver diseases PubMed, Web of Science, Scopus, and Cochrane for related articles
following PRISMA guidelines. Our endpoint was to evaluate the
PP0276 association between NLR, PLR, MPV, PDW, and RDW with fibrosis and
cirrhosis outcomes in patients with hepatitis B and C.
Dynamic Fluctuation Patterns and Levels of Anti-HBs on the Risk
Result: Thirty-seven studies were ultimately included in the analysis.
of HBsAg Relapse
PLR was higher in mild fibrosis (SMD = -0.48, 95% CI: -0.90; -0.06),
Shiji Xu1, Jin Yang1, Lili Wu1, Bingliang Lin1, Zhiliang Gao1 with no significant differences observed by hepatitis type. Both MPV
1
The Third Affiliated Hospital of Sun Yat-sen University and RDW were higher in advanced fibrosis (MPV: SMD = 0.36, 95%
Background: There is a limit of 255 characters, including spaces, for CI: 0.19; 0.53, RDW: SMD = 0.32, 95% CI: 0.14; 0.50), and they
the title of an abstract. First letter of each word in uppercase, except were significantly increased in advanced hepatitis C fibrosis. PDW
for articles, prepositions, and conjunctions. Identifying information was higher in advanced fibrosis (SMD = 0.32, 95% CI: 0.02; 0.61),
such as author or institution names should not be included in the title. significantly in hepatitis B. In cirrhotic versus non-cirrhotic patients,
Method: This research involved 366 patients who attained HBsAg MPV (SMD = 0.22, 95% CI: 0.07; 0.38) and RDW (SMD = 1.35, 95%
loss following treatment at the outpatient clinic of the Third Affiliated CI: 0.62; 2.08) were higher in the cirrhotic group, while PLR (SMD =
Hospital of Sun Yat-sen University from 2018 to 2022. All of them -1.15, 95% CI: -2.16; -0.15) was higher in the non-cirrhotic group. NLR
had received nucleos(t)ide analog therapy for at least one year and showed no significant difference between mild and advanced fibrosis
subsequently switched to or added pegylated interferon-α therapy or between cirrhotic and non-cirrhotic groups.
over an unfixed course. Follow-up demographic and biochemical data Conclusion: This meta-analysis reveals the importance of
within 144 weeks of these individuals were gathered for analysis. hematological parameters of MPV, PDW, RDW, and PLR aspredictors
Result: In the study of 366 patients, 71 experienced HBsAg relapse of viral hepatitis progression. MPV, PDW, and RDW are elevated in
(HBsAg>0.05 IU/ml) during follow-up, accounting for 19.4%. Patients advanced fibrosis, while PLR is notably higher in mild fibrosis.
were divided into six groups based on anti-HBs dynamic fluctuations
over 144-week follow-up: persistently negative (<2 IU/L, 2.46%),
PP0278
transiently positive (14.48%), fluctuations within 1000 IU/L (2 IU–1000
IU/L, 54.37%), fluctuations above 1000 IU/L (9.84%), progressively To construct a prediction model of recompensation in HBV-
increasing above 1000 IU/L (>1000 IU/L, 12.84%), and secondary related decompensated cirrhosis patients combined with the
reappearance after negative turns (6.01%). The corresponding HBsAg inflammation index MLR
relapse rates were 33.3%, 60.38%, 10.05%, 5.56%, 2.13%, and Xu Huaqian1, Tang Shanhong1
27.27%, respectively. Factors like transaminases did not significantly 1
Department of Gastroenterology, The General Hospital of Western
affect antibody fluctuation patterns. There was a significant difference Theater Command, Chengdu 610083, Sichuan, China
in baseline HBsAg quantification (qHBsAg) between the group with Background: Systemic inflammation plays an important role in the
anti-HBs levels below 1000 IU/L and the group with peak anti-HBs progression of end-stage liver disease. This study aims to explore
above 1000 IU/L. In terms of antibody levels, the highest relapse rate the relationship between inflammation and liver recompensation in
was found in the anti-HBs level between 2-10 IU/L (50%), followed by patients with hepatitis B virus (HBV) -related decompensated cirrhosis.
10-100 IU/L (40.45%) and <2 IU/L (33.33%). The relapse rate was
Method: Systemic inflammation plays an important role in the 1
Department of Gastroenterology, The General Hospital of Western
progression of end-stage liver disease. This study aims to explore Theater Command, Chengdu 610083, Sichuan, China
the relationship between inflammation and liver recompensation in Background: Acute-on-chronic liver failure (ACLF) is a clinical
patients with hepatitis B virus (HBV) -related decompensated cirrhosis. syndrome characterized by high short-term mortality. Among the
Result: The incidence of recompensation in this study was 41.19% many influencing factors, inflammation is related to the progression
(180/437). Logistic regression multivariate analysis showed that of ACLF. We aim to explore the value of inflammation biomarkers in
the occurrence of liver failure, MLR and Child-Pugh score were the prognosis of hepatitis B acute-on-chronic liver failure (HBV-ACLF)
independent influencing factors for the occurrence of recompensation. patients and create a new predictive model.
The nomogram model was constructed by combining the multivariate Method: A total of 247 HBV-ACLF patients were retrospectively
results. The model calibration curve of the training set and the validation analyzed. The clinical value of inflammatory biomarkers for participants
set had a good consistency with the clinical decision curve. The area was evaluated and compared. Univariate and multivariate regression
under the ROC curve of the training set and validation set was 0.815 models were used to analyze the risk factors of 90-day mortality, and a
(95%CI: 0.767-0.863) and 0.823 (95%CI: 0.767-0.863), respectively. new model was established.
0.767-0.863), which was better than MLR, Child-Pugh score, MELD, Result: There were statistical differences in age, total bilirubin(TBiL),
MELD-Na, iMELD, and ALBI score (P<0.05). prothrombin time(PT), international normalized ratio(INR), inflammation
Conclusion: MLR is an independent risk factor for recompensation level and MELD series scores between the survival group and the
in patients with decompensated hepatitis B cirrhosis. The nomogram death group(P<0.05). The new model(MLR-iMELD model) could
prediction model combined with MLR can better predict the occurrence effectively predict the 90-day survival of HBV-ACLF patients. The area
of recompensation. under the ROC curve was 0.792, and the best cut-off value of 90-day
Table and Figure:Figure 1.Flow chart prognosis prediction was -0.33(sensitivity 0.577, specificity 0.898).
Figure 2.NOMOGRAM Conclusion: The MLR-iMELD model including inflammatory
biomarkers was better than the MELD series model in predicting 90-
PP0279 day mortality in HBV-ACLF patients.
Table and Figure:Figure 1.Flow chart
Socioeconomic determinants of chronic liver disease : Experience
Figure 2.Highlight
from Karachi, Pakistan.
Bushra Shahid1
1
Jinnah post graduate medical centre PP0281
Background: Pakistan has one of the world’s highest viral hepatitis Ethnic disparities in extrahepatic manifestations among people
rates. A considerable number of people develop chronic liver disease with HCV infection: a population-based study in British Columbia
(CLD). Social determinants of health (SDOH), including multiple Dahn Jeong1,2, Stanley Wong2, Hector A Velasquez Garcia1,2, Prince
physiological and behavioral risk variables, have an effect on the A Adu2, Jean D Makuza1,2, Sofia R Bartlett1,2, Alnoor Ramji1, Eric M
course of chronic liver disease (CLD), as well as death. The influence of Yoshida1, Richard L Morrow1,2, Amee R Manges1,2, Mohammad E
inequities in social and economic determinants of health has received Karim1,3, Amanda Yu2, Georgine Cua2,1, Mel Krajden2,1, Naveed Z
little attention, despite the fact that tackling these socioeconomic Janjua2,1,4
factors is critical to improving the management and prevention of 1
University of British Columbia, 2British Columbia Centre for Disease
chronic liver disease in Pakistan. Control, 3Centre for Advancing Health Outcomes, St. Paul‘s Hospital,
Method: It is an ongoing cross sectional study being conducted in
4
Centre for Advancing Health Outcomes, St. Paul‘s Hospital
the Department of Hepato-gastroenterology, Jinnah Post Graduate Background: While Asian populations bear a significant burden of
Medical Centre, Karachi from August 2024. This study examined HCV infection globally, ethnic disparities in extrahepatic manifestations
chronic liver disease patients and associated SDOH characteristics (EHMs) remain poorly understood. Up to 35% of HCV infections in
in the areas of financial position, healthcare access, education, social Canada occur among immigrants, predominantly from HCV-endemic
and community context, and neighborhood-built environment. Interest- regions. We aimed to examine ethnic disparities in EHMs among
related outcomes included hospitalizations or readmissions, as well as individuals diagnosed with HCV in British Columbia (BC), Canada.
illness complications Method: Using linked administrative health data from the BC
Result: A total of 500 patients with chronic liver disease were enrolled Hepatitis Testers Cohort (1990-2015), we assessed EHMs incidence
with majority residing in Sindh 470(94%), 258 (51%) were females, and and risk by ethnicity (East Asian, South Asian, and Other) among
242 (48%) were males with mean age of 50±14 years. The majority had 41,874 individuals. EHMs included chronic kidney diseases (CKD)
HCV 334 (66%) as the etiology , followed by HBV 101 (20%). Only 186 and end-stage renal diseases (ESRD), type 2 diabetes (T2DM),
(48%) were treated for etiology, 277 (69%) had decompensated CLD stroke, major adverse cardiac events (MACE), and neurocognitive
at presentation with a CTP-B score 226 (56%). In city Karachi, Orangi disorders (NCD). We assessed incident EHMs across three groups:
(West District) had the most patients (75/15%), followed by Korangi untreated (n=16,135), treated (n=21,558), and spontaneous clearance
(72/14%). The majority of them were lower middle class, making less (n=4,181). To assess risk of EHMs by ethnicity, we used multivariable
than <20,000PKR (277, or 69%), living in a two-room home (165, cause-specific proportional hazards models, adjusted for sex, birth
or 41%), and were illiterate (212, or 51%). The majority, 172 (43%), year, material/social deprivation, and relevant clinical factors including
had at least one admission as a result of the disease’s progression, hypertension, cirrhosis, and substance use.
while 90 (22.5%) had two admissions in a single year. Increased Result: South and East Asians had higher incidence rates of CKD
hospital readmissions among CLD patients were associated with poor & ESRD, T2DM, stroke, and MACE compared to other ethnicities,
household/environmental conditions, social support, and economic especially among untreated individuals (Figure). Among untreated
stability. individuals, adjusted analyses showed that South Asians had
Conclusion: Poor living conditions, literacy rate, financial burden are significantly elevated risks for CKD & ESRD (adjusted cause-specific
determinants for ongoing spread of hepatitis along with detection of hazard ratio [acsHR] 1.27, 95% CI 1.02-1.60) and T2DM (acsHR 2.12,
liver disease at an advanced stage. Therefore its crucial to analyze 95% CI 1.53-2.94). East Asians had lower risks of MACE (acsHR
the economic and social challenges confronting chronic liver disease 0.74, 95% CI 0.60-0.92) and NCD (acsHR 0.66, 95% CI 0.50-0.87).
patients in Karachi,Pakistan. Following treatment completion, EHMs incidence rates decreased in
both groups. Adjusted analyses showed that most ethnic disparities
PP0280 observed among untreated individuals and before treatment
decreased or disappeared after treatment, except for diabetes.
Prognostic value of inflammation-related model in hepatitis B
South Asians consistently had greater risk of diabetes, regardless of
acute-on-chronic liver failure
treatment status (Table 1).
Xu Huaqian1, Tang Shanhong1
Conclusion: This study highlights the disproportionate burden Department of infection, the first Hospital of Shanxi Medical
1

of EHMs among Asians in British Columbia and underscores the University

potential of HCV treatment to reduce ethnic disparities. Ensuring timely Background: Direct-acting antiviral agents (DAAs) for the treatment
access to HCV diagnosis and treatment is crucial for public health, as of hepatitis C have achieved very high sustained virological response
it contributes to mitigating ethnic disparities in multiple extrahepatic (SVR) rates. However, there are relatively few long-term follow-up
diseases, offering broad health benefits across diverse populations. studies on the outcomes of cured patients. In this study, we aimed to
Further research should focus on developing culturally appropriate explore the long-term prognosis and its influencing factors in patients
strategies to enhance HCV screening, linkage to care, and treatment with hepatitis C who achieved SVR12 after treatment.
uptake among underserved ethnic populations. Method: Clinical data of HCV-infected patients who achieved SVR12
Table and Figure:Figure 1.IR of EHMs per 1,000 PYs by ethnicity at the Department of Infection, the First Hospital of Shanxi Medical
among individuals who were never treated, those who were treated: University, from September 2017 to September 2022 were collected.
pre- and post- treatment completion, and those who spontaneously The long-term virological response and clinical outcomes of patients
cleared HCV at various time points from 12 to 240 weeks were analyzed. The rate
Figure 2.Risk of incident EHMs among East Asians, South Asians of disease progression and recovery in patients with different baseline
and Other BC residents in the BC-Hepatitis Testers Cohort, using levels were compared using the Chi-square test or Fisher’s exact test,
multivariable cause-specific proportional hazards models and Cox proportional hazards analysis was conducted to identify
predictors. A p-value of < 0.05 was considered statistically significant.
PP0282 Result: During the follow-up period, ranging from 12 to 240 weeks
post-DAAs treatment, 35 (13.83%) of 253 patients developed disease
Resistance-Associated Substitution in patients with HCV
progression, while 27 (10.67%) showed disease improvement. Table 1
genotype 1b hepatitis: Outcomes of treatment with Ledipasvir and
presents a comparative analysis of disease progression rates before
Sofosbuvir in Mongolia
and after the 96-week mark. The incidence of disease progression
Purevsod Lkhagvasuren1,2, Naranzul Nyamsuren1,2, Tulgaa events within 96 weeks after treatment was significantly higher than
Khosbayar3, Jazag Amarsanaa2, Oidov Baatarkhuu1,2 that beyond 96 weeks, with most cases involving compensated liver
1
Mongolian National University of Medical Sciences, Department cirrhosis (CLC) (P < 0.05). The disease progression rate differed
of Infectious disease, 2Mongolian Association for the Study of Liver significantly among patients with different baseline HCV RNA levels at
Diseases, Ulaanbaatar, Mongolia, 3Department of Molecular Biology 24 and 48 weeks post-treatment (P < 0.05), with a higher progression
and Genetics, School of Bio-Medicine, Mongolian National University rate in patients with a high viral load. However, there was no significant
of Medical Sciences, Ulaanbaatar, Mongolia
difference in prognosis among patients with different genotypes
Background: Mongolia has the highest prevalence of hepatitis C and baseline liver function levels. Multivariate Cox regression model
virus (HCV) infection worldwide, with chronic hepatitis C (CHC) being analysis indicated that the LSM value was associated with an increased
a major public health concern. Since 2016, Ledipasvir/Sofosbuvir risk of disease progression (HR 1.043, 95% CI 1.006-1.081).
(LDV/SOF) has been used in Mongolia for HCV eradication. However, Conclusion: After achieving SVR12 with DAAs treatment, liver
resistance-associated substitutions (RASs) in the HCV genome have lesions can be reversed to a certain extent. However, some patients
been shown to affect the effectiveness of LDV/SOF treatment in still experience disease progression, mostly within 96 weeks after
Western CHC patients. This study aims to investigate the effectiveness treatment. Baseline viral load and the degree of fibrosis may be
of LDV/SOF and evaluate the impact of RAS on treatment outcomes in contributing factors to this progression. It is recommended to eliminate
Mongolian CHC patients. the virus as early as possible and control fibrosis progression to
Method: Patients with genotype 1b hepatitis C virus (HCV) infection were improve long-term prognosis. Even after viral clearance, it is important
prospectively enrolled in Mongolia and treated with a 12-week regimen to continue monitoring liver-related indicators, such as LSM, regularly.
of Ledipasvir/Sofosbuvir (LDV/SOF). Prior to treatment, the presence It is recommended to increase the frequency of monitoring within 96
of the NS5A Y93H resistance-associated substitution (RAS) in the viral weeks after treatment to guard against disease progression events
quasispecies was assessed using next-generation sequencing (NGS). such as hepatocellular carcinoma (HCC).
The primary endpoint for evaluating the effectiveness of the LDV/SOF Table and Figure:Figure 1.Comparison of the incidence of disease
treatment was the sustained virological response at 12 weeks post- progression or improvement events during follow-up before and after
treatment (SVR12), which indicates the absence of detectable HCV 96w
RNA and serves as a reliable marker for successful eradication of the
virus.
Result: A total of 94 CHC patients were evaluated. The baseline Y93H
PP0284
proportion was <1% in74 patients, 1e15% in 7, 15e50% in 2, and 50% HCV epidemiological characteristics in Qinghai province, China.
in 11. All patients completed 12-week LDV/SOFtreatment and the Yajing Li1, Zhaolan Yan1, Jinhua Deng1, Liping Yang1, Hongmei Zu1
SVR rate was 90.4%. The rate of failure to achieve SVR12 for patients 1
The fourth people’s hospital of Qinghai province.
withY93H < 1%, 1e15%, and _15% were 0%, 14.3%, and 61.5%, Background: Qinghai province is a high-risk area for HCV, according
respectively (p for trend Z0.001). In univariable analysis, older age, to the national CDC report in 2020, the incidence of HCV in Qinghai
baseline alanine transaminase level <40 U/mL, and a higherproportion province ranked No.1 in the country, however, there are no published
of Y93H were associated with treatment failure. In multivariable analysis, data on the epidemiological characteristics of HCV in Qinghai province.
only a higher proportion of Y93H was associated with treatment failure Method: To understand the infectious status and viral genotypes
(p Z 0.022). of HCV in Qinghai province and facilitate the elimination of HCV in
Conclusion: This study found that the sustained virological response Qinghai province.
(SVR12) rate for Ledipasvir/Sofosbuvir (LDV/SOF) treatment in Result: A total number of 854 patients with HCV infection were included
Mongolian patients with genotype 1b HCV was 90.4%. Treatment in the statistical analysis, with an average age of 51.88±22.20years,
failure was significantly higher in patients with a higher proportion of approximately 58% male and 42% female, and a majority of Han
the NS5A Y93H resistance-associated substitution, particularly those ethnicity(n=651), accounting for 76%, followed by Hui ethnicity(n=105)
with ≥15% Y93H (61.5% failure rate). Monitoring Y93H levels is crucial and Zang ethnicity(n=80), accounting for 12% and 9% respectively.
for predicting treatment success in chronic hepatitis C patients. The median HCV RNA was 1.33×107IU/mL(3.60×106, 3.23×107),
ALT was 63U/L(30.00,120.00) and AST was 48U/L(28.00,83.00). The
PP0283 most common genotype was GT2a(n=304), followed by GT1b(n=252),
Beyond Viral Clearance: Evaluating Long-Term Clinical Outcomes GT3b(n=140), GT3a(n=134), GT6(n=8), indeterminant genotype(n=8),
in HCV Patients After DAAs Therapy GT1a(n=5) and GT2b(n=3), accounting for 35.6%%, 29.5%, 16.4%,
15.7%, 0.9%, 0.9%, 0.6% and 0.4% respectively. Cirrhosis was
Xiao Yan Wang, Bin Niu1, Liao Yun Zhang1, Yi Hui Hou1
diagnosed in 158 patients (18.5%), of which 58 had decompensated clinic (MMTC) and treatment status in China are unclear. We aim to
cirrhosis (36.7%), indicating a severe disease state. Most patients were establish an multidisciplinary collaborative model for HCV elimination
treated with SOF-based regimens (n=760, 89.0%) including SOF/VEL among PWID.
and LDV/SOF. One hundred and five patients had concomitant fatty Method: General information was collected on PWID attending MMTC
liver disease, ten patients had combined HCC, three patients were co- from January 2020 to September 2024. Patients were screened for HCV
infected with HBV. antibody. Patients with HCV antibody positive were required HCVRNA
Conclusion: The epidemiological characteristics of HCV in testing. A multi- collaborative approach was used for the patients.
Qinghai Province showed a diversity of genotype distribution, with a Social work organizations provided psychological intervention. Peers
predominance of GT3 type and a high percentage of GT2 and GT1 were responsible for educating patients through their experience
type, which not only enriched the characteristics of HCV genotype and benefit from HCV cure. The health care professionals (HCPs) in
distribution in China, but also provided evidence for individualized MMTC trained by hepatologists provided HCV disease education, and
treatment of patients. In addition, HCV patients had more severe liver chronic health insurance will support this programme, while a green
disease states and a higher proportion of combined HCC and fatty referral pathway for HCV RNA-positive patients has been established.
liver, suggesting that HCV screening and linkage to care (SLTC) should Hepatologists will provide patients with face-to-face counselling ,
be actively carried out to reduce the HCV disease burden. treatment assessments and SOF/VEL ±RBV treatment.
Result: A total of 538 PWID were tested for HCV antibodies, 462 patients
(85.9%) were HCV antibody positive, while 285 patients (61.7%) were
PP0285
HCV RNA positive including 73 patients were co-infected with HCV and
The Risk Factors Associated with Liver Cancer and Cirrhosis in HIV. The median age of patients with hepatitis C was 50 years (range
Chronic Hepatitis C Patients and a Case Report of Resistance- 45-56 years), with 230 males (80.7%) and 55 females (19.3%).Of HCV
associated Substitutions to Sofosbuvir-velpatasvir Treatment RNA-positive patients, 92 underwent genotype testing. Genotype
Hao Xiong1, Shaokun Pan2, Chaohui Zhou1, Hong Shi1, Youhua Xie2, 3b was the most common genotype (41 cases, 44.6%), followed by
Jinsheng Guo1 genotype 6a (24 cases, 26.1%). Of the 285 HCV patients, 85 patients
1
Department of Gastroenterology and Hepatology, Zhong Shan (30%) had received DAA treatment and SVR12 was 100%. The main
Hospital, Shanghai Institute of Liver Diseases, Department of Internal reasons for those who didn’t receive DAA treatment were poor financial
Medicine, Shanghai Medical College, Fu Dan University, Shanghai, situations (45%), insufficient understanding of hepatitis C hazards
2
00032, China, 2 Key Laboratory of Medical Molecular Virology, (30%), perceived high cost of medication (15%), and advanced age
Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai (10%). Another 200 patients are still being followed and some are
Frontiers Science Center of Pathogenic Microbes and Infection, applying for chronic disease insurance for treatment in the near future.
School of Basic Medical Sciences, Shanghai Medical College, Fudan Conclusion: The prevalence of HCV infection in MMTC is high, but
University, Shanghai, China the treatment rate still low. Collaboration between methadone clinics,
Background: The treatment landscape for hepatitis C viral (HCV) social work organizations, and hepatologists is essential to support the
infection has evolved significantly with the introduction of pan-genotypic micro-elimination of hepatitis C among PWID.
direct-acting antiviral agents (DAA). This study retrospectively analyzed Table and Figure:Figure 1.Screening, diagnostic and treatment status
the characteristics and prognosis-associated factors of chronic
hepatitis C (CHC) patients. The treatment efficacy and resistance-
PP0287
associated substitutions (RAS) to sofosbuvir-velpatasvir (SOF-VEL)
were further investigated. Relationship between Systemic Immune-inflammation Index (SII)
Method: A genotype (GT) based baseline comparison was performed and Hepatitis C Virus Infection: NHANES 2005-2012
on 358 HCV-infected patients with positive HCV RNA load. Single and Zhang Kai Ge1, Zeng Yu Yu2, Xie Zheng Yuan1
multivariate factor analyses were performed to explore the risk factors 1
Department of Gastroenterology, The Second Affiliated Hospital,
associated with liver cancer and cirrhosis. Among them, 80 patients Jiangxi Medical College, Nanchang University, 2Department of
treated with SOF-VEL were further investigated for the efficacy and Infection, The First Affiliated Hospital , Jiangxi Medical College,
safety. An unusual SOF-VEL resistance case was investigated for the Nanchang University
RAS sites using next-generation sequencing. Background: The Systemic Immune-inflammation Index (SII) is a
Result: HCV GT1 infection (45.5%) was most prevalent in this Chinese novel inflammatory marker that reflects local immune responses
cohort. GT3 infection had a poorer prognosis. Age ≥50 years, male and systemic inflammation in the human body and has been shown
gender, Child-Pugh Grade B and C, and FIB-4 ≥3.25 were risk factors to be associated with the risk and severity of various liver diseases.
for liver cancer, while age ≥50 years, with diabetes, and ANA positive However, there is a lack of research on its role and clinical significance
were risk factors for cirrhosis. Treating CHC patients with SOF-VEL in Hepatitis C Virus (HCV) infection. This study aims to investigate the
revealed a sustained virologic response (SVR12) rate reaching 95%. relationship between SII and HCV infection.
The patient who experienced response-relapses once SOF-VEL was Method: We analyzed data from the National Health and Nutrition
withdrawn had HCV GT2a infection. The isolated HCV strain harbored Examination Survey (NHANES) between 2005 and 2014, which
F28S mutation in NS5A, and T273A, M289L, A421V mutations in NS5B included complete HCVAB and SII information. The SII was calculated
as RAS sites. as platelet count × neutrophil count/lymphocyte count. Due to the
Conclusion: SOF-VEL-based antiviral treatment for patients with skewed distribution of SII, natural logarithm (ln) transformation
CHC resulted in a high rate of achieving primary endpoint of SVR12. was applied to approximate a normal distribution. The association
However, caution should still be taken for RAS, and the patients should between ln SII and HCV infection was studied using logistic regression
be carefully monitored after the end of treatment. models, and subgroup analyses were conducted to explore potential
influencing factors. Additionally, we performed smooth-fitting curve
PP0286 and threshold effect analyses to describe the nonlinear relationship
between SII and HCV infection.
A Multi-Organizational Collaborative Model for HCV Mlimination in
Result: A total of 29,546 participants were included in this cross-
Methadone Maintenance Clinics
sectional study, drawn from four cycles of NHANES data. The logistic
Cailian Cai1, Shan Shi2, Hangfeng Liu2, Ruyi Luo2, Lanjuan Li2, Likui regression model results indicated that lower ln SII values were
Wei2, Hongjiang Li2, Hongyu Liu1, Fangpeng Ling1, Bingling Fan1, associated with a higher likelihood of HCV infection. This association
Minghua Su1 remained significant in our unadjusted model (OR = 0.502; 95% CI,
1
The First Affiliated Hospital of Guangxi Medical University, 2Nanning 0.427, 0.592, p < 0.001), partially adjusted model (OR = 0.525; 95%
Red Cross Hospital CI, 0.448-0.617, p < 0.001), and fully adjusted model (OR = 0.455;
Background: The situation of HCV infection and treatment status 95% CI, 0.381-0.543, p < 0.001). The smooth-fitting curve results
among people who inject drugs (PWID) in methadone maintenance showed a U-shaped relationship between ln SII and HCV infection,
with an inflection point at 6.12. old, 96% were male. The median alanine aminotransferase (ALT) was
Conclusion: This study found that decreased ln SII levels were 58.10 (29.75, 113.65) IU/L. In Group 1, for CHC treatment, 85% of
associated with HCV infection. Further large-scale prospective studies the patients were treated with SOF/VEL, 15% with RBV, 85% of the
are needed to confirm the findings of this research. treatment courses lasted for 12 weeks. Propensity score matching
(PSM) was performed. After PSM, there were 12 patients in each
group, baseline characteristics were comparable (Table 1). In Group 1,
PP0288
comparing pre- and post- treatment , ALT decreased from 94.20 (54.00,
A standardized HCV management process in a county contributes 145.00) IU/L to 13.50 (7.75, 22.28) IU/L, aspartate aminotransferase
to HCV elimination : an HCV elimination project in Xing’an County (AST) decreased from 95.58 ± 50.82 IU/L to 23.93 ± 10.29 IU/L,APRI
Huanwen Chen1, Zengxue Lu1, Zhongyuan Zhou1, Xianxin Tang1 index decreased from 1.09 (0.68, 3.70) to 0.37 (0.17, 0.73) ,FIB4 score
1
Xing ‘an County People‘s Hospital decreased from 2.22 (1.54, 5.68) to 1.40 (0.86, 3.39), all P < 0.05.
Background: The awareness of hepatitis C virus among health SVR 12 rate was 100%, the cure and improvement rate for TB was
providers and patients from rural areas is very limited. We aimed to 100%. In Group 2, the APRI was significantly higher post-treatment (P
evaluate the effectiveness of a standardize HCV management process = 0.042). There was a statistically significant improvement in albumin
in Xing’an County of Guangxi province. (P < 0.001). The cure and improvement rate for TB was 66.7%. (Figure
Method: A serious of HCV disease education and training were 1). Comparison between two groups showed the improvements in ALT,
conducted for primary care physicians and rural doctors. The rural AST, and APRI in Group 1 were significantly better than Group 2 (P =
doctors provide public HCV education and propaganda for general 0.002, P < 0.001, P = 0.023), the incidence of AEs was lower in Group
population. The standardized HCV management process in remote 1 (P=0.001). The increase in albumin in Group 2 was significantly
areas mainly includes below steps: HCV antibody screening for better (P = 0.045). There was no treatment discontinuation in Group 1,
high-risk rural population, alert system for high-risk of HCV infection while 33.3% in Group 2. There was no difference in the TB treatment
population and timely referral to the hepatology department of Xing‘an outcome between two groups (P=0.093).
People’s hospital. HCV antibody positive patients will be required to Conclusion: For TB combined with CHC, especially those with
complete HCV RNA test by the alert system. The hepatology specialists elevated transaminase levels, simultaneous treatment strategy brings
would provide appropriate treatment and follow-up plan for the HCV more clinical benefits compared to treating TB first.
patients who were referred to them. Table and Figure:Figure 1.Table 1 :Baseline characteristics of the study
Result: From Jan. 2020 to Oct.2024, a total of 78,395 population population before and after propensity score matching (PSM)
were screened for HCV antibody, with the HCV antibody positive Figure 2.Figure 1: Comparison within the same treatment strategy
rate of 3.63% (2844/78395). Of 2844 HCV antibody positive patients, group pre- and post- treatment
1,909(67%) were received HCV RNA detection, while 940 (49.24%)
patients were HCV RNA (+). The link-to-treatment rate was 74.89% PP0290
(704/940). 90% (634/704) of whom had a history of compensated
Efficacy and Safety of Coblopasvir and Sofosbuvir in Patients with
blood donation or transfusion. Overall, 700 (99.43%) patients achieved
Hepatitis C in Northwest China
an SVR12.The annual overview of HCV screening, diagnosis and
treatment situation each year were shown in Figure 1. Lu Yan1, Maimaitijiang Wubuliaishan2, Xiaoni Kou3, Maimaitiaili
Conclusion: The standardized HCV management process in Xing’an Tuerxun4, Mingbo Yang5, Fanpu Ji6, Yingli He7, Jiuping Wang8,
County has significantly improved the HCV screening, HCV RNA Longdong Zhu9, Xiaohong Gao10, Fuchun Jing11, Xiangchun Ding12,
detection and treatment linkage rate for HCV which can accelerate the Du Du1, Ye Zhang1, Hong Jiang1
process of hepatitis C elimination in remote areas.
1
Center for Diagnosis and Treatment of Infectious Diseases, The
Table and Figure:Figure 1.The annual overview of HCV screening, second affiliated Hospital of Air Force Medical University, Xi’an
diagnosis and treatment situation each year 710038, 2Department of Liver disease, Hotan Regional infectious
Diseases Hospital, Sinkiang, Hotan, 848000, 3Department of
Hepatology, Affiliated Hospital of Shaanxi University of Traditional
PP0289 Chinese Medicine, Xianyang, 712000, 4Department of Infection,
Compare the efficacy and safety of different treatment strategies Kashgar First People‘s Hospital, Sinkiang, Kashgar, 844000;,
for patients with tuberculosis combined with Chronic hepatitis C
5
Hepatology Department of TCM, Xi’an No.8 Hospital, Xi’an, 710061;,
6
Department of Infectious Diseases, The Second Affiliated Hospital
Qiong Hu1, Yongping Xie2, Guoen Lv3, Changzheng Hu1, Chunyu
of Xi‘an Jiaotong University, Xi‘an,710004;, 7Department of Infectious
Chen1, Longting Xie1, Junyi Lin1, Xiangling Liu1, Gang He1
Diseases, The First Affiliated Teaching Hospital, SOM, Xi‘an Jiaotong
1
Jiangmen Central Hospital, 2Jiangmen Tuberculosis Prevention and University, Xi‘an,710061;, 8Department of Infectious Diseases, The
Control Institute, 3Shunde People‘s Hospital first affiliated Hospital of Air Force Medical University, Xi’an 710038;,
Background: It is unclear whether simultaneous treatment or 9
Department of Infectious diseases, the First Hospital of Lanchow
sequential treatment can bring more benefits to tuberculosis (TB) University, Lanchow, 730030;, 10Department of Infection, Affiliated
combined with Chronic hepatitis C (CHC) patients, so we evaluate the Hospital of Yan ‘an University, Yan’an, 716000;, 11Department of
efficacy and safety of different treatment strategies. Infectious diseases and Hepatology, Baoji People‘s Hospital, The
Method: This was a multicenter, retrospective study. The data of School of Medicine, Yan‘an University, Baoji 721000;, 12Department of
patients with TB combined with CHC who were admitted to Jiangmen Infection, Affiliated Hospital of Ningxia Medical University, Yinchuan
Central Hospital, Jiangmen Tuberculosis Prevention and Control 750000;
Institute, and Shunde People’s Hospital from March 2010 to June 2024 Background: To evaluate the efficacy and safety of a 12-week course
were collected. Sofosbuvir/Velpatasvir (SOF/VEL) ± ribavirin (RBV) of colopivir and sofosbuvir in patients with hepatitis C in northwest
for 12 weeks was major regimen to treat CHC. For TB treatment, a China.
combination of first line (isoniazid, ethambutol, pyrazinamide) and Method: This prospective clinical study included patients with
second-line anti-tuberculosis drugs other than rifamycin were used. hepatitis C of any genotype who received sofosbuvir and Coblopasvir
The efficacy was evaluated as follows:SVR 12 for CHC, TB was for 12 weeks in 12 hospitals in northwest China. The clinical data of
evaluated based on whether patients’ symptoms improved, sputum patients diagnosed with hepatitis C in the aforementioned 12 clinical
smear results, and imaging findings of the TB lesion sites to determine medical centers, in accordance with the China Hepatitis C Prevention
whether they were cured or improved. Adverse events (AEs) and and Treatment Guidelines (2022 edition). All patients received colopivir
treatment discontinuation were also evaluated. 60mg and sofosbuvir 400mg orally once daily for 12 weeks. Clinical
Result: 50 patients were included: 27 patients were in the Treat TB data, including quantification of HCV RNA, genotype, liver and kidney
and CHC Simultaneously group (Group 1) and 23 patients were in the biochemical markers, B-ultrasound results, and liver fibrosis scan
Treat TB first group (Group 2). The mean age was (47.92 ± 6.81) years results were collected at three time points: baseline, 12 weeks after
starting medication, and 12 weeks after cessation of medication. The 244(130-395)±5.4 db/m. After completion of treatment with antivirals,
presence of cirrhosis in the patient was determined based on the specific carbohydrate metabolism disorders HOMA- IR index changes
findings from abdominal B-ultrasound and liver fibrosis scan. from 3.5(1-10.9) ± 2 to 2.4( 1-1.9)±1.4, biochemical markers of liver
Result: A total of 209 patients initiated antiviral therapy, out of which inflammation showed ALT 103.35(25-477)±84.4 to 45 (11-215)±26.6,
170 patients successfully completed a 12-week treatment course AST 81.1(22-277)±52.6 to 42.1(17-167)±20.1, GGT 102.3( 15-
and underwent subsequent follow-up. Additionally, 129 patients were 562)±91.8 to 57.1(11-324)±45.8, cholesterol 4.8(2.1-7.5)±1 to 4.3(3.3-
followed up after discontinuing treatment for a period of 12 weeks. 6.4)±0.7. All the results showed statistical significance of P<0.001.
Among the cohort of 170 patients who successfully underwent Conclusion: It shows that when HCV infection is eradicated by
treatment included 73 males and 97 females, with a median age of DAA’s, carbohydrate metabolism significantly changes. Markers of
53 years old (ranging from 17 to 81), 50 patients with cirrhosis among Carbohydrate metabolism (HOMA-IR index) biochemical markers of
these individuals. The patients’ genotypes were distributed as follows: inflammation have also decreased after completion of drug therapy. It
genotype 1 accounted for 1.18%, genotype 1a for 0.59%, genotype 1b is s safe to use antiviral therapy in patients with IR and DM.
for 38.24%, genotype 2 for 4.71%, genotype 2a for 31.18%, genotype
2b for 1.76%, genotype 3a for 12.35%, genotype 3b for 7.06%,
PP0292
genotype 6a for 0.59%, and untyped patients made up 2.35%. The rate
of virus clearance was 98.8% among the 170 patients who completed The SVR10K study: A Real-World Data with Pangenotypic Direct-
a 12-week follow-up period, while sustained virologic response (SVR) Acting Antivirals Across Multiple Diverse Regions
was achieved by 99.4% of the 129 patients who completed follow-up Grace LaiHung Wong1, Mario Reis ALVARE-DA-SILVA2, Fatima
after discontinuation. Compared to baseline, significant increases in Higuera-de-la-Tijera3, Ming Lung Yu4, Soo Aleman5, Javier Garcia-
RBC levels were observed at both 12 and 24 weeks (P=0.04/0.0035), Samaniego6, Joaquin Cabezas7, Marta Casado8, Mohamed Alzaabi9,
along with decreases in TBil (P=0.02/0.038), ALT (P<0.001), and AST Aastha Chandak10, Marta Martínez10, Artak Khachatryan10, Linda
(P<0.001). Additionally, there was a decrease in ALP (P=0.04/0.6) and Chen11, Candido Hernandez11, Yu Jun Wong12
GGT (P=6.57E-5/2.85E-4). No statistically significant changes were 1
The Chinese University of Hong Kong, 2Hospital de Clínicas de
noted for ALB, TBA, CHE, UA, UREA, and Cr (P>0.05). Importantly, no Porto Alegre – Federal University of Porto Alegre, 3Hospital General
significant adverse events were reported. de México “Dr. Eduardo Liceaga“, 4Kaohsiung Medical University
Conclusion: The combination of Colopaivir and sofobuvir in patients Hospital, 5Karolinska University Hospital, 6Hospital Universitario La
with various genotypes of hepatitis C in Northwest China demonstrated Paz, 7Hospital Marques de Valdecilla, 8Hospital de Torrecárdenas,
superior viral clearance and SVR12 rates, irrespective of the presence
9
Zayed Military Hospital, 10Certara, 11Global Medical Affairs, Gilead
or absence of cirrhosis. The administration of this treatment also Sciences, 12Changi General Hospital, SingHealth
facilitates improvements in liver biochemical markers and exhibits no Background: A previous real-world data analysis demonstrated high
significant adverse effects on renal function, thereby demonstrating a effectiveness of sofosbuvir/velpatasvir (SOF/VEL) without ribavirin
favorable safety profile (RBV) in > 6,000 HCV patients from 12 clinical cohorts across Australia,
Table and Figure:Figure 1.HCV genotype distribution Canada, Europe & USA. Expanding this research to include even more
Figure 2.Alterations in hematological parameters and hepatic patients from additional geographical areas will allow assessing SOF/
biochemical marker VEL (without RBV) effectiveness across multiple diverse populations
and the evaluation of HCV patient characteristics across Western
countries, Asia, Middle Eastern and Latin-American (LATAM) regions
PP0291
(the ongoing SVR10K study).
CHANGES IN CARBOHYDRATE METABOLISM DURING Method: This real-world analysis includes patients ≥ 18 years treated
ERADICATION OF HCV INFECTION with SOF/VEL without RBV for 12 weeks, as decided by the treating
Olga Tarasova1, Yannick Ngameni1, Elena Kukhareva1, Lahana HCP, from 10 sites across Brazil, Mexico, Singapore, Sweden, Spain,
Ravoori1, Nataliya Mazurchik1 , some Asian regions, and the United Arab Emirates, grouped into five
1
Peoples‘ Friendship University of Russia named after Patrice regions for analysis purposes: LATAM, Asian, Nordic, Southern-Europe
Lumumba and Middle East. Age, sex, whether treatment experienced (TE),
Background: It is noted that the basis of the metabolic syndrome and cirrhosis stage (F4, no decompensated), genotype, coinfections were
its manifestation is IR and/or DM. In 70% of patients with chronic HCV described, and time to treatment initiation (TTI) from HCV diagnosis,
infection, IR and/or DM can be observed. The effect of IR and/or DM and overall SVR at any time, were assessed.
on the outcome of interferon (IFN)-based therapy was studied and it Result: Overall, 6,633 patients were included, with Asian region
was found that in patients with HCV associated with IR and/or DM, the contributing more than half of cases, LATAM sites with 496 patients
addition of metformin at a dose of 20mg/kg/day as the third component (Table). Median age in the overall population was 55 years [IQR 46-
of antiviral therapy increases its effectiveness irrespective of BMI. 64]; highest in Asian sites (57 yo); lowest in the Middle Eastern site
PURPOSE: to study changes in carbohydrate metabolism during (31 yo). Patients over 50 yo represented two thirds (65%) of the overall
eradication of HCV infection. population, with the highest percentage in Asian and Southern-Europe
Method: The study included 60 patients with sustained virological sites (71%%) and lowest in the Middle Eastern site (28%). Cirrhosis
response (40 male and 20 femal), who were examined before and was reported in 20% [18%-24%] of the overall population, with the
after direct-acting antivirals (DAAs) therapy (12 weeks). The average highest rate in LATAM. Regarding HCV genotypes, overall GT 3 and 1
age is 44.30 (min 25; max 71)±9.1 years; among them 20 patients were the most prevalent (31% and 30%, respectively); GT 3 genotype
with HCV (control group), which make up 33.3% of total patients, 20 was particularly prevalent in Nordic (57%), GT1 - in Middle East (49%).
patients with HCV associated with insulin resistance (IR) in 33.3% and The TTI was available in 72% (n=4,772) of the sample, with 13% [4%-
20 patients with HCV associated with DM2 in terms of mild glycemia, 40%] treated in ≤30 days. Overall SVR was achieved in 99% [97.1%-
compensation and subcompensation phase in 33.3%. The genotype 100%] of the treated population.
was also determined – 25 patients with genotype 1 (41.7%), 12 Conclusion: Real-world efficacy of SOF/VEL is consistency high
patients with genotype 2 (20%) and genotype 3 in the amount of 23 across a diverse population of HCV patients. There is still a significant
(38.3%).All patients underwent measurement of the degree of fibrosis room for improvement in the time to treatment initiation for all the
and steatosis for instrumental diagnostics on the Fibroscan 502 touch regions. Further work should focus improve timely treatment initiation
before and after DAAs therapy. Liver stiffness was evaluated by to achieve the WHO goal of HCV elimination by 2030.
METAVIR scale modified for chronic HCV infection and fatty liver by Table and Figure:Figure 1.Table: Key demographics, Time to Treatment
CAP scale. initiation, and SVR rate of patients by region
Result: The level of liver fibrosis averaged 9.9 (4.2-25.1) ± 4.3
Kpa before to after therapy 8.1( 4.5-19.9)±3.2 kpa, the level of liver PP0293
steatosis averaged 259(143-400) ± 63.2 db/m before and after therapy
Research on Intervention Measures to Improve the Diagnosis and complementary methods.
Treatment Rates of Hepatitis C in Hospitals Result: A total of 14 extrahepatic cancer were included in this study and
Jian Li1, Lei Luo1, Wenlong Yang1 4 single nucleotide polymorphisms (SNPs) were used as instrumental
1
Department of Infectious Diseases, The Second Affiliated Hospital of variables (IVs) for HCV infection. The results of IVW method indicated
Nanchang University that genetic liabilities of HCV infection were strongly associated with
colorectal cancer (OR: 1.353, P = 4.05e-06) and lung cancer (OR:
Background: Hepatitis C is a silent liver disease, if not intervention, it is
1.341, P = 7.03e-04). Also, we found that the genetic liability of HCV
easy to progress to cirrhosis or liver cancer, seriously affecting public
infection was suggestively causally associated with gastric cancer
health safety. Because of the emergence of Direct-Acting Antiviral
(OR: 1.224, P = 0.017). However, HCV infection was not significantly
Agents, treatment becomes very easy, discovering the patients
associated with ovarian, cervical cancer, biliary cancer, pancreatic
become the core of diagnosis and treatment of hepatitis C.
cancer, ovarian cancer, esophageal cancer, pharyngeal and laryngeal
Method: In order to improve the diagnosis and treatment rate of
cancer, skin cancer, thyroid cancer, endometrial cancer, and breast
hepatitis C virus (HCV) in hospital, we have taken some measures.
cancer. And no pleiotropy was observed.
1: In 2021, we held a seminar and training session on the project of
Conclusion: HCV infection have causal effect on extrahepatic
the elimination of HCV, and established a real-time query platform for
cancers including colorectal and lung cancers. Enhanced screening
anti-HCV and HCV RNA. 2: From 2023, we started to follow up HCV
for extrahepatic cancers in chronically HCV-infected individuals for
RNA positive patients and recall untreated patients to reduce missed
early detection of cancer is recommended.
diagnosis and missed treatment. 3: Starting from 2024, through
Table and Figure:Figure 1.
monitoring the hepatitis C platform, we notify the doctor in charge or
the patient with positive antibody by telephone or short message in
time, and improve the RNA detection in time to further improve the PP0295
diagnosis rate. Analysis of the efficacy and safety of coblopasvir and sofosbuvir
Result: The HCV RNA detection rate in our hospital has been increasing treatment for Chinese patients with hepatitis C virus genotype 3
year by year from 2.76% in 2017 to 60.18% in 2022, and the treatment infection
rate has been increasing year by year from 48.78% in 2017 to 65.17% Li Liu1, Yan Su2, Jiabao Chang3, Jing Zhang4, Yali Liu4
in 2023. A total of 753 HCV RNA-positive patients from 2017-2023 were 1
Kunming Third People‘s Hospital, Third Department of Hepatology
contacted by telephone. According to telephone follow-up as well as , 2Xichang People‘s Hospital, Department of Gastroenterology, 3The
the hospital system, 459 patients (60.96%) had been treated. A total Second Hospital of Nanjing, Second Department of Hepatology,
of 87 patients (11.55%) qualified for the recall, 48 patients (55.17%) 4
Beijing You‘an Hospital, Capital Medical University, Third Department
were successfully recalled to begin oral direct antiviral therapy as of of Hepatology
October 31, 2024, and a total of 47 patients (97.92%) have achieved
Background: Real-world studies on pan-genotypic direct-acting
sustained virological response. After the recall, the total treatment rate
antivirals (DAAs) for chronic hepatitis C with different genotypes are
of our hospital increased from 60.96% (459/753) to 67.33% (507/753).
limited in China. Coblopasvir (CLP), a highly selective pan-genotypic
At the same time, it is also concluded that the earlier HCV RNA positive
NS5A inhibitor, is often used in combination with sofosbuvir (SOF) in
patients are informed for further treatment, the easier it is for them to
routine clinical practice in China. This study evaluates the efficacy and
receive treatment. The total HCV RNA detection rate from January to
safety of coblopasvir plus SOF regimen for treating chronic hepatitis C
October 2024 has increased to 53.52%, and the treatment rate has
virus (HCV) genotype 3 infection in China.
reached 75.78%.
Method: This prospective, multi-center study included patients
By analyzing the diagnostic and treatment rates of HCV RNA in
with genotype 3 chronic HCV infection treated with coblopasvir
infectious and non infectious diseases department, it was found that
(CLP) combined with SOF from February 2022 to January 2024 at
the HCV RNA detection rate in infectious diseases department has
four hospitals in China. Clinical data, including HCV RNA and liver
been increasing year by year from 40.91% in 2017 to 97.56% in 2024,
biochemical indices, were collected at baseline, after 12 weeks of
and the treatment rate has been increasing year by year from 66.67%
treatment, and 12 weeks post-treatment. The primary outcome was
in 2017 to 86.79% in 2024. Besides, the HCV RNA detection rate in
sustained virologic response at 12 weeks post-treatment (SVR12).
non infectious diseases department also has been increasing year by
Liver stiffness measurement (LSM), estimated glomerular filtration rate
year from 1.09% in 2017 to 45.12% in 2024, and the treatment rate has
(eGFR), and adverse events were also assessed. Significant fibrosis
been increasing year by year from 23.53% in 2017 to 68.00% in 2024.
was defined as LSM ≥9.3 kPa or FIB-4 ≥3.25.
Conclusion: In-hospital hepatitis C elimination programs do
Result: A total of 62 patients were analyzed, including 29 with SVR12
significantly improve diagnosis and treatment rates for hepatitis C,
data (75.9% male). The median age was 49 years (P25–P75: 45–53),
especially in non-infected departments.
and 17.2% had a history of injection drug use. The baseline median
Table and Figure:Figure 1.
RNA was 1.10 × 106 IU/mL (P25–P75: 3.57 × 105 – 3.26 × 106 IU/mL).
Figure 2.
Genotype distribution was 31.0% for 3a and 69.0% for 3b. Significant
fibrosis was present in 37.9% of patients at baseline.
PP0294 At 12 weeks of treatment and 12 weeks post-treatment, HCV RNA
Mendelian randomization analysis reveals Hepatitis C infection is was undetectable in all 21 and 29 patients, respectively, achieving an
causally associated with extrahepatic cancer SVR12 rate of 100%. ALT and AST levels significantly decreased from
Xiaoqing Liu1, Yunling Xue1, Peng Hu2 baseline (47.0 U/L for ALT and 55.0 U/L for AST) to 18.0 U/L (p <0.05)
1
Department of Infectious Diseases, The Second Affiliated Hospital of and 26.0 U/L (p <0.05) at 12 weeks of treatment. These changes were
Chongqing Medical University, 2Department of Infectious Diseases, maintained at 12 weeks post-treatment, with median ALT at 20.0 U/L
The First Affiliated Hospital of Chongqing Medical University and AST at 25.0 U/L. Serum albumin (ALB) levels remained stable
during treatment (39.8 g/L) but increased post-treatment to 43.1 g/L (p
Background: Hepatitis C virus (HCV) infection is prevalent worldwide.
<0.05). GGT levels decreased significantly from 80.0 U/L at baseline to
Observational studies have shown that HCV infection is associated
33.4 U/L at 12 weeks of treatment (p <0.05) and 29.0 U/L at 12 weeks
with extrahepatic cancer. However, the results are inconsistent and
post-treatment. Liver stiffness measurements decreased from 7.1 kPa
causality remains to be established.
to 6.9 kPa (p <0.05). Median eGFR levels were 109.5 at baseline and
Method: A two-sample Mendelian randomization (MR) was conducted
121.9 mL/min/1.73m² post-treatment (p >0.05). No adverse events
to explore whether HCV infection is causally associated with
related to treatment were reported.
extrahepatic cancers. Based on the summary-level genome-wide
Conclusion: The combination of coblopasvir and sofosbuvir achieved
association studies (GWAS) data from a publicly available database,
a high SVR12 rate and favorable biochemical response in Chinese
the variance weighted inverse (IVW) was applied as the primary
patients with genotype 3 chronic hepatitis C. These findings suggest
method to estimate causality, and other estimators were used as
that the coblopasvir plus sofosbuvir regimen is both effective and well-
tolerated in this population. populations and often underrecognized in clinical practice. Data on
Table and Figure:Figure 1.Figure 1 Changes in biochemical markers, the effectiveness and safety of direct-acting antiviral agents, such as
liver stiffness measurements, and glomerular filtration rate before and sofosbuvir-velpatasvir (SOF-VEL), in treating acute hepatitis C (AHC) in
after treatment with coblopasvir plus sofosbuvir in patients with chronic children are limited. This report aims to present the effectiveness and
HCV genotype 3 infection in China safety profiles of SOF-VEL in two children diagnosed with AHC.
Method: Two 4-year-old children (Nos. 1 and 2) acquired HCV
infection through unsafe injections and were diagnosed with AHC. Both
PP0296
children were infected with genotype 1b HCV and displayed no clinical
Real-World Observational Study on Acute Hepatitis C symptoms and signs. Liver biopsies were performed prior to initiating
Yanqin Ai1, Qinglei Zeng2 an 8-week regimen of half-dose SOF-VEL (200/50mg [1/2 tablet, tablet
1
Xuchang Central Hospital, 2The First Affiliated Hospital of Zhengzhou splitting], a total of one bottle of SOF/VEL [Epclusa®️] for each child)
University once daily. The HCV RNA levels, liver function, complete blood counts,
Background: This study explores the early detection, treatment and renal function, lipid profiles, and other relevant parameters were
management strategies for AHC, aiming to address the challenges in monitored through week 12 post-treatment. The primary endpoint was
its timely identification and effective care. sustained virologic response at 12 weeks (SVR12) post-treatment, and
Method: Infectious Disease Department of our hospital identified the secondary endpoint was the safety profiles.
several cases of HCV RNA-positive patients with significantly elevated Result: Child No. 1 had an HCV RNA level of 1500 IU/mL and an
ALT from the same geographical location. Further screening was soon ALT level of 316 U/L, and the liver biopsy indicated mild hepatitis and
conducted in this region. A total of 630 individuals were screened, 72 moderate fibrosis (G1S2, Figure 1). Child No. 2 had an HCV RNA
patients diagnosed with hepatitis C. A thorough clinical assessment level of 2300 IU/mL and an ALT level of 15 U/L, and the liver biopsy
was conducted, Antiviral therapy (DAAs) were initiated. For untreated indicated moderate hepatitis and mild fibrosis (G2S1, Figure 2). After
patients, a multidisciplinary care team was established to provide 1 week of treatment, Child No. 1’s HCV RNA level decreased to 49.2
follow up and education. After 3 months, these untreated patients were IU/mL, with ALT normalization; and Child No. 2 had undetectable HCV
recalled for reassessment (Figure 1). RNA and ALT normalization. By week 2, Child No. 1 had undetectable
Result: A total of 630 individuals were screened, resulting in 72 HCV RNA. Finally, both children achieved SVR12, and no specific
confirmed cases of hepatitis C, including 11 families with familial adverse events were observed during treatment or follow-up period;
clustering of infections, 58 (80.6%) patients reported history of Injection additionally, blood counts, renal function, lipid profiles, and electrolyte
or dental treatment within the last 6 months. Among the 72 patients, levels maintained normal.
38 (52.8%) were male. The mean age was 57 (range: 5-89) years , Conclusion: Even in young children with AHC, liver damage can be
with 4 (5.6%) patients aged 5-12 years, 4(5.6%) patients aged 12-18 severe, and an 8-week regimen of half-dose SOF/VEL demonstrated
years. Of the 72 patients tested for HCV antibodies, 71 were positive. a rapid virological response and recovery of liver function, with a
The mean HCV RNA was 5.60 ± 1.64 Log IU/mL. 64 (88.9%) cases favorable safety profiles. Further large-scale studies are needed to
were infected with HCV genotype 1b, followed by 2a (2 cases), and 6 validate these findings.
cases without HCV genotype evaluation. Among the 37 patients with Table and Figure:Figure 1.Figure 1. Microscopic pathology revealed
ALT results, 31 (83.8%) had elevated ALT levels( 41 -1779 U/L), with significant infiltration of inflammatory cells, predominantly lymphocytes,
21.6% having ALT >10 ULN. Only 8 (11.1%) patients presented with in the portal areas (Hematoxylin-eosin staining, 200× magnification).
significant clinical symptoms, including nausea, fatigue, jaundice etc. Portal fibrosis was pronounced, with fibrous tissue extending into the
(Table 1). Among the 72 patients, 47 initiated DAAs within one month, surrounding regions. Fibrous septa were observed between hepatic
with 37 cases of 12-week regimen, 8 cases of 8-week regimen, and 2 lobules, although no bridging fibrosis was present (Masson staining,
cases of 4-week regimen. DAA regimens included SOF/VEL (n=24), 80× magnification).
LDV/SOF (n=2), EMV/SOF (n=20), and CLP/SOF (n=1). After follow- Figure 2.Figure 2. Microscopic pathology revealed more significant
up, 9 patients achieved SVR12, 21 achieved SVR4, and the remaining infiltration of inflammatory cells, predominantly lymphocytes, in the
17 are still being monitored. For the 25 untreated patients, reasons portal areas (Hematoxylin-eosin staining, 200× magnification). The
for non-treatment included financial constraints, advanced age with distribution of fibrous tissue was relatively limited, primarily confined
impaired mobility etc. A standardized recall and follow-up program to the portal areas, with no significant fibrous septa extending into the
“HepC No One Left Behind” was subsequently initiated via SMS and hepatic lobules (Masson’s trichrome staining, 80× magnification).
phone calls. The follow-up process was strictly structured, educating
patients about hepatitis C and the potential benefits of DAA. Three PP0298
months later, 7 patients were successfully recalled, with 2 achieving
Incidence of hepatic decompensation after viral hepatitis C (VHC)
undetectable HCV RNA, 4 patients maintaining stable or slightly
eradication using direct-acting antiviral treatmentsDAAs
elevated HCV RNA levels, and 1 patient showing a decrease in HCV
RNA levels from 5.26 to 3.41 Log IU/mL, The remaining patients are Hajar Elibrahimi1, Maryeme Kadiri2, Fatimazahra Chabib3, Nawal
undergoing continued follow-up. Lagdali3, Mohamed Borahma3, Fatimaezzahrae Ajana3
Conclusion: This study offers key clinical evidence on the early
1
ibn sina university hospital, department C , 2ibn sina university
identification, prompt treatment, and management of AHC. Antiviral hospital , hepatology unit, department c, 3ibn sina university hospital ,
therapy could be considered to prevent progression to chronic department c
infection. Background: Direct-acting antiviral treatments (DAAs) have
Table and Figure:Figure 1.FIGURE 1 The Enrollment of Study Patients revolutionized the management of hepatitis C, with cure rates
and Data Analyses reaching over 95%. They significantly reduce viral load and liver
Figure 2.Table 1 Baseline demographics and characteristics inflammation, improving long-term outcomes. However, patients with
advanced cirrhosis, even after virological cure, may still progress to
decompensation due to irreversible pre-treatment liver damage.
PP0297
The aim of our study is to explore the prevalence of decompensation
Effectiveness and Safety of Sofosbuvir-Velpatasvir in Children in treated hepatitis C patients and the factors influencing this
with Acute Hepatitis C: A Case Series Study complication.
Ruyue Chen1, Xueyan Lv1, Yuehang Wang1, Zhuangzhuang Zhai1, Method: This is a retrospective, preliminary, descriptive study of
Xuejing Yu1, Yajie Pan1, Qinglei Zeng1 patients with treated viral hepatitis C, covering a 4-year period (2021-
1
Department of Infectious Diseases, The First Affiliated Hospital of 2024). Patients lost to follow-up were excluded.
Zhengzhou University, China Result: Our study included 81 patients with viral hepatitis C treated
Background: Acute hepatitis C virus (HCV) infection is rare in pediatric with direct-acting antivirals (DAAs) achieving a sustained virologic
response (SVR). The prevalence of decompensation was 22.22%
(n=18). the HCV screening rate in prefectural medical centers has significantly
The mean age was 61.5 years (range 24–82), with a female increased from 53.95%(50745/94076) in 2023 to 88.68%(49379/55565)
predominance, and a male-to-female sex ratio of 0.38. in 2024, the anti-HCV positive rate was 1.52%(733/50745) in 2023
The circumstances of diagnosis varied: it was incidental in 33.3% of and 0.49%(244/49379) in 2024, the HCV RNA testing rate has also
cases (n=6), followed by jaundice in 27.7% (n=5), hepatic colic in increased from 31.43%(243/733) to 68.01%(574/842), and the referral
22.2% (n=4), and asthenia in 16.6% (n=3). rate of patients with HCV has also achieved a simultaneous increase
Half of the patients (50%) had associated comorbidities, including from 34.98%(85/243) to 68.11%(391/574).
hypertension in 88.8% of cases (n=8) and diabetes in 22.2% (n=2). Conclusion: It is a proven and worthwhile model to expand the
Regarding co-infections, 22.2% of patients (n=4) had chronic HBV screening, diagnosis, and referral rate of hepatitis C patients in rural
infection. areas of Qinghai through four-level collaboration, closed management
Genotype 2 was identified in 38.3% of cases (n=7), followed by and joint grassroots education aiming on improving the knowledge of
genotype 1 in 27.7% (n=5). However, the genotype was not determined the medical staff about hepatitis C and the healthcare policies.
in 33.3% of cases (n=6).
Portal hypertension (PH) was present in 88.8% of patients (n=16).
PP0300
The degree of fibrosis varied among patients: 25% (n=6) were
classified as F1, 22.2% (n=4) as F2, 15.7% (n=3) as F3, and 72.2% Hepatitis C virus elimination in methadone maintenance treatment
(n=13) as F4. patients in Beijing
Decompensation presented as ascites in 44.4% of cases (n=8), Yijin Zhang1,2, Nan Liu1,2, Yaping Liu1,2, Ping Gao1,2, Hongjie Li1,2, Lili
hemorrhage in 27.7% (n=5), and neurological symptoms in 16.6% Gao1,2, Xuesong Gao1,2, Xuefei Duan1,2
(n=3). Additionally, hepatocellular carcinoma (HCC) was observed in 1
International Medical Department, Beijing Ditan Hospital, Capital
27.7% of cases (n=5). Medical University, 2National Center for Infectious Diseases (Beijing)
Conclusion: Although modern antiviral treatments have Background: One of the obstacles to elimination of chronic hepatitis C
successfully eliminated the hepatitis C virus in most patients, hepatic virus (HCV) infection (CHC) is identification CHC of high-risk groups in
decompensation remains a concerning complication, especially in Beijing. Methadone maintenance treatment (MMT) patients are at the
those with advanced cirrhosis. highest risk, mostly due to previous needle sharing.
In our study, the prevalence of decompensation was 22.22%. Portal Method: It was a prospective study. MMT clinics were visited. MMT
hypertension (PH) was present in 88.8% of patients, 22% had patients with CHC were screened on site for HCV RNA. Patients with
associated co-infections, and 72.2% were cirrhotic. positive HCV RNA were referred our outpatient clinic. The sustained
Hepatocellular carcinoma (HCC) was observed in 27.7% of cases virologic response (SVR) was tested at 12 weeks post-treatment.
(n=5). Result: In this study, 8 MMT clinics visits were conducted and 78 MMT
Prevention, early detection, and effective management of comorbidities patients were screened which identified 38 subjects with HCV RNA
are crucial in reducing the prevalence of decompensation. positive. Nineteen patients received HCV treatment during the study
period, including 13 males and 6 females. Out of the 19 patients, 42.1%
PP0299 (8 patients) were identified with genotype 1b, 5.3% patients (1 patient)
had genotype 3a, 36.8% had genotype 3b (7 patients) and 15.8% had
Four systems of closed-loop management combined with
genotype 6a (3 patients). Four of the patients had cirrhosis, 2 of whom
grassroots education to enhance screening and linkage to care of
were decompensated. Twelve patients (63.2%) had undetectable HCV
hepatitis C patients in Qinghai, China.
RNA levels at the end of treatment. Seven patients (36.8%) achieved
Guoying Yu1, Jie Ma1 sustained virological response (SVR) at 12 weeks post-treatment. Five
1
The fourth people’s hospital of Qinghai province. patients (26.3%) achieved SVR 24. The remaining patients were lost
Background: To expand the screening and linkage to care of hepatitis to follow-up.
C patients in Qinghai rural areas and carry out regional hepatitis C Conclusion: Direct-acting antiviral therapy is effective among MMT
elimination, we established a closed-loop management system with patients. Integrating HCV treatment into MMT programs is a strategy to
the provincial CDC as the dominant, infectious disease specialist treat HCV in a very high risk population. However, treatment adherence
hospital, and the prefectural CDC and healthcare centers as the remains suboptimal.
implementation units, to explore the Hepatitis C elimination model in Table and Figure:Figure 1.Table 1 Demographics of patients who
rural areas in Qinghai. received treatment for HCV
Method: Four-system closed-loop management was established Figure 2.Figure1 A:number of patients at each step; B:result of DAA
including Level 1 Provincial Hepatitis C Control Office; Level 2 Provincial ttreatment
Infectious Disease Specialist Hospital; Level 3 Prefectural Hepatitis C
Control Office; and Level 4 Prefectural Hepatitis C Healthcare Centers, PP0301
to improve the diagnosis and linkage to care of HCV patients through
the decentralized, multi-party collaboration model. 43 prefectural HCV Screening and Treatment Cascade in a tertiary hospital of
healthcare centers were identified based on all HCV-positive patients North China
in the provincial CDC system from 2014 to 2024, all were in HCV high Pang Chunmiao1, Zhang Guomin1
prevalence areas (HPAs), such as Haidong city and six prefectures 1
The Affiliated Hospital of Chengde Medical College
of Qinghai (Huangnan, Hainan, Haibei, Haixi, Yushu, and Luopu) etc. Background: The World Health Organization (WHO) put forward an
Universal screening of HCV in these HPAs were conducted. Rapid initiative, which aims to eliminate HCV infection as a major public
Diagnostic Test (RDT) and HCV RNA reflex testing were performed. health threat by 2030. At present, the diagnosis and treatment rates
All confirmed patients with HCV infection were referred to designated of HCV infections are generally lower than the goal in various regions
provincial specialist hospital for further treatment. Two educational across the country. The purpose of this study was to conduct statistics
seminars were provided to prefectural CDCs and healthcare centers on HCV screening and treatment in general hospitals in Chengde,
by provincial CDC and designated hospitals. Hebei, a high-prevalence area of hepatitis C, and analyze the cascade
Result: From January 2023 to October 2024, we organized 50 HCV relationship among different groups of people and to compare the
educational campaigns, covered with a total of 1,224 medical staffs, screening situation of different departments.
and collected 1,108 questionnaires successfully. The survey results Method: A total of 82,926 patients who underwent hepatitis C antibody
showed that the medical staffs had a high level of awareness of Hepatitis screening during hospitalized for surgical treatment in Affiliated
C, as shown in the following: the knowledge rate of the transmission Hospital of Chengde Medical University from 2021 to 2023 were
routes of HCV reached 96.50%, the knowledge rate of the dangers included in this study. Their age, gender, distribution of departments,
of HCV disease was 97.20%, and the knowledge rate of the medical hepatitis C antibody testing, HCV RNA testing, and treatment situation
insurance policy for HCV was 89.53%. In addition, after the education,
were analyzed. Chi-square test was used for statistical analysis. drug use (χ²=22.32, P<0.001). No significant differences in pregnancy
Result: The overall positive rate of hepatitis C antibody was 1.91%. outcomes were observed between genotype 1b and non-1b groups.
Among the 1,581 patients with positive hepatitis C antibody, the number However, all cases of adverse neonatal outcomes occurred in mothers
of those who further underwent HCV RNA testing was 610 (38.58%), with genotype 1b.
and among them, the number of those with HCV RNA replication was Conclusion: In Nanjing, genotype 1b is the dominant HCV genotype
253 (41.48%). The number of patients who received treatment was among pregnant women, with genotype 3b accounting for a smaller
112 (44.47%). Stratified analysis of patients with positive hepatitis C proportion (5%). While maternal and infant outcomes did not vary
antibody revealed that the proportion of male patients was significantly significantly across genotypes, adverse neonatal outcomes were
higher than that of female patients (2.32% vs 1.5%, p < 0.01), and exclusively associated with genotype 1b. These findings underscore the
the proportion in the 50 - 69 age group was significantly higher than importance of prioritizing health education, pregnancy management,
that in other groups. With the increase of age, the positive rate of HCV and the incorporation of DAAs during preconception and postpartum
antibody was increased, and the proportion of HCV antibody in 40-69 care to mitigate risks associated with HCV infection.
people was significantly higher than that in other groups. The positive
rate of hepatitis C antibody decreased gradually in the higher age
PP0303
group. Among different departments, the department with the highest
positive rate of hepatitis C antibody was hepatobiliary surgery (7.51%), “Test and Treat” Simplified Strategy for in-Hospital HCV Micro-
and the department with the lowest rate was pediatric surgery (0) Elimination in Zigong City, Sichuan, China
and obstetrics (0.22%). The HCV RNA testing rate was the highest Chunfang You1, Yangyang Pu2, Jing Tang1, Wei Deng1, Chunqi
in cardiothoracic surgery(70.00%), and the lowest 8.39% in ENT, Zheng1, Xuerong Wang1, Dan Song1, Jie Wang1, Yuting Diao1, Juan
Ophthalmology and stomatology. It was only 48.97% in hepatobiliary Tang1
surgery although the HCV antibody positive rate was the highest. 1
Department of Infectious Diseases, Zigong First People’s Hospital,
Conclusion: Even though doctors had received training on hepatitis Zigong, Sichuan Province, China, 2Department of Disease Prevention
C-related knowledge, a large proportion of patients with positive and Control, Zigong First People’s Hospital, Zigong, Sichuan
hepatitis C antibody still failed to complete the next steps of testing Province, China
and treatment. Hepatitis C screening is more likely to yield positive Background: Sichuan Province is a region with a high prevalence of
results among male patients and those over 40 years old; the hepatitis hepatitis C virus (HCV) infection, characterized by complex genotypes,
C-related knowledge of doctors in all the hospital especially ENT, including a notably higher proportion of genotype 3 (GT3) cases in
Ophthalmology and stomatology needs to be further strengthened. some areas. Current national guidelines recommend HCV genotype
Table and Figure:Figure 1.elimination of HCV cascade testing in such regions. However, prolonged diagnostic procedures—
Figure 2.Anti-HCV (+)rates and percentages in different departments including HCV antibody screening, HCV RNA testing, and genotype
analysis—result in significant delays in treatment initiation, leading
PP0302 to high rates of patient loss to follow-up. To address this challenge,
we implemented a simplified “Test and Treat (TNT)” strategy aimed at
Hepatitis C Genotype Distribution in Pregnant Women and Its
facilitating in-hospital HCV micro-elimination.
Impact on Pregnancy Outcomes
Method: The “TNT” strategy was implemented for all inpatients and
Yue Xin1, Cai Min2 outpatients. During the “Test” step, HCV antibody screening was
1
Department of Obstetrics and Gynecology, The Second Hospital of conducted. Patients with anti-HCV(+) would receive an automated
Nanjing, 2Office of Drug Clinical Trial Agency, The Second Hospital of notification in their hospital information system (HIS), prompting
Nanjing immediate HCV RNA testing. For “Treat” step, patients would initiate
Background: The World Health Organization has set an ambitious reimbursed Sofosbuvir/Velpatasvir (SOF/VEL) treatment on the same
goal to eliminate viral hepatitis as a public health threat by 2030. In day when receiving HCV RNA positive results.
line with this, China has continuously refined its hepatitis C virus (HCV) For patients with compensated cirrhosis or populations at higher
screening and management strategies. Women of reproductive age risk for GT3b infection (e.g history of people who injected drugs and
represent a critical population for intervention, as timely diagnosis people with HIV infection), they would not only initiate reimbursed SOF/
and treatment can prevent adverse outcomes in mothers, offspring, VEL treatment when getting HCV RNA (+) result, but also receive HCV
and surrounding populations. Although the anti-HCV positivity rate genotype testing on the same day. If GT3b infection was confirmed
among pregnant women in China ranges from 0.08% to 0.50%, the (results typically available in median seven days), ribavirin (RBV) was
HCV RNA positivity rate reaches 81.93%. However, the distribution added to the SOF/VEL treatment. This integrated approach aimed to
of HCV genotypes and their association with pregnancy outcomes streamline the diagnostic and therapeutic process (Fig. 1).
remain poorly understood. This study analyzed HCV genotypes in Result: Between January and December 2023, 81,021 patients
pregnant women with chronic HCV infection admitted to our institution underwent HCV screening, identifying 1,169 anti-HCV positive cases.
between 2018 and 2023, exploring genotype distributions, infection Among these, 94% (1,096/1,169) completed HCV RNA testing, with
routes, and pregnancy outcomes. The findings aim to inform optimized 431 patients were HCV viremic. 82% (352/431) initiated SOF/VEL ±
management protocols and guide the use of direct-acting antivirals RBV treatment. Sustained virological response at 12 weeks post-
(DAAs) during pregnancy and postpartum. treatment (SVR12) was achieved in 99.7% (351/352) (Fig. 2a).
Method: This retrospective study included 113 pregnant women with The median time from the first visit (HCV RNA testing) to treatment
chronic HCV infection genotyped at the Second Hospital of Nanjing initiation was significantly reduced from 12.5 days to 3.8 days (Fig.
from January 2018 to December 2023. Epidemiological survey 2b). Prior to implementing the TNT strategy, only 49.8% (147/295) of
methods were employed to assess genotype distribution, infection patients underwent HCV RNA testing, and 74 were confirmed as HCV
routes, and pregnancy outcomes. RNA positive. Of these, 55.4% (41/74) initiated treatment, achieving a
Result: Six HCV genotypes (1b, 2a, 3a, 3b, 6a, and 6n) were SVR12 rate of 97.6% (40/41) (Fig. 2a).
identified, with genotype 1b being predominant (76.1%), followed by Conclusion: The in-hospital TNT strategy substantially improved
genotypes 6 and 3. The prevalence of genotype 1b increased in more linkage-to-care rates and reduced the time from diagnosis to treatment
recent birth cohorts (χ²=24.35, P<0.001). Significant associations were initiation for HCV-infected patients. This streamlined approach also
observed between genotype distribution and educational attainment demonstrated excellent virological outcomes with a high SVR12 rate
(χ²=14.74, P<0.001) as well as employment status (χ²=19.50, while mitigating loss to follow-up. The TNT strategy holds promise
P<0.001), with non-1b genotypes being more prevalent among for broader implementation in regions with high HCV prevalence and
women with lower education levels or unemployment. Genotype 1b complex genotypic distributions, offering a practical framework for
was associated with infection via blood transfusion or hospitalization advancing HCV elimination efforts.
during infancy (χ²=5.17, P=0.023; χ²=5.57, P=0.018), whereas non- Table and Figure:Figure 1.Fig. 1 TNT plan for in-hospital HCV
1b genotypes were more common among women with a history of elimination. GT3, genotype 3; HCC, hepatocellular carcinoma; HCV,
hepatitis C virus; RBV, ribavirin; RNA, ribonucleic acid; SOF/VEL, Zheng1, Xuerong Wang1, Dan Song1, Jie Wang1, Yuting Diao1, Juan
Sofosbuvir/Velpatasvir; TNT, test and treat. Tang1
Figure 2.Fig. 2 Outcome of TNT simplified model (a) and median time 1
Department of Infectious Diseases, Zigong First People’s Hospital,
from the first visit to treatment initiation (b) (2022 vs. 2023). * Prior to Zigong, Sichuan Province, China, 2Department of Disease Prevention
establishment of the in-hospital TNT plan; ** Number screened not and Control, Zigong First People’s Hospital, Zigong, Sichuan
reported; Ab, antibody; HCV, hepatitis C virus; RNA, ribonucleic acid; Province, China
SOF/VEL, Sofosbuvir/Velpatasvir; TNT, test and treat. Background: World Health Organization (WHO) set the goal of
eliminating viral hepatitis as a major public health threat by 2030.
PP0304 The current challenge in eliminating hepatitis C visur (HCV) lies in
identifying patients and linking them to care. In Zigong, a tier 3 city
HCV Self-Testing (HCVST): A Feasible and Acceptable Approach
in Southwest of China, large population of diagnosed but untreated
for Hepatitis C Screening in the Urban Slum Population of
(DBU) patients and increased new reports urged us to establish
Northern India
efficient management models. So, we explored a call-back program
Ajeet Singh Bhadoria1, Amrita Mehndiratta2, Kathirvel Selv3, Rajesh
targeting HCV elimination in our city.
Somvanshi4, Muhammad Shahid Jamil5, Niklas Luhmann5
Method: The Zigong First People’s Hospital initiated the collaborative
1
ALL INDIA INSTITUTE OF MEDICAL SCIENCES RISHIKESH, 2AIIMS HCV micro-elimination model (call-back program). For all the individuals
Rishikesh, 3PGIMER Chandigarh, 4NHM Uttarakhand, 5WHO HQs with anti-HCV positive results but untreated, the local township health
Background: Globally, only 36% of people with hepatitis C are aware center called them back. Free HCV RNA testing and HCV education
of their infection, highlighting a significant diagnosis gap. Furthermore, were provided. HCV viremic patients could be linked to the infectious
access to treatment remains limited, with just 20% of those diagnosed specialists once confirmed. With pre-treatment assessment, patients
receiving necessary treatment. Hepatitis C virus (HCV) infection could receive reimbursed sofosbuvir/velpatasvir (SOF/VEL) within 1
disproportionately affects people living in urban slums, many of whom day.
remain undiagnosed. World Health Organization (WHO) recommends Result: From January to April 2023, a total of 23% (500/2,200) patients
HCV self-testing (HCVST) as an additional strategy to increase access with positive anti-HCV were re-linked to care and received HCV RNA
to HCV diagnosis. We conducted a study in Northern India to evaluate testing. Thirty-eight percent (189/500) of the patients were HCV RNA
the usability and acceptability of blood-based HCVST among residents positive. Twenty-one percent (40/189) of the patients initiated SOF/VEL
of urban slums. treatment (Fig. 1). However, there were still a large number of DBU
Method: Among 465 residents of urban slums, mostly aged 26-35 patients who have not come back for HCV RNA testing. We conducted
years with primary education, performed self-tests under observation. a questionnaire survey to analyze the reasons. The main reasons
Usability was high, with over 90% correctly performing critical steps for rejecting treatment were the absence of clinical symptoms and
like finger pricking and 96% accurately interpreting results. However, financial reasons (Fig. 2). The awareness rate of knowledge on the
higher education levels >8th class (96.7%vs87.5%; p<0.001) prevention and treatment of hepatitis C was only 39%. The average
and younger age <30years (93.6%Vs98.1%, p<0.05) have better cost of curing hepatitis C was ¥ 4,500 in our city. However, half of the
interpretation accuracy. Most participants found test easy to use and participants accepted less than ¥ 2,000 to treat hepatitis C, and 32%
trusted its accuracy, valuing the privacy and autonomy it offered. of the patients could accept more than ¥ 4,000.
Concerns arose regarding lack of counseling for positive results outside Conclusion: We have established a city-wide collaborative HCV
healthcare settings. Self-test demonstrated high accuracy, with 96.9% micro-elimination model for recalling and managing anti-HCV positive
(kappa: 0.93) inter-reader concordance and 98.7% (kappa:0.96) inter- patients. The rate of link-to-treatment was significantly improved
operator concordance. Sensitivity and specificity were 97.4% and after the cooperation model was established. And we investigated
99.6%, respectively. the reasons for loss of follow-up and poor compliance. Given these
Result: Among 465 residents of urban slums, mostly aged 26-35 reasons, we plan to reimburse testing fees for the patients, launch
years with primary education, performed self-tests under observation. educational campaigns, and scale up treatment to facilitate early
Usability was high, with over 90% correctly performing critical steps detection and improve linkage to care.
like finger pricking and 96% accurately interpreting results. However, Table and Figure:Figure 1.Fig. 1 Outcome of call-back program in
higher education levels over 8th Class (96.7% vs 87.5%; p<0.001) Zigong City, China (Jan-Apr 2023). * Number screened not reported;
and younger age <30years (93.6% Vs 98.1%, p<0.05) have better Ab, antibody; HCV, hepatitis C virus; RNA, ribonucleic acid; SOF/VEL,
interpretation accuracy. Most participants found the test easy to use sofosbuvir/velpatasvir.
and trusted its accuracy, valuing the privacy and autonomy it offered. Figure 2.Fig. 2 Analysis of reasons for rejecting treatment in 189
Concerns arose regarding the lack of counseling for positive results recalled DBU patients. SOF/VEL, sofosbuvir/velpatasvir.
outside healthcare settings. The self-test demonstrated high accuracy,
with 96.9% (kappa: 0.93) inter-reader concordance and 98.7%
PP0306
(kappa: 0.96) inter-operator concordance. Sensitivity and specificity
were 97.4% and 99.6%, respectively. High rates of active hepatitis C (HCV) infection and rapid treatment
Conclusion: HCVST proved highly usable and acceptable among initiation: results from Thailand’s first key population-led HCV test
residents of urban slums. Most participants successfully performed and treat intervention
test and interpreted results, though challenges arose with blood Artit Wongsa1, Rena Janamnuaysook1, Kanokwan Sinchai1, Atachai
collection and understanding instructions. While appreciating privacy Phunkron2, Supakarn Sangtong3, Jakkrapatara Boonruang1, Supanat
and convenience, participants highlighted need for counseling support Thitipatarakorn1, Sirin Tangcharoensathien1, Saman Sumalu2, Surang
for positive results and greater awareness regarding locally available Janyam2, Pongpeera Patpeerapong3, Nittaya Phanuphak1, Reshmie A
treatment options. Integrating self-testing with existing healthcare Ramautarsing1
services could improve HCV diagnosis access across India. 1
Institute of HIV research and Innovation, 2Service Worker in Group
Table and Figure:Figure 1.Usability and required assistance for Foundation, 3MPLUS Foundation
hepatitis C self testing Background: Key population (KP)-led health services in Thailand have
Figure 2.Participants performing Hepatitis C self testing at Facility and effectively enhanced access to HIV and health services for gender-
at home diverse populations. To address high hepatitis C (HCV) prevalence and
low treatment initiation among KPs, a one-stop HCV service delivered
PP0305 by KP-lay providers was piloted in two community-based organizations
(CBOs) in Thailand. Here we report baseline client characteristics from
Collaborative HCV micro-elimination model in Zigong city,
the first 9 months of implementation.
Sichuan, China: a call-back program
Method: Thai clients aged >18 with positive anti-HCV who provided
Chunfang You1, Yangyang Pu2, Wei Deng1, Jing Tang1, Chunqi
consent were enrolled and received onsite, same-day HCV-RNA 119 (95.2%, 119/125) individuals undergoing RNA testing, of whom
testing, specimen collection for pre-treatment laboratory testing 84.3% (86/102) tested RNA-positive. The referral rate for RNA-positive
(e.g. sexually transmitted infections (STIs) and non-invasive markers individuals was 44.2% (38/86), and 89.5% (34/38) of those referred
to identify advanced liver disease), and physical examination, all initiated DAA treatment. Multivariable analysis showed low referral rates
conducted by trained KP-lay providers. Those with active HCV were significantly associated with poor disease awareness (86.8% vs.
infection received telehealth consultations with physicians from 43.8%, p < 0.001) and financial constraints (81.6% vs. 60.4%, p =
affiliated sites, and clients eligible for simplified treatment (absence of 0.034). This approach increased the EDUs’ HCV diagnosis rate from
cirrhosis, hepatitis B co-infection, or other medical concerns) received 46.4% to 95.2% and the overall treatment rate from 22.4% to 50.4%.
12 weeks of once-daily fixed dose combination of sofosbuvir (400mg) Conclusion: This study is the first to report on an HCV elimination
and velpatasvir (100mg). Follow-up visits will be conducted at weeks model targeting EDUs in CDRCs in mainland China. The HCV infection
12 and 24. Descriptive analyses were conducted to describe baseline rate among EDUs is significantly higher than in the general population.
characteristics. The four-party linkage model significantly improved HCV screening,
Result: Between January-September 2024, 167/9,412 (1.8%) clients referral, and treatment rates. However, economic barriers and low
had a positive anti-HCV test; 137/167 (82%) were eligible and enrolled. disease awareness remain key challenges to referral. Future efforts will
Median age (interquartile range, IQR) was 29 (25-36) years; 123/137 focus on refining the screening and referral model to address these
(89.8%) were men who have sex with men and 7/137 (5.1%) were challenges and meet the WHO’s HCV elimination targets.
transgender women. 88/137 (64.2%) were HIV-negative, with 73/88 Table and Figure:Figure 1.Four-party linkage model for EDUs
(83.0%) on PrEP, 49/137 (35.8%) were living with HIV, and 18/137 Figure 2.EDUs HCV elimination cascade
(13.1%), 24/137 (17.5%), 26/137 (19.0%), 9/137 (6.6%) had syphilis,
chlamydia, gonorrhoeae and hepatitis B, respectively. High-risk sexual
PP0308
behaviour was reported by 91/137 (66.4%), 20/137 (14.6%) injected
drugs and 12/137 (8.8%) engaged in chemsex. 100/137 (73.0%) HEPATOCELLULAR CARCINOMA ASSOCIATED WITH CHRONIC
were HCV-RNA positive, and 74/100 (74.0%) met simplified treatment HEPATITIS C, CLINICAL PROFILE, MANAGEMENT OUTCOMES
requirements. 74/74 (100%) initiated treatment, within a median (IQR) AND SURVEILLANCE STRATEGY OF THE PUNJAB HCV MODEL:
of 5.0 (2.3–7.0) days. The remaining 26/100 (26.0%) participants were REAL WORLD DATA FROM THE PUBLIC HEALTH PERSPECTIVE.
referred out for treatment, 6 of whom initiated treatment within a median ANCHAL SANDHU1, MADHUMITA PREMKUMAR1,
(IQR) 71 (45.0-78.0) days. RADHAKRISHANN DHIMAN2, AJAY KUMAR DUSEJA3, PRERNA
Conclusion: We observed high HCV infection rates among men who SHARMA3, ARKA DE3, SUNIL TANEJA3, NIPUN VERMA3, SAHAJ
have sex with men and transgender women, as well as high rates of co- RATHI3
infections with HIV and other STIs. Onsite HCV-RNA testing facilitated 1
Postgraduate Institute of Medical Education and Research
the rapid identification of active HCV infection and all clients eligible (PGIMER), Chandigarh , 2Sanjay Gandhi Postgraduate Institute of
for simplified treatment initiated direct acting antivirals within a week. Medical Sciences (SGPGI) is a medical Institute Lucknow, Uttar
Clients referred out for treatment were less likely to initiate treatment, Pradesh, 3Post Graduate Institute of Medical Education & Research,
or did so with significant delays. Follow-up data, including rates of Chandigarh
treatment completion and rates of sustained virological response, will Background: The Punjab HCV Model, a decentralized multicentric
further inform efforts to scale-up this model to enhance access to HCV public health cohort,
services for KPs in Thailand. has resulted in cure rates of 91.6% using free-of-charge generic direct-
Table and Figure:Figure 1.Service flow of KP-Led HCV Test and Treat acting antiviral
Figure 2.Demographic data of KP-Led HCV Test and Treat participants. agents (DAAs) in patients with chronic hepatitis C (CHC) infection.
Real world data on the
PP0307 risk of hepatocellular carcinoma (HCC) in CHC patients with or without
cirrhosis, and
Hepatitis C Screening and Elimination Among Ex-Drug Users in benefit of surveillance in a population-based cohort is needed to guide
Community Drug Rehabilitation Centers in Guangdong, China health policy.
Guan Jiajun1, Chen Xiaoqiao1, Ouyang Yanling1, Liang Zhiming2, Method: The association of hepatocellular carcinoma with CHC at first
Huang Yong1, Tong Long2, Liang Huixin1, He Tingshan1, Fan Liting1, enrolment, clinical course,
Hong Li1 outcomes and new incidence of HCC following post sustained
1
Shunde Hospital of Southern Medical University, 2Foshan Shunde virological response (SVR-12)
District Center for Disease Control and Prevention surveillance was assessed between December 2017 and December
Background: There are no reports on the prevalence of hepatitis C 2022. The treatment
virus (HCV) infection among ex-drug users (EDUs) in community drug given and outcomes were recorded.
rehabilitation centers (CDRCs) in mainland China. This study aimed to Result: Of the 51865 viremic patients with CHC in the Punjab Model
evaluate the burden of HCV infection in this population and establish cohort, 652 patients with HCC
a feasible screening-to-referral model. A micro-elimination approach at 1 presentation were reported, of whom 287 referred patients (mean
tailored for EDUs was implemented in Shunde District, Guangdong age 63.6± 11.1
Province, to assess its effectiveness. years, 58.5% men median MELDNa 15.6, 15.5% non-cirrhotic, mean
Method: This prospective observational study was initiated by Shunde ALBI score: -1.9,
Hospital of Southern Medical University, in collaboration with the Office median AFP 160 ng/ml) managed at the nodal centre PGIMER,
of Drug Control (ODC), the Center for Disease Control and Prevention Chandigarh were enrolled.
(CDC), CDRCs. This novel four-party linkage model included recruiting The patients with HCC were classed as BCLC stage A (53,18.5%), B
EDUs, conducting surveys, performing HCV antibody (HCV-Ab) reflex (79,27.5%), C (27,9.4%)
testing, recalling HCV RNA-positive individuals for referral, initiating and D(128,44.6%). About 22% had decompensation including
direct-acting antiviral (DAA) therapy, and treatment follow-up. ascites(20.9%) and variceal
Result: Over one year, 11 free consultations were conducted across bleeding (3.2%), at enrolment. HCC characteristics were as follows;
10 CDRCs in Shunde, Guangdong Province, enrolling 246 EDUs. The 193, 67.2%-single
fingerstick HCV-Ab testing rate was 99.2% (244/246). The median age nodule, mean size as 4.4± 2 cm, 50 (17.4%)-tumoral portal vein
of participants was 48 years (range: 42-53), with 91.8% male. Of the thrombosis. The SVR-12
participants, 79.1% had an education level of middle school or below, was 87.1%, which is lower than the Punjab cohort cure rate of 91.6%.
25.4% lacked stable income, and 48.8% had a history of intravenous 220 (76.4%) patients
drug use. Liver fibrosis was observed in 39.3% of participants, and died, and 7 (2.4%) underwent liver transplantation. Ablative procedures
cirrhosis in 14.3%.The HCV-Ab positivity rate was 49.2% (120/244), with included
radiofrequency ablatio (7), microwave ablation (5) and cryoablation score at diagnosis was 6.6/7.0. DAA was started in all 16 subjects with
(2). In intermediate good tolerance. Among 7 PIC who completed DAA, onsite POC HCV
HCC, transarterial (TA) chemoembolization (95), transarterial RNA test revealed undetectable HCV RNA in all 7 PIC with turn-around
radioembolization (32), bland time of 60 minutes. Paired venous blood confirmed concordance of
embolization (2) and stereotactic body radiation (SBRT-6) were done. HCV RNA undetectability between POC (fingerstick) and laboratory
Patients with measurement (venous blood).
advanced HCC received sorafenib (20.9%), lenvatinib (14.6) following Conclusion: Outreach program for HCV treatment is highly effective
or in combination in Hong Kong. POC HCV RNA test can be used to confirm HCV cure
with locoregional therapy. Independent predictors of mortality were after DAA therapy to evaluate treatment outcome in a timely manner.
BCLC Stage C or D The novel approach to use POC HCV RNA for SVR12 confirmation
(aHR 1.03 ,95%CI:1.008-1.28, P=0.002, age( aHR 1.3 ,95%CI:1.2- can strengthen the care cascade for HCV in the prison setting where
1.8,P<0.01 and baseline constant migration of individuals is expected.
MELD(aHR 1.5 , 95%CI:1.2-1.8, P=0.022). New incidence of HCC Table and Figure:Figure 1.Flow diagram illustrating the utility of POC
was detected in 29/6516 (0.45%) cirrhotic patients following SVR-12; tests in the outreach program for hepatitis C virus screening and
during a follow-up period of 35.5months (24- treatment for prisoners in Hong Kong
48months). Better overall survival [(median 28.2 (interquartile range;
IQR 18.5-45) vs 20.2
PP0310
(IQR 12.5-40) months); P<0.01], higher chance of curative intent
therapy [15 (48.3 %) vs Prevalence and Trends of Hepatitis C Infection in Pregnant Women
14(4.8%); P<0.001] and earlier BCLC stage was noted in those on in in Xi’an, China: A 10-Year Retrospective Study
surveillance than in those He Ying Li1, Liu Geng Wen2, Zhang Qiao1
with HCC at enrolment, suggesting clinically meaningful lead time and 1
The First Affiliated Hospital of Xi‘an Jiaotong University, 2Xi‘an
better outcomes People‘s Hospital (Xi‘an Fourth Hospital)
with surveillance. Background: This study was to understand the prevalence of hepatitis
Conclusion: The Punjab HCV Model demonstrates patients with CHC C virus (HCV) infection in pregnant women in China, and to provide
should remain on strict HCC data basis for the formulation of HCV prevention and control strategies
surveillance following virological cure to provide survival benefit. in pregnant women.
Table and Figure:Figure 1.Fig 1.Methods and Materials, Figure 2. KM Method: We selected the Obstetrics and Gynecology Specialized
curve for survival based on BCLC grade. Hospital of Xi’an and reviewed the data of pregnant women who were
Figure 2.Table. Comparison of patients with HCC at first diagnosis vs hospitalized in the hospital during the period from January 2014 to
HCC detected on surveillance. December 2023. All patients underwent either quantitative or qualitative
anti-HCV detection, and HCV RNA detection was performed on those
PP0309 who were anti-HCV positive. We described the 10-year prevalence of
HCV antibody and HCV RNA positivity.
Novel use of point-of-care hepatitis C virus RNA test for rapid
Result: A total of 116, 171 pregnant women were screened, of which
confirmation of sustained virological response after direct acting
621 were positive for anti-HCV, with a median age of 30 years (IQR
antivirals among prisoners in Hong Kong SAR, China
27.5,32). The anti-HCV positive rate showed a significant increase (P
Loey Mak1, Rex Hui1, James Fung1, WaiKay Seto1, Manfung Yuen1 = 0.047) from 0.49% (264 cases) in the first five years (2014-2018) to
1
The University of Hong Kong 0.57% (357 cases) in the second five years (2019-2023).
Background: The first point-of-care (POC) test for hepatitis C virus Of the621 anti-HCV-positive patients, the rate of HCV RNA test was
(HCV) RNA was granted marketing authorization by the U.S. Food and 68.92% (428/621) , 70 (16.36%) (70/428) were HCV RNA positive, with
Drug Administration since June 2024. In regions with low general HCV a median age of 29 years (IQR 27,32). In contrast to the increasing
prevalence, POC test in high-risk population allow rapid diagnosis with anti-HCV trend, the HCV RNA positive rate showed a significant
the test-and-treat approach that enhanced linkage to care. Prisoners/ decrease (P = 0.005) from 22.16% (41/185) in the first five years to
person-in-custody (PIC) are one of the high-risk groups for HCV. The 11.93% (29/243) in the second five years.
mobility of PIC between correctional facilities and the community casts Conclusion: This study represents the largest known domestic
difficulty for HCV-infected PIC to be retained in the care cascade. screening for HCV infection among pregnant women in China. We
We aimed to explore the role of POC HCV RNA to assess treatment found a 0.535% prevalence of anti-HCV antibodies in pregnant women
response in the HCV care cascade among PIC in Hong Kong. in western China, which is comparable to the prevalence reported in
Method: Method: We initiated an outreach program in prisons in the general population during the same period. While the anti-HCV
Hong Kong that are operated by the government. Eligible participants positive rate appears to be increasing, the HCV RNA positive rate is
were first screened with POC test for antibody to HCV (anti-HCV) decreasing. This suggests potential improvements in screening and
by Oraquick®. PIC with positive POC anti-HCV received reflex treatment rates for hepatitis C patients in China. However, a significant
venipuncture for HCV RNA (lower limit of detection [LLOD]: 15 IU/ number of cases (193, 31.08%) remain undiagnosed due to the lack
mL). PIC with confirmed HCV viremia were treated with 8-week or of HCV RNA testing following a positive anti-HCV test. To address this
12-week course of direct acting antivirals (DAA) in the prison upon issue and support the action plan to eliminate hepatitis C in Shaanxi
diagnosis of HCV infection. Sustained virological response 12 weeks Province, we plan to implement a recall program for both anti-HCV-
after DAA (SVR12) was evaluated by onsite POC HCV RNA by Xpert® positive and HCV RNA-positive patients. This initiative will facilitate
VL Fingerstick, an automated in vitro RT-PCR test for quantitative diagnosis and treatment with Direct-Acting Antivirals (DAA), ultimately
evaluation of HCV RNA, on the Cepheid GeneXpert® system that was improving overall diagnosis and treatment rates.
installed inside the prison (Figure). The test targets HCV genotypes Table and Figure:Figure 1.Trend of hepatitis C antibody positivity rate
1-6, with LLOD ranging from 22 to 35 IU/mL depending on genotype. from 2014 to 2023
Health-related quality of life was assessed by the Chronic Liver Disease Figure 2.Trend of HCV RNA positivity rate from 2014 to 2023
Questionnaire (CLDQ).
Result: Results: In this interim analysis, 11 site visits were conducted PP0311
and 346 PIC were screened: median age was 42 years old, 2.4%
admitted history of injection drug use. The average duration of Sex and ethnic differences in long-term mortality following
custody was 3.2 years for sentenced PIC, with variable duration of hepatitis C cure: A real-world multinational cohort study
custody in the same facility for on remand cases. A total of 17 PIC Fanpu Ji1, Mindie NGUYEN2
had positive anti-HCV (seroprevalence rate: 4.9%), with 16 having 1
Xian, 2Stanford University School of Medicine
detectable RNA (viremic rate 4.6%; mean viral load 7 log). CLDQ
Background: Hepatitis C virus (HCV) cure by direct-acting antiviral patients to seek specialized care, though reducing the rate of ignored
agents (DAA) is associated with better outcomes including reduced alerts remains a challenge. Despite many flagged patients not being
mortality, but few data exist for detailed risk factors associated with treatment candidates, the system contributed to improved outcomes in
mortality after HCV cure. We aimed to determine mortality following 28 HBV-infected and 34 HCV-infected patients through the prevention
HCV cure and associated risk factors. of HBV reactivation or therapeutic interventions for chronic HBV/HCV
Method: The study included HCV patients with sustained virological cases.
response following DAA (DAA-SVR) from 39 REAL-C centers in North
America, Europe, and Asia-Pacific. The primary outcome was all- PP0313
cause mortality in DAA-SVR patients.
Result: The study included 10,034 DAA-SVR patients: 5611, 4153, and A government-leading HCV elimination model for diagnosed but
270 with no cirrhosis, compensated and decompensated cirrhosis, untreated patients in Yuxi, China
respectively. 491 (4.9%) patients died during follow-up, yielding an Shifu Li1, Rusong Yang1, Yang Luo1
all-cause mortality rate (per 1000 PY) of 10.4, 6.2, 13.1, and 60.0 1
Centers for Disease Control and Prevention of Yuxi, Yuxi Prefecture,
overall and for patients without cirrhosis, compensated cirrhosis, and Yunnan, China
decompensated cirrhosis, respectively. The 5-year cumulative survival Background: Diagnosed but untreated (DBU) hepatitis C virus (HCV)
rates for the overall cohort were 95.1% (94.5-95.6%), with the lowest infected patients are a key group for HCV elimination efforts. We aimed
(73.9%) rates for decompensated cirrhosis. The main cause of death in to explore a government-leading model for HCV elimination by relicking
the non-cirrhosis (5.2 vs. 0.8 per 1000 PY) and compensated cirrhosis DBU patients in Yuxi prefecture, Yunnan Province, China.
groups (8.2 vs. 4.8 per 1000 PY) was non-liver (vs. liver) related death, Method: Yuxi Center for Disease Control(CDC) collaborated with
with opposite findings for decompensated cirrhosis (liver-related vs. hospitals, civil affairs and polices center to developed a model to
non-liver: 33.8 vs. 24.7 per 1000 PY). Older age (>65 years: 3.3-fold), increase relinking rate for DBU population. CDC searched the records
male (1.5-fold), cirrhosis (7.6-fold for decompensated, 1.8-fold for from the Chinese Infectious Disease Information System to identify
compensated), baseline diabetes mellitus (1.5-fold), and non-Asian HCV DBU patients (defined as HCV antibody positive but no prior
(2.1-fold) were associated with higher mortality. treatment or not cured information recorded) from 2004- 2022 period.
Conclusion: This study showed significant age, sex, ethnic, and CDC staff and primary health care workers out-reach provided face-to-
region-specific differences in mortality and causes among DAA-SVR face education to patients in remote areas. HCV-Ab(+) patients would
patients. It provided subgroup data for precision medicine to support receive free HCVRNA testing and then referred to hospital to receive
individualized care, future modeling studies and public health planning. reimbursed SOF/VEL treatment. A full-time nurse will follow up the
Table and Figure:Figure 1.Factors associated with mortality among patients. The police centers support to relink DBU patients who were
HCV patients with SVR. in compulsory drug rehabilitation facilities. The civil affairs department
Figure 2.Incidence rates for liver and non-liver mortality outcomes in coordinate financial assistance(Fig.1).
DAA-SVR patients by severity of liver disease. Result: From July 2023 to June 2024, 14 medical educations were
hold by CDC for healthcare professionals and government workers
PP0312 from 9 countries and 11 hospitals. 4692 DBU HCV patients needed
contacted, 3813(81.27%, 3813/4692) patients were called back
Alert system for HBV and HCV: challenge to eliminate viral
and completed HCVRNA testing, 40.13% patients (1530/3813) were
hepatitis
HCVRNA positive, 68.89%(1054/1530) DBU HCV patients received
Kazuyoshi Kon1, Akira Uchiyama1, Hiroo Fukada1, Shunhei SOF/VEL treatment. Till the end of November 2024, 93.64% (987/1054)
Yamashina1, Kenichi Ikejima1 completed treatment and follow-up period and 99.29% (980/987)
1
Juntendo University Graduate School of Medicine achieved SVR12(sustained virological response12 weeks after
Background: Advances in antiviral therapy have significantly improved therapy), (Fig. 2).
the prognosis of chronic viral hepatitis caused by HBV or HCV. Conclusion: This collaborative model successfully relink DBU HCV
However, identifying infected patients remains a critical challenge. patients and accelerate HCV elimination in high-prevalence areas.
Since September 2016, our hospital has implemented a “Viral Hepatitis Table and Figure:Figure 1.Figure 1. Flowchart for the study in Yuxi
Alert System” which prompts consultation with the Department of prefecture, Yunnan Province, China.CDC, Centers for Disease Control
Gastroenterology when HBs antigen or HCV antibody tests ordered by and Prevention; HCV, Hepatitis C virus; RNA, ribonucleic acid
non-gastroenterology departments yield positive results. In this study, Figure 2.Figure 2. HCV care cascade of DBU patients between 2004
we evaluated the efficacy of this system. to 2022 in Yuxi prefecture, Yunnan Province, China.HCV, Hepatitis C
Method: We analyzed 642 HBs antigen-positive patients and 613 HCV virus; RNA, ribonucleic acid; SVR12, sustained virological response12
antibody-positive patients flagged by the alert system in electronic weeks after therapy
medical records from September 2016 to December 2023.
Result: Analysis of alerts by department revealed that HBV alerts were PP0314
most frequently issued by ophthalmology, gynecology, and neurology,
while HCV alerts were most common in ophthalmology, neurology, Resident physician-leading HCV micro-elimination strategy in a
and cardiology. Among HBV alerts, 215 patients (33%) and, among tertiary hospital: identification of diagnosed but untreated patients
HCV alerts, 114 patients (19%) were referred to the Department of and linkage to care
Gastroenterology within 48 weeks of the alert. Among the HBV-alerted Shuhan Yang1, Zehong Tan1, Hao Pang1, Na Yang1, Yao Tang1,
patients referred, 197 (92%) were asymptomatic or inactive HBV Xinglin Fu1, Lvping Chen1, Fan Yang1, Bo Qin1
carriers. Of these, 9 required nucleoside analog therapy to prevent 1
Department of Infectious Diseases, The First Affiliated Hospital of
HBV reactivation during chemotherapy for malignant tumors, and Chongqing Medical University, Chongqing, People’s Republic of
4 due to immunosuppressive therapy for autoimmune diseases. China
Additionally, 11 patients had chronic hepatitis B, and 4 had untreated Background: Hepatitis C virus (HCV) elimination by 2030 is one of the
cirrhosis, necessitating nucleoside analog therapy. For HCV-alerted main goals of the World Health Organization (WHO). HCV infection is a
patients referred, 45% were HCV-RNA negative, likely due to prior major public health burden in China. We explored a resident physician
antiviral therapy. Eleven percent were ineligible for antiviral treatment leading in-hospital screening and treatment strategy targeting HCV
because of advanced malignancies. Direct-acting antivirals (DAAs) micro-elimination among diagnosed but untreated (DBU) patients in a
were administered to 34 patients (30%), all achieving sustained tertiary hospital in Chongqing, China.
virologic response (SVR). Method: We searched the records from the hospital information
Conclusion: A significant number of HBs antigen- and HCV system (HIS) to identify HCV DBU patients (either with HCV antibody
antibody-positive cases were identified in minor specialties such as or HCV RNA positive results but no prior treatment or not cured
ophthalmology. The Viral Hepatitis Alert System effectively prompted
information recorded) from the 2023-2024 period in the First Affiliated 2, The survey results showed that the primary reasons for rejecting
Hospital of Chongqing Medical University. Resident physician with at treatment were financial problems(78.26%), fear of AE(34.78%) and
least 1-year clinical experience in infectious disease area will take part believing the virus would clear spontaneously (8.70%). Additionally,
as medical navigator in relinking DBU patients. They will provide a logistic regression analysis revealed that the presence or absence of
maximum of 3 calls with standard patients’ education to DBU patients medical insurance was a significant factor influencing the decision to
and help them go back to hospital. When patients came back, resident receive treatment.
physician will provide a “fast-track referral pathways” throughout 3, After ZERO-HD project implementation, more potential HCV infected
screening and treatment—no appointment required, free infectious patients were identified from hemodialysis centers. From 2023 to 2024,
disease(ID) department specialist clinic visit, immediate HCV RNA a total of 95.85% (185/193) of HCV-Ab(+) patients received HCV-RNA
testing, and reimbursed Sofosbuvir/Velpatasvir (SOF/VEL) treatment. screening and 84.07% (95/113) completed HCV treatment, which were
Patients’ characteristics and the success of their linkage to care will higher than before( 85.03% in screening and 55.56% in treatment in
be described. 2023)(Figure2).
Result: Over the past 17 months, 129 inpatients were identified as Conclusion: A low treatment rate is observed among hemodialysis
HCV-Ab(+) patients. 47.3% (61/129) were identified as DBU patients, patients with HCV infection in Sichuan province, primarily due to lack of
including 21 HCV-Ab(+) patients and 40 HCV RNA(+) patients. disease awareness and financial problem. Through the implementation
Among those patients, 82% (50/61) were from non-ID department, of ZERO-HD project, the screening rate, diagnosis rate and antiviral
including 40% from surgical departments and 60% from non-surgical treatment rate of hepatitis C in hemodialysis centers in Sichuan
departments. Among all DBU patients, 60.7% were male, with a median Province have been comprehensively improved.
age of 55 years. Additionally, 41.0% (25/61) already had advanced Table and Figure:Figure 1.ZERO-HD project among 22 hemodialysis
liver diseases or mortality: 27.9% (17/61) had advanced cirrhosis, centers in Sichuan Province
3.3% (2/61) were diagnosed with hepatocellular carcinoma, and 9.8% Figure 2.The Changes in HCV-RNA Screening and Antiviral Treatment
(6/61) experienced liver-related deaths. 3.3% (2/61) died from non- Rates Before and After the ZERO-HD Project
liver-related causes and 23.0% (14/61) had other severe comorbidities
or frailty. Between September to November 2024, resident physicians
PP0316
contacted 37 DBU patients. Through patient education and fast-track
referral pathways, 8 patients (21.6%) were referred to ID department at Outcomes of systematic HCV screening and treatment among
our hospital, while 14 patients linked to care at external facilities. A total refugees, Cox’s Bazar humanitarian emergency, Bangladesh
of 22 patients (59.5%) initiated treatment with SOF/VEL. For patients SM Niaz Mowla1, Debashish Paul2, Polin Chan3, Jorge Martinez2, Md
completed treatment period, 100% (18/18) achieved SVR12. Shahidul Islam2, Farhad Hussain4,5, Abu Toha Bhuiyan6, Charles Erik
Conclusion: Resident physician took an important role through this Halder7, Abdullah Al Noman8,9, Aarti Shrikrishana Singh2,10
in-hospital HCV micro-elimination strategy. We helped to identify 1
World Health Organization, Cox‘s Bazar Sub-Office, Cox‘s Bazar,
47.3% DBU patients and found that many patients were from non-ID Bangladesh, 2World Health Organization, Cox‘s Bazar Sub-Office,
departments. Unfortunately, more than 40% of the patients had already Cox‘s Bazar, Bangladesh, 3World Health Organization, Southeast
experienced advanced liver disease progression or death, which Regional Office (SEARO), Delhi, India, 4Cox‘s Bazar Medical College,
demonstrate the importance of establish the stander of process for Cox‘s Bazar, Bangladesh, 5Directorate General of Health Services,
HCV micro-elimination in non-ID department. Dhaka, Bangladesh, 6Office of the Refugee Relief and Repatriation
Table and Figure:Figure 1.Fig.1 Study flow of HCV micro-elimination in Commissioner, Cox‘s Bazar, Bangladesh, 7International Organization
a tertiary hospital in Chongqing, China. for Migration, Cox‘s Bazar, Bangladesh, 8Save the Children, Cox‘s
Figure 2.Fig.2 Department distribution and stage of disease among Bazar, Bangladesh, 9Umeå University, Sweden (Course), 10World
Health Organization, Eastern Mediterranean Regional Office (EMRO),
DBU patients.
Cairo, Egypt
Background: Infection with hepatitis B (HBV) and C viruses (HCV)
PP0315 are major global health problems, including among high-risk and
ZERO-HD project accelerate HCV elimination in 22 hemodialysis vulnerable groups. Rohingya refugees were estimated to have 20%
centers in Sichuan, China HCV viraemic infections from studies. We report on screening and
Xiaoxia Geng1, Yiheng Yang2, Yao Cao3, Xianbo Wang2, Daqing treatment outcomes among the Rohingya refugees in Cox’s Bazar,
Hong1, Ting Feng1, Jingyu Yang1, Hengjian Du1, Rongzhen Tang1 Bangladesh, a WHO initiative with partners. Launched on 6 March
1
Sichuan Provincial People’s Hospital, 2North Sichuan Medical 2024, the HCV screening and treatment program aims to reduce the
College, 3The People‘s Hospital of Wenchuan burden of the disease among this vulnerable group.
Background: It is necessary to prevent HCV infection among Method: 110 primary care facilities provided screening, and
hemodialysis patients. We aimed to analysis the status of HCV individuals who tested positive were referred to higher centers for
screening and treatment among hemodialysis patients and implement diagnostic confirmation and treatment for HCV. WHO-prequalified
a ZERO-HD project among 22 hemodialysis centers in Sichuan rapid diagnostic tests (RDTs) for HBsAg and anti-HCV were used.
Province. Quantification of HCV ribonucleic acid (HCV RNA) was conducted by
Method: Standard survey was provided to hemodialysis patients to real-time reverse transcription polymerase chain reaction (RT-PCR)
assess the awareness of HCV. Screening and treatment status of each (lower limit of detection, 13 IU/mL [52 copies/ml]) to confirm positive
center and the clinical characteristics of patients would be analyzed. HCV screening tests. Eligible participants were started on direct-
Then the ZERO-HD project(Figure1) was carried out targeting HCV- acting antivirals (DAAs) following WHO guidelines. An APRI score was
Ab(+) patients. ID-specialist-leading medical education campaigns calculated for each patient before initiating treatment. HCV cure was
would be provided to medical worker and patients in hemodialysis defined as sustained virological response (SVR) 12 weeks after the
centers. A specialty multidisciplinary collaborative team would be end of the therapy.
established in each center. HCV-RNA testing would be provided to Result: By 28 November 2024, of 9,599 individuals screened (mean
HCV-Ab(+) patients. We would also establish a patient referral channel age 32.94 years, 83.4% female), anti-HCV positive was 42.8% (95%
between hemodialysis center and hospital to help HCV viremic patients CI: 41.7-43.7%). HCV-screened-positive women had 41.3% (95% CI:
receive reimbursed SOF/VEL treatment. Additionally, online consultant 40.2-42.4%) and 16.8% (95% CI: 15.6-18.1%) pregnant women. The
from ID-specialist would be provided for remote patients during follow- overall HBsAg prevalence was 4.6% (95% CI: 4.2-5.1%). The HBV-
up period. HCV co-infection rate was 2.2% (95% CI: 1.9-2.5%). Of 1,748 HCV
Result: 1, A total of 7059 hemodialysis patients from 22 hemodialysis RNA tests conducted, 67.4% (95% CI: 65.2-69.5%) showed viraemic
centers in Sichuan Province were included.Current rate of HCV-Ab infection with a median viral load of 5.96 × 106 copies/mL. Among
(+),HCV-RNA screening, HCV-RNA(+) and treatment rate were 2.65% pregnant women with RNA confirmation, 75.1% (95% CI: 68.0-81.2%)
(187/7059), 85.03% (159/187), 90.57%(144/159) and 55.56%(80/144). had a viraemic infection. To date, sofosbuvir-daclatasvir was provided
to 723/1,178 (61.4%) of viremic cases. Out of 723, 86 are cirrhosis High HCV prevalence among pregnant Rohingya refugee women:
F3 and F4. The SVR12 rate was 100% (n=122) in an intention-to-treat implications for public health response in humanitarian settings,
analysis among those who completed follow-up. Cox’s Bazar, Bangladesh
Conclusion: This initiative confirms high HBV and HCV prevalence SM Niaz Mowla1, Debashish Paul2, Polin Chan3, Jorge Martinez2, Md
among refugees in the Cox’s Bazar humanitarian emergency. The Shahidul Islam2, Farhad Hussain4,5, Abu Toha Bhuiyan6, Charles Erik
higher numbers of positive cases in pregnant women suggest a cohort Halder7, Abdullah Al Noman8,9, Aarti Shrikrishana Singh2,10
effect and possibly other risk factors that require further analysis. 1
World Health Organization, Cox‘s Bazar Sub-Office, Cox‘s Bazar,
While initial treatment outcomes are promising with high SVR12 Bangladesh, 2World Health Organization, Cox‘s Bazar Sub-Office,
rates, scaling-up capacities to front-line facilities will be needed for Cox‘s Bazar, Bangladesh, 3World Health Organization, Southeast
sustainability. Linkage to care could be enhanced via point-of-care Regional Office (SEARO), Delhi, India, 4Cox‘s Bazar Medical College,
HCV RNA testing and decentralized care models. Mobilizing resources Cox‘s Bazar, Bangladesh, 5Directorate General of Health Services,
is needed to provide hepatitis testing and treatment services to this Dhaka, Bangladesh, 6Office of the Refugee Relief and Repatriation
vulnerable group. This initiative shows that the provision of hepatitis Commissioner, Cox‘s Bazar, Bangladesh, 7International Organization
services is feasible and relevant as part of HCV micro-elimination in for Migration, Cox‘s Bazar, Bangladesh, 8Save the Children, Cox‘s
refugee settings, contributing to global efforts to eliminate it as a public Bazar, Bangladesh, 9Umeå University, Sweden (Course), 10World
health problem. Health Organization, Eastern Mediterranean Regional Office (EMRO),
Table and Figure:Figure 1.Cascade of Hep C Care Cairo, Egypt
Figure 2.Hep C RDT Positive by Age Background: Hepatitis C virus (HCV) infection during pregnancy
poses significant risks to maternal and perinatal health. Rohingya
PP0317 refugees were estimated to have an overall 20% viraemic infection
based on studies. WHO launched the screening and treatment
Impact of the Characteristics Distribution of In-Hospital Hepatitis
initiative in March 2024, offering routine hepatitis B and C testing
C Patients on the Current Diagnosis and Treatment Situation
among pregnant women. We report on the screening outcomes among
Sun Sheng Nan1, Xu Jin2, Shi Xiao Lin1 refugee pregnant women.
1
Shenyang Sixth People‘s Hospital, 2Shenyang Sixth People‘s Hospital Method: Between 6 March to 28 November 2024, pregnant women
Background: Hepatitis C virus (HCV) infections are globally in the refugee camps in Cox’s Bazar were offered routine screening
widespread and unevenly distributed, posing significant challenges as part of obstetric services. Women were screened on-site using
to hepatitis C screening and diagnosis/treatment. This study aimed rapid diagnostic tests for anti-HCV and HBsAg. Real-time reverse
to analyze the current status of HCV diagnosis and treatment in transcription polymerase chain reaction (RT-PCR) was used for
hospitals, identify factors influencing HCV management elimination, confirmatory quantification of HCV ribonucleic acid (HCV RNA), with a
and contribute to the elimination of in-hospital HCV. lower detection limit of 13 IU/mL. Test-positive women were referred to
Method: A retrospective review was conducted on the HCV diagnosis higher centres for further management.
and treatment data in Shenyang Sixth People’s Hospital from January Result: Out of 3,597 pregnant women screened for Hepatitis B and C,
2022 to October 2024 to evaluate the impacts of gender, age, and 16.8% (n=606; 95% CI: 15.6–18.1%) were anti-HCV positive and 2.7%
genotype on HCV diagnosis and treatment. (n=96; 95% CI: 2.2–3.2%) for positive HBsAg. HBV-HCV co-infection
Result: Among the 1,346 HBVRNA-positive patients under was found in 1.0% (n=35; 95% CI: 0.7–1.4%). Of the 169 pregnant
management, ages were mainly clustered in two ranges: 60 - 79 years women who had HCV RNA testing, 75.1% (n=127; 95% CI: 68.0–
(665 cases, 49.4%) and 40 - 59 years (544 cases, 40.4%), trailed by 81.2%) were found to have active HCV (viraemic) infections.
20 - 39 years (98 cases, 7.28%). Dominant HCV genotypes were 1b Conclusion: The high prevalence of HCV among pregnant Rohingya
(39.9%) and 2a (38.8%), differing significantly from others; 3b followed women highlights an urgent public health concern requiring immediate
at 11.6% (Table 1). Genotype distribution varied by gender and age, intervention. While no approved HCV treatment using direct-acting
with more male patients. 1b prevailed in 60 - 79 years, 2a in 40 - 59 antivirals (DAAs) exists for pregnant women, these findings emphasize
years, and 3b mainly in 40 - 59 years. Treatment-wise (Table 2), the the need for: Enhanced screening and monitoring programs in refugee
overall rate was 57.4%. Of 773 treated patients, females had a higher settings for timely identification and prompt case management of
rate (58.3% vs 56.9%). Those <20 and ≥80 years had low rates (33.3% pregnant women and their infants Development of safe and effective
and 33.9%), and 20 - 39 years had the highest (64.3%), though female antiviral treatments for use during pregnancy. Strengthened infection
rate was lower. Analysis of 748 patients’ SVR12 data showed 432 prevention and control in humanitarian settings Comprehensive
(57.8%) cured, 37 (4.9%) failed (3b most, 14 cases, 37.8%), 5 died postpartum care strategies, including treatment initiation and follow-
(0.6%), and 274 (36.6%) lost to follow-up, mostly in 40 - 79 years (269 up for both mothers and infants. Risk communication and community
cases, 98.1%). engagement efforts to promote practices that reduce transmission.
Conclusion: The ages of HCV patients in this study were mainly Active participation in global registries and clinical trials to inform future
concentrated in the 40 - 79 age range. Although the treatment rate protocols and improve care outcomes. In addition, shared decision-
was relatively higher compared to other age groups, it was significantly making approaches between patients and providers will be required.
lower than the WHO target, and this age group had the highest loss- The findings highlight that prevention of mother-to-child transmission
to-follow-up rate, especially among women under 59 years old. of hepatitis B and C is an important part of the humanitarian response.
Strengthening patient education and flow tracing in this age group Addressing HCV during pregnancy is a critical component of maternal
is necessary to improve the treatment and cure rates. Meanwhile, health care, particularly in resource-limited refugee settings.
genotype is also a crucial factor affecting the cure rate. Newly infected Table and Figure:Figure 1.Cascade of care (Hep C positive pregnant
individuals under 40 years old warrant attention. Additionally, the women)
relatively lower treatment rate of females aged 20 - 39 compared to
males requires further investigation. Therefore, continuous attention PP0319
should be paid to investigating the characteristics of HCV infection in
clinical practice to facilitate HCV elimination. Comparison of Outcomes Between Spontaneous Bacterial
Table and Figure:Figure 1. Stratified Statistical Table of Genotyping Peritonitis and Culture Negative Neutrocytic Ascites among Liver
Figure 2.Stratified Statistical Table of Treatment Rates Cirrhosis Patients with End-Stage Renal Disease on Hemodialysis
JoseOrlando Mendoza Nicolas1, Jade Jamias1
1
National Kidney and Transplant Institute
PP0318
Background: Chronic kidney disease is an independent risk factor
that affects mortality among cirrhotic patients with ascitic fluid
infections. It can be classified into two groups based on the result of
culture: spontaneous bacterial peritonitis (SBP) and culture-negative hypertensive gastropathy, splenomegaly, and hypoalbuminemia.
neutrocytic ascites (CNNA). Several studies have reported that SBP Outcome: After three years of treatment reduced IgG from 45.6 g/L to
and CNNA have the same prognosis, whereas others have indicated 21.1 g/L, IgG4 from 4.96 g/L to 2.25 g/L, and LSM E-index from 38 kpa
that the SBP group has a higher mortality rate. The aim of this study is to 24.1 kpa. Child-Pugh score from 8 to 5, grading from B to C, and
to determine the outcomes between SBP and CNNA among patients MELD score from 9.1 to 5.9.
with end-stage renal disease on hemodialysis.Chronic kidney disease Discussion: This case highlights the importance of early diagnosis
is an independent risk factor that affects mortality among cirrhotic and the potential benefits of steroid therapy in patients with IgG4-
patients with ascitic fluid infections. It can be classified into two groups AIH. liver biopsy is crucial for establishing the diagnosis. There are
based on the result of culture: spontaneous bacterial peritonitis (SBP) few studies and reports on IgG4-AIH and a lack of relevant guidelines
and culture-negative neutrocytic ascites (CNNA). Several studies have and established treatment protocols, An important question that needs
reported that SBP and CNNA have the same prognosis, whereas to be addressed is whether IgG4-AIH is a subtype of autoimmune
others have indicated that the SBP group has a higher mortality rate. hepatitis or a hepatic manifestation of IgG4-related disease. The
The aim of this study is to determine the outcomes between SBP and patient had a complete examination of the pancreas, bile duct, thyroid
CNNA among patients with end-stage renal disease on hemodialysis. gland, parotid gland, and other relevant examinations and did not have
Method: This is a retrospective cohort study which included 428 other systemic involvement, the clinical manifestations and therapeutic
patients with chronic kidney disease on hemodialysis admitted with response were close to AIH, we preferred it to be a subtype of AIH.
SBP or CNNA. All patients underwent abdominal paracentesis and Conclusion: IgG4-AIH is a rare condition and early detection and
the ascitic fluid was processed for cell count and culture. Clinical appropriate treatment can significantly improve outcomes for patients.
and laboratory parameters of these patients were recorded at index
admission.
PP0321
Result: Between January 2011 to January 2024, 428 patients with
ascitic fluid infection and chronic kidney disease on hemodialysis Tuberculous Cystic Hepatic Mass with EBV-related Smooth Muscle
were evaluated. Out of 428 patients included in the study, 201 patients Tumors of the Liver and Spleen in an Immunosuppressed Patient
had SBP. Among the 201 patients with SBP, 183 patients were culture Kevindaeile Simbulan Torralba1, James Malicdem Montesa1, Karen
positive SBP (culture positive SBP with ascitic fluid PMNL ≥250 cells/ Joaquin Sotalbo1
m3) and 18 patients were CNNA (culture negative SBP with ascitic 1
Manila Doctors Hospital
fluid PMNL ≥250 cells/m3. The majority of patients in this study This is a case of a 25 year old male presenting with abdominal pain. The
notably received empiric antimicrobials within 24 hours at 67% (287 patient is a known case of AIDS since 2019 currently on lamivudine,
of patients), contributing to improved outcomes. Seven-day mortality tenofovir, lopinavir, ritonavir with note of opportunistic infections and
was higher in the SBP group but there was no significant difference in AIDS-related malignancies: Chronic Hepatitis B since July 2021,
30-day mortality rate. pulmonary tuberculosis treated for six months with HRZE in 2020, and
Conclusion: Patients with CNNA have a lower incidence of hepatic CNS lymphoma diagnosed 2020.
encephalopathy and variceal bleeding. Patients in the SBP group had The patient has noted predominantly right upper quadrant pain over
a higher MELD score, ascites neutrophil count, and ascitic fluid culture three years, increasing in intensity thus eventual consult. Work up done
growth rate. Although seven-day mortality rate was higher in the SBP revealed hepatomegaly and 2 types of masses: the first is found in the
group, the 30-day mortality rate was similar in the two groups. left hepatic lobe, is well-encapsulated and predominantly cystic, with
thick enhancing smooth walls, measuring 18.9 x 19.3 x 15.9 cm. The
PP0320 aforementioned mass is seen displacing adjacent bowel segments
posterolaterally as well as some small bowel segments inferiorly
IgG4-AIH in a Young Male Patient with Decompensated Cirrhosis:
into the pelvic cavity. The second type of liver mass are complex
A Case Report
heterogeneously enhancing masses with thickened irregular enhancing
Wen Gao 1 walls and necrotic centers and are seen scattered in both hepatic
1
Department II of liver diseases, Beijing Youan Hospital Affiliated to lobes. The foci range in size, from 1.5 x 1.2 x 1.1 cm to 5.9 x 6.6 x 7.4
Beijing Capital Medical University, Beijing, China cm. At least two similar looking complex heterogeneously enhancing
Abstract: This case report describes a young male diagnosed with masses with thickened irregular enhancing walls and necrotic centers
IgG-AIH, confirmed through markedly elevated IgG and IgG4 levels, are likewise seen on the body of the spleen, measuring 5.6 x 5.0 x 4.8
abnormal autoantibody profiles, imaging findings, and liver biopsy. cm and 2.1 x 1.7 x 2.2 cm.
Following treatment with glucocorticoids and immunosuppressive For the first hepatic mass - cyst drainage was done thru pigtail catheter.
therapy, the patient showed significant improvement in liver function Cytology revealed no malignant cells but fluid was positive in TB PCR,
and finally achieved cirrhosis re-compensation. thus HRZE was started. For the second type of hepatic masses, UTZ
Case Presentation: A 24-year-old male patient was admitted to the guided liver biopsy was done which revealed spindle cell lesion.
hospital with a 5-year history of drug-related liver injury and a 1-month Further immunohistochemistry was done which revealed: Caldesmon -
history of abdominal discomfort. A liver biopsy five years ago showed POSITIVE, Desmin - POSITIVE, Smooth Muscle Actin - POSITIVE, S100
that he had DILI. - POSITIVE in sporadic cells, Cytokeratin - POSITIVE (aberrant staining
One month before admission, the patient developed epigastric is considered), STAT6 - NEGATIVE, CD31 - NEGATIVE. Because of
discomfort without fever, malaise, anorexia, or abdominal distension. the clinical context, EBER-ISH testing was recommended due to
Laboratory tests revealed ALT 56 U/L, AST 136 U/L, Tbil 42.9 umol/L, consideration of an Epstein-Barr virus-associated smooth muscle tumor
GGT 133 U/L, ALP 252 U/L, IgG 45.6 g/L, IgG4 4.96 g/L. Viral hepatitis which turned out negative. However, an EBV associated smooth muscle
markers were negative, ANA 1:1000 (nuclear-speckled pattern). tumor was still the primary diagnosis since the immunohistochemistry
Figure 1. Upper abdominal computed tomography (CT) scan showing is not compatible with the other main differentials of Kaposi sarcoma
liver cirrhosis, cirrhosis, splenomegaly and mycobacterial spindle cell pseudotumor.
Figure 2. Gastroscopic showed severe esophageal vein varices, and Literature on EBV associated smooth muscle tumors is scarce. Most
portal hypertensive gastropathy. literature to date are case series with similar profiles to our patient -
Figure 3.Histopathology: Multi-branched areas of post-necrotic immunosuppressed individuals (AIDS, post transplant) with multifocal
collapse with early fibrosis are seen, and moderate to severe interface disease. There is limited data on its management, with surgery,
inflammation is present, with large aggregates of plasma cells at the chemotherapy, and immunotherapy finding varying levels of success.
interface. In conclusion, with the rising numbers of immunosuppressed patients,
Figure 4. 1gG4 staining showed that IgG4+ cells had more than 10/ whether AIDS or post transplant related; we must keep in mind EBV
HPF in the necrotic collapse zone and the confluent area. related smooth muscle tumors as a differential diagnosis and continue
Diagnosis: The patient was diagnosed with decompensated cirrhosis, to study its best diagnostic approaches and management strategies.
IgG4-related autoimmune hepatitis, severe esophageal varices, portal
 PP0322 of Medicine, Al-Azhar University, Damietta, Egypt., 10Faculty of
Medicine, Sohag University, Sohag, Egypt.
A MYSTERIOUS SPONTANEOUS RESOLUTION OF PORTAL VEIN
THROMBOSIS AND PSEUDOANEURYSM IN A 30-YEAR-OLD Background: The efficacy of ursodeoxycholic acid (UDCA) in
MALE: A CASE REPORT managing cholestatic liver disease is well-established. UDCA inhibits
IRSON THURS DORIA1, CLARISSE ENRIA PORRAS1, AARON the farnesoid X receptor (FXR), leading to the down-regulation of ACE2,
VELASCO1 a critical entry receptor for SARS-CoV-2. Despite this mechanism, the
1
SOUTHERN PHILIPPINES MEDICAL CENTER impact of UDCA on patients with COVID-19 remains controversial. This
study aims to assess the association between UDCA administration
Portal vein thrombosis (PVT) and hepatic pseudoaneurysms are rare and COVID-19-related mortality, hospitalization, and symptoms.
but serious conditions often requiring intervention. PVT is typically Method: We conducted a systematic search of PubMed, Scopus,
associated with cirrhosis, but can also occur in malignancy, pancreatitis, and Web of Science (WOS) from inception until September 30, 2024.
infections, and hypercoagulable states. Hepatic pseudoaneurysms All observational studies involving patients treated with UDCA and
can result from trauma, surgery, or infection. Though these conditions infected with COVID-19 were included. We utilized Review Manager
usually require surgical or endovascular procedures, there are few (RevMan 5.4 for Windows) for statistical analysis.
reports of spontaneous resolution with conservative therapy. Hepatic Result: Nine observational studies published between 2023 and 2024,
tuberculosis, an uncommon cause of both PVT and pseudoaneurysm, encompassing 30,066 patients, were included in the meta-analysis. We
may trigger these complications through its inflammatory effects. found no statistically significant differences between UDCA and non-
Objective: To present the case of a 30-year-old male who experienced UDCA groups regarding mortality (RR = 0.99; 95% CI [0.80, 1.23]; P
spontaneous resolution of portal vein thrombosis and hepatic = 0.94), or COVID-19-related hospitalization (RR = 0.98; 95% CI [0.89,
pseudoaneurysm following treatment anti koch treatment 1.08]; P = 0.74). However, the UDCA group demonstrated significant
Case Description and Results: improvements in COVID-19 symptoms, including cough (OR = 0.43;
A 30-year-old male from South Cotabato, Philippines, presented 95% CI [0.31, 0.60]; P < 0.00001), muscle or joint pain (OR = 0.70;
with jaundice, abdominal pain, and fever. Two months prior, he was 95% CI [0.51, 0.96]; P = 0.03), and pharyngalgia (OR = 0.28; 95% CI
diagnosed with hepatic abscess, nodules, and portal vein thrombosis [0.09, 0.82]; P = 0.02).
with cavernous transformation on CT. Due to financial constraints, Conclusion: Our results showed a limited role of UDCA in reducing
follow-up care was not possible. A month later, whole abdomen mortality rates or COVID-19-related hospitalization. However, they
and doppler imaging confirmed intrahepatic and common bile duct provide insights into the efficacy of UDCA in managing mild to
ectasia, with persistent portal vein thrombosis. moderate symptoms of COVID-19 as cough, muscle or joint pain,
On admission, noted progression of symptoms hence he sought and pharyngalgia. Further clinical trials are warranted to validate our
consult at our institution. He was immediately schedule for ERCP which results.
revealed a 15mm stricture and a mass effect in the left intrahepatic
duct, which was managed with stent placement. Liver biopsy was
inconclusive, but sputum testing revealed Mycobacterium tuberculosis, PP0324
diagnosing pulmonary and potential hepatic tuberculosis. Anti-TB A novel nomogram for the early identification of coinfections in
therapy was initiated, alongside antibiotics for hepatic abscesses. elderly patients with COVID-19
On repeat CT imaging, there was note of Klatskin tumor, progressive Ju Zou1, Xiaoxu Wang1, Jie Li1, Min Liu1, Xiaoting Zhao2, Ling Wang1,
portal vein compression, cavernous transformation, and a hepatic Xuyuan Kuang1, Yang Huang 1, Jun Quan1, Ruochan Chen1
pseudoaneurysm. Treatment with anti-TB therapy, hepatoprotective 1
Xiangya Hospital, Central South University, 2The First Affiliated
agents, and anticoagulation led to clinical improvement, and the Hospital Of Xinxiang Medical University
patient was discharged in stable condition. He was later readmitted
Background: This study aimed to establish a novel, precise, and
for ERCP and stent removal, during which a repeat ultrasound showed
practical nomogram for use upon hospital admission to identify
complete resolution of the pseudoaneurysm and portal vein thrombosis
coinfections among elderly patients with coronavirus disease 2019
following isoniazid, rifampicin, and ethambutol treatment. The biliary
(COVID-19) to provide timely intervention, limit antimicrobial agent
stricture was no longer present, and the patient’s condition continued
overuse and hospitalisation costs, finally reduce unfavourable
to improve.
outcomes.
Conclusion
Method: This prospective cohort study included COVID-19 patients
This case highlights the importance of suspecting hepatic TB,
consecutively admitted at multicenter medical facilities in a two-
especially in high TB-burden areas like the Philippines. It also
stage process. The nomogram was built on the multivariable logistic
emphasizes the value of a multidisciplinary approach to complex
regression analysis. The performance of the nomogram was assessed
hepatobiliary conditions. While surgery is typically needed for portal
for discrimination and calibration using receiver operating characteristic
vein thrombosis and pseudoaneurysms, careful medical management
curves, calibration plots, and decision curve analysis (DCA) in rigorous
can lead to spontaneous resolution. Further studies are needed to
internal and external validation settings.
optimize treatment for patients with coexisting portal vein thrombosis,
Result: Between 7 December 2022 and 1 February 2023, in the
pseudoaneurysm, and hepatic TB.
first stage of this study, 916 COVID-19 patients were included. The
coinfection rates in non-elderly and elderly patients determined to
PP0323 be 16.22% and 26.61%, respectively. Pneumonia caused by other
Impact of Ursodeoxycholic Acid on COVID-19 Outcomes: A pathogens (85.45%) was the most common coinfection-associated
Systematic Review and Meta-Analysis illness in the elderly group. Bacteria were the most common
Omar Elkoumi1, Ahmed Elkoumi2, Mariam Khaled Elbairy1, Younes pathogens associated with coinfections in the elderly, especially
F. Samara3, Abdullah Yousef Aldalati4, Mostafa Adel T. Mahmoud5, gram-negative bacteria (48%) of Acinetobacter baumanii, Klebsiella
Ahmad Beddor6, Ayah Abdulgadir7, Mohamed S. Elgendy8, Ahmed pneumoniae, and Pseudomonas aeruginosa. Fungi (38%) were
Lotfy9, Mohamed A. Aldemerdash10 the second most common pathogens isolated from coinfections in
elderly patients with COVID-19. The nomogram was developed with
1
Faculty of Medicine, Suez University, Suez, Egypt., 2Faculty of Oral
and Dental Medicine, Egyptian Russian University, Badr City, Cairo, the parameters of diabetes comorbidity, previous invasive procedure,
Egypt., 3Faculty of Medicine, Hashemite University, Zarqa, Jordan., and procalcitonin (PCT) level, which together showed areas under the
4
Faculty of Medicine, Jordan University of Science and Technology, curve of 0.86, 0.82, and 0.83 in the training, internal validation, and
Irbid, Jordan., 5Faculty of Medicine, Beni Suef University, Beni Suef, external validation cohorts, respectively. The nomogram outperformed
Egypt., 6Faculty of Medicine, Yarmouk University, Irbid, Jordan., both PCT or C-reactive protein level alone in detecting coinfections in
7
Faculty of Medicine, University of Khartoum, Khartoum, Sudan., elderly patients with COVID-19; in addition, we found the nomogram
8
Faculty of Medicine, Tanta University, Tanta, Egypt., 9Faculty was specific for the elderly compared to non-elderly group. Calibration
plots of the nomogram revealed excellent agreement between the Delhi, 4Department of Hepatology, Max Centre for Liver and Biliary
predicted and actual probabilities of coinfection occurrence, and the Sciences, New Delhi
DCA indicated favourable clinical consistency of nomogram results. Background: Acute liver failure (ALF) is a critical medical condition
Conclusion: This novel nomogram will assist in the early identification where liver transplant (LT) serves as a life-saving intervention. The
of coinfections in elderly patients with COVID-19. challenge often lies in deciding the timing of transplantation. Listing
Table and Figure:Figure 1.Figure. Summary of elderly COVID-19 criteria are often not reliable in infectious hepatitis especially in a
patients with coinfections. living donor program. We share our experience from a single centre
Figure 2.Figure. Validation of the predictive nomogram model for in managing ALF.
elderly COVID-19 patients with coinfections. Method: We analysed the data of 70 ALF patients who presented
to us between June 2017 and February 2023. It was a retrospective
PP0325 single centre study. We especially analysed the clinical characteristics,
medical/surgical interventions, and outcomes.
Development of a human-neutralizing monoclonal antibody that
Result: Of our 70 patients with ALF with a median age of 24.5 years
effectively blocks hepatitis A virus infection both in vitro and in
(IQR:13–35years), 26 were women (37%) and 28 children (40%) below
vivo
the age of 18 years. The leading cause of ALF was hepatitis A virus
XIN ZHENG1,2, Asuka Hirai-Yuki1, Kazutaka Terahara1, Noriyuki
infection in 39 (55.7%) followed by indeterminate causes in 14 (20%).
Watanabe1, Ryosuke Suzuki1, Osamu Kotani1, Noriyo Nagata1,
The overall cohort had 40% survival with the native liver. Our patients
Michiyo Kataoka1, Bryan Yonish3, Kento Fukano1, Daisuke Yamane4,
were divided into three categories (Figure 1): Liver transplant group (34
Eriko Ohsaki5, Keiji Ueda5, Tomoyuki Shiota2, Kazuhiro Takimoto1,
patients), survivors with their native liver group (SNL, 28 patients), and
Tadaki Suzuki1, Masanori Isogawa1, Takayuki Uchihashi6, Stanley M
deceased group (8 patients, not transplanted). The SNL group had a
Lemon3, Yoshimasa Takahashi1, Masamichi Muramatsu1,2
median hospital stay of 12 days (IQR:9–20); 13 of these patients met
1
National Institute of Infectious Diseases, 2Foundation for Biomedical the King’s College Hospital criteria for LT listing. Of the 34 LT recipients,
Research and Innovation at Kobe, 3The University of North Carolina at 10 died postoperatively, most commonly due to persistent intracranial
Chapel Hill, 4Tokyo Metropolitan Institute of Medical Science, 5Osaka hypertension leading to brain death. In the deceased group, patients
University Graduate School of Medicine, 6Nagoya University
had multiorgan dysfunction or were too sick to transplant. In univariate
Background: Hepatitis A virus (HAV) is a small, quasi-enveloped, analysis (Table 1), admission INR, arterial-lactate levels, jaundice-to-
positive-sense, single-stranded RNA virus belonging to the encephalopathy (J-E) interval, and advanced hepatic encephalopathy
Picornaviridae family. Although the hepatitis A vaccine has been were found to predict the need for LT, while multivariate analysis
available for 30 years, the low vaccination rate (less than 0.1% identified elevated admission arterial lactate and a J-E interval
annually) has resulted in 99% of the population under 65 years old exceeding 7 days as significant predictors for the requirement for LT.
lacking protective anti-HAV antibodies in Japan. Currently, there is no Conclusion: Hepatitis A is the main cause of ALF, with high arterial
available antiviral therapy for hepatitis A, leading to reported fatalities lactate levels and prolonged J-E interval indicating poor outcomes.
among elderly or immunocompromised individuals infected with The choice between medical and surgical management is challenging
HAV. Our study focused on the development of an anti-HAV human due to postoperative risks and potential for native liver survival.
monoclonal antibody (Ab8) as a potential approach for the prevention Table and Figure:Figure 1.Figure 1: Study cohort
and treatment of hepatitis A. Figure 2.Table 1: Predictors of liver transplant in patients with ALF
Method: Anti-HAV human monoclonal antibodies were generated from (Univariate analysis).
PBMC of an HAV-vaccinated individual. The virus-neutralizing activity
of the antibody (Ab8) was examined using the HAV experimental
strain (HAV/18f/NLuc) and clinical HAV strains (HM175, TKM031 and
PP0327
KRM005). Atomic force microscopy (AFM) was performed to evaluate Clinical analysis of severe patients with hepatitis E overlapping
the impact of Ab8 on viral morphology and stability. The epitope of chronic hepatitis B in Nantong area
Ab8 was determined by isolating Ab8-resistant viruses and sequence Guo Jian Shao1, Mei Ling Yang1
them. The antiviral activity of Ab8 was tested in vivo by administering 1
Nantong
Ab8 to Ifnar1-/- mice (an acute infection model). The viral titer in feces, Background: Hepatitis E is an acute viral hepatitis caused by hepatitis
blood, and liver, as well as serum ALT levels, were measured to assess E virus (HEV) and mainly transmitted through the fecal-oral route. There
antiviral effects. are about 20 million new cases of HEV infection globally every year.
Result: Ab8 significantly inhibited HAV infection in a dose-dependent Among them, 3.3 million cases have hepatitis symptoms, and about
manner, by blocking both viral attachment and endocytosis in vitro. 70,000 people die. In China, the reported incidence rate of hepatitis
Additionally, Ab8 directly destabilized viral particles, leading to the E is on the rise.
degradation of the viral RNA. The isolation and sequencing of Ab8- Method: A retrospective analysis was conducted on 54 severe
resistant virus indicated the epitope targeted by Ab8 involves residues patients admitted to Nantong Third People’s Hospital from April 2019
in VP1. In the acute infection model, administration of Ab8 immediately to May 2024, including 14 patients with HEV and CHB co-infection and
after infection significantly suppressed viral levels in serum and feces, 40 patients with simple HEV infection. According to whether antiviral
and reduced liver injury. treatment was administered, patients with HEV and CHB co-infection
Conclusion: The results suggest that Ab8 inhibits HAV infection by were further divided into an antiviral group and a non-antiviral group.
targeting viral attachment and endocytosis. Ab8 is also effective in Laboratory indicators of each group were compared.
suppressing HAV infection in vivo. Thus, Ab8 should be a promising Result: The ascites symptom in the HEV and CHB group was
therapeutic agent for HAV-infected patients. higher than that in the simple hepatitis E group, and the difference
was statistically significant (P<0.05), while there was no significant
PP0326 difference in fatigue, anorexia, nausea and vomiting, hepatic
Timing Transplantation versus Medical Treatment in Acute Liver encephalopathy, gastrointestinal bleeding, average length of hospital
Failure and Associated Outcomes: Insights from an Indian High- stay, number of cases of artificial liver treatment and prognosis
Volume Transplant Centre between the two groups; the levels of total bilirubin, immunoglobulin
G, rheumatoid factor and type IV collagen in the HEV and CHB group
Vipul Gautam1, Dibya Jyoti Das2, Shaleen Agarwal3, Vikram Kumar1,
were significantly higher than those in the simple hepatitis E group,
Sanjiv Saigal4, Subhash Gupta3
while the lymphocyte count, platelet (PLT), lymphocyte count, total T
1
Department of Pediatric hepatology, Max Centre for Liver and Biliary
lymphocyte count, and suppressor/cytotoxic T lymphocyte levels in
Sciences, New Delhi, 2Department of Critical Care, Max Centre
the simple hepatitis E group were higher than those in the hepatitis E
for Liver and Biliary Sciences, New Delhi, 3Department of Liver
and hepatitis B group, and the difference was statistically significant
Transplant Surgery, Max Centre for Liver and Biliary Sciences, New
(P<0.05). The levels of total bilirubin, immunoglobulin G, rheumatoid Hospital of Nanjing Medical University, Suzhou Municipal Hospital,
factor and type IV collagen in the antiviral group were significantly Suzhou Key Laboratory of Intelligent Critical Illness Biomarkers
higher than those in the non-antiviral group, while the lymphocyte Translational Reserach, Jiangsu, China
count, platelet (PLT), lymphocyte count, total T lymphocyte count, Background: Hepatitis E virus (HEV) is among the most common
suppressor/cytotoxic T lymphocyte and HBV-DNA levels in the non- but least diagnosed etiologies of acute viral hepatitis. A minority of
antiviral group were significantly higher than those in the antiviral the infected individuals may experience acute liver failure (ALF) , and
group, and the difference was statistically significant (P<0.05). the mortality rate of ALF is high if no intensive treatment support and
Conclusion: The condition of patients with HEV and CHB co- liver transplantation are provided. Thus, timely and effective prognostic
infection is more serious than that of patients with simple hepatitis E. biomarkers for HEV-ALF are urgently needed.
In particular, the severity and chronicity of the overlapping infection Method: We performed four tandem mass tag (TMT)-labeled
group are significantly higher than those of the simple hepatitis E quantitative proteomic and targeted proteomics parallel reaction
group; patients receiving antiviral treatment are superior to the non- monitoring (PRM) studies on cross-sectional cohort 1 and 2 including
antiviral group in clinical symptoms and laboratory indicators such as 20 acute hepatitis E and 20 HEV-ALF patients respectively. Multiple
liver function, immune function and fibrosis indicators, suggesting that machine learning (ML) classification models are integrated to
antiviral treatment has certain clinical value in delaying the severity and analyze and identify the optimal model, and Shapley Additive
chronicity of overlapping infections. Early identification and intervention exPlanations (SHAP) interpretation was developed for personalized
of these risk factors can help improve the prognosis of patients. risk assessment. RandomForest for classification and 10-fold cross
validation were performed to analyze and identify the serum proteomic
PP0328 profiles prognostic model, which had good predictive performance
and practical application value both in training set and test set.
One-Pot Assay Based on CRISPR/Cas13a Technology for HEV
Result: Pregnancy zone protein (PZP) was identified by TMT and PRM
RNA Point-of-Care Testing
quantitative proteomics, and verified in cross-sectional cohort 3, which
Zihao Fan1, Ling Xu1, Yaling Cao1, Tianxu Liu2, Yao Gao1, Xiangying showed that PZP level was highly correlated with survival time, clinical
Zhang1, Zhongping Duan1, Calvin Q Pan3, Lin Wang2, Feng Ren1 course and organ failure in HEV-ALF patients. PZP-TRFIA method was
1
Beijing Institute of Hepatology/Beijing Youan Hospital, Capital successfully constructed to provide the possibility for rapid detection
Medical University, 2Department of Microbiology and Infectious for patients with hepatitis E, which contribute to reduce the mortality
Disease Center, School of Basic Medical Sciences, Peking University of HEV-ALF.
Health Science Center, 3NYU Langone Medical Center, New York Conclusion: PZP is a promising prognostic biomarker for HEV-ALF
University School of Medicine
patients, and machine learning-based serum proteomic profiles model
Background: Hepatitis E virus (HEV) poses a serious threat to is a high-performance prognostic score for HEV-ALF, which contribute
both public health and animal food safety, thereby highlighting the to clinical decision-making in the management of HEV-ALF.
demands for rapid, sensitive, and easy-to-use detection. This study
aimed to develop a One-Pot assay using CRISPR/Cas13a for detecting
HEV RNA, suitable for point-of-care testing (POCT) in resource-limited
PP0330
settings. Does glucocorticoid therapy improve the short-term outcomes in
Method: CRISPR/Cas13a combined with reverse transcription patients with acute hepatitis E?
polymerase chain reaction (RT-PCR) and reverse transcription YUYI ZHANG1, LIUJUAN JI1, YU LIU1, YING ZOU1, HUI ZHU1,
recombinase-aided amplification (RT-RAA) was applied to a One-Pot ZHENGGUO ZHANG1, WEI YUAN1, ZHIPING QIAN1, XUE MEI1
assay device. Additionally, a large cohort of HEV-infected patient (154) 1
Department of Liver Intensive Care Unit, Shanghai Public Health
and animal (104) specimens was utilized for validation. Clinical Center, Fudan University
Result: The RT-PCR/RT-RAA+CRISPR/Cas13a assays for HEV RNA Background: Hepatitis E virus (HEV) is the most common cause
detection (genotypes: HEV-1, HEV-3, and HEV-4) were established, of acute hepatitis. However, there is no specific therapy for acute
optimized, and validated, achieving a limit of detection (LoD) of 1 copy/ hepatitis, the current treatment is symptomatic and supportive, and
μL and 100% specificity. In the application validation for HEV infection, severe cases may require ribavirin or artificial liver for intervention.
the positive rates of the RT-PCR+CRISPR and RT-RAA+CRISPR assays Whether the use of glucocorticoids could prevent the progression
were 98.6% and 89.6% for patients, and 96.6% and 88.8% for animals, of severe disease and reduce the incidence of a poor short-term
respectively, which were superior to those of RT-qPCR. Furthermore, prognosis remains controversial.
sample rapid lysis, reagent lyophilization, and the One-Pot device Method: All 816 hospitalized patients diagnosed with acute hepatitis
were integrated to construct a One-Pot assay with a LoD of 102 E between January 2019 and June 2024 were included in our study
copies/μL. Despite slight decreases in sensitivity, the One-Pot assay and divided into survival and non-survival groups according to 90-day
significantly reduces the assay time to 35 minutes, making it easy to outcomes. The univariate analysis explored factors associated with
perform, minimizing contamination, and meeting the requirements for severe acute hepatitis E, matched the with-glucocorticoid and without-
screening. glucocorticoid groups using propensity score matching (PSM), and
Conclusion: We developed a One-Pot assay of HEV RNA using the explored the effect of glucocorticoid use on the incidence of severe
CRISPR/Cas13a which effectively realizes a “sample in, result out” hepatitis E and poor short-term outcomes.
POCT test and maximizes the impetus for POCT implementation and Result: The incidence of severe hepatitis E (high jaundice, liver
shows potential as a valuable tool for detecting and monitoring HEV failure, and pre-liver failure) was 50.3 % (411 / 816), 37 patients
infection. (4.53 %) had a 90-day poor prognosis, and 137 patients (16.79 %)
Table and Figure:Figure 1.Schematic of CRISPR/Cas13a Assays: HEV received corticosteroids during hospitalization. In univariate analysis,
RNA. patient age, combined chronic liver disease, MELD score, and NLR at
Figure 2.One-Pot Assays of HEV RNA based CRISPR/Cas13a System admission were closely associated with severe severity in patients with
in HEV-infected Samples. acute hepatitis E. After matching the basic conditions of patients with
glucocorticoid and those without glucocorticoid therapy, we found that
PP0329 glucocorticoid therapy was able to decrease the incidence of severe
Machine learning-based serum proteomic profiles for predicting hepatitis E(severe jaundice, liver failure, and pre-liver failure), mainly
prognosis for patients with HEV-related acute liver failure severe jaundice, but was unable to reduce the risk of liver failure and
90-day poor prognosis.
Changyi Ji1, Mengmeng Gu2, Luyu Wang1, Hongtao Wang1, Jian Wu2,
Conclusion: Corticosteroid therapy may prevent the worsening of
Chinese Consortium for the Study of Hepatitis E
diseases in patients with acute hepatitis E, mainly in those with severe
1
Research Center of Laboratory, Bengbu Medical University, Bengbu, jaundice, but it cannot prevent the occurrence of liver failure or improve
China, 2Department of Clinical Laboratory, The Affiliated Suzhou
short-term prognosis. Div. Headquarter Teaching Hospital MIRPUR AJK in Kashmir, 2MIMC,
1

Table and Figure:Figure 1.Clinical characteristics of all enrolled Mirpur AJK

participants Background: Leptospirosis, a bacterial infection often linked to
Figure 2.Baseline characteristics and outcomes of enrolled patients contaminated water, is common in many parts of Pakistan, including
with hepatitis E with and without corticosteroid therapy Kashmir. While it’s known to affect the liver, there’s limited research
on how this infection specifically impacts liver function in the Kashmiri
PP0331 population. This study aimed to explore changes in liver function
tests (LFTs) in people with leptospirosis in Kashmir to gain a better
Single-Cell Sequencing of Peripheral Blood Mononuclear Cells
understanding of how the disease affects the liver.
Reveals Distinct Immune Response Landscapes in Mild versus
Method: This study was conducted at the Divisional Headquarters
Severe Hepatitis E Virus Infection
Teaching Hospital in Mirpur, Azad Jammu and Kashmir, from
Xiaoman Liu1, Jian Wu2, Yijin Wang1
January to December 2023. We looked at 150 patients diagnosed
1
Department of Pharmacology, Joint Laboratory of Guangdong-Hong with leptospirosis, confirmed by an IgM ELISA test. On admission,
Kong Universities for Vascular Homeostasis and Diseases, School of we measured key liver function tests: alanine aminotransferase
Medicine, Southern University of Science and Technology, Shenzhen (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline
518055, China, 2Department of Clinical Laboratory, The Affiliated
phosphatase (ALP). We then grouped patients based on the severity
Suzhou Hospital of Nanjing Medical University, Suzhou Municipal
of their liver involvement—mild, moderate, or severe—and recorded
Hospital, Jiangsu, China
any related symptoms.
Background: Hepatitis E virus (HEV) infection is the most common Result: The 150 patients in our study had an average age of 38.2
cause of acute viral hepatitis worldwide, which is usually asymptomatic years, with 63% being male. We found that 88% of patients had
and self-limiting in healthy individuals. However, some may progress abnormal liver tests. For most of them (60%), the liver enzyme levels
fulminant hepatitis, resulting in a relatively high mortality rate. were mildly to moderately elevated, with average ALT levels of 125.4
Therefore, we applied single-cell RNA sequencing (scRNA-seq) U/L and AST levels of 118.7 U/L. However, 25 patients (about 16.7%)
to elucidate pathways in peripheral immune cells that might lead to had significantly high ALT levels, over 500 U/L, suggesting severe liver
immunopathology or protective immunity in severe HEV. dysfunction. Around 70% of patients also had elevated bilirubin, with
Method: We performed single-cell RNA sequencing from 20 samples, an average of 1.6 mg/dL. Additionally, 35% of patients had increased
including 8 with acute hepatitis E(AHE), 8 with HEV-ALF and 4 HEV- ALP. We found that patients who had been exposed to contaminated
free healthy controls (HCs). Bioinformatic analyses and multiplex water were more likely to show liver abnormalities (p = 0.01). For those
immunohistochemistry were performed to assess the functional with the most severe liver dysfunction, nearly half (48%) developed
properties, transcriptional regulation, phenotypic switching and cell- complications such as jaundice or hepatic encephalopathy, and these
cell interactions of different cell subtypes. patients generally had worse outcomes (p < 0.05).
Result: We sequenced 170,000 cells with an average of 8500 cells per Conclusion: Liver dysfunction is common in patients with leptospirosis
sample. After creating a cells-by-genes expression matrix, we identified in Kashmir, with most experiencing mild to moderate changes in liver
124 clusters by UMAP and graph-based clustering. Eight distinct cell enzymes. Though less frequent, severe liver damage is linked to more
types were identified based on the molecular markers. The relative serious complications and poorer outcomes. Early detection and
percentage of CD8+ T cell, megakaryocyte and NK cell peaked in monitoring of liver function are critical for managing severe cases and
AHE group. Of note, the relative abundance of CD4+ T cell, monocyte improving patient outcomes.
and DCs decreased with disease severity. In contrast, the relative
percentage of macrophage and B cell increased with disease severity.
Sub clustering analysis revealed the proportions of a CD8+ naïve T PP0333
cell subset, paired with robust contractions of cytotoxic T lymphocytes Identification and function of G-quadruplex in genomic RNA of
(CTLs) and proliferating T cells, were increased in the HEV-ALF group hepatitis E virus
compared with the AHE group. Thus, the functional damage of CTLs Yuebao Li1, Tianxu Liu1, Lin Wang1
may have predisposed HEV patients to severe disease. Notably, the 1
Department of Microbiology and Infectious Disease Center, School
proportion of plasma B cells and memory B cells were increased in of Basic Medical Sciences, Peking University Health Science Center,
the HEV-ALF group compared with that in the AHE group. Our finding Beijing, China.
suggested that more severe cases may be associated with a more Background: Hepatitis E virus (HEV) is one of the most common
robust humoral immune response. Macrophage subsets play a central causes of acute hepatitis worldwide, it results in 20 million infections
role in immunosurveillance of the homeostatic liver and in initiating at least annually with approximately 3.3 million cases of acute illness
inflammatory response when encountering pathogen invasion. Sub and 44,000-70,000 deaths. G-quadruplex (G4s) is a kind of non-
clustering analysis revealed an increased proportion of angiogenic canonical structure formed in DNA or RNA which is composed of 4
macrophages and a decreased proportion of IFN-stimulated guanine stretches into stacked quartets. Because the genetic material
macrophage in HEV-ALF group compared with that in AHE group, of viruses is also nucleic acids, which have the structural basis for
indicating innate immune suppression in the HEV-ALF group. the formation of G4s. Currently, G4s have been found in the genomes
Conclusion: CTLs and IFN-stimulated macrophage become of many species of viruses, and they play an important role in the
dysfunctional in severe HEV patients. Exhaustion of CTLs and IFN- regulation of replication, transcription, and translation of different
stimulated macrophage may be one explanation why patients with viruses (such as YFV, HCV, HIV). Given the widespread distribution
severe disease failed to control HEV infection. In addition, plasma and function of G4s in viruses, it is of particular interest to explore the
B cells and memory B cells were enriched in the ALF group, further potential involvement of G4s in the genomic RNA of hepatitis E virus.
supporting the conclusion that a more robust humoral immune Method: Firstly, the genome of HEV KernowC1-p6 was predicted for
response is stimulated in severe cases compared with the mild cases. G4s by using QGRS Mapper online tool, and the multiple sequence
Table and Figure:Figure 1.Fig 1. Single-cell transcriptional profiling of alignment analysis of potential G4s sequence using 497 complete
PBMCs from HDs and patients with HEV genomic sequences of HEV retrieved from the NCBI database. At the
Figure 2.Fig 2. Single-Cell Analysis of CD8+T Cell,B Cell and same time, we examined the effect of Pyridostatin (PDS), a structural
macrophage by scRNA-Seq stabiliser of G4s on HEV-infected HepG2/C3A cells by RT-qPCR, ELISA,
Western blot. To verify formation of the potential G4s structure, we
PP0332 performed Circular dichroism (CD) analysis, a dependable biophysical
Liver function tests alterations in leptospirosis in the Kashmir, method and Native PAGE to monitor G4s conformation in vitro.
Pakistan. A retrospective analysis Result: According to the prediction of the HEV KernowC1-p6 genome
with the QGRS Mapper tool and the multiple sequence alignment
Usman Ghani1, SyedLal Shah1, Sultan Salahuddin1,2
analysis, we obtained a total of 8 sequences that are more conserved PP0335
and have the potential for G4s structure formation. At the same time, Hepatitis E virus infection and kidney injury in
we found that HEV-infected HepG2/C3A cells was inhibited after the nonimmunocompromised host: Clinical investigation and rabbit
treatment of PDS, as evidenced by a dose-dependent decrease in model study
its supernatant and intracellular HEV RNA, secreted antigens, and
Weigang Zhang1, Qiyu He2, Hao Wang3, Lei Qin4, Yu Wang5, Yuting
ORF2/3 protein. The recorded CD spectra of 4 of these sequences
Wang 6, Wei Chen 7, Wei He 8, Lin Wang9, Yunjie Lu4
displayed the characteristic 260 nm positive peak and 240nm negative
peak in the presence of K+ ion (100 mM) indicating a parallel G4s
1
Department of Hepatopancreatobiliary surgery, The First Affiliated
Hospital of Soochow University, Suzhou, China, 2Department of
topology. In-gel staining with ethidium bromide, different band patterns
Microbiology and Infectious Disease Center, School of Basic Medical
were present in PQSWT and PQSMUT RNAs, confirming an impact
Sciences, Peking University Health Science Center, Beijing, China.,
of the mutations on the RNA folding landscape. Expectedly, in-gel 3
Department of General Surgery, Children‘s Hospital of Nanjing
staining with NMM, a light-up probe for G4s show bands with strong
Medical University, Nanjing, China., 4Department of General Surgery,
fluorescence for PQSWT, whereas the bands of PQSMUT were much The First Affiliated Hospital of Soochow University, Suzhou, China,
weaker or completely devoid of signal. 5
Department of Hepatobiliary Surgery, Jintan Affiliated Hospital of
Conclusion: In combination, these data provide evidence that 4 Jiangsu University, Changzhou, Jiangsu 213200, China., 6Department
conserved PQSs in the HEV RNA can fold stable, parallel G4s in vitro. of Infectious Diseases, Kunshan First People‘s Hospital affiliated to
Owing to the high G-tract conservation and clear G4s formation in the Jiangsu University, Kunshan, Jiangsu, 215300, China., 7Department of
biochemical and biophysical assays, we will focus on characterizing IDepartment of Infectious Diseases, Kunshan First People‘s Hospital
the structural and functional of the critical PQS in HEV RNA. affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, China.
nfectious Diseases, Kunshan First People‘s Hospital affiliated to
PP0334 Jiangsu University, Kunshan, Jiangsu, 215300, China., 8Department
ofDepartment of General Surgery, Wujin Affiliated Hospital of Jiangsu
Prevalence and determinants of hypoglycaemia in acute hepatitis University and the Wujin clinical college of Xuzhou medical university,
due to hepatitis A and hepatitis E. Insights from the Kashmir, Changzhou, Jiangsu, China IDepartment of Infectious Diseases,
Pakistan. Kunshan First People‘s Hospital affiliated to Jiangsu University,
Usman Ghani1, Abrar Umar2 Kunshan, Jiangsu, 215300, China.nfectious Diseases, Kunshan First
1
Div. Headquarter Teaching Hospital MIRPUR AJK in Kashmir, 2MIMC People‘s Hospital affiliated to Jiangsu University, Kunshan, Jiangsu,
MIRPUR AJK in Kashmir 2
15300, China., 9 Department of Microbiology and Infectious Disease
Center, School of Basic Medical Sciences, Peking University Health
Background: Hypoglycaemia, or low blood sugar, is a potentially
Science Center, Beijing, China.
dangerous complication that can occur in patients with acute hepatitis.
Hepatitis A (HAV) and Hepatitis E (HEV) are common viral infections in Background: Hepatitis E virus (HEV)-related kidney injury is mainly
Kashmir, yet the prevalence and risk factors for hypoglycaemia in these reported in immunocompromised patients. Here, we investigated HEV-
conditions remain poorly understood. This study aims to assess how related kidney injury in nonimmunocompromised acute hepatitis E
often hypoglycaemia occurs in patients with acute hepatitis caused by (AHE) patients and rabbits.
HAV and HEV and to identify the factors that make some patients more Method: Thirty-five nonimmunocompromised AHE patients were
vulnerable to developing this complication. tested for kidney function parameters and HEV markers. HEV3- and
Method: This study was conducted at Div. Headquarter Teaching HEV4-infected rabbits were tested for alanine aminotransferase,
Hospital MIRPUR AJK in Kashmir, between July-2023 to Aug-2024 creatinine (Cr) and HEV markers. HEV-related kidney injury and renal
and included patients diagnosed with acute hepatitis due to HAV or HEV replication were analyzed by histopathology and RT-qPCR.
HEV. The diagnosis was confirmed using clinical signs and laboratory Result: Nonimmunocompromised AHE patients all showed normal
tests. Blood glucose levels were monitored regularly from admission serum Cr, Blood Urea Nitrogen (BUN) and urine acid (UA). However,
until discharge. We also collected information on each patient’s age, twenty-five percent of nonimmunocompromised AHE patients showed
gender, nutritional status, liver function (via liver enzyme levels), and proteinuria. In the rabbit model, HEV replication was observed in
any other health conditions such as diabetes. Hypoglycaemia was kidney tissues. HEV-infected rabbits showed transient elevated Cr
defined as blood glucose levels below 70 mg/dL. To analyze the data, level. Kidney injury, including focal lymphocytic infiltration and tubular
we used statistical tests to determine which factors were most closely protein casts was observed in rabbits at acute, recovery and chronic
linked to hypoglycaemia. phases of HEV infection.
Result: A total of 150 patients participated in the study, with an equal Conclusion: Proteinuria is not uncommon in nonimmunocompromised
split of 75 patients diagnosed with Hepatitis A and 75 with Hepatitis E. AHE patients, indicating that HEV infection affects kidney. We further
Overall, 42% of the patients experienced hypoglycaemia, but this was proved that HEV can cause renal impairment in a rabbit model.
more common in those with Hepatitis E (50%) than those with Hepatitis Table and Figure:Figure 1.Figure 1. Dynamics of liver and kidney
A (34%) (p=0.03). The average age of patients was 32 years (ranging function in the HEV-infected rabbit model.
from 18 to 60 years), and 58% were male. Hypoglycaemia was Figure 2.Figure 2. Histopathology of kidney and liver in rabbits with
particularly prevalent in patients with severe liver damage. Of those acute and chronic hepatitis E virus (HEV) infection.
with liver failure (bilirubin >10 mg/dL), 55% developed hypoglycaemia,
compared to just 28% in patients with milder liver damage (bilirubin <5 PP0336
mg/dL) (p=0.001). Our analysis showed that severe liver dysfunction,
The diagnostic value of gut microbiota analysis for acute hepatitis
younger age, and poor nutrition were the strongest predictors of
E infection in the elderly
hypoglycaemia. Interestingly, diabetic patients were also at higher risk,
with 15% of them developing hypoglycaemia, compared to 5% in non- Mengmeng Gu1, Changyi Ji2, Jian Wu1, Chinese Consortium for the
diabetic patients (p=0.02). Study of Hepatitis E
Conclusion: Hypoglycaemia is a frequent and concerning
1
Department of Clinical Laboratory, The Affiliated Suzhou Hospital
complication in patients with acute hepatitis caused by both Hepatitis of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu,
A and Hepatitis E in Kashmir. The risk is higher in those with severe liver China, 2Research Center of Laboratory, Bengbu Medical University,
damage, poor nutrition, and younger age. Hepatitis E, in particular, Bengbu, China
appears to be linked with a greater likelihood of hypoglycaemia Background: Hepatitis E virus (HEV) infection is a leading cause of
than Hepatitis A. This underscores the importance of regular blood acute hepatitis worldwide, and results in high morbidity and mortality
glucose monitoring, early intervention, and nutritional support for rates among elderly people in China. Gut dysbiosis has been reported
these patients. Further research is needed to better understand the in severe liver disease. However, the information regarding the effect
mechanisms behind hypoglycaemia in viral hepatitis and to develop of HEV infection on gut microbiota and the relationship between gut
strategies to prevent it. microbiota dysbiosis and acute hepatitis E (AHE) is limited, especially
in elderly patients with AHE. We aimed to identify elderly patients with Gastrointestinal tuberculosis accounts for 1-3% of all TB cases
AHE-specific microbiome and its association to patients’ outcomes. globally(1), with ileocolonic TB comprising 50-70%(2). Hepatic
Method: Fecal samples and clinical data were collected from 58 tuberculosis occurs in 0.3-0.7%(3), while biliary TB is found in 0.2-
AHE elderly patients (46 self-healing patients and 12 non-self-healing 1%(4) of extra-intestinal tuberculosis. We present to you an extremely
self-healing) and 30 healthy elderly controls. The gut microbiota rare case of an immunocompetent male who presented with co-
community was analyzed using 16S ribosomal RNA gene sequencing. infection of hepatic and gastrointestinal tuberculosis initially masking
Bioinformatic analysis including alpha diversity and STAMP was as a case of Crohn’s disease with biliary sclerosis.
performed. The predictive power of Bacteroides fragilis was assessed A 42-year-old male presented with a three-month history of intermittent
by statistical analysis and receiver operating characteristic (ROC) abdominal pain, initially treated as acid peptic disease. His symptoms
curve analysis. worsened to include weight loss (11 kg), fever (40°C), fatigue, and
Result: Shannon and Simpson’s indices showed no significant watery diarrhea, prompting admission in Spain. During his stay, he
differences in bacterial diversity between the AHE-Elderly and HCs- developed jaundice and icteresia.
Elderly groups. According to the rarefaction analysis Estimates, the Tests revealed elevated alkaline phosphatase, bilirubin, and liver
trend of species richness in AHE-Elderly was lower than that of the enzymes. Viral hepatitis and autoimmune tests were negative. CT scan
HCs-Elderly group. In the AHE-Elderly group, the relative abundance showed strictures in the terminal ileum and cecum, along with dilated
of Firmicutes, Lactobacillales, bacilli increased significantly, while hepatic ducts, raising suspicion for primary sclerosing cholangitis
Proteobacteria, Xanthomonas, Gammaproteobacteria, Bacteroidetes or biliary cholangiocarcinoma. MRI confirmed Crohn’s disease with
decreased significantly. The cladogram revealed the microbiome possible primary sclerosing cholangitis. He responded to mesalazine
differences between the two groups across multiple phylogeneti levels. and steroids and was discharged stable.
Compared with the AHE-Elderly group with self-healing, Bacteroidetes A month later, the patient returned with epigastric pain, fever, and
were more abundant in the non-self-healing group. a productive cough. Antibiotics and steroids were started, but
Conclusion: The abundance of Bacteroidetes could discriminate inflammatory markers remained high. CT imaging showed thickened
AHE-Elderly patients from HCs-Elderly, and could better predict the bowel walls and liver calcifications. A biopsy of the hepatic mass
recovery of AHE-Elderly patients, providing new strategies for the revealed hepatic tuberculosis, and ERCP with cytology brushing was
prevention and treatment of AHE recurrence in patients with elderly. positive for tuberculosis. Colonoscopy showed ileocolonic ulcers, and
TB PCR testing confirmed disseminated tuberculosis affecting both
the gastrointestinal and hepatobiliary systems. Crohn’s medications
PP0337
were stopped, and anti-tuberculosis therapy was started. The patient
Changing etiology of HCC in Mongolia, an A-HOC initiative update improved and was discharged with anti-tuberculosis medications.
Amarsanaa Jazag1,2,3, Erdenebayar Gonchig1,2, Byambatsetseg Disseminated tuberculosis involving the gastrointestinal tract is rare
Togtuunbayar1,2, Enkhbold Chinbold1,4, Erkhembayar Dimaa1,5, and can pose diagnostic challenges due to the nonspecific nature of
Bolorchimeg Batsaikhan1, Oidov Baatarkhuu1,6 symptoms, which often overlap with other conditions like inflammatory
1
Mongolian Association for the Study of Liver Diseases, 2Happy bowel disease and malignancies. In this case, the patient initially
Veritas Hospital, 3Otoch Manramba University, 4Second General presented with symptoms suggestive of Crohn’s disease, but further
Hospital, 5Mongolia-Japan teaching hospital, 6Department of workup, including biopsy, TB PCR testing, and ERCP, ultimately
Infectious Diseases, Mongolian National University of Medical confirmed the diagnosis of disseminated tuberculosis. Ileocolonic,
Sciences hepatic, and biliary tuberculosis are less common but important
Background: According to WHO statistics, in 2022, more than 19.9 manifestations of extrapulmonary TB, particularly in endemic areas.
million people were diagnosed with cancer and 9.7 million people died
from cancer. Mongolia leads the world in terms of total cancer deaths, PP0340
liver cancer incidence and mortality. In 2023, 7,244 new cancer cases
were registered among the Mongolian population, of which liver cancer Aneurysmal Splenic Vein With Arteriovenous Fistula In A 57-year-
accounted for 32.8%. The incidence rate of liver cancer is the highest old Cirrhotic Patient With Refractory Portal Hypertension: A Case
in either gender, at 80.3 cases per 100,000 male population and 60.3 Report
cases per 100,000 female population. Yrah Damiene Magdaluyo Fernandez1, Ferdinand Maitim Anzo1, Ma.
Method: The study included 586 patients who were registered with Cristina Caluag Africa1, Kevin Rae Ramirez Lumunsad1
post, or current HCC diagnosis at Happy Veritas Hospital and 4 other 1
St. Luke‘s Medical Center Quezon City
hospitals between 2023 and 2025, and the causes of liver cancer ANEURYSMAL SPLENIC VEIN WITH ARTERIOVENOUS FISTULA IN
were determined based on the clinical data of the study participants. A 57-YEAR-OLD CIRRHOTIC PATIENT WITH REFRACTORY PORTAL
A-HOC database was used to analyse the information. All HCC cases HYPERTENSION: A CASE REPORT
were registered without age limitations. HCC patients diagnosed prior Yrah Damiene M. Fernandez, MD [1], Ferdinand M. Anzo, MD [1],
to 2013 were excluded. Kevin Rae R. Lumunsad, MD [1] Ma. Cristina C. Africa, MD [1]
Result: Of the 586 people diagnosed with liver cancer, 116 or 19.7% 1 – Institute of Digestive and Liver Diseases, St. Luke’s Medical Center
had viral hepatitis C virus as the cause of HCC and 287 or 48.7% had Quezon City, Philippines
hepatitis B or co-infection of HBV and HDV as the cause, 18 or 3.9% ABSTRACT
had alcohol related HCC, and 165 or 28.1% had other or unknown BACKGROUND: Splenic vein aneurysms are rare, with fewer than five
causes. cases reported. They can be congenital or acquired, with acquired
Conclusion: HCC etiology dynamics is changing rapidly in the last 10 lesions primarily associated with portal hypertension and cirrhosis.
years due to eradication of HCV and other unknown reasons. MAFLD Most patients are asymptomatic, and these aneurysms are often found
is one of major causes of HCC in modern world. This changing trend is incidentally. However, they may pose a risk for fatal complications,
not an exception for Mongolia. such as rupture, particularly in patients with severe portal hypertension
or bleeding due to liver failure.
PP0339 CASE PRESENTATION: A 57-year-old Filipino male with cirrhosis
secondary to chronic hepatitis B presented with recurrent massive
Disseminated Hepatic and Gastrointestinal Tuberculosis
hematemesis and hematochezia despite multiple rubber-band ligations.
Mimicking Crohn’s Disease with Biliary Sclerosis: A Rare Case in
His current regimen included Tenofovir Alafenamide, Aminoleban, and
an Immunocompetent Patient
Carvedilol. After hemodynamic stabilization, emergency gastroscopy
Kimberly Nadine Mendez Manalastas1, Louie Figueroa1, James revealed large esophageal varices with red whale signs, and a total of
Malicdem Montesa1 three rubber bands were deployed. Although bleeding did not recur,
1
Manila Doctors Hospital new-onset ascites developed and paracentesis indicated ascites from
portal hypertension (SAAG 2.0), prompting initiation of Spironolactone.
Liver ultrasound with Doppler showed non-occlusive portal vein treating echinococcosis remains a great challenge, especially with
thrombosis and portosystemic collaterals in the splenic region. A albendazole as the preferred drug of choice. Receptor tyrosine
4-phase dynamic CT confirmed a stable aneurysm of the distal splenic kinases (RTKs) signaling controls normal cellular proliferation,
vein (5.5 x 3.5 cm), with associated portosystemic shunting and an differentiation, and metabolism in humans and mammals, which are
arteriovenous fistula (AVF) contributing to portal hypertension. Despite intermediate hosts for E. granulosus and E. multilocularis. Disruption
recommendations for endovascular repair or surgical resection, the of RTKs signaling can cause various carcinogenesis and exacerbates
patient’s clinical condition and thrombocytopenia posed significant the progression of certain parasitosis. As a result, a large number
risks. Given financial constraints, medical management was optimized, of studies on tyrosine kinase inhibitors (TKIs) have been conducted
and the patient was discharged in stable condition. for the therapy of cancers and parasitosis, with some TKIs already
CONCLUSION: Splenic vein aneurysms are rare and can be congenital approved for clinical cancer treatment. Notably, RTKs signaling has
or acquired. Due to their low incidence, treatment guidelines remain been identified in the parasites E. granulosus and E. multilocularis, but
unclear. In low-risk patients, prophylactic surgery may be considered, the mechanisms of RTKs signaling response in Echinococcus-host
while decompression may be the preferred option for difficult-to-excise intercommunication are not fully understood.
portal aneurysms with portal hypertension. High-risk or asymptomatic Method: Thus, understanding the RTKs signaling response in
patients may only require observation. As more cases are reported, Echinococcus-host intercommunication and the potential effect of
treatment strategies will evolve, but each case should be individually RTKs signaling is crucial for the treatment of echinococcosis.
assessed. Result: This review illustrates that RTKs signaling in the host is over-
activated by the parasite E. granulosus or E. multilocularis infection,
and can further facilitate the development of E. granulosus or E.
PP0341
multilocularis metacestodes in vitro. At the same time, some TKIs exert
Isolated Gastric Varices (SARIN IGV1) Secondary to a Porta strong parasiticidal effects on E. granulosus or E. multilocularis both
Hepatis Mass in a Patient with Disseminated TB: A Rare Case in vitro and/or in vivo through the down-regulation of RTKs signaling
Report molecules.
Sam Nogoy Fandood1 Conclusion: These findings suggest that RTKs signaling may be
1
East Avenue Medical Center Quzeon City a promising drug-target, and that TKIs could be a potential anti-
BACKGROUND Echinococcus drug for the future control of echinococcosis.
Isolated gastric varices (IGVs) are an uncommon but potentially life- Table and Figure:Figure 1.RTK signaling as apotential drug target for
threatening manifestation of portal hypertension. While commonly thetreatment of liver echinococcosis
associated with liver cirrhosis, IGVs can arise due to localized venous
obstruction, such as compression by a porta hepatis mass. PP0343
CASE SUMMARY
Global Research Trends and Hotspots of Autophagy in Liver
We report a rare case of a 45-year-old patient presenting with
Failure: A Bibliometric and Visualized Study Based on Web of
hematemesis. Laboratory results showed anemia (Hgb: 5.1 g/L),
Science from 2007 to 2024
coagulopathy (PT 15.0, INR 1.17, aPTT 47.8), jaundice (TB 66.55
mmol/L) and hypoalbuminemia (23.3 g/L). Patient was started on Huan Wu1, Long Wu1, Can Li1, Quan Zhang1, Mao Mu1
Octreotide drip. Esophagogastroduodenosocpy showed large
1
No. 28 Guiyi Street
tortuous violaceous vessels at the cardia with signs of recent bleed Background: Autophagy is a conservative catabolic process, which
(red wale signs). Histoacryl injection was planned. CT Scan was plays a vital role during the liver failure and is a potential therapeutic
done which a 3.6 x 4.7 x 3.7 cm (CCxWxAP) fairly-to-well defined, target for preventing and treating liver failure. However, there is a lack
peripherally-enhancing, hypodense mass-like lesion with few internal of bibliometric analysis regarding the relationship between autophagy
air locules as well as calcifications at the porta hepatis. which abuts and liver failure. To highlight the knowledge structure and evolutionary
the celiac axis and common hepatic artery and encroaches the portal trends in research on autophagy in liver failure.
vein at the region of splenoportal confluence. It also revealed markedly Method: The Web of Science Core Collection (WOSCC) was utilized
enlarged liver, measuring 19.0 cm at the midclavicular line, with to extract all publications related to autophagy and liver failure from
smooth borders but with multiple coarse, parenchymal calcifications, 2007 to 2024. The contributions of various countries, institutions,
and fairly-defined, hypoenhancing nodules in both hepatic lobes with journals, authors, keywords, and references in this field were analyzed.
largest nodule is noted in segment 3, measuring 2.9 x 1,4x 2.0 cm Furthermore, research hotspots and promising future trends were
(CCxWxAP). Work ups for disseminated TB was done. Sputum Gene identified through data processing was carried out using R package
Xpert detected mycobacterium Tuberculosis. She was started on anti “Bibliometrix”, VOSviewers, and CiteSpace network visualization.
Tuberculosis regimen. Result: From 2007 to 2024, research on autophagy in liver failure
CONCLUSION: developed rapidly, a total of 238 related publications were identified
Isolated gastric varices secondary to a porta hepatis mass are a rare and collected, showing rising trends in annual publications and
but important differential diagnosis in non-cirrhotic portal hypertension. citations. China produced the most publications (n=143), prior to
Early diagnosis, variceal bleeding prevention, and addressing the USA (n=55), Germany and Spain (n=13). Zhejiang University
the underlying etiology are crucial for successful outcomes. (n=37), Frontiers in Pharmacology (n=11), and Jaeschke, H (n=13)
Multidisciplinary care ensures optimal management of both varices were the most productive and influential institution, journal, and
and the mass. author, respectively. Journal of Hepatology has the highest total
number of citations (n=51) and the average citation times (n=8.5).
An analysis of keyword co-occurrence showed that oxidative stress,
PP0342
apoptosis, and cell-death were the latest high-frequency research
Receptor tyrosine kinases signaling involves Echinococcus- hotspots that represented promising future research directions. Novel
host intercommunication: a potential therapeutic target in liver drugs targeting specific molecules such as Mfn2 and PPAR have
echinococcosis demonstrated therapeutic potential but are still in the preclinical stage
Haijun Gao1, Fangye Zhou1, Xiaojin Mo2, Ting Zhang2 of development.
1
Chengdu Fifth People‘s Hospital, 2China CDC Conclusion: This is the first comprehensive bibliometric study
Background: Echinococcosis, one of the most serious and life- summarizing the knowledge structure and emerging frontiers of
threatening parasitic zoonosis worldwide, is caused by the larvae research on autophagy in liver failure from 2007 to 2024. The findings
of Echinococcus granulosus (E. granulosus) and Echinococcus aid in identifying recent research frontiers and hot topics, providing
multilocularis (E. multilocularis). Various therapeutic strategies are valuable references for scholars investigating the role of autophagy
being applied clinically to treat this zoonosis, but their efficacy in in liver failure.
Table and Figure:Figure 1.
 PP0344 tool for diagnosing unexplained liver injury. Expanding the sample size
Neurogenic shock after liver biopsy: A case report in future studies will allow us to better verify the initial findings.
Table and Figure:Figure 1. Screening and enrollment of patients in the
Bahejianati NUERBOLATI1, Songsong XIE2
respective cohort analysis
1
SHIHEZI UNIVERSITY, 2First Affiliated Hospital, Shihezi University Figure 2.Venn diagram of the diagnostic matching in pairwise
Abstract: Background: Shock is life-threatening circulatory failure comparisons among subjects in Admission, Histological and Final
with inadequate tissue perfusion. Risks of percutaneous liver biopsy diagnosis groups.
include bleeding, organ perforation, sepsis and death. The major
complication most commonly reported in the literature is bleeding,
PP0346
without any report about neurogenic shock. Case Summary: Here we
report a case of a 53-year-old female. She was admitted to the hospital A novel model for distinguishing infections from patients with
with elevated serum transaminase levels, total bilirubin. Considering the acute-on-chronic liver disease (AoCLD) and systemic inflammatory
highly elevated autoimmune proteins and antigenic antibodies, a liver response syndrome (SIRS): A nationwide, multicenter, prospective
biopsy was performed in order to determine whether she had comorbid cohort study
autoimmune hepatitis. After liver puncture was performed, the patient’s Hui Zhou1, Hai Li2,3,4, Guo Hong Deng5,4, Xian Bo Wang6,4, Xin
vital signs were stable, the liver biopsy was successfully completed, Zheng7,4, Jin Jun Chen8,4, Yan Huang1,4, Ruo Chan Chen1
and she was taken to the ward accompanied by medical staff. Half 1
Department of Infectious Diseases, Hunan Key Laboratory of Viral
an hour after the liver puncture, the patient suddenly had abdominal Hepatitis, Xiangya Hospital, Central South University, Changsha,
pain and severe pressure pain in the abdomen, accompanied by China, 2Department of Gastroenterology, School of Medicine, Ren
pallor, rapid pulse and dyspnea. On examination, he was diagnosed Ji Hospital, Shanghai Jiao Tong University, Shanghai, China, 3Key
with “neurogenic shock”. Neurogenic shock after liver biopsy is rare, Laboratory of Gastroenterology and Hepatology, Shanghai Institute
so we summarize the pathologic features and prognostic factors of of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong
neurogenic shock in this case and in the light of previous reports of University), Shanghai, China, 4Chinese Chronic Liver Failure (CLIF)
cases of shock. Conclusions: Therefore, the occurrence of neurogenic Consortium, Shanghai, China, 5Department of Infectious Diseases,
shock is unpredictable, and clinicians should always be alert to the Southwest Hospital, Third Military Medical University (Army Medical
possibility of shock, focusing on sensitive index values such as blood University), Chongqing, China, 6Center of Integrative Medicine, Beijing
pressure and heart rate to ensure prognosis and regression. Ditan Hospital, Capital Medical University, Beijing, China, 7Department
of Infectious Diseases, Institute of Infection and Immunology, Tongji
Medical College, Union Hospital, Huazhong University of Science
PP0345 and Technology, Wuhan, China, 8Hepatology Unit, Department of
A single-center, retrospective cohort study on the histological and Infectious diseases, Nanfang Hospital, Southern Medical University,
clinical features of unexplained liver injury Guangzhou, China
Lingling Yang1,2, Zhikun Wang1,2, Ke Bai 1, Linqian Wu1, Hui Zhu1, Background: In the context of systemic inflammatory response
Lifang Chen1, Liangtao Zeng3, Zhili Wen1 syndrome (SIRS), acute-on-chronic liver disease (AoCLD) patients
1
Department of Gastroenterology, The Second Affiliated Hospital of often exhibit significant inflammatory responses, but this does not
Nanchang University, 2Department of Molecular Biosciences, The necessarily indicate the presence of infection. Therefore, it is necessary
University of Kansas, Lawrence, USA,, 3Department of Pathology, The to establish an early diagnostic model that can effectively distinguish
Second Affiliated Hospital of Nanchang University whether infection is present in AoCLD patients with SIRS.
Background: Liver biopsy has been a valuable diagnostic tool Method: This study analyzed 515 patients with AoCLD and SIRS from
in identifying liver diseases with unknown etiology, however, there two multicenter, prospective cohorts of the Chinese Acute-on-Chronic
are remained instances where liver biopsy does not provide a clear Liver Failure (CATCH-LIFE) study. The dataset was randomly divided
diagnosis. This study aimed to determine the etiology of unexplained into training cohort (n=361) and validation cohorts (n=154) in a 7:3 ratio.
liver injury and assess the accuracy of the histological diagnosis. In the training cohort, logistic regression and least absolute shrinkage
Method: A retrospective analysis was conducted on the clinical and and selection operator regression analyses were performed to identify
histological data of patients with chronic liver disease of unknown independent risk factors for infection in patients with AoCLD and SIRS,
aetiology at the Second Affiliated Hospital of Nanchang University, and a simple nomogram was established. The diagnostic performance
China, who underwent liver biopsy between September 2019 and June and calibration of the model were evaluated using receiver operating
2024. Diagnoses were divided into admission diagnosis, histological characteristic curves, calibration curves, and decision curves in both
diagnosis and final diagnosis groups. the training and validation cohorts.
Result: A total of 104 patients were included, comprising 64 women Result: The early diagnostic model in this study includes five
(61.5%) and 40 men (38.5%), 96 (92.3%) patients of whom received variables: jaundice, ascites, neutrophil count (N), albumin (ALB),
a definitive diagnosis undergoing liver biopsy. They were: autoimmune and C-reactive protein (CRP). The Area Under the Curve (AUC) and
liver disease (AILD, 49 cases, 44.1%), non-alcoholic fatty liver disease its 95% Confidence Interval (CI) in the training and validation cohorts
(NAFLD, 26 cases, 23.4%), drug-induced liver injury (DILI, 22cases, were 0.816 (95% CI: 0.772-0.855) and 0.857 (95% CI: 0.792-0.908),
19.8%), porto-sinusoidal vascular disease (PSVD, 4 casess, 3.6%), respectively, significantly outperforming the use of CRP, procalcitonin
obstructive jaundice (3 cases, 2.7%), Toxic hepatitis due to infection (PCT), or N alone. The calibration and decision curves confirmed that
(3 cases, 2.7%), alcoholic steatohepatitis (2 case, 1.8%), Wilson’s our model demonstrated good calibration and clinical utility.
disease (1 cases, 0.9%) and immune checkpoint inhibitor-induced liver Conclusion: We have successfully developed an early diagnostic
injury (1 case, 0.9%). The most common etiology was AILD in women model that can effectively distinguish between infected and non-
(40 cases, 55.6%) versus NAFLD in men group (19 cases, 40.4%). infected patients with AoCLD and SIRS, providing guidance for clinical
Venn diagram of the diagnostic matching in pairwise comparisons decision-making.
showed that 60 cases (57.7%) matched between the admission- Table and Figure:Figure 1.Evaluation of Model Diagnostic Performance
and histological diagnosis, 63 cases (60.6%) matched between the and Calibration
admission- and final diagnosis, 96 cases (92.3%) matched between
the histological- and final diagnosis. It indicated that nearly half of PP0347
patients could not be diagnosed upon hospital admission but that liver Meta analysis of the safety and efficacy of fibrates in the treatment
biopsy was highly effective in diagnosing the underlying cause of liver of non-alcoholic fatty liver disease
injury in the majority of cases.
Yunfei Hu1
Conclusion: The main causes of unexplained liver injury were AILD, 1
First People‘s Hospital of Fuzhou
NAFLD, and DILI. Although there are instances (7.7%) where liver
biopsy does not match the diagnosis, it remains a crucial and effective Background: Systematic review of the efficacy and safety of fibrates
in the treatment of non-alcoholic fatty liver disease. (GB) integrity, and uncontrolled intrahepatic immune responses.
Method: Retrieve all literature from multiple databases including CNKI Clostridium butyricum (C. butyricum), a probiotic bacterium known
and PubMed using search terms in both Chinese and English until for its anti-inflammatory and gut-stabilizing properties, produces
November 1, 2024. Two professional evaluators will gradually select beneficial metabolites such as short-chain fatty acids (SCFAs) and
studies that meet the criteria based on their titles, abstracts, and full promotes microbial diversity.
texts. Extract relevant data for inclusion in the study and conduct bias Method: SPF and germ-free (GF) male mice were divided into four
risk assessment. Use RevMan 5.3 software for data analysis. groups: C. butyricum- vehicle and LPS, PBS-LPS, and vehicle.
Result: Fourteen randomized controlled studies were included, and Mice received oral C. butyricum (1 × 10⁸ CFU) three times weekly
the meta-analysis results showed that compared with the control group, for 21 days, followed by intraperitoneal LPS (10 mg/kg) to induce
the treatment group was superior to the control group in improving inflammation 24 hours before sacrifice. Serum alanine transaminase
liver function, liver fibrosis indicators, and blood lipid metabolism, with (ALT) and aspartate aminotransferase (AST) levels were measured to
statistically significant differences and fewer adverse reactions. assess liver injury. Fecal samples were collected for SCFA analysis
Conclusion: Fibrates have good clinical efficacy in the treatment of and GM composition via 16S rRNA sequencing. Liver tissues were
non-alcoholic fatty liver disease, with few adverse reactions. analyzed for mitochondrial ROS (MitoSOX), apoptosis (Annexin V/
PI), immune cell profiling (flow cytometry), and tight junction protein
ZO-1 expression (confocal microscopy). In vitro, Caco-2 monolayers
PP0348
were treated with C. butyricum metabolites to evaluate GB function,
Prevention of Nosocomial Cross-Infection of Special Pathogens including ZO-1 localization and transepithelial resistance (TER).
during Digestive Endoscopy Examination in Infectious Disease Result: Oral administration of C. butyricum demonstrated significant
Specialty Hospitals hepatoprotective effects in mice with LPS-induced liver injury. Serum
Liping Chen1,2, Jing Wang3, Zhenyu Fan4, Jingmao Yang4, Cuili Lu4, ALT and AST levels were significantly reduced in the C. butyricum-
Xiangjun Ji3, Chunyan Lu 4, Yahong Xu4, Jilin Cheng4,5 treated group compared to PBS-LPS controls, indicating attenuated
1
Zhongshan Hospital Minhang Meilong Campus,Shanghai , 2Shanghai liver damage. Histological analysis revealed reduced necrosis and
Geriatrics Medical Center, 3Tianjin Second People‘s Hospital, inflammatory cell infiltration, along with decreased levels of pro-
4
Shanghai Public Health Clinical Center, 5Shanghai YiDa Hospital inflammatory cytokines TNF-α and IL-6, suggesting suppression of
Background: Infectious disease hospitals are gathering places for hepatic inflammatory pathways.Microbiota analysis showed that C.
patients infected with special pathogenic microorganisms such as butyricum significantly increased beneficial taxa, such as Lactobacillus
hepatitis B, hepatitis C, tuberculosis, HIV, and COVID-19. This study johnsonii and Parasutterella, while reducing pathogenic species like
aims to explore whether the routine endoscopic disinfection methods Shigella flexneri. Fecal SCFA levels, particularly butyrate and acetate,
used in general hospitals are also applicable to infectious disease were markedly elevated in the C. butyricum-treated group, reflecting
specialty hospitals following digestive endoscopy examinations and enhanced microbial fermentation. These SCFAs serve as critical
treatments. energy sources for colonocytes, strengthen gut barrier function, and
Method: Data were collected from two infectious disease specialty modulate systemic inflammatory responses, thereby contributing
hospitals in Tianjin and Shanghai over the past six years, involving to the protective effects observed within the gut-liver axis.In vitro,
48,458 patients who underwent digestive endoscopy and endoscopic treatment with C. butyricum metabolites significantly increased TER
ultrasound examinations. 32,163 cases of special infections and 15,895 and enhanced ZO-1 expression in Caco-2 monolayers, indicating
cases of non-special infections were included. Patients underwent improved GB integrity and reduced gut permeability.
one or more digestive endoscopy and ultrasound endoscopic Conclusion: These findings highlight the therapeutic potential of C.
examinations, and were tested for markers of special infectious butyricum as a GM-targeted intervention for liver diseases associated
pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), with gut-liver axis dysfunction, paving the way for novel probiotic-
and human immunodeficiency virus (HIV). The disinfection methods based treatments.
for endoscopes were the same as those in general hospitals. The
presence of special pathogenic markers in each test and any disputes PP0350
regarding nosocomial cross-contamination during the six-year period
Clinical Features and Treatment Outcomes of Hepatobiliary
were used as criteria for determining nosocomial cross-infection.
Tuberculosis: A Case Series and Literature Review
Result: Over the six years, there was no case of nosocomial
cross-infection resulting in positive markers for special pathogenic Tristan Paulo Madrigal1, Cyruz Jan David2, Ariane Marielle Valle3,
microorganisms such as HBV, HCV, or HIV among all patients, and no Mara Teresa Panlilio1
medical disputes arose due to nosocomial cross-infection.
1
Division of Gastroenterology, Department of Medicine, Philippine
Conclusion: Although the disinfection methods used in general General Hospital, 2Department of Radiology, Philippine General
hospital endoscopy centers are also applicable to infectious disease Hospital , 3Department of Laboratories, Philippine General Hospital -
specialty hospitals, the long-term repeated disinfection processes Manila, Philippines
may still lead to potential damage to the endoscope body and internal Background: Hepatobiliary tuberculosis (HBTB) accounts for only
channels. As a gathering place for patients infected with special 0.8-1.2% of tuberculosis cases worldwide. Disease may be limited
pathogenic microorganisms, infectious disease specialty hospitals to the liver, bile ducts, and gallbladder or, more frequently, as part
face a significant risk of cross-infection. Therefore, it is essential to treat of a disseminated infection. The diagnosis is often delayed when
every patient undergoing endoscopic treatment as a potential source complications have set in due to its non-specific clinical manifestations,
of infection to effectively prevent nosocomial cross-infection of special inconclusive liver test abnormalities, and varied imaging findings.
pathogens. Method: Eight patients with HBTB were reviewed. Diagnosis was made
using acid-fast stain, PCR test, or histologic finding of granulomatous
inflammation with Langhans giant cells.
PP0349
Result: Most patients were male (62.5%), with a mean age of 39.6 years.
Clostridium butyricum-Derived Metabolites Enhance Gut-Liver The most common site involved was the liver (87.5%), followed by bile
Axis Integrity to Mitigate LPS-Induced Hepatic Inflammation ducts (50%) and gallbladder (12.5%). All patients had extrahepatic
Jui Chen Tsai1, Kai Hung Tsai1, Ho Yu Kuo1, Pei Han Fan1, Hsiao Li involvement, predominantly in the lungs and lymph nodes. The mean
Chuang1, Hsiao Li Chuang1 duration from onset of symptoms to presentation was 4.8 months. Most
1
National Yang Ming Chiao Tung University patients had non-specific symptoms, most frequently abdominal pain
Background: LPS-induced hepatic damage is closely linked to and jaundice, and a cholestatic pattern of liver test abnormalities.
dysregulation of the gut-liver axis, including perturbations in gut The most common imaging findings were dilated biliary ducts,
microbiota (GM) composition, metabolomic shifts, impaired gut barrier hepatic nodules with internal calcification, and hepatic masses. Four
patients completely improved with treatment. Two patients developed
secondary biliary cirrhosis. Two patients succumbed to complications, Result: A total of 37 patients with perihepatic and hepatic tuberculosis
one due to pulmonary embolism and the other to bacterial peritonitis. and CT follow-up were collected, of which 14 cases (37.8%) exhibited
Conclusion: HBTB frequently occurs as part of a disseminated paradoxical reactions characterized by an enlargement of existing
disease. Most patients respond to treatment; however, select cases lesions or the appearance of new lesions upon review. Among these
require adjunct procedures, such as abscess aspiration or biliary 14 cases, 7 were male, 7 were female, with ages ranging from 17 to 46
drainage. A high index of suspicion, particularly in endemic regions, years and a median age of 23 years. Twelve patients had concurrent
is important to prevent treatment delays and the development of pulmonary tuberculosis, and 13 had other extrapulmonary tuberculosis.
sequelae and death. Thirteen patients tested positive for tuberculosis infection by interferon-
Table and Figure:Figure 1.Table 1. Summary Table on the Clinical gamma release assay (IGRA), and 8 had positive etiological results.
Features and Treatment Outcomes of Patients Diagnosed with HBTB Twelve patients showed a decrease in CD4+ T-cell counts. The time
to paradoxical reaction onset after initial diagnosis ranged from 13 to
PP0352 183 days, with a median of 82 days. Initial CT presentations in these 14
patients included 11 cases of perihepatic peritoneum/hepatic capsule
The clinical characteristics of drug-induced liver injury among linear or nodular thickening (capsular type), and 3 cases of combined
brucellosis patients perihepatic peritoneum/hepatic capsule linear or nodular thickening
Zhongshu Pu1, Xin Xue1, Xiaohong Niu1, Xinren Zhou1 with hepatic parenchymal lesions (mixed type). Capsular type
1
The 940th Hospital of Joint Logistics Support Force of the Chinese paradoxical reactions manifested as new or enlarged nodules of the
People’s Liberation Army perihepatic peritoneum/hepatic capsule and intrahepatic lesions, with
Background: The epidemic geography and the incidence of human marked ring enhancement on enhanced scans. Mixed type paradoxical
Brucellosis have been on a steady rise in recent years, posing reactions showed significant enlargement of perihepatic peritoneum/
a significant public health issue that impacts Aisa’s economic hepatic capsule lesions and intrahepatic lesions, with enhanced scans
development and people’s health. Drug-induced liver injury can occur showing higher ring enhancement than the initial presentation. Among
during the treatment of Brucellosis, affecting patients’ adherence to the 12 patients with long-term follow-up, lesion improvement began
treatment. Currently, the clinical cal characteristics, and influencing at 6 to 20 months, with a median of 12 months. CT imaging showed
factors related to liver injury caused by antibacterial drugs for gradual lesion size reduction, decreased ring enhancement density,
Brucellosis remain unclear. absence of ring enhancement, or lesion calcification.
Method: The clinical and laboratory data of 378 brucellosis patients Conclusion: During anti-tuberculosis treatment, perihepatic and
were retrospectively evaluated. All cases were re-evaluated using the hepatic tuberculosis can develop paradoxical reactions, often
international consensus of drug-induced liver injury. presenting as ring enhancement. After treatment, these paradoxical
Result: 26 patients were confirmed as drug-induced liver injury, drug- reaction lesions can show improvement, and CT enhanced scans have
induced liver injury occurred with a prevalence of about 6.88% among diagnostic value in the occurrence and progression of perihepatic and
brucellosis inpatients receiving drug therapy. The age of patients with hepatic tuberculosis.
drug-induced liver injury ranged from 10 to 71 years old. The patients Table and Figure:Figure 1.CT imaging manifestations of perihepatic
of drug-induced liver injury had lower age (P =0.045) and higher and hepatic tuberculosis
proportion of smoking than common infection (P =0.045). Comparison
of clinical symptoms showed that the proportion of poor appetite and PP0354
nausea in patients with drug-induced liver injury was significantly
Beyond the Blush: Managing Hepatic Arterioportal Fistula in a
higher than that in common infected patients (P <0.001; P = 0.031), the
77-Year-Old Female with Hepatocellular Carcinoma
proportion of cough, chest tightness and spleen enlargement was also
higher than that of common infected persons (P = 0.033; P = 0.003; P Christine Paredes Velasquez1, Sharlene Chan1, Madalinee D Labio1
= 0.012). The proportion of pneumonia and renal cyst in patients with
1
Makati Medical Center
drug-induced liver injury was higher than that in common patients (P Hepatic arterioportal fistulas (HAPFs) are rare vascular abnormalities
= 0.005; P = 0.012). The results of liver function comparison showed characterized by abnormal connections between the hepatic arterial
that alanine aminotransferase, aspartate transferase, albumin/globulin, and portal venous systems. These fistulas can complicate the
alkaline phosphatase and low-density lipoprotein were lower in patients management of hepatocellular carcinoma (HCC).
with drug-induced liver injury than those with common infection (P = A 77-year-old female was incidentally found to have a hepatic mass
0.002; P = 0.011; P = 0.010; P < 0.001; P = 0.002). during routine workups over the past three years, but no intervention
Conclusion: Drug-induced liver injury occurred in a minority of patients was performed. She remained asymptomatic until one month before
diagnosed with brucellosis receiving based therapeutic regimen. The her hospital visit, when she developed intermittent right upper
age and smoking status may be associated with drug-induced liver quadrant abdominal pain radiating to her back. The pain was mild and
injury observed in patients diagnosed with brucellosis. not associated with other symptoms such as nausea, vomiting, fever,
jaundice, or weight loss.
PP0353 Seeking further evaluation, the patient underwent several tests,
including blood work and imaging. Abdominal ultrasound revealed
CT Imaging Characteristics of Paradoxical Reactions in Perihepatic a well-defined solid mass in the left lobe of the liver, suggesting a
and Hepatic Tuberculosis neoplastic process. Additional investigations, including an elevated
Xiang Li1 alpha-fetoprotein (AFP) level, were consistent with hepatocellular
1
Kunming Third People’s Hospital carcinoma (HCC). A whole abdominal CT scan with IV contrast
Background: Hepatic tuberculosis, a rare form of extrapulmonary revealed a 3 x 3 cm ill-defined isodense mass in segment II of the liver
tuberculosis. Paradoxical reaction refers to the worsening of existing with arterial phase washout and an enhancing lesion in segment VII
lesions or the development of new lesions during anti-tuberculosis (1.2 cm). A liver biopsy confirmed well-differentiated HCC.
therapy. Reports of paradoxical reactions in hepatic tuberculosis The patient was referred to a hepatologist for further management
are rare. However, the precise pathological processes and disease and was scheduled for TACE to treat the tumor. During the procedure,
progression remain unclear. a selective angiogram revealed a tumoral blush supplied by the
Method: Retrospective review of patients diagnosed with perihepatic middle hepatic artery and A2 arterial branches. There was also
and hepatic tuberculosis at the Kunming Third People’s Hospital early visualization of a portal vein shunt, indicative of an arterioportal
from 2020 to 2024. We selected patients with CT imaging follow- fistula (APF). Superselective catheterization was performed, and a
up showing paradoxical reactions and summarized their initial CT combination of Lipiodol, alcohol, doxorubicin, mitomycin, and EG-
findings, paradoxical reaction CT manifestations, and follow-up CT Gel was infused until vascular stasis was achieved. Following TACE,
presentations. minimal residual tumoral blush persisted, so microwave ablation
(MWA) was performed under ultrasound and CT guidance. Post-
ablation imaging revealed air locules within the tumor and an increase the AUROC to 0.7775 (p = 0.0027, sensitivity 55%, specificity 100%) in
in hypodense zones, consistent with post-ablation changes. distinguishing sepsis from viral infection. Correlation analysis revealed
Follow-up MRI showed changes consistent with post-TACE treatment, TIFA expression positively correlated with platelet count, while S100A9
including the development of an adjacent small nodule, likely due to correlated with creatinine levels.
inflammatory granulation tissue. The tumor showed signs of coagulation Conclusion: LC-MS/MS identified TIFA and S100A9 as common
necrosis and blood products, suggesting a favorable response to the differential proteins in both LPS and CLP sepsis-induced liver injury
combined treatments. models. Their elevated plasma levels in sepsis patients and high
This case highlights the use of TACE and MWA as an effective treatment sensitivity and specificity in ROC curve analysis support their diagnostic
strategy for hepatocellular carcinoma, particularly in the presence of potential. Additionally, their expression correlates with sepsis SOFA
an arterioportal fistula. MWA played a critical role in ensuring complete scores. The combination of S100A9 and TIFA can differentiate sepsis-
tumor necrosis and reducing the risk of complications such as portal induced liver injury from viral infection, suggesting they may serve as
vein thrombosis or liver infarction. The multimodal approach enabled potential biomarkers and therapeutic targets.
the patient to receive curative treatment for her HCC, providing a safe Table and Figure:Figure 1.
and effective method for managing complex cases involving HAPF. Figure 2.

PP0355 PP0357
Analysis of a case of Clonorchis sinensis infection treated by GSTA3-mediated Prdx4 S-glutathionylation maintains
traditional Chinese medicine mitochondrial homeostasis and inhibits hepatocyte pyroptosis to
Xia Ning1,2, Jun Chun Xu3 protect against sepsis-associated liver injury.
1
Beijing University of Traditional Chinese Medicine, 2Beijing Hospital Peng Qu1, Xu Li2
of Traditional Chinese Medicine, 3 Beijing Hospital of Traditional 1
Department of Gastroenterology , Nanfang Hospital, Southern
Chinese Medicine Medical University, , 2Department of Emergency Medicine, Southern
Hepatic flukes, also known as clonorchiasis, is a zoonotic parasitic Medical University Nanfang Hospital,
disease caused by liver flukes parasitic in the bile ducts of the Background: Liver dysfunction is considered a powerful independent
human liver. This disease is mostly infected by eating raw or semi- predictor of sepsis mortality in intensive care units. Oxidative stress
raw freshwater fish and shrimp containing cysts, and is often is involved in the pathogenesis sepsis -associated liver injury, and
misdiagnosed and missed in clinical practice due to insidious onset protein S-glutathionylation plays an important role in cellular antioxidant
and atypical clinical symptoms. In this paper, we report the TCM defense.GSTA3, which is mainly found in the liver, is an important
diagnosis and treatment process of a female patient with abnormal transfer enzyme in glutathionylation modification, but the mechanism
liver function after being infected with Clonorchis sinensis, and analyze involved is not clear.
the etiology, pathogenesis, clinical syndrome types, and syndrome Method: We collected serum from septic and healthy volunteers to
differentiation and treatment from the perspective of TCM according detect the level of GSTA3 by ELISA, constructed a mouse model of
to the characteristics of the patient’s place of residence, duration of sepsis-associated acute liver failure by LPS+(d-GalN) and CLP, and
infection, and clinical manifestations, in order to provide help for the determined the level of GSTA3 by quantitative polymerase chain
diagnosis and treatment of clonorchiasis sinensis by TCM. reaction (qPCR), ELISA, and western blotting. Then, we constructed
GSTA3 overexpression and knockdown cell lines in vitro, and detected
hepatocyte viability by CCK8 and LDH levels in culture supernatants,
PP0356
cellular oxidative stress levels by MDA and ROS, and hepatocyte
Sepsis-Induced Vascular Endothelial Cell Injury: The Crucial Role mitochondrial damage and death by electron microscopy and WB.
of Mitochondrial Quality Control The downstream proteins of gsta3 mediating S-glutathionylation were
Tian Xia1, Jiachi Yu1, Ruibing Li1, Chengbin Wang1 searched by COIP and protein profiling. Finally, the mechanism of
1
Department of Laboratory Medicine, The First Medical Center of action of GSTA3 in liver failure was further demonstrated by adenovirus
Chinese PLA General Hospital, Beijing, 100853, China in an in vitro mouse model.
Background: Sepsis is marked by a dysregulated response to Result: Our results revealed that LPS+(d-GalN) and CLP-induced
infection, causing circulatory dysfunction, organ failure, and high acute liver failure showed hepatocyte pyroptosis. GSTA3 levels
mortality, which burdens both patients and healthcare resources. Early were significantly decreased in the serum of septic patients and
intervention remains limited, and liver dysfunction is an early indicator of negatively correlated with the liver function indexes of AST and ALT.
sepsis severity. This study aims to use LC-MS/MS to identify differential GSTA3 was significantly down-regulated in the mouse model of
proteins, and preliminarily validate them as potential biomarkers for LPS+(d-GalN) and CLP-induced acute liver failure, confirming that
sepsis-induced liver injury. the in vitro overexpression as well as knockdown of GSTA3 regulates
Method: We established sepsis-induced liver failure mouse models the protective role of S-glutathionylation in the hepatocytes. In
using cecal ligation and puncture(CLP) and LPS injection. And then vitro overexpression as well as knockdown of GSTA3 regulated the
ELISA, Western blotting, and H&E staining were performed to analyze protective role of S-glutathionylation in hepatocytes. Further results
liver pathology, function. Through LC-MS/MS, we explored key suggest that GSTA3 alleviates mitochondrial dysfunction and cellular
proteins and their functional and biological characteristics. Finally, pyroptosis in hepatocytes through s-glutathionylation modification. The
we evaluated key proteins’ performance in the validation cohort results of protein profiling of COIP as well as glutathione modification
using ROC and external validation from GEO datasets (GSE65682, histology results showed that GSTA3-mediated glutathione modification
GSE145227, GSE60088). of Prdx4 protein enhances the antioxidant capacity of hepatocytes to
Result: A total of 113 common differential proteins were identified in maintain mitochondrial homeostasis as well as to alleviate hepatocyte
the CLP model and LPS model. GO, KEGG and WikiPathways analysis pyroptosis.
highlighted their association with inflammation, protein cascade Conclusion: GSTA3-mediated protein S-glutathionylation protects
activation, and lipid metabolism. TIFA and S100A9 were identified as against sepsis-associated liver injury by maintaining mitochondrial
key proteins related to acute inflammation. Plasma TIFA and S100A9 homeostasis and inhibiting hepatocyte pyroptosis. This study provides
levels were significantly elevated in sepsis-induced liver injury patients a new theoretical basis for the pathogenesis of sepsis-associated
compared to healthy controls (p < 0.05), consistent with external liver injury and an experimental basis for the development of effective
validation. S100A9 was significantly higher in sepsis vs. viral infection therapeutic strategies.
(p < 0.05), while TIFA showed no significant difference. ROC curve
analysis showed TIFA and S100A9 can distinguish sepsis-induced liver PP0358
injury patients from healthy controls. The combination of both increased
MTM16 ameliorates diet-induced cholesterol gallstones by endoscopic interventions and conservative monitoring. Whole exome
inhibiting LXRα sequencing was recommended to investigate underlying vascular
CHI YIRONG1, PENG ZIYI1, ZHANG JIE1, ZHANG RUIJIA1, ZHAO connective tissue disorders. This case adds to the growing body
JINGWEN1 of evidence on rare vascular causes of NCPH and underscores the
1
Department of Gastroenterology and Hepatology, Tianjin Medical importance of early detection and management. The patient was
University General Hospital advised to undergo whole-exome sequencing for vascular Ehlers-
Danlos syndrome.
Background: Gallstone is a common disease of the biliary system,
mainly including gallstones and bile duct stones. The cause of
its formation is related to a variety of factors, including genetic PP0360
predisposition, weight, eating habits, gender, age, and certain Portal vein thrombosis caused by hereditary protein S deficiency:
disease states. Cholesterol stones (CGs) are the most common a report of 2 cases
type of gallstone. Patients with asymptomatic CGs can be observed Xiaoying Ye1,2, Xiaoxiao Mi3,2, Ling Gong3,2
conservatively, but those with symptoms usually need to be treated 1
Hangzhou Normal University, 2Lishui People ‘s Hospital, 3Hangzhou
with medication or surgery. However, surgical treatment often affects Normal University Affiliated Hospital
patients, such as steatosis, dyspepsia, post-cholecystectomy
syndrome and so on. There are currently limited drugs available to Thrombophilia typically presents as deep vein thrombosis, pulmonary
treat gallstones. In our preliminary study, MTM16 was found to be an embolism, or thrombophlebitis. However, less common manifestations,
LXRα inhibitor, and we wanted to explore whether MTM16 could have a such as thrombosis in the portal vein, mesenteric veins, sagittal sinus,
preventive/therapeutic effect on gallstones by inhibiting LXRα. or cerebral venous sinuses, can also result from defects in protein S.
Method: Mice were fed a stone-inducing diet and given daily In this report, we analyze the clinical characteristics of two patients
inadministration of MTM16. We evaluated the improvement effect of diagnosed with thrombophilia who presented with non-cirrhotic portal
MTM16 on cholesterol-induced gallstones by biochemical analysis, vein thrombosis. Clinical data were collected from these two patients,
bile CSI calculation, and pathological section analysis, and analyzed After excluding acquired thrombophilia, anticoagulant proteins were
the mechanism of MTM16 on cholesterol-induced gallstones by liver measured. Following the clinical diagnosis of protein S deficiency,
sequencing, RT-PCR, 16s rRna, and bile acid-targeted metabolites in whole exome sequencing (WES) was carried out to identify genetic
liver and stool. alterations associated with thrombotic diseases, which were then
Result: MTM16 improves cholesterol-induced gallstones by regulating verified by Sanger sequencing. Pathogenicity predictions for the
cholesterol absorption. MTM16 can inhibit the expression of LXRα and identified variants were performed using functional prediction software
ABCG5/ABCG8 in liver, reduce cholesterol entering gallbladder, and such as SIFT, PolyPhen-2, and MutationTaster.
directly reduce the formation of CGs. MTM16 can also reduce the Both patients were admitted to the hospital with abdominal pain. Patient
abundance of intestinal harmful bacteria, increase the abundance of 1 had a history of deep vein thrombosis in the lower extremities, while
beneficial bacteria, improve the bile acid imbalance, and thus alleviate Patient 2 had a history of psoriasis. Imaging studies revealed portal
the formation of CGs. vein thrombosis, superior mesenteric vein thrombosis, and splenic vein
Conclusion: Our results suggest that MTM16 can regulate cholesterol thrombosis in both patients. Protein S activity was significantly reduced
transport by acting on liver LXRα-ABCG5/ABCG8 pathway, improve in both patients diagnosed with thrombophilia and presenting with non-
intestinal flora and bile acid disorders, and thus reduce the formation cirrhotic portal vein thrombosis, while protein C activity, antithrombin
of CGs, and may be a new choice for future CGs treatment. activity, platelet count, coagulation indices, various coagulation factors,
Table and Figure:Figure 1. and autoantibody levels were all normal. Therefore, a clinical diagnosis
of protein S deficiency was established for both patients. Acquired
protein S deficiency was ruled out, and hereditary protein S deficiency
PP0359 was suspected. Whole exome sequencing was performed for genetic
Non-cirrhotic Portal Hypertension from a Portal Vein Fusiform testing. This analysis identified two mutations in the PROS1 gene:
Aneurysm with Arteriovenous Malformation: A Case Report c.1574C>T (p.Ala525Val), a heterozygous missense mutation, and
Derek Caisip Clutario1, Angelo Banzon Lozada1 c.1552del (Thr518ArgfsTer41), a heterozygous frameshift mutation. In-
1
Makati Medical Center silico analysis of c.1574C>T (p.Ala525Val) using SIFT and PolyPhen-2
predicted the variant as pathogenic and likely pathogenic, respectively
Esophagogastroduodenal varcies are usually formed from increased
(SIFT: -3.404; PolyPhen-2: 0.892). The c.1552del (Thr518ArgfsTer41)
pressures portal pressures more commonly a complication of cirrhosis.
variant was predicted as pathogenic by Mutation Taster.
This case report aims to describe a unique case of a young male whose
In conclusion, to the best of our knowledge, this report is the first
portal hypertensions was from a non-cirrhotic cause. A 16-year-old male
to identify mutations in the PROS1 gene (c.1574C>T, p.A525V) and
presented with severe right lower quadrant pain and melena. He was
(c.1552del, Thr518ArgfsTer41) in Chinese patients with extensive
initially managed as a case of ruptured diverticulosis. He underwent
thrombosis of the portal vein and superior mesenteric vein due to protein
diagnostic laparoscopy with peritoneal lavage and drainage of a pelvic
S deficiency. Both patients were diagnosed with hereditary protein S
abscess. He was later readmitted with left lower quadrant pain and
deficiency, a known high-risk factor for venous thromboembolism.
dark watery stools, managed again as another episodes of ruptured
Timely genetic testing is crucial for early diagnosis and appropriate
diverticulitis. Five weeks later, the patient was admitted for anemia
treatment.
leading to loss of consciousness. At this time, diverticulosis were stable
however on upper endoscopy, findings revealed esophageal varices
grade 1-2 where rubber band ligation was performed, stabilizing the PP0361
patient’s anemia. Imaging later revealed a non-cirrhotic liver with a Analysis of Factors Associated with Liver Dysfunction in Patients
fusiform aneurysm involving the confluence of the common hepatic with Brucellosis: A Retrospective Observational Study
artery, with arteriovenous malformation connecting to the right portal Rong Wang1,2, Bin Niu1,2, Yinghan Wang1,2, Xin Zhang1,2, Yuke
vein. This case demonstrates a rare instance of non-cirrhotic portal Wang1,2, Haiyan Tian1,2, Liaoyun Zhang1
hypertension which can be caused by arteriovenous malformation 1
Department of infectious Diseases, The First Hospital of Shanxi
which was caused by a portal vein & common hepatic artery aneurysm. Medical University, 2Graduate School, Shanxi Medical University
This lead to melena from bleeding esophageal varices from increased
portal pressures causing significant anemia. Background: Brucellosis is a zoonotic disease with multisystem
This case report highlights a rare cause of non-cirrhotic portal involvement and varying clinical presentations. Liver dysfunction is a
hypertension due to a fusiform aneurysm with arteriovenous common complication of brucellosis, but its contributing factors remain
malformation which was complicated by upper gastrointestinal unclear. This study aimed to analyze the factors associated with liver
bleeding from ruptured varices. The patient was managed with dysfunction in patients with brucellosis to guide early detection and
management strategies. scrub typhus.
Method: A retrospective analysis was conducted on 307 brucellosis Table and Figure:Figure 1.CECT- GB contracted with 7mm stone in
patients, categorized into liver dysfunction (n = 221) and non- neck of gall bladder with diffuse thickening , pericholecystic edema ;
dysfunction (n = 86) groups based on elevated ALT, AST, ALP, GGT, B/L minimal pleural effusion
TBIL and DBIL levels. Clinical features, laboratory parameters, Figure 2.liver biopsy
and systemic complications were compared using univariate and
multivariate analyses to determine significant associations.
PP0363
Result: Among the cases of liver dysfunction, ALT abnormalities were
found in 127 cases, AST abnormalities in 124 cases, ALP abnormalities HOMA-IR AS A MARKER FOR DIAGNOSIS OF METABOLIC
in 63 cases, GGT abnormalities in 169 cases, TBIL abnormalities in ASSOCIATED FATTY LIVER DISEASE(MAFLD) IN WOMEN WITH
17 cases, and DBIL abnormalities in 44 cases. GGT elevation and POLYCYSTIC OVARIAN DISEASE(PCOD)
cholestatic liver damage appear to be the most common types of liver Siddhant Jain1
injury associated with brucellosis.Statistically significant differences 1
Dr. RML Hospital
were observed between the two groups in terms of gender, fever, Background: Metabolic dysfunction-associated fatty liver disease
headache, splenomegaly, joint pain, arthritis, body temperature, pulse, (MAFLD) affects around 25% of adult people worldwide, About 7%
respiratory rate, body weight, red blood cell count, platelet count, of women who are of reproductive age have PCOD, a highly common
albumin, and procalcitonin levels. Logistic regression analysis identified endocrine condition.
male, fever, headache, splenomegaly, elevated body temperature, • Insulin resistance is calculated by homeostasis model assessment-
increased pulse and respiratory rates, reduced red blood cell and insulin resistance, {HOMA-IR}- calculated as [fasting glucose (mg/dl)
platelet counts, decreased albumin, and elevated procalcitonin as x basal insulin(uUl/ml)/405] or{insulin(mIU/l) x glucose (mmol/l)/22.5}.
independent risk factors for liver dysfunction. Conversely, joint pain :More than equal to 2.9 show significant insulin resistance.
and arthritis were identified as independent protective factors. :More than equal to 1.9 -2.8 borderline insulin resistance.
Conclusion: This study highlights that GGT elevation and cholestatic :Less than 1.8 -no insulin resistance
liver damage are the most common liver dysfunction types in Method: A cross-sectional observational study was conducted
brucellosis. Risk factors such as male, fever, splenomegaly, and involving 65 women diagnosed with PCOD at a tertiary care hospital
abnormal vital signs should be closely monitored. These findings in New Delhi, India.
provide essential insights for the timely diagnosis and management of • Participants were evaluated for insulin resistance using the HOMA-IR
liver dysfunction in brucellosis patients. index, calculated from fasting insulin and glucose levels.
• Liver steatosis was assessed using ultrasonography and fibroscan,
PP0362 MAFLD was diagnosed based on hepatic steatosis and metabolic
dysfunction criteria.
A rare presentation of scrub typhus: as acute liver failure
• The association between HOMA-IR levels and the presence of
Sonali Chaturvedi1 MAFLD was analysed using statistical methods, including ROC
1
TNMC analysis to determine diagnostic accuracy.
Background: Scrub typhus is an acute febrile illness, caused by Inclusion Criteria
Orientiatsutsugamshi. Common presentation of Typhus is fever, Women of reproductive age (20-45 years) with a confirmed diagnosis
eschar formation and lymphadenopathy, With complications like of PCOD based on the Rotterdam 2004 criteria (presence of at
acute respiratory distress syndrome, acute kidney injury. ALF is rare least two of the following: hyperandrogenism, oligo/anovulation, and
presentation of scrub typhus polycystic ovaries on ultrasound).
Here we report a case of scrub typhus with acute liver failure Exclusion Criteria
Method: A 43-year-old man, with history of forest travel, without any Patients with irregular menstruation or androgen excess,
co morbidities, including hyperprolactinemia, uncontrolled thyroid disease, androgen-
presented with fever for 10 days, jaundice for 6 days and altered secreting tumours, congenital adrenal hyperplasia, and Cushing’s
sensorium 2 days prior to admission. Fever was high grade, without chill syndrome.
, rigor. The jaundice was progressive with no features of cholestasis. Diagnosed chronic liver disease.
Patient presented with altered sensorium with no sign of meningitis. History of medication use known to affect the levels of liver enzymes.
He had no history of any co morbidities or alcohol consumption, CAM Post liver transplant patients.
intake. History of alcohol consumption > 20gm/day.
On physical examination was unremarkable except for icterus and Other chronic medical diseases like CKD.
deranged GCS of E4V4M6, flapping tremors were absent. Any treatment for hormone replacement therapy.
Investigation revealed increased liver echogenicity on Ultrasonography. Treatment for connective tissue disorder /autoimmune disorder.
On blood investigation tbil-14, creatinine-7 , INR-3 , negative for Hbs Result: The findings confirm a strong association between elevated
Ag, Anti HCV , HIV and ANA , serum ceruloplasmin level were with HOMA-IR scores and MAFLD in women with PCOD. 58.5% of
in normal limit. In view of febrile illness patient under went testing for participants were diagnosed with MAFLD.
tropical infections of malaria, dengue and typhus in the mean time Participants with MAFLD had significantly higher HOMA-IR
patient undergone liver biopsy also which showed granuloma scores (4.12 ± 3.13) compared to those without MAFLD (0.95 ± 0.42).
Patient tested positive for IgM Antibody against scrub typhus detected A HOMA-IR score ≥2.9 was strongly associated with MAFLD,
by ELISA while none of the participants with a HOMA-IR ≤1.8 had MAFLD.
The patient was treated symptomatically for ALF and intravenous This suggests that insulin resistance is a critical factor in
doxycycline for 14 days. the pathogenesis of MAFLD. ROC analysis revealed high diagnostic
The patient improved gradually and became asymptomatic with accuracy of HOMA-IR with a cutoff score of 2.9, demonstrating 76.3%
normalization of liver enzymes. sensitivity and 85.2% specificity.
Result: The patient was treated symptomatically for ALF and Conclusion: HOMA-IR is a valuable and effective marker for
intravenous doxycycline for 14 days. diagnosing MAFLD in women with PCOD
The patient improved gradually and became asymptomatic with Early identification of MAFLD using HOMA-IR can facilitate
normalization of liver enzymes. timely intervention and improve patient outcomes.
Conclusion: Elevation of liver enzymes is common in scrub typhus but Table and Figure:Figure 1.Association of HOMA-IR Categories with the
acute liver failure is rarely reported in literature . In a tropical country Presence of MAFLD (Metabolic-Associated Fatty Liver Disease)
like India,TROPICAL fever shuld be always ruled out in cases of ALF, Figure 2.Graphical Representation of the Association Between HOMA-
Severe acute liver injury. Timely diagnosis and management with IR Categories and MAFLD Prevalence
doxycycline/or azithromycin leads to excellent prognosis in case of
 PP0364 pro-inflammatory functions. c4, highly expressed Ccr7, increased in
Integrated analysis of the role of gut microbiome-associated MASLD and was linked to antigen presentation. c5 and c6, marked
metabolites in the detection of MASH-related cirrhosis by Mki67 and Cd3, were associated with cell proliferation and TCR
function, respectively. In MASLD mice models, the expression of
Feixiang Xiong1, Xuejie Zhang1, Yuyong Jiang1, Peipei Meng1, Yang
marker genes and functional molecules within each cluster was
Zhou1, Xiaomin Ji1, Jialiang Chen2, Tong Wu2, Yixin Hou2
verified by flow cytometry. Additionally, the subsets discovered in
1
Beijing Ditan Hospital, Capital Medical University, 2 Beijing Ditan the MASLD mice models were also confirmed in the MASLD human
Hospital, Capital Medical University
model. Notably, besides CCR2+ MoMFs, we found that CCR3+ and
Background: The prevalence and adverse outcome of metabolic CCR7+ MoMFs also significantly increased in MASLD. CellChat
dysfunction associated steatotic liver disease (MAFLD) are increasing. analysis revealed CCR3+ MoMFs may interact with endothelial cells
The changes in gut microbiota and metabolites associated with or hepatic stellate cells via CCR3/CCL5 and CCR3/CCL26, inducing
metabolic dysfunction associated steatohepatitis(MASH) are gradually their chemotactic migration into the liver. For the c0 (CCR2+ MoMFs)
regarded as an essential part in the progression of MAFLD. This study subset, pseudotime analysis showed that c1 can differentiate into both
aimed to identify relevant gut microbiota and metabolites involved in c0 (CCR2+) and c4 (CCR7+). This indicates that CCR2+ MoMFs in
the development of MAFLD in patients. MASLD livers may originate not only from the bone marrow but also
Method: This study enrolled 90 patients (heathy control, HC: n = 30; from c1, a resident basal subset, suggesting a novel source of CCR2+
MASH, n = 30;MASH-related cirrhosis, MC: n = 30) and their fecal MoMFs.
samples were collected for 16S rRNA sequencing and non-targeted Conclusion: This study used single-cell RNA sequencing to reveal
LC-MS/MS metabolomics analysis, respectively. Data preprocessing MoMFs heterogeneity and functional diversity in MASLD mice livers.
and statistical analysis were performed by QIIME2 software, pynast, We identified two new subsets, CCR3+ and CCR7+ MoMFs, which
QIIME2 package, Progenesis QI and R program. significantly increased in MASLD. CCR3+ MoMFs could migrate into
Result: The abundance of Prevotellaceae at family level and Prevotella the liver via chemokines, while CCR7+ MoMFs might be converted
at genus level were decreased in MASH and NC samples compared from the c1 resident basal subset. Additionally, we discovered that
with that in HC samples. Both Prevotelacae and Prevotella showed the c1 subset as a novel source of CCR2+ MoMFs. These findings
the strongest correlation in the progression of MASH via random forest enhance our understanding of MASLD pathogenesis and highlight
analyze. Untargeted metabolomics was applied to quantitatively potential therapeutic targets to modulate MoMFs functions in liver
screen discrepant metabolites between three groups’ stool samples. disease.
Linolenic acid(LA)-related metabolites levels are significantly lower in
MASH and NC samples. Whether Prevotella or LA related metabolites
PP0366
are associated with liver function. High abundance of Prevotella is
connected to LA related metabolites and MASH. Study on the mechanism of action of Qi Zhu Formula in the
Conclusion: This study identified that gut microbiota and metabolites treatment of metabolic associated fatty liver disease based on
are associated with MASH-related metabolic dysfunction. The LA network pharmacology and experimental validation
and Prevotella were depleted during MASH progression, additional JUNRAN YANG1, Qiuyi Zhang1, Zhenhua Zhou1
supplement with Prevotella may be a potential target for the future 1
Shanghai
treatment of MAFLD. Background: To investigate the mechanism of action of Qi Zhu Formula
Table and Figure:Figure 1. (QZF) in treating metabolic associated fatty liver disease(MAFLD)
Figure 2.Linolenic Acid Metabolism Promotes the Onset and through network pharmacology and experimental validation.
Progression of MAFLD Method: Network pharmacology was used to analyze the molecular
targets of QZF in the treatment of MAFLD, and PPI, GO, and KEGG
PP0365 analyses were performed to identify the potential pathways and
Single-cell RNA Sequencing Reveals the Heterogeneity of therapeutic targets of QZF in the treatment of MAFLD. The Elisa
Monocyte-derived Macrophages in Metabolic Dysfunction- method detected serum levels of inflammation and oxidative stress-
associated Steatotic Liver Disease related factor secretion. The levels of SREBP1C, FASN, and ACC1
mRNA expression in rat liver tissue were detected by Real-time PCR.
Haozhe Xu1, Lu Yang2, Dong Zhang1, Guangyong Sun1
The expression levels of SREBP1C, FASN, and ACC1 in rat liver tissue
1
Department of Gastroenterology, Beijing Chao-Yang Hospital,
were detected by immunohistochemical staining. p-AMPK, SREBP1C,
Capital Medical University, Beijing 100020, China, 2General Surgery
FASN, and ACC1 protein expression levels in rat liver tissue were
Department, Beijing Friendship Hospital, Capital Medical University,
detected by western blotting.
Beijing 100050, China
Result: The network pharmacology screened 36 active ingredients
Background: The inflammatory response is crucial in the pathogenesis and 236 targets of QZF in the treatment of MAFLD, and 138
of metabolic dysfunction-associated steatotic liver disease (MASLD). intersecting targets were obtained. The AMPK signaling pathway and
Monocyte-derived macrophages (MoMFs) play a key role in liver its downstream targets SREBP1C, FASN, and ACC1 were enriched
inflammation and fibrogenesis, with their heterogeneity affecting by PPI, GO, and KEGG analyses, and QZF significantly reduced lipid
MASLD progression. deposition, steatosis, and inflammatory necrotic areas in the liver of
Method: We developed various MASLD models and conducted rats with MAFLD, and significantly reduced serum liver function, lipid,
single-cell RNA sequencing on liver-infiltrating 7AAD-CD45+Ly6G- glucose, IL-6, IL-1β, TNF-α, FFA, MDA, and TNF-α levels in MAFLD rats,
CD11bintF4/80low MoMFs from MASLD and control mice. Flow QZF increased the level of p-AMPK protein expression in liver tissue of
cytometry was used to verify the expression of marker genes and MAFLD rats and significantly decreased the level of SREBP1C, FASN,
functional molecules within each MoMFs cluster. ACC1 mRNA and protein expression in MAFLD rats.QZF reduced the
Result: MoMFs were clustered into seven clusters (c0–c6). c0, aggregation of fat droplets in fatty liver cells and narrowed down the
marked by Cd14 and recognized as CCR2+ MoMFs, increased the area of lipid deposition, and the effect of QZF on the 24h was the most
most in MASLD mice. Further analysis showed that this cluster, known obvious. QZF could significantly increase the expression of p-AMPK
primarily for its pro-inflammatory effects, also plays roles in fibrosis protein and decrease the expression of SREBP1C, FASN, and ACC1
promotion, phagocytosis, and antigen presentation. c1, a basal state protein in fatty liver cells.
cluster, decreased significantly in MASLD mice livers. c2, highly Conclusion: QZF can reduce serum liver function, and lipid and
expressed Mrc1, also decreased and was linked to anti-inflammation. blood glucose levels, inhibit lipid synthesis, reduce the secretion of
Further analysis revealed that lipid droplet accumulation causing inflammatory factors, and attenuate hepatocellular injury in MAFLD rats
mitochondrial damage reduced the survival of c2. c3, marked by induced by high-fat and high-glucose diets. The mechanism of action
Ccr3, increased in MASLD. Deeper analysis showed that the MASLD of QZF in the treatment of MAFLD is related to the up-regulation of
group exhibited increased oxidative stress in c3, leading to enhanced the phosphorylation level of AMPK, inhibition of SREBP1C expression,
down-regulation of the levels of FASN and ACC1, and inhibition of lipid fibrosis with a correlation coefficient (r = -0.34, p = 0.003). Mean folate
synthesis. levels were 2.52 ng/mL with the strongest negative correlation (r =
Table and Figure:Figure 1.QZF reduces lipid accumulation, improves -0.45, p= 0.0001) with fibrosis. Mean magnesium levels were 1.62 mg/
liver function and blood glucose levels, and improves inflammation dL and showed a moderate negative correlation (r = -0.31, p=0.008).
and oxidative stress in MAFLD rats. Conclusion: Serum levels of Vitamin B12, folate, and magnesium
Figure 2.Effect of QZF on SREBP1c, FASN, and ACC1 protein were significantly correlated with the severity of liver fibrosis in
expression in liver tissues of MAFLD rats NAFLD patients with folate showing the most negative correlation.
These findings highlight the importance of micronutrients in NAFLD
progression and suggest their monitoring could be crucial for
PP0367
managing the disease.
THE ROLE OF GENES AND OXIDATIVE STRESS MARKERS IN THE
DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE.
Hina Parveen1, Sumit Rungta2
PP0369
1
King George Medical Univercity, 2King George Medical University Non alcoholic fatty liver disease associated with cancer
Background: Non-alcoholic fatty liver disease (NAFLD) is frequently Harshita Dubey1, Sathya Veera Merla1, Jaideep Menda1, Amar
associated with metabolic disorders and is highly prevalent in obese Ranajn1
and type 2 diabetes mellitus (T2DM) patients. Oxidative stress plays a
1
All India Institute of Medical Sciences, New Delhi
major role in the pathogenesis of NAFLD. This study aimed to associate Background: Chemotherapy induced liver injury is one of the
the role of oxidative parameters with genes in NAFLD. common causes of mortality in cancer patient. One of the mechanisms
Method: In this case-control study, 100 participants were enrolled and of development of fatty liver is hepatic steatosis induced by
classified into two groups: NAFLD (n=70) and healthy controls (n=30). chemotherapeutic agents. Here in this study we are evaluating the
Levels of oxidative parameters, including superoxide dismutase development of fatty liver during the therapy for ovarian cancer.
(SOD), catalase, and malondialdehyde (MDA), were assessed using Method: A prospective study was conducted on cases of ovarian
chemiluminescence and qRT-PCR. Data analysis was performed using cancer with normal liver function test, which developed fatty liver after
GraphPad Prism 10, with significance set at P < 0.05. getting chemotherapy.
Result: The study demonstrated a significant decrease in SOD2 Result: We evaluated 154 cases of ovarian cancer for the development
enzyme activity in NAFLD patients (1.008 ± 0.957 U/ml) compared to of complications following therapy. The age ranged from 17- 72 years.
controls (4.029 ± 3.20 U/ml, P = 0.0014). Catalase activity was also We found 28 cases developed fatty liver while, 126 cases didn’t. Mean
significantly reduced in NAFLD patients (32.2 ± 6.36 U/ml) compared age of the two group was 48.8 and 49 respectively. The cases that
to controls (41.2 ± 8.70 U/ml, P < 0.0001). Plasma MDA levels were developed fatty liver were having age 36-72 years.
significantly increased in NAFLD patients. Gene expression analysis We correlated fatty liver with different clinical parameters. These
revealed that catalase was significantly downregulated by 1.94 folds are age, CA125, he4, CEA, CA199 age at menopause, FCB, LCB
(P=0.0045) and SOD2 by 1.02 folds (P=0.46) in NAFLD patients and menarche, tumor size (cm), weight, height, GFR, BSA and TFI
compared to healthy controls. (months).
Conclusion: The study suggests that decreased levels of oxidative Most of them didn’t show any significant correlation except p- values
stress markers, particularly antioxidant enzymes like catalase, may for weight, neuropathy, mucositis and diarrhea were 0.006, 0.00, 0.003
contribute to oxidative damage in the progression of NAFLD in T2DM and 0.00 respectively. Parameters near about to the significant values
patients. These findings provide insights into the molecular mechanisms were TFI and p53 expression showing p-values as 0.08 for each one.
underlying the role of hepatic inflammation in the development and Conclusion: Development of fatty liver following chemotherapy
progression of NAFLD. follows the common mechanism, but the process is fast. This may be
Table and Figure:Figure 1. due to an altered metabolic process. Higher weight, age and BSA are
common predisposing factors the development of fatty liver. Following
chemotherapy, factors affecting BMI will aid on the process.
PP0368
Key words: fatty liver, ovarian cancer, chemotherapy, weight
CORRELATION OF SERUM VITAMIN B12, FOLATE, AND
MAGNESIUM LEVELS WITH SEVERITY OF FIBROSIS IN NON-
ALCOHOLIC FATTY LIVER DISEASE PP0370
Kartik Goel1, Shailesh Kumar1, Vijay Kumar1, Lokesh Kumar Sharma1 The Impact of Parental Non-Alcoholic Fatty Liver Disease and
1
ABVIMS and DR. RML HOSPITAL, NEW DELHI Alcoholic Liver Disease on the risk of Fatty Liver Disease in their
offspring: A Meta-Analysis
Background: Non-alcoholic fatty Liver Disease (NAFLD) ranges
from simple steatosis to severe stages like NASH and cirrhosis. Regina Dimaculangan1, Nikko Raymundo1, Joseph Dumagpi1, Juliet
Micronutrients like Vitamin B12, folate, and magnesium influence Cervantes1
NAFLD pathogenesis involving lipid metabolism, oxidative stress, and
1
St. Luke‘s Medical Center - Global City
inflammation.This study focussed on studying the correlation of serum Background: Non-alcoholic fatty liver disease (NAFLD) and alcoholic
vitamin B12, folate, and serum magnesium levels with the severity of liver disease (ALD) represent two major forms of liver pathology. Both
fibrosis in NAFLD using NAFLD fibrosis score. conditions are characterized by abnormal fat accumulation in the
Method: A cross-sectional observational study was conducted at Dr. liver, which can lead to cirrhosis or worse, hepatocellular carcinoma.
RML Hospital, New Delhi, from April 1, 2023, to June 30, 2024, and Emerging evidence suggests that parental history of liver disease
included 70 NAFLD patients above 18 years based on ultrasound may increase the risk of developing fatty liver disease in offspring,
and exclusion criteria. Secondary causes of fatty liver disease were highlighting the potential genetic and environmental factors involved.
excluded. Blood samples were analyzed for biomarkers such as This meta-analysis aims to evaluate the impact of parental NAFLD and
Vitamin B12, folate, and magnesium. Demographic characteristics and ALD on the risk of fatty liver disease in their children.
metabolic derangements were assessed. B12, folate, and magnesium Method: A comprehensive search of literature was done through
levels were correlated with NAFLD Fibrosis Score. multiple electronic databases and grey literature sources until
Result: The mean age was 50.09 years, which consisted of 54.29% December 2023. This study included three cohort studies, and
males and 45.71% females. Obesity was present in 70% of patients. RevMan 5.4 was utilized to compute.
Diabetes and hypertension were noted in 44.28% and 42.85% Result: The three cohort studies by Long, Park and Jepsen all showed
respectively. Dyslipidemia was common, with high cholesterol, and low that offspring of patients with NAFLD or ALD have nearly two-fold
HDL levels in 30% and 64% respectively. Vitamin B12 levels showed a increased risk of developing fatty liver disease. Resulting I2 of 57%
mean of 503.17 pg/mL and were associated with less severe NAFLD implies that heterogeneity exists, hence a subgroup analysis of the two
studies involving only NAFLD was done, achieving a heterogeneity of Center of Infectious Diseases, West China Hospital, Sichuan
1

0% (p=0.001). The resulting pooled odds ratio of 2.25 (95% CI 1.63 to University, Chengdu, China
3.10) and diamond market were also deemed significant, favoring the Background: The aim of this study was to describe the overall changes
group with no family history of liver disease, suggesting that the odds in the gut microbiome alongside the fecal and serum metabolome
ratio is significant in increasing the risk of liver disease to their children. among individuals diagnosed with Metabolic Associated Fatty Liver
Conclusion: This study demonstrates the significant association Disease (MAFLD).
between parental NAFLD and ALD, most distinctively with NAFLD, and Method: This study included 19 patients diagnosed with MAFLD and
the heightened risk of fatty liver disease in their offspring. These results 10 healthy individuals, recorded basic clinical characteristics and
highlight the importance of early screening and targeted preventive laboratory test results of all participants, including routine biochemistry,
strategies for families with a history of liver disease, paving the way for and collected their serum and fecal samples. Some fecal samples
improved health outcomes for the future generations. underwent 16S rDNA sequencing, while the remaining fecal and
Table and Figure:Figure 1.Forest Plot 1. Offspring with a parental serum samples underwent untargeted metabolomics detection based
history of NAFLD or ALD are at increased risk for developing fatty liver on liquid chromatography-mass spectrometry (LC-MS). Statistical
disease analysis was primarily conducted using R software (V. 4.4.1), while
Figure 2.Forest Plot 2. Offspring with a parental history of NAFLD are at metabolomics data analysis was mainly performed using CD 3.1
increased risk for developing fatty liver disease software. A two-tailed p-value of <0.05 was considered statistically
significant.
PP0371 Result: At the phylum level, the two groups exhibited a similar
bacterial community composition, both dominated by Firmicutes
CD73 enhances the immunoregulatory functions of hepatic
and Bacteroidota, with Firmicutes accounting for over 50% of the
Tregs through enzymatic and nonenzymatic pathways in MASLD
abundance in both groups, followed closely by Bacteroidota. At
development
the genus level, bacterial communities displayed more pronounced
Xinjie Zhong1, Hua Jin1, Chunpan Zhang2, Yongle Wu1, Dong Zhang1,
differences. The genus Prevotella_9 was relatively more abundant
Guangyong Sun1
in the MAFLD group and significantly lower in the healthy control
1
Beijing Chao-yang Hospital, 2Beijing Friendship Hospital group. Additionally, the abundance of Bacteroides was lower in the
Background: Regulatory T cells (Tregs) play a critical role in MAFLD group and significantly higher in the healthy control group. A
immunosuppression and delay the progression of metabolic total of 1,574 metabolites were identified in this study, with the top 14
dysfunction-associated steatotic liver disease (MASLD). CD73, a upregulated fecal metabolites in NAFLD patients compared to healthy
functional molecule highly expressed on Tregs, shows increased controls including: tri(2-n-butoxyethyl) phosphate, tributyl phosphate,
expression in both peripheral blood of MASLD patients and liver tissue 9-octadecenoic amide, anisic acid, sinococcin, POS7536, ethyl citrate
of MASLD mouse models. However, CD73’s role and its mechanism of tributyl ester, dibutyl phthalate, 1,10-epoxygibberellin, POS10433,
modulating Tregs in MASLD pathogenesis remain unknown. POS7722, 16-hydroxypalmitic acid, 13-hydroxy-7,14-labdadien-
Method: Wild-type (WT) and CD73 knockout (KO) mice, or specifically 6-one, and jasmonine. Metabolomic pathway analysis suggests
transferring WT or CD73 KO Tregs into Rag1-/- mice were fed either the involvement of metabolic pathways such as steroid hormone
a choline-deficient high-fat diet (CD-HFD) for 16 weeks or choline biosynthesis, amino acid metabolism, probiotic metabolism, carbon
deficient diet (MCD) for 4 weeks to establish MASLD model. Liver metabolism, and retinol biosynthesis.
injury and fat accumulation were evaluated via liver histopathology Conclusion: This study found that while the MAFLD and healthy
and serum biochemical parameters. The activation, differentiation, and control groups shared similar bacterial compositions at the phylum
cytokine secretion of liver infiltrated immune cells were determined. level, significant differences emerged at the genus level, with
Transcriptome sequencing of hepatic Tregs from WT or CD73 KO Prevotella_9 being more abundant in MAFLD patients and Bacteroides
MASLD mice were analyzed. The mechanisms of CD73 regulating more prevalent in healthy controls. Metabolomic analysis identified
Tregs survival and immunoregulatory functions were explored in vitro. key upregulated metabolites linked to altered metabolic pathways,
Result: CD73 expression increased significantly in nonparenchymal including steroid hormone biosynthesis and amino acid metabolism.
cells, particularly Tregs, in MASLD mice livers. Both soluble CD73 These results suggest that gut microbiota and metabolic alterations
concentrations and Treg CD73 expression were elevated in MASLD play a crucial role in MAFLD development, providing insights for
patients plasma. CD73 KO mice fed CD-HFD or MCD showed more potential diagnostic and therapeutic approaches.
severe liver inflammation, fibrosis, and lipid accumulation compared Table and Figure:Figure 1.Comparison of Bacterial Community
to WT mice, along with impaired Treg survival and immunosuppressive Composition at Phylum and Genus Levels
function. While transferred WT Tregs protected Rag1-/- mice against
MASLD development, CD73 KO Tregs failed to reduce liver injury,
PP0373
evidenced by higher plasma ALT, AST, TBIL, and fasting glucose levels,
with increased proinflammatory monocyte infiltration and cytokine Association of NAFLD and chronic hepatitis B: A bi-directional
secretion. Transcriptome analysis revealed that liver free fatty acids in two-sample mendelian randomization
MASLD promoted GATA2 transcription factor through p38 signaling, Bei Jiang1
leading to CD73 upregulation on Tregs. CD73 protected Tregs through 1
Tianjin Second People‘s Hospital Department of Gastroenterology
both enzymatic pathways, preventing AMP-induced apoptosis and Background: Several observational studies have indicated a link
exhaustion while generating adenosine (ADO) to enhance cell survival, between non-alcoholic fatty liver disease (NAFLD) and chronic
and non-enzymatic pathways, by interacting with DR5 to prevent Trail- hepatitis B (CHB) or chronic HBV infection (CBI). However, the
induced apoptosis and maintain immunoregulatory function. causal relationship remains inconclusive because of multifactorial
Conclusion: CD73 downregulates liver inflammation and MASLD confounding. We aimed to explore the causal role of NAFLD and CHB
pathogenesis by regulating Tregs. Our study reveals a novel or CBI.
intrinsic mechanism that CD73 is crucial for Tregs homeostasis and Method: A bi-directional two-sample mendelian randomization (MR)
immunosuppressive function in MASLD development. These findings study analysis was conducted to estimate the causal effect between
provide a promising immunotherapy strategy for MASLD treatment and NAFLD and CHB or CBI. The primary analysis utilized the inverse
its feasibility for clinical application. variance weighting (IVW) technique to evaluate the causal relationship
between NAFLD and CHB or CBI. In addition, we conducted a series
PP0372 of rigorous analyses to bolster the reliability of our MR results.
Result: The bi-directional MR analysis showed a significant causal
Integrative Analysis of Gut Microbiota and Metabolites in
association between NAFLD and CHB as well as CBI. The inverse-
Individuals with Metabolic Associated Fatty Liver Disease
variance weighting (IVW) method revealed that NAFLD was associated
Ning Han1, Libo Yan1, Hong Tang1
with an increased risk of both CHB (OR = 1.34, 95% CI: 1.05-1.70, P = these effects. QSHY restored gut microbiota balance and colonic
0.018) and CBI (OR = 1.72, 95% CI: 1.04-2.82, P = 0.031). Conversely, barrier function. FMT from QSHY-treated mice improved liver health
reverse MR analysis showed no causal effect of either CBI or CHB on and metabolic tolerance in recipients. Metabolomic analysis identified
NAFLD. Sensitivity analyses, including heterogeneity and pleiotropy increases in the tryptophan metabolite IPA in QSHY-treated mice and
tests, confirmed the robustness of the results, with no evidence of FMT recipients. IPA supplementation alone replicated QSHY’s benefits,
horizontal pleiotropy or undue influence from individual SNPs. underscoring its therapeutic role in MASH.
Conclusion: The bi-directional two-sample MR analyses showed that Conclusion: QSHY’s anti-MASH effects are mediated through gut
NAFLD increases the risk of CHB and CBI, but CHB and CBI do not microbiota modulation, with IPA playing a crucial role.
increase the risk of NAFLD. Table and Figure:Figure 1.Graphic Abstract
Table and Figure:Figure 1.Fig1
Figure 2.Fig2
PP0376
Baicalein Alleviates Insulin Resistance by Regulating YTHDF1
PP0374 Expression through the AKT Signaling Pathway to Reduce
Rifaximin improves nonalcoholic steatohepatitis in mice by Gluconeogenesis in MAFLD Mice
modulating the Helicobacter-DCA-Fxr signaling pathway Huilian Shi1, Yuanyuan Chen2
Jie Jian1 1
Affiliated Hospital of Nanjing University of Chinese Medicine, 2Nanjing
1
Second affiliated hospital of Nanchang University Medical University
Background: To investigate the anti-NASH effect of rifaximin and its Background: One of the main characteristics of obesity-induced
specific molecular mechanism. metabolic disorders is insulin resistance. Increasing evidence suggests
Method: Mice were treated with methionine choline deficiency (MCD) that the development of various metabolic diseases is closely linked
diet to induce NASH formation. We treated NASH mice with rifaximin to epigenetic dysregulation. Baicalein, a naturally occurring flavonoid,
to observe its effects on liver fat deposition, inflammation, and fibrosis. has been found to have beneficial effects on lipid and glucose
Intestinal flora of NASH mice was detected by 16S rRNA assay and metabolism. Previous studies have indicated that baicalein can reduce
terminal ileal bile acid was detected by LS-MS assay. To investigate the insulin resistance and affect the incidence and progression of cancers
relationship between terminal bile acids of ileum and intestinal flora. by modulating the expression of m6A-modified related proteins.
Using decontamination mice and HNF1-HKO mice as experimental However, the precise mechanisms by which baicalein operates in both
subjects, the molecular mechanism of rifaximin to improve NASH was in vitro and in vivo models remain unclear.
investigated. Method: In this study, we investigated the effects of baicalein on
Result: Rifaximin treatment significantly improved liver steatosis, insulin resistance and blood sugar levels in mice with high-fat diet-
interlobular inflammation and liver fibrosis in McD-induced NASH induced diabetes. We assessed the expression levels of two key
mice. Rifaximin regulates intestinal flora in NASH mice, especially gluconeogenic enzymes, G6Pase and PEPCK, through both in
Helicobacter hepatis. Rifaximin inhibited the Helicobacter-DCA- vitro and in vivo experiments. Our mechanistic analysis focused on
Fxr signaling pathway in NASH mice, thereby exerting anti-NASH examining the transcriptional activity of PEPCK and the mRNA stability
biological effect. of G6Pase. Additionally, we explored the expression and function of
Conclusion: Rifaximin can improve NASH in mice by regulating YTHDF1, an m6A reader, and FOXO1, a traditional regulator of glucose
Helicobacter-DCA-Fxr signaling pathway, providing theoretical basis and lipid metabolism. Furthermore, we evaluated baicalein’s influence
for the clinical treatment of NASH patients with rifaximin. on these molecular pathways in relation to the AKT signaling pathway.
Result: Baicalein was found to reduce blood sugar levels and alleviate
insulin resistance in high-fat diet-induced diabetic mice, potentially by
PP0375
affecting gluconeogenesis. Both in vivo and in vitro studies confirmed
Microbiota-derived Indole-3-propionic acid mediates the that baicalein down-regulated the expression of the key gluconeogenic
therapeutic effects of Qushi Huayu Prescription on metabolic enzymes G6Pase and PEPCK. Mechanistically, baicalein promoted
dysfunction-associated steatohepatitis the degradation of G6Pase mRNA while inhibiting the transcription of
Binbin Zhang1, Yuqing Pan1, Yiyang Hu1, Yu Zhao1 PEPCK. Further investigation revealed that baicalein down-regulated
1
Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai the expression of YTHDF1, which binds to the m6A site of downstream
University of Traditional Chinese Medicine genes and affects their stability. Additionally, baicalein promoted the
Background: Metabolic dysfunction-associated fatty liver disease degradation of G6Pase and FOXO1 mRNA. The down-regulation
(MAFLD), a growing health concern, is significantly influenced by of FOXO1, in turn, inhibited the expression of PEPCK. It was also
gut dysbiosis and associated metabolites. In our prior clinical trial, found that baicalein down-regulated YTHDF1 expression via the AKT
Qushi Huayu (QSHY), a traditional Chinese medicine, demonstrated signaling pathway
therapeutic effects on MAFLD by correcting gut dysbiosis and lowering Conclusion: This study suggests that baicalein reduces excessive
serum aromatic amino acid levels. We hypothesized that QSHY’s anti- gluconeogenesis by down-regulating YTHDF1 through the AKT
MAFLD effects involve modulation of gut microbiota and microbial signaling pathway, thereby providing a new target for the treatment of
metabolites. This study investigates the anti-MAFLD efficacy of QSHY diabetes and MAFLD.
through gut microbiota modulation and explores key bacterial-derived
metabolites in its therapeutic effect. PP0377
Method: A high-fat, high-sugar (HFHS) diet-induced model of metabolic
Inositol Hexaphosphate and inositol ameliorate metabolic
dysfunction-associated steatohepatitis (MASH) was developed.
dysfunction-associated steatohepatitis in WD/CCl4 treatment
Antibiotic-treated and fecal microbiota transplantation (FMT) mice were
mice
used to assess the microbiota-dependent anti-MASH effects of QSHY
and to identify efficacy-related metabolites. Colonic barrier function Zhao Chen1,2, Chenxiao Qu1, Wenhui Song1, Danjuan Lu1, Yi Wang1,
was measured using serum lipopolysaccharides, cytokines, electron Yuxin Song1, Xiangmei Chen1
microscopy, and protein expression, while gut microbiota composition
1
Department of Microbiology & Infectious Disease Center, School of
and metabolites were analyzed using 16S rRNA sequencing and liquid Basic Medical Sciences, Peking University, Beijing 100191, China.,
chromatography-MS/MS. Colonic Indole-3-propionic acid (IPA) levels
2
School of Public Health, Qingdao University, Qingdao 266071, China
were determined by the air-flow-assisted desorption electrospray Background: Inositol Hexaphosphate (IP6) and inositol (INS),
ionization–mass spectrometry imaging (AFADESI–MSI) analysis. primarily extracted from plants, possess anti-oxidative and anti-tumor
Result: QSHY improved hepatic steatosis, inflammation, and effects. However, whether they can alleviate metabolic dysfunction-
metabolic parameters in HFHS-fed mice, while antibiotics diminished associated steatohepatitis (MASH) remains unclear. This study aimed
to assess and compare the effects of IP6 and INS on MASH, as well as explore the therapeutic effects and potential mechanisms of the
the underlying mechanisms. traditional Chinese medicine ZhiGan formula (ZG) in treating NASH.
Method: A western diet combined with low doses of CCl4 (WD/CCl4) Method: A NASH mouse model was established using a high-
was used to induce MASH in mice and evaluate the protective effects fat, choline-deficient diet (HFCD) and treated with ZG for 6 weeks.
of IP6 and INS. Assessments of transcriptomics, metabolomics, and Therapeutic effects were assessed via histopathological staining,
lipidomics analyses were conducted to explore potential molecular serum biochemical analysis, gut microbiota profiling, and bile
mechanisms. Additionally, the effects of IP6 and INS in vitro using free acid metabolism analysis. Fecal microbiota transplantation (FMT)
fatty acid (FFA)-treated HepG2 cells and activated hepatic stellate experiments were conducted to validate the gut microbiota-mediated
cells were investigated. effects of ZG.
Result: Treatment with IP6 or INS significantly reduced obesity, fibrosis Result: Liver Improvement: ZG significantly reduced hepatic lipid
and lipid accumulation, improved insulin sensitivity and glucose deposition and fibrosis (H&E, Oil Red O, Sirius Red staining) and
homeostasis, and prevented hyperglycemia in MASH mice. However, improved serum ALT, AST, TC, and TG levels (Figures B and C).
IP6 exerted more beneficial effects against inflammation and oxidative Intestinal Structure Optimization: ZG protected the intestinal
stress. IP6 and INS also alleviated FFA-induced lipid accumulation in mucus layer and increased villus length, improving intestinal structural
HepG2 cells. Liver transcriptomics revealed the deleterious effects integrity (Figure D).
of WD/CCl4 on gene expression and their reversal by IP6 and INS. Gut Microbiota Regulation: Metagenomic analysis showed
Metabolomics and lipidomics analyses indicated that IP6 and INS can ZG increased Verrucomicrobiota and decreased Bacillota proportions,
effectively improve disorders in glycerophospholipid metabolism by reshaping gut microbiota ecology (Figure E).
regulating the expression of related genes and metabolites. Especially Microbiota-Mediated Mechanism: FMT experiments
in the aspect of oxidative phosphorylation metabolism, IP6 is more demonstrated that microbiota from ZG-treated mice (ZG-FMT)
effective than INS. significantly reduced hepatic lipid deposition in recipient mice,
Conclusion: Both IP6 and INS effectively improve MASH primarily by confirming a gut microbiota-mediated therapeutic mechanism (Figures
ameliorating disorders in glycerophospholipid metabolism. This finding F and G).
provides a theoretical basis for the prevention and treatment of MASH Bile Acid Metabolism Modulation: ZG regulated bile
in patients through the rational intake of foods containing IP6 and INS. acids, including dehydrocholic acid, ursodeoxycholic acid, and
Table and Figure:Figure 1. taurolithocholic acid, alleviating gut-liver axis metabolic dysregulation
(Figure I).
Conclusion: This study validated the therapeutic effects of ZhiGan
PP0378
formula in a NASH animal model and preliminarily elucidated its
MiR-210-3p ameliorates MASH-related fibrosis by targeting ISCU mechanisms, highlighting the regulation of gut microbiota homeostasis
and induces ferroptosis in hepatic stellate cell. and bile acid metabolism as key pathways. These findings suggest
Zixing Dai1, Chuanlong Zhu1 that improving the gut-liver axis may be a vital pharmacological
1
Nanjing Medical University mechanism of ZhiGan formula.
Background: Metabolic dysfunction-associated steatohepatitis Table and Figure:Figure 1.Figure 1
(MASH) related fibrosis played an important role in the prognosis
of MASH, whose mechanism remained unknown. We explored the PP0380
mechanism of miR-210-3p in MASH associated with fibrosis.
Trans Fatty Acids Regulate the Growth and Proliferation of
Method: We searched for miR-210-3p through microarray of
Hepatocellular Carcinoma Cells via the OPN-NF-κB Signaling Axis
miRNA in MASH patient with either fibrosis or not. The real-time
quantitative reverse tranion PCR (qRT-PCR) was utilized to validate the Peici Yan1, Xiao Hu1, Yunting Shao2, Lizhe Liu1, Ran Guo3, Rui Hu4,
expression of miR-210-3p in vivo and in vitro. The target gene and Wenbin Li1
mechanism were explored using western blot, dual luciferase assay
1
Department of Pathophysiology, Hebei Medical University,
and Immunofluorescence staining. The ferroptosis biomarker was Shijiazhuang China, 2Affiliated Hospital of North China University of
demonstrated though three assays including malondialdehyde (MDA), Science and Technology,Tangshan, Hebei, China, 3The Third General
Surgery Department, The Second Affiliated Hospital of Hebei Medical
glutathione (GSH) and iron level.
University, Shijiazhuang, China, 4General Clinical Laboratory, The
Result: The expression of miR-210-3p was decreased significantly in
Second Affiliated Hospital of Hebei Medical University, Shijiazhuang,
methionine-choline deficient (MCD)-fed mice and palmitate acid (PA)-
China
stimulated LX2 and primary HSC, which was the same to the result
of microarray. miR-210-3p could alleviated the MASH-related fibrosis Background: Primary liver cancer has been posed a serious threat
through inducing ferroptosis in hepatic stellate cells. The ISCU was to global public health. Elaidic acids (EAs), a type of industrial trans
validated as the downstream gene of miR-210-3p and could reverse fatty acids (TFAs) that most commonly found in fried and baked foods,
the effect of ferroptosis induced by miR-210-3p. The ISCU-IRP1-TFR are known to almost have no health benefits and even cause liver cell
axis play a vital role in miR-210-3p inducing ferroptosis. dysfunction and oxidative stress. Our previous studies have shown
Conclusion: miR-210-3p was decreased in MASH-related fibrosis and that TFAs accelerate HCV related-HCC by interfering with fibrotic
had a novel role in ferroptosis through miR-210-3p-ISCU mechanism. process. This study aims to elucidates whether industrial TFAs could
further promote malignant behavior in liver cancer cells by inducing
hepatic stellate cell activation in HCC-microenvironment, and also to
PP0379 reveal its related mechanism.
Mechanistic Insights Into ZhiGan Formula for Treating Method: LX-2 cells were seeded into the lower chamber of a 6-well
Nonalcoholic Steatohepatitis Through Gut-Liver Axis Modulation transwell culture plate, simultaneously HepG2 cells were placed in the
Yousheng Mo1, Shuangwei Li2, Langping Yi2, Bowen Gao1, Ming Lin1, upper chamber after activating with 100 μM EAs, and both were co-
Meijie Shi1, Huanming Xiao1, Xiaoling Chi1,3 cultured for 48 hours. LX-2 cells and HepG2 cells were respectively
1
Department of Hepatology, Guangdong Provincial Hospital of collected, subsequently assessed the morphological changes,
Chinese Medicine, The Second Affiliated Hospital of Guangzhou cell viability, the expression levels of fibrosis-related factors and the
University of Chinese Medicine, Guangzhou, China., 2Science and activation of the OPN-NF-κB signaling pathway.
Technology Innovation Center, Guangzhou University of Chinese Result: Following co-culture with EAs-activated HepG2 cells, LX-2 cells
Medicine, Guangzhou, China., 3Chinese Medicine Guangdong displayed elongated spindle shapes with protrusions (pseudopodia)
Laboratory and transitioned from a resting to an activated state. The expression
Background: Nonalcoholic steatohepatitis (NASH) is a chronic liver of various fibrosis-related factors in LX-2 cells was significantly
disease characterized by lipid deposition, inflammation, and fibrosis, increased. Gene clustering heatmaps revealed that the osteopontin
with no effective therapies currently available. This study aimed to (OPN, gene name:Spp1) in HepG2 cells was markedly activated after
EAs treatment. In addition, the NF-κB pathway and its downstream to WT mice fed with a methionine-choline sufficient (MCS) diet,
genes related to cell proliferation were showed significantly higher suggesting a protective role of intestinal NLRP3. The Vil1creNlrp3fl/fl-
expression levels. MCD vs. Nlrp3fl/fl-MCD mice exhibited elevated hepatic lipid deposition
Conclusion: Industrial TFAs could further promote growth and and increased expression of α-SMA. Additionally, they displayed
proliferation of HepG2 cells via inducing HCC-microenvironment, thus compromised intestinal mucosal barrier function characterized by
aggravating the malignant behavior of liver cancer cells. The related shortened villi, reduced goblet cell count, and decreased expression
mechanism may be associated with the activation of the OPN-NF-κB of Reg3a and Cldn7. The co-housed Vil1creNlrp3fl/fl-MCD with Nlrp3fl/
signaling axis . These findings underscore the importance of dietary fl-MCD mice showed a significantly ameliorated liver phenotype,
habits in preventing HCC in patients with hepatic injury. characterized by reduced steatosis and fibrosis, in comparison with
Table and Figure:Figure 1.Gene clustering heatmaps separately-housed Vil1creNlrp3fl/fl-MCD mice. This improvement
Figure 2.mRNA levels of genes was accompanied by an increased abundance of Faecalibaculum
rodentium, a well-known butyrate producer. The in vivo administration
of butyrate significantly ameliorated hepatic lipid accumulation and
PP0381
fibrogenesis in Vil1creNlrp3fl/fl-MCD mice. Further, a significant
The proportion of the rs738409 GG homozygous and risk of upregulation of activating protein-1 (AP-1) mRNA levels was observed
fibrosis in patients with biopsy-proven NAFLD the meta analysis in the liver of Vil1creNlrp3fl/fl-MCD mice, while both co-housed
: Exploring mediation pathways through intermediate histological Vil1creNlrp3fl/fl-MCD mice and butyrate administration significantly
features. exhibited downregulated expression of AP-1.
Shuixian Du1 Conclusion: Deletion of NLRP3 in intestinal epithelial cells leads to a
1
Qingdao Municipal Hospital reduction in the abundance of Faecalibaculum rodentium and butyrate
Background: Some studies reported that PNPLA3 rs738409 GG production, resulting in the upregulation of hepatic AP-1 expression,
homozygous has risk with liver disease severity in patients with biopsy- thereby exacerbating MASLD.
proven NAFLD . We conducted a systematic review and meta-analysis
to evaluate the proportion of the rs738409 GG homozygous on the PP0383
histological severity of nonalcoholic fatty liver disease and exploring
Myricetin ameliorates MAFLD by enhancing mitochondrial
mediation pathways through intermediate histological features.
function and promoting PINK1/Parkin-dependent mitophagy
Method: PubMed, Cochrane Library, Embase Database were
subjected to case control study retrieving, from inception to July Weilong Xu1, Jiangyi Yu1, Hideki Fujii2, Xiqiao Zhou1
3, 2024. Following key words were used: fatty liver, PNPLA3, and
1
Department of Endocrinology, Affiliated Hospital of Nanjing University
rs738409 gene or variants or polymorphism or alleles. Meta-analysis of Chinese Medicine, 2Department of Hepatology, Graduate School of
was performed based on the retrieved articles. Medicine, Osaka Metropolitan University
Result: A total of 13 eligible studies and 3823 people were included in Background: Metabolic associated fatty liver disease (MAFLD),
this study. The pooled PNPLA3 rs738409 GG homozygous proportion particularly its severe form metabolic dysfunction-associated steatotic
of NAFLD was estimated to be 30% (95% CI:0.22- 0.37), 24% (95% liver disease (MASH), poses significant health risks, leading to liver
CI:0.15- 0.33), 33% (95% CI:0.26- 0.39), 25% (95% CI:0.22- 0.28), 39% fibrosis and cirrhosis. While traditional Chinese medicine has shown
(95% CI:0.32- 0.47) in adult ,adolescent,Asian population,Japanese potential in treating MAFLD, the mechanisms and efficacy of specific
and Chinese, And advanced fibrosis (≥2) was estimated to be 11% compounds like myricetin remain under-explored. This study aims to
(95% CI:0.07- 0.16), 11% (95% CI:0.06- 0.16),15 %(95% CI:0.07- 0.23) investigate the effects of myricetin on liver steatosis, mitochondrial
in adult, Asian population and Japanese. Two articles from the Chinese function, and mitophagy in MAFLD models, hypothesizing that myricetin
population were showed that Advanced fbrosis (≥2) was estimated could serve as a therapeutic agent by enhancing mitochondrial
to be 5.9% and 4.8%. Our results showed that the incidence of GG function and promoting PINK1/Parkin-dependent mitophagy.
homozygous in patients with advanced fibrosis (≥2) had 1.24-fold Method: Using a high-fat diet (HFD) and choline-deficient and high-
greater proportion compared with Low level fibrosis(<2) . fat diet (CD-HFD)-induced mouse models, we evaluated the impact
Conclusion: The PNPLA3 rs738409 GG homozygous proportion of myricetin on MAFLD. Hepatic steatosis, inflammation, and systemic
in biopsy-proven NAFLD is different because of geographic and insulin resistance were assessed through various biochemical and
population heterogeneity. Our results showed that rs738409 GG histological analyses. RNA sequencing (RNA-seq) was conducted to
homozygous exerted a strong influence on developing fibrosis. elucidate underlying molecular mechanisms, focusing on fatty acid
oxidation and mitophagy pathways.
Result: Myricetin treatment significantly reduced hepatic triglyceride
PP0382
accumulation, lowered serum AST and ALT levels, and improved
Intestinal NLRP3 deficiency aggravates MASLD mice via reduced insulin sensitivity in HFD and CD-HFD diet-induced mice. RNA-seq
butyrate production analysis revealed an upregulation of genes involved in fatty acid beta-
Li Chen1, Haoyu Jia1, Shanshan Li1, Jing Li1, Changqing Yang1 oxidation and mitochondrial function. Additionally, myricetin promoted
1
389 Xincun Road, Putuo District, Shanghai mitophagy as evidenced by increased PINK1 and Parkin protein levels
Background: Metabolic dysfunction-associated steatotic liver disease and enhanced mitophagy marker expression.
(MASLD) imposes a substantial global disease burden. This study Conclusion: Myricetin effectively ameliorates MAFLD by enhancing
aims to elucidate the role of intestinal NOD-like receptor thermal fatty acid beta-oxidation and mitochondrial function, offering a
protein domain associated protein 3 (NLRP3) inflammasome in the gut- promising therapeutic strategy for MASH. The promotion of PINK1/
liver axis and provide novel insights for potential therapeutic targets. Parkin-dependent mitophagy further supports its role in protecting
Method: Mice were fed with a methionine-choline deficient (MCD) diet hepatic cells, suggesting broader implications for metabolic disease
for four weeks to induce MASLD models. Nlrp3fl/fl and Vil1creNlrp3fl/ treatment.
fl mice, with specific knockout of NLRP3 in intestinal epithelial cells, Table and Figure:Figure 1.TOM20 and LAMP1 immunohistochemical
were housed either separately or together to establish models for staining was performed to evaluate mitolysosomes in indicated
MASLD. Liver and intestinal tissues were collected for the assessment treatment hepatic cells
of hepatic steatosis, inflammation, fibrosis, and integrity of the intestinal Figure 2.The proposed mechanism of myricetin-mediated induction of
mucosal barrier, while fecal microbiota composition was analyzed the mitophagy via STING1/PINK1 pathway in MAFLD
using 16S rDNA sequencing. The in vivo effects of intragastric butyrate
were evaluated using Vil1creNlrp3fl/fl-MCD mice. PP0384
Result: Wild-type (WT)-MCD mice exhibited exacerbated hepatic
steatosis and reduced intestinal NLRP3 mRNA expression compared
Trans Fatty Acids Induce the Construction of HCC- vitality of primary
Microenvironment by Accelerating the Process of Liver Fibrosis hepatocytes were detected by MTT; Observation of lipid accumulation
Xiangnan Wang1, Xiao Hu1, Peici Yan1, Ran Guo2, Gang Li3, Naoki and ROS level of primary
Tanaka4 hepatocytes by fluorescence microscopy; changes in JNK, NF-κB,
1
Department of Pathophysiology, Hebei Medical University, and P38 signaling pathways
Shijiazhuang China, 2The Third General Surgery Department, The were analyzed by Western blot; mRNA levels of inflammatory factors
Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, IL-1β and TNF-α were
China, 3Cardiology Division in Geriatric Institute, Hebei General detected by real-time quantitative PCR.
Hospital, Shijiazhuang China, 4Department of Metabolic Regulation, Result: In vivo, metformin can effectively reduce the fatty degeneration
Institute on Aging and Adaptation, Shinshu University Graduate of liver tissue and
School of Medicine, Matsumoto, Japan the increase of transaminase production caused by high-fat diet, and
Background: Polyunsaturated fatty acids with a trans double bond inhibit the recruitment of
are known as trans fatty acids (TFAs). The primary source of TFAs in neutrophils; In vitro, oleic acid and metformin co-treatment significantly
the diet occurs as a byproduct of vegetable oils’ partial hydrogenation enhanced the cell
process. It has been proposed that TFAs might raise the risk of viability (P < 0.001), reduced the lipid accumulation and ROS level of
MASLD, nevertheless, the association between TFAs and HCC is still primary hepatocytes. In
indecisive. The persistent fibrosis process has been proven to play an addition, metformin can significantly inhibit the mRNA level of IL-1 β
intensified role in the development of HCC, and activated HSCs are and TNF – α and inhibit
a major contributor to fibrosis and a major source of CAFs in HCC- the activation of JNK, NF - κ B, p38 signaling pathway in non-alcoholic
microenvironment. This study aims to evaluate whether TFAs worsen fatty liver disease.
the occurrence and progression of HCC via promoting hepatic fibrosis Conclusion: Metformin can effectively inhibit the occurrence of
and assist in inducing the construction of HCC-microenvironment. inflammation in
Method: Thioacetamide (TAA) was used to represent chronic liver nonalcoholic fatty liver disease, and has a significant protective effect
injury in six-month-old wild-type C57BL/6 mice, while TFAs-feed (TFA) on hepatocytes.
made from the AIN93G standard feed (AIN) preparation was used to Table and Figure:Figure 1.Figure 1: Metformin reduces liver damage
model an experimental group. Three groups were established: distilled and liver steatosis
water (DW)+AIN, TAA+AIN, and TAA+TFA, and modeled severally for Figure 2.Figure 2: Metformin reduces neutrophil recruitment in mouse
10 and 20 weeks. We identified and contrasted the alterations in the livers
liver phenotype and extracellular matrix; the expression of factors
associated with fibrosis and those governing the activation of HSCs; PP0386
the expression of factors linked to apoptosis and proliferation and the Traditional Medicine Yiqi Huoxue Relieves Nonalcoholic
hepatic proto-oncogenes in the liver. Steatohepatitis by Remodeling Intestinal Microbiota and
Result: There were visible neoplasms on the liver surface in TAA+TFA Metabolites
group. The intrahepatic hydroxyproline content in the TAA+TFA
Yaoyao Mao1, Jiawei Cui1, Zhandong Lin1, Congyue Zhang1, Yuemin
group was substantially higher than DW+AIN and TAA+AIN groups,
Nan1
noteworthy it also grew progressively as the modeling time was
extended. In contrast to others group, the TAA+TFA group’s Mallory
1
The Third Hospital of Hebei Province
staining results showed a much higher blue hue. Additionally, the Background: The Chinese herbal medicine Yiqi Huoxue (YQHX) is a
expression of fibrosis- and HSCs activation-related factors, including compound of 8 traditional Chinese herbs, which is clinically used to
α-SMA, COL1A1, CTGF and TGF-β, was significantly higher in the treat nonalcoholic steatohepatitis, but its mechanism of action is still
TAA+TFA group. Compared with the 10-week TFA-fed group, the unclear. We created a mouse disease model and used multi-omics to
20-week TFA-fed group showed further enhanced expression levels. study its molecular mechanisms and active components.
Significantly increased expression levels of cell proliferation and proto- Method: A high-fat and high-fructose diet was used to establish
oncogenes factors, such as c-Myc, PCNA, and Ccnd1, were also a nonalcoholic steatohepatitis model in mice. The body weight and
observed in TAA+TFA group. liver specific gravity of each group of mice after different treatments
Conclusion: In chronic liver injury, TFAs was found to trigger the were recorded. The therapeutic effect was evaluated by pathological
activation of HSCs and aggravate hepatic fibrosis, which accelerated staining of liver tissue and detection of serum ALT and liver tissue
the progression of chronic liver injury to HCC via inducing the αSMA. Metagenomic sequencing was used to detect intestinal flora,
construction of an HCC fibrotic microenvironment. ultra-performance liquid chromatography tandem mass spectrometry
Table and Figure:Figure 1.Liver Phenotypic Difference was used to detect serum metabolites, transcriptome sequencing
Figure 2.mRNA Levels of Genes technologywas used to detect the expression profile of liver tissue
mRNA, and ultra-performance liquid chromatography analysis
was used to detect the effective ingredients contained in the YQHX
PP0385
prescription. A molecule-target network was constructed by combining
Effects of metformin on inflammation and triglyceride the differentially expressed genes screened by transcriptomics with the
accumulation in non-alcoholic fatty liver mice effective ingredients detected by UPLC, and key effective ingredients
Zeng Bin1 and therapeutic targets were screened. In vitro studies used palmitic
1
First Affiliated Hospital of Gannan Medical University acid to induce AML 12 to construct a cell model, and cell viability, lipid
Background: To explore whether metformin can inhibit the occurrence droplets and metabolic status were detected after intervention with the
and development of screened effective ingredients.
non-alcoholic fatty liver disease, and to preliminarily elaborate the Result: After the YQHX prescription intervened, the body weight and
molecular mechanism related liver proportion of the disease model mice were significantly reduced
to metformin’s protection of liver cells. compared with the control group.After YQHX intervention, the liver
Method: The high-fat diet of C57BL6/J mice and oleic acid-stimulated lipid droplets decreased, inflammation and fibrosis decreased in
primary hepatocytes the disease mouse model. There were statistical differences in the
were selected as a non-alcoholic fatty liver model; H&E, Oil Red intestinal flora and serum metabolites between YQHX intervention
staining and transaminase and control mice. YQHX may improve the metabolism of long-
biochemistry analysis were used to evaluate pathological state of liver chain fatty acids by increasing the proportion of beneficial bacteria
tissue; Immunofluorescence such as lactobacilli, further improved liver energy metabolism and
was used to display the recruitment of neutrophils in the liver, and the Intestinal barrier function.We screened out paeoniflorin as one of the
potential active ingredients, and in vivo studies further confirmed its
effectiveness. In vitro studies have confirmed that paeoniflorin can disruptions in hepatic iron metabolism and the occurrence of
rescue hepatocyte necroptosis induced by palmitic acid. The specific ferroptosis. We observed increased mRNA level of transferrin receptor
mechanism is related to inhibiting the production of mitochondrial ROS TFRC in C3-/- mice, suggesting that complement C3 may interact with
and improving fatty acid β-oxidation. TFRC, affecting intracellular iron metabolism and accelerating the
Conclusion: YQHX can alleviate nonalcoholic steatohepatitis in progression of NAFLD.
disease model mice by remodeling intestinal flora and improving Conclusion: Intrahepatic complement C3 can regulate intracellular
metabolites, and its active ingredient paeoniflorin has an anti- iron homeostasis by interacting with TFRC, thereby delaying the
necroptosis effect. These results can provide some basis for further progression of NASH. Activating the transcriptional level of complement
clinical research and development of effective and safe drugs for the C3 may be a target for attenuating the progression of NAFLD
treatment of liver fibrosis. Table and Figure:Figure 1.C3-deficient mice develop spontaneous
NASH
Figure 2.C3 deficiency affects mitochondrial function
PP0387
The Metabolic Status in Non-alcoholic Fatty Liver Disease and its
Subtypes: A Pilot Study PP0389
Yanqi Lan1, Ying Lu1, Shiqi Hu1, Shuohua Chen2, Yanhong Wang1, The Impact of MAFLD on the Clinical Cure of NAs-treated Chronic
Shouling Wu2, Li Wang1 Hepatitis B Patients add-on PEG-IFN-alfha Therapy
1
Department of Epidemiology and Biostatistics, Institute of Basic Hui Li Li1, Xia Wang1, Ling Li1, Yi Ru Zhao1, Juan Juan Fu1, Li Li1,
Medical Sciences Chinese Academy of Medical Sciences; School Guang De Yang1, Xiu Cheng Pan1
of Basic Medicine Peking Union Medical College, Beijing, China., 1
The Affiliated Hospital Of Xuzhou Medical University
2
Cardiology Department, Kailuan General Hospital, Tangshan, China.
Background: Metabolic dysfunction-associated fatty liver disease
Background: To unravel novel circulating metabolites relevant to non- (MAFLD) is prevalent among patients with chronic hepatitis B (CHB).
alcoholic fatty liver disease (NAFLD) and its subtypes, lean NAFLD The Impact of MAFLD on the Clinical Cure of Chronic Hepatitis B
(LN) and overweight/obese NAFLD (ON). Patients with PEG-IFN-alfha Therapy remains unclear.This study aimed
Method: A case-control study was undertaken involving 72 newly to determine whether MAFLD influences the clinical cure of NAs-
onset NAFLD and 72 sex and age-matched non-NAFLD in Kailuan treated CHB patients add-on Pegylated Interferon (PEG-IFN) therapy.
cohort. Untargeted liquid chromatography-tandem mass spectrometry Method: A retrospective analysis was performed on nucleoside-
was performed to detect serum metabolomics. Significantly altered treated CHB patients who underwent PEG-IFN combination therapy
metabolites were selected. Logistic regressions were used to validate at a single center. The patients were divided into CHB group and
the associations between candidate metabolites and NAFLD, or its CHB-MAFLD group based on whether they were complicated with
subtypes. fatty liver. The primary endpoint was to assess the difference in HBsAg
Result: Compared to non-NAFLD, the glycerophospholipid metabolism seroclearance rates between the two groups, and the secondary
pathway was evidently changed in NAFLD, LN and ON. Panels endpoint was to evaluate the differences in biochemical parameters
containing seven, sixteen, and four specific glycerophospholipids were and adverse reactions.
found to discriminate NAFLD, LN and ON. The glycerophospholipid Result: A total of 158 nucleoside treated CHB patients were enrolled
metabolism pathway was also reprogrammed in LN vs. ON. There in the study, including 91 CHB patients and 67 CHB-MAFLD patients.
was a positive correlation between choline and LN [odds ratio=4.35, After 48 weeks of PEG-IFN treatment, 20.3% of patients achieved
95% confidence interval: 1.36-13.90]. A panel containing choline, HBsAg seroclearance. Before and after propensity score matching,
phosphatidylcholine and lysophosphatidylcholine had an area the difference in the cumulative probability of HBsAg seroclearance
under curve of 0.73 to distinguish LN from ON. Moreover, a positive between the CHB group and the CHB-MAFLD group was not significant
relationship was discovered between lysophosphatidylcholine respectively (25.3% vs 13.4%, P=0.067; 35.3% vs 14.7%, P=0.063).
(20:3(8Z,11Z,14Z)) and very-low-density lipoprotein (odds ratio=3.13, Logistic regression analysis indicated that baseline HBeAg status was
95% confidence interval: 1.20-8.19). independently associated with HBsAg seroclearance rates. Further
Conclusion: The reprogramming of the glycerophospholipid analysis revealed that MAFLD did not significantly affect HBsAg loss,
metabolism pathway may be principal in NAFLD and its subtypes. LN regardless of HBeAg status, both before and after propensity score
and ON may differ in glycerophospholipid metabolism and subsequent matching (P=0.123, 0.118). Moreover, the group with MAFLD had a
very-low-density lipoprotein secretion. higher rate of abnormal ALT levels at 24 and 48 weeks of treatment
compared to the alone CHB group (31.9% vs 12.3%; 70.8% vs 47.4%,
PP0388 P=0.009, 0.007). However, there was no significant difference in the
normalization of ALT levels between the two groups 24 weeks post-
Intracellular C3 Prevents Non-alcoholic Fatty Liver Disease Via
treatment (88.9% vs 77.2%, P=0.074).
Regulatiing Iron Homeostasis in Hepatocytes
Conclusion: MAFLD has no effect on PEG-IFN therapy for NAs-
Yinling Li1, Binbin Zhang1, Junping Shi1 treated CHB patients to achieve clinical cure, but CHB patients with
1
The Affiliated Hospital of Hangzhou Normal University, Center for MAFLD are less likely to achieve ALT normalization during treatment.
Translational Medicine Table and Figure:Figure 1.The patients flowchart
Background: During the initiation and progression of non-alcoholic Figure 2.Cumulative probability of HBsAg seroclearance stratified by
fatty liver disease (NAFLD), there are significant alterations in baseline MAFLD
complement component levels. However, serving as the principal
site for complement synthesis and storage, our understanding of the PP0390
function of complement within hepatocytes is currently limited.
Method: Isolate primary mouse hepatocytes using a two-step method. Gremlin1 Regulates the Expression of Dlk1 in Adipose Tissue
Using Real-time quantitative PCR and Western Blot to detect the Qinghong Yu1, Yifei Qi1, Shijin Bai1, Shiyu Wang1, Tianhui Liu1
mRNA and protein levels of iron metabolism and ferroptosis-related 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
proteins as well as inflammatory factors; Using electron microscopy University, State Key Lab of Digestive Health, National Clinical
to observe the morphological structure of liver tissue organelles; Research Center of Digestive Diseases
Using Co-Immunoprecipitation mass spectrometry to detect protein Background: Gremlin1, an adipokine essential for adipose tissue
interactions of complement C3, and ufluorescence resonance energy homeostasis, increases in the serum, liver, and adipose tissue
transfer (FRET) is applied to validate protein interactions. of metabolic dysfunction-associated fatty liver disease (MAFLD)
Result: C3-/- mice exhibit spontaneous lipid accumulation and patients and positively correlates with disease severity. However, the
progression towards NASH. During this process, C3-/- mice show mechanism underlying the role of Gremlin1 in MAFLD remains unclear.
In this study, we investigated the possible regulatory mechanism of 1
[email protected]
Gremlin1 in adipose tissue. Background: Objective: To investigate IFI44’s regulatory role in a dual-
Method: rAAV of the recombinant serotype Rec2 with highly efficient disease model of chronic experimental colitis and non-alcoholic fatty
and specific transduction of adipose tissue was used to knock liver disease (NASH).
down Gremlin1 in adipose tissue. AAV-Rec-GFAP-Sh-Gremlin1 was Method: Male C57BL/6 mice were divided into CON (n=5), MCD (n=6),
generated and administered to C57BL/6 mice by intraperitoneal and MCD+DSS (n=8) groups. MCD+DSS mice received a methionine-
injection. PCR Array was used to analyze the differential genes related choline-deficient diet and cyclic 1% DSS solution. After 4 weeks,
to adipogenesis after Gremlin1 knockdown in adipose tissue. 3T3- mice were euthanized, and tissues collected. Colon inflammation was
L1 cells were treated with LPS, TNF-α, H2O2 and palmitic acid (PA) assessed by DAI, morphology, and histopathology. Liver inflammation
to mimic the pathological conditions of MAFLD in vitro, respectively. was evaluated using NAS score and Oil Red O staining. IFI44, TNF-α,
RT-PCR was utilized to detect the expression of Gremlin1 and the IL-1β, and IFN-γ mRNA expression were measured by qPCR. IFI44
differential genes identified by PCR Array. Additionally, recombinant protein expression was assessed by immunohistochemistry and
mouse Gremlin1 was administered to 3T3-L1 cells as well as to primary Western blot.
murine adipocytes. The expression of the differential genes identified Human LO-2 liver cells and HT-29 colon cancer cells were cultured.
by PCR Array were detected. LO-2 cells were induced into a fatty liver model with free fatty acids (FFA),
Result: RT-PCR results showed that Gremlin1 was knockdown in white and HT-29 cells into an inflammatory model with lipopolysaccharides
adipose tissues successfully. PCR array showed that some genes (LPS). IFI44 expression was knocked down using siRNA. Cells were
related to anti-adipogenesis increased when Gremlin1 was knockdown. divided into CON, FFA/LPS, siNC, and siIFI44 groups. IFI44 mRNA and
Among these genes, delta-like 1 homolog (Dlk1) plays a key role in protein expression were measured by qPCR and Western blot. TNF-α,
preadipocyte homeostasis and adipose tissue expansion. After treated IL-1β, and IFN-γ levels were assessed by ELISA.
with LPS, TNF-α, H2O2 and PA, the expression of Gremlin1 increased, Result: MCD and DSS+MCD mice showed significant weight loss,
while the expression of Dlk1 decreased in undifferentiated 3T3-L1 increased DAI, and reduced colon length compared to CON, with
cells. These data suggested that Gremlin1 was negatively correlated DSS+MCD showing more severe changes (P<0.05).. Liver tissues
with dlk1 in the context of MAFLD, and might have a regulatory effect of MCD and DSS+MCD mice showed hepatocyte swelling, necrosis,
on Dlk1. Accordingly, recombinant Gremlin1 inhibited the expression and inflammation, with higher NAS scores in DSS+MCD (P<0.05).
of Dlk1 in both 3T3-L1 cells and primary murine adipocytes. Successful IFI44 siRNA transfection was confirmed in HT-29 and LO-2
Conclusion: Gremlin1 regulates Dlk1 in adipose tissue, which might cells. LPS-induced HT-29 cells showed increased IFI44 mRNA and
be one of the mechanisms of its role in MAFLD pathogenesis. protein expression, which were reduced by siIFI44 (P<0.05). TNF-α, IL-
1β, and IFN-γ levels were elevated in LPS-induced cells and reduced
PP0391 by siIFI44 (P<0.05). FFA-induced LO-2 cells also showed increased
IFI44 mRNA and protein expression, which were decreased by siIFI44
Clusterin/Apolipoprotein J expression modulates tamoxifen
(P<0.05). Intracellular TG and ALT concentrations were higher in FFA-
metabolism in liver and mitochondrial imbalancing in breast
induced cells and lower in siIFI44-treated cells (P<0.05).
cancer
Conclusion: Intestinal inflammation promotes NASH progression
Ya Wen Chang1, Hung Yu Sun1
in mice, possibly through a compromised intestinal mucosal barrier,
1
National Cheng Kung University leading to increased circulating IFI44 and liver inflammatory factors via
Background: Tamoxifen is converted to active metabolites by the gut-liver axis.
cytochrome P450 (CYP) enzymes in the liver, but leads to hepatic Reducing intracellular IFI44 alleviates cell damage in both
toxicity and increases the risk of non-alcoholic fatty liver disease colonic inflammation and fatty liver models. Targeting IFI44 may
(NAFLD). Apolipoprotein J (ApoJ), also known as clusterin (CLU), is effectively inhibit the progression of ulcerative colitis (UC) and NASH,
majorly produced by liver. Previously, ApoJ has been shown to be offering a novel therapeutic strategy for their combined treatment
associated with cancer progression and elevated in NAFLD patients.
This investigation addresses the role of ApoJ in hepatic tamoxifen
PP0393
metabolism and mitochondrial reprogramming in breast cancer.
Method: The hepatocytes were treated with tamoxifen to assess the Ethnicity based differences in liver and abdominal fat distribution
impact on ApoJ expression and lipid accumulation. Human hepatoma Charlie Diamond1, Vivian Lee2, Yiying Han3, Desiree Faye Toh2,
cells with ApoJ silencing were applied to investigate the effects of Jennifer A Bryant3, Redha Boubertakh2,4, Sophie Riddell1, Elizabeth
ApoJ on tamoxifen-induced lipid droplet formation. The mitochondrial Shumbayawonda1, Helena Thomaides Brears1, Thu Thao Le2,4, Calvin
reprograming and ROS accumulation of breast cancer cells cultured WL Chin2,3,4
in medium collected from tamoxifen-treated hepatocyte and was 1
Perspectum Ltd., 2National Heart Research Institute Singapore
addressed. The hepatocyte-specific ApoJ knockout mice were utilize (NHRIS), National Heart Centre Singapore, 3Department of
to examine the relationship between ApoJ and hepatic tamoxifen Cardiology, National Heart Centre Singapore , 4Cardiovascular
metabolism. Academic Clinical Program (ACP), Duke-NUS Medical School,
Result: The results showed that tamoxifen treatment induces ApoJ Singapore
expression in hepatocytes, which leads to lipid accumulation. Background: Ethnicity influences body composition and the risk of
Silencing of ApoJ in human hepatoma cells significantly reduced cardiometabolic disease. Here we explore ethnicity-based differences
tamoxifen-induced lipid droplet formation. Additionally, tamoxifen in body composition and liver fat using quantitative MRI in Singaporean
promoted the hepatic secretion of ApoJ, which was then taken up individuals with existing cardiometabolic risk factors, adjusting for
by breast cancer cells to facilitate mitochondrial fission and enhance ethnicity specific BMI categories.
cancer malignancy. Furthermore, hepatocyte-specific ApoJ knockout Method: 124 Chinese adults with ≥1 cardiometabolic risk factors were
increased the expression of CYP enzymes, highlighting the role of recruited from National Heart Centre Singapore (NHCS) and compared
ApoJ in regulating tamoxifen metabolism in liver. to 124 White matched individuals from the UK Biobank (matched by
Conclusion: Our research demonstrates that ApoJ plays a crucial age, sex, ethnicity-adjusted BMI category, hypertension and type 2
role in tamoxifen-induced hepatic dysfunction and contribute to diabetes status). Individuals underwent multiparametric magnetic
dysregulation of mitochondrial homeostasis in breast cancer. resonance imaging (MRI) for quantification of body composition and
liver fat content. Body composition comprised of cross-sectional area
PP0392 measurements of subcutaneous adipose tissue (SAT) and visceral
adipose tissue (VAT), derived semi-automatically from a single slice at
The Regulatory Role of IFI44 in the Chronic Experimental Colitis
L3 vertebra. Values were indexed to an individual’s height (SATi and
and Non-alcoholic Fatty Liver Disease Dual-Disease model
VATi). Liver fat content (as proton density fat fraction) was acquired using
Huan Yu1
LiverMultiScan. A threshold of ≥5% liver fat was considered abnormal. a distinct individual BA, i.e., NorCA that was markedly upregulated
We used ethnicity-adjusted BMI categories to compare groups, as per in MAFLD patients with abnormal albuminuria, and that was also
WHO guidelines. For Chinese individuals, normal BMI was defined as positively correlated with albuminuria. Moreover, the combination of
≤23kg/m2 and obesity ≥27.5kg/m2. For White individuals, thresholds NorCA, tauro-deoxycholic acid, tauro-lithocholic acid and cholic acid,
of ≤25kg/m2 and ≥30kg/m2 were used, respectively. Wilcoxon rank improved identification of abnormal albuminuria in MAFLD patients in
sum and Fisher’s exact tests were used for groupwise comparisons. a predictive model, that also included diabetes, hypertension, body
Linear regression was used to control for confounding. mass index, and serum alanine aminotransferase levels (AUC=0.80,
Result: Of the 124 Chinese individuals (59±13 years; 65% males; 39% 95%CI 0.740-0.863). In addition, in the vivo and vitro experiment,
obese; 88% hypertensive; 40% type 2 diabetes), 65% had elevated renal function and renal tubules were severely damaged and fibrosis
levels of liver fat, a comparable prevalence to the White individuals tendency occurred after the stimulation of NorCA
(56%, p = 0.242). Chinese individuals showed significantly lower levels Conclusion: BA biomarkers are increased in patients with MAFLD and
of both mean SATi (Chinese 64 vs 79cm2/m2, p = 0.009) and VATi abnormal albuminuria. Among them, NorCA could exacerbate kidney
(65 vs 80cm2/m2, p = 0.005). Amongst both ethnicities, increasing injury in MAFLD population
BMI was associated with increasing liver fat content, SATi and VATi. Table and Figure:Figure 1.Bile acid changes in patients with MAFLD
Ethnicity had no differential effect on liver fat at any BMI (Figure 1A). stratified by presence abnormal albuminuria
This was not the case for SATi and VATi, as White people with obesity
had significantly higher values relative to Chinese individuals (Figure
PP0395
1B). No differences were observed in normal or overweight individuals.
These associations persisted after controlling for differences in age, Blautia wexlerae Enhances Intestinal Indole Levels to Inhibit Lipid
sex, hypertension and type 2 diabetes status. Absorption via the Ahr/Cyp1A1 Pathway and Suppress NASH
Conclusion: Adjusting for ethnicity-based thresholds of BMI, Progression
prevalence of high liver fat was substantial and comparable in both Binbin Zhang1, Junping Shi
Chinese and White populations with cardiometabolic risk factors. 1
The Affiliated Hospital of Hangzhou Normal University
However, subcutaneous and visceral adiposity were higher in Background: The prevalence of non-alcoholic steatohepatitis (NASH)
White individuals with obesity. MRI body composition illustrates this is increasing annually, posing a significant threat to physical and
disparity in fat distribution across ethnicities beyond anthropometric mental health and imposing a substantial economic burden.
measurements and can assist with accurate treatment planning in Method: This project aims to recruit eligible NASH and non-NASH
obesity and cardiometabolic disease. patients, collect fecal samples, and perform metagenomic analysis
Table and Figure:Figure 1.Figure 1: Comparison of A) Liver fat content to identify differential biomarker genera significantly enriched in non-
and B) VAT index in White vs Chinese individuals at different levels of NASH individuals. Selected biomarker genera will be incubated in vitro,
BMI. purified as monoclonal strains, and stored, cultured, and expanded.
Male C57 mice will be used to establish a NASH model via an
PP0394 8-week high-fat, high-cholesterol diet, followed by a 6-week microbial
transplantation with the identified biomarker genera to evaluate their
Norcholic acid: a novel risk factor of early kidney injury with
effects on NASH progression. Additionally, the identified genera will
metabolic dysfunction-associated fatty liver disease
be administered preemptively, and the mice will be subjected to high-
Danqin Sun1, Mengyang Zhong1, Cuifang Xu2, Jiahui Zhang3, dose olive oil gavage. Triglyceride levels in peripheral blood, colonic
Wenying Chen4, Fuqiang Yuan5, Giovanni Targher6, Christopher D tissue, and gut contents will be measured to assess the impact of these
Byrne7, Jing Zhao1, Ana Liu2, Mingming Su2, Junping Shi8, Yan Ni2, genera on lipid absorption. Metabolomics and transcriptomics will
Minghua Zheng4 be employed to explore the metabolic products and potential target
1
Department of Nephrology, Jiangnan University Medical Center, 2The pathways of the biomarker genera, and their effects will be validated
Children’s Hospital, Zhejiang University School of Medicine, National using in vivo and in vitro models.
Clinical Research Center for Child Health, 3Department of Paediatrics, Result: Biomarker genera with statistically significant differences
The Affiliated Wuxi Children‘s Hospital of Jiangnan University, 4MAFLD
between the NASH and non-NASH groups were analyzed, identifying
Research Center, Department of Hepatology, the First Affiliated
Blautia wexlerae, significantly enriched in the non-NASH group, as a
Hospital of Wenzhou Medical University, 5Department of Pediatric
potential probiotic. In vivo studies demonstrated that transplantation
Laboratory, The Affiliated Wuxi Children‘s Hospital of Nanjing Medical
of Blautia wexlerae into NASH model mice alleviated disease
University, 6Section of Endocrinology, Diabetes and Metabolism,
Department of Medicine, Azienda Ospedaliera Universitaria Integrata progression by improving body weight and biochemical indicators.
Verona, 7Southampton National Institute for Health and Care Research In acute experiments involving high-dose olive oil intervention, pre-
Biomedical Research Centre, University Hospital Southampton treatment with Blautia wexlerae reduced jejunal triglyceride levels,
and University of Southampton, Southampton General Hospital,, serum triglyceride levels, and increased fecal triglyceride content
8
Department of Translational Medicine Center, Affiliated Hospital of compared to untreated mice. This intervention enhanced the excretion
Hangzhou Normal University, Institute of Hepatology and Metabolic of olive oil through feces, inhibited intestinal absorption of olive oil,
Diseases, Hangzhou Normal University and consequently mitigated hepatic steatosis.Metabolomic analysis
of intestinal contents revealed that Blautia wexlerae impacts amino
Background: Bile acids (BAs) are signaling molecules that regulate
acid metabolism, particularly by promoting tryptophan catabolism.
numerous metabolic processes in metabolic dysfunction-associated
This led to increased levels of indoleacetate (IAA) and indole-3-lactic
fatty liver disease (MAFLD) and chronic kidney disease (CKD).
acid (I3LA) in the gut, activating the intestinal Ahr/Cyp1A1 signaling
Whether BAs are also associated with early abnormalities in renal
pathway and reducing intestinal lipid absorption.
function in MAFLD is uncertain.
Conclusion: Blautia wexlerae promotes the metabolism of tryptophan
Method: We quantitatively measured plasma BA concentrations in
into indole derivatives in NASH model mice. This process increases
biopsy-proven MAFLD patients with or without abnormal albuminuria
intestinal levels of indoleacetate (IAA) and indole-3-lactic acid (I3LA),
(defined as albumin-to-creatinine ratio ≥30 mg/g) and in healthy
activating the intestinal Ahr/Cyp1A1 signaling pathway. Consequently,
controls, by using ultraperformance liquid chromatography coupled
it inhibits intestinal lipid absorption, thereby suppressing hepatic
to tandem mass spectrometry. Next, we demonstrated the effect of
steatosis induced by a high-fat diet in NASH model mice.
norcholic acid (NorCA) on renal injury in vivo and in vitro.
Result: Plasma BA profiles (conjugated BAs, glycine-conjugated
BAs, glycine-conjugated primary BAs, total conjugated primary BAs, PP0396
and glycine-conjugated primary BAs) were up-regulated in MAFLD
patients with abnormal albuminuria compared to their counterparts with
normal albuminuria and healthy controls. In particular, we identified
Salvianolic acid B mitigates metabolic dysfunction-associated Method: TPM4 expression were analyzed in MASH patients and models.
steatohepatitis in mice via up-regulating SIRT1 to inhibit A western diet combined with intraperitoneal carbon tetrachloride
hepatocyte ferroptosis (WD/CCl4) and a choline-deficient, L-amino acid-defined, high-fat
Xiaoxi Zhou1, Yadong Fu1,2, Jinxing Lv1, Zheng Zhang1, Yue Liang1, diet (CDAHFD) were used to induce MASH in mice. TPM4-plasmid
Wei Liu1, Jiamei Chen1, Ping Liu1,3 or small interfering RNA targeting TPM4 was used to upregulate
1
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), or downregulate TPM4 expression in HSCs. Scratch assay was
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai performed to detect cell migration, and the differential centrifugation
University of Traditional Chinese Medicine, 2School of Traditional followed by density gradient centrifugation was performed to isolate
Chinese Medicine, Shanghai University of Traditional Chinese the migrasomes.
Medicine, 3Institute of Interdisciplinary Medicine, Shanghai University Result: We found that the expression of TPM4 in the liver of MASH
of Traditional Chinese Medicine patients, the liver of mice in the WD/CCl4 group, and the liver of mice
Background: Globally, metabolic dysfunction-associated steatotic in the CDAHFD group was higher than that in the control group.
liver disease (MASLD) is now the most prevalent chronic liver disease. TPM4 content was positively correlated with liver weight, liver index,
Hepatocyte ferroptosis plays an essential role in the progression of liver fibrosis stage and Nonalcoholic Fatty Liver Disease Activity
metabolic dysfunction-associated steatohepatitis (MASH). Salvianolic Score (NAS) score. We further found that the expression of TPM4
acid B (Sal B), a natural and potent antioxidant active ingredient, has was increased in activated HSCs. Upregulating TPM4 promoted the
an anti-MASH effect, but its mechanism is still unclear. activation of HSCs, while downregulating TPM4 inhibited the activation
Method: In vivo, MASH models were induced by a high-fat and high- of HSCs. Upregulating TPM4 also enhanced the migration ability of
cholesterol (HFHC) diet for 30 consecutive weeks in C57/BL mice, and HSCs. Importantly, activated HSCs-derived migrasomes aggravated
treated with Sal B, obeticholic acid (OCA) or a SIRT1 agonist, SRT1720 hepatocyte inflammatory injury and promoted macrophage M1
in the beginning of 24th week. In vitro, stable over-expression and polarization.
knockdown of SIRT1 in hepatocytes were constructed with lentivirus, Conclusion: TPM4 is upregulated during MASH. TPM4 activates HSCs
subsequently, a hepatocyte lipid deposition model induced by palmitic and promotes migracytosis of HSCs, thereby aggravating MASH.
acid/oleic acid (PO) and a hepatocyte ferroptosis model induced by Table and Figure:Figure 1.Figure1. Upregulating TPM4 promoted
erastin were used to investigate the efficacy and mechanism of Sal activation of hepatic stellate cells (HSCs).
B. Furthermore, the interaction and the binding kinetics of Sal B and Figure 2.Figure2. Activated HSCs-derived migrasomes aggravated
SIRT1 were determined by molecular docking and molecular dynamics inflammation.
simulation, as well as DARTS, CESTA and SPR.
Result: Sal B and SRT1720 both attenuated hepatic inflammation, PP0398
lipid deposition and fibrosis. Liver tissue from HFHC-induced NASH OX40L-PIP5K1a-MAPK pathway upregulates bone-marrow derived
mice showed typical hepatocyte ferroptosis structural changes via macrophages activation and M1 polarization promoting MASLD
in situ scanning electron microscopy. Sal B treatment and SRT1720
Zihan Zhang1
treatment both led to a reduction in the degree of hepatocyte
ferroptosis, pathologically and morphologically, suggesting that Sal
1
Beijing Chao-Yang Hospital, Capital Medical University
B inhibited hepatocyte ferroptosis in HFHC-induced mice. Moreover, Background: The progression mechanism of metabolic dysfunction-
iron metabolism disorders and lipid peroxidation damages were also associated steatotic liver disease (MASLD) represents a significant
alleviated after treatment with Sal B or SRT1720. Mechanistically, Sal scientific inquiry at present. Earlier investigations have indicated that
B up-regulated hepatic SIRT1 protein and inhibited p53 acetylation. the recruitment, stimulation, and M1 polarization of hepatic bone
Molecular docking and molecular dynamics simulation showed marrow-derived macrophages (BMDM) are instrumental in fostering
potentially high binding affinity (-9.9 kcal/mol) between Sal B and SIRT1, the onset and advancement of MASLD. Furthermore, the activation
and the Sal B-SIRT1 complex had very nice stability. Furthermore, Sal of the OX40/OX40L pathway in BMDM has been identified as a
B showed the moderate-affinity to recombinant human SIRT1 protein pivotal factor in MASLD development. Nevertheless, the fundamental
with a KD of 2.132E-5, and enhanced the enzyme and thermal stability mechanism underlying the inflammatory impact of BMDM induced by
of SIRT1 protein, as determined by SPR, DARTS and CETSA. In vitro, the OX40L stimulation remains elusive.
Sal B alleviated PO- or erastin-induced hepatocyte lipid deposition and Method: OX40L levels were evaluated in patients with biopsy proven
ferroptosis, up-regulating SIRT1 protein and inhibiting p53 acetylation. MASLD diagnosis and correlated with clinical and biochemical
Similarly, SIRT1 overexpression exerted the consistent pharmacological parameters. Wild-type (WT) or OX40L overexpression in monocytes
effect of Sal B. Strikingly, genetic knockdown of SIRT1 reduced the (OX40Lflag/flagLyzcre) mice were fed a CD-HFD diet for 16 weeks.
inhibitory effect of Sal B on hepatocyte lipid deposition and ferroptosis. IP-MS and co-immunoprecipitation (co-IP) were employed to validate
Conclusion: The activation of SIRT1 inhibits hepatocyte ferroptosis the interaction between OX40L and PIP5K1α. Gene expression was
and represents a novel therapeutic target for the treatment of MASH. suppressed using OX40L or PIP5K1α siRNAs and augmented through
Sal B ameliorates MASH in mice via regulating SIRT1/p53 signaling to transfection with plasmids containing OX40L cDNA. Enzyme-linked
inhibit hepatocyte ferroptosis, providing experimental data support for immunosorbent assays (ELISA) were used to detect and quantify
the treatment of MASH with Sal B. the levels of PIP2, IP3 and DAG. Bioinformatic analyses indicated
Table and Figure:Figure 1.Graphical Abstract that OX40 Fc stimulation upregulated genes enriched in the MAPK
signaling pathway. Rescue experiments were performed to confirme
the effect of OX40 on the MAPK pathway via the OX40L-PIP5K1α-PIP2
PP0397
axis. Flow cytometry was conducted to assess the phosphorylation
Tropomyosin-4 aggravates metabolic dysfunction-associated status of ERK, JNK and P38.
steatohepatitis by promoting hepatic stellate cell migracytosis Result: OX40L increased in the liver infiltrated monocytes
Zhiping Wan1,2, Xiang Cai1,2, Xiaoquan Liu1,2, Xiaoan Yang1,2, Qingqing (CD11bintF4/80low) of patients with metabolic-associated steatotic
Feng1,2, Hong Deng1,2 liver disease, correlating with liver steatosis, lobular inflammation,
1
Department of Infectious Diseases, the Third Affiliated Hospital of and focal liver necrosis. Consistently, OX40L overexpression in
Sun Yat-sen University, 2Guangdong Key laboratory of Liver Disease monocytes aggravated CD-HFD-induced hepatic steatosis and
Research, the Third Affiliated Hospital of Sun Yat-sen University necrosis. In addition, compared to wild-type (WT) monocytes,
Background: Migracytosis is the process by which cells release OX40flag/flag monocytes exhibited upregulated levels of cytokines,
cellular contents through migrasomes during migration. Tropomyosin-4 cytokine receptors, chemokines, chemokine receptors, and antigen
(TPM4) is associated with migracytosis of hepatic stellate cells processing and presentation molecules upon OX40/FC stimulation.
(HSCs), but their mechanism in metabolic dysfunction-associated Mechanistically, OX40L interacted with PIP5K1α, and OX40L
steatohepatitis (MASH) remains unclear. overexpression significantly increased the production of PI (4,5)P2 and
its hydrolysis products, including IP3 and DAG. Additionally, DAG and
IP3 activated the MAPK pathway to enhanced inflammation response Background: With the rising prevalence of obesity and diabetes,
in monocytes. metabolic dysfunction-associated steatotic liver disease (MASLD)
Conclusion: Within the context of MASLD pathogenesis, the expression has emerged as a significant chronic liver condition that poses a
of OX40L on hepatic macrophages is enhanced upon OX40 ligation, substantial threat to human health. In China, its incidence rate is as high
resulting in the enrichment of PIP5K1a at the cell membrane. This as 29.2%. MASLD encompasses a spectrum of dynamic pathological
stimulation of the PI(4,5)P2-DAG-MAPK signaling axis orchestrates an processes, ranging from simple fatty liver to metabolic dysfunction-
inflammatory cascade within these macrophages, contributing to the associated steatohepatitis (MASH), characterized by hepatocellular
initiation and propagation of MASLD. inflammatory damage. Some patients may progress to cirrhosis
or even hepatocellular carcinoma. Currently, there are no effective
PP0399 therapeutic interventions available. Recent studies have indicated
that the accumulation of cellular senescence is closely associated
Deletion of HO-1 perturbs Hepatocyte Mitochondria-associated with the progression of MASLD. Therefore, a comprehensive analysis
Endoplasmic Reticulum Membranes Dynamics and Calcium of senescent cells, key signaling pathways, and molecular regulatory
homeostasis networks involved in the dynamic progression of MASLD can enhance
Dong Dong Li1, Chang Min Cai1, Wen Zhao1, Yuemin Nan2 our understanding of the disease’s pathogenesis and may provide
1
First Affiliated Hospital of Bengbu Medical University, 2Hebei Medical novel therapeutic insights for MASLD.
University Third Hospital Method: To comprehensively delineate the phenotype and ontogeny
Background: HO-1 reduces apoptosis and attenuates oxidative of senescent hepatic sinusoidal endothelial cells (LSECs) in
stress in chronic hepatitis. In this study, we showed that deletion of murine metabolic dysfunction-associated steatohepatitis (MASH),
HO-1 injured the structural integrity of MAM in the liver-specific HO-1 we integrated single-cell RNA sequencing (scRNAseq), spatial
knockout mice. We further explore how HO-1 display its protective role transcriptomics, and immunofluorescence to characterize the
in MAM dynamics. molecular features, spatial distribution, and interactions with immune
Method: Animal models were developed in liver-specific HO-1 cells of Cd74+ LSECs in MASH
knockout (HO-1HepKO) and wild-type (WT) mice. Ultrastructure Result: We constructed a MASH disease progression model and
changes in MAM were observed under TEM. Immunofluorescence validated, using both internal and external datasets, the specific
double labeling was used to determine the co-localization of important reduction of endothelial cells in MASH progression, while observing
proteins on MAM. The Ca2+ content of mitochondria was detected by a selective increase in Cd74+LSECs, which we define as senLSECs
calcium content detection kit under Flow cytometer. due to their antigen-presenting, senescent, and pro-inflammatory
Result: HO-1HepKO mice were constructed successfully and could phenotypes. Within these senLSECs, the transcription factor BHLHE40
be stably inherited. Our findings suggest that the Liver-specific HO-1 is specifically activated, inducing a glycolytic reprogramming in
knockout mice do not significantly affect daily food intake, body weight, senLSECs that leads to lactate accumulation and promotes senLSEC
plasma liver enzyme levels, or liver morphology under the experimental senescence. Furthermore, senLSECs secrete CCL5 to recruit pro-
conditions. Deletion of HO-1 up-regulated Parkin expression and down- inflammatory Ccr1+MDMs, which also exhibit a senescent phenotype,
regulated MFN2 expression, resulting in a decrease in Mito [Ca2+] thereby advancing MASH progression in a BHLHE40-Ccl5 dependent
level in vivo and in vitro. However, HO-1 overexpression showed manner. We define the senLSECs/MDM as a senescent niche, which
opposite results. Mechanically, HO-1 may negatively regulate the is also present in aged livers, and integrate these findings to provide a
Parkin/MFN2/Ca2+ signaling pathway, leading to MFN2 ubiquitination comprehensive understanding of the cellular dynamics in MASH.
and proteasome degradation. This process leads to changes in MAM Conclusion:
length, reduces Ca2+ transfer to mitochondria, and exacerbates MAM These data delineate the characteristics of the senescent niche
damage. Overexpression of Parkin by pcDNA3.1 plasmid in vivo leads in MASH livers, centered around Cd74+ LSECs and Ccr1+ MDMs,
to MAM abnormalities similar to those observed in Liver-specific HO-1 establishing a crucial blueprint for targeting these senescent cells and
knockout mice, and knockdown of Parkin by siRNA plasmid in vivo has their key molecules in future therapeutic approaches for MASH.
the opposite results. Moreover, immunofluorescence co-localization
showed increased co-localization of Parkin and MFN2 in the MAM PP0401
region, and their interaction may lead to MAM injury, which was more
CD73 enhances the immunoregulatory functions of hepatic
significant in the liver tissue of HO-1HepKO mice.
Tregs through enzymatic and nonenzymatic pathways in MASLD
Conclusion: We have successfully established a HO-1HepKO mice.
development
It will be an invaluable tool to explore their physiological functions
and pathological mechanisms. Furthermore, HO-1 may restore MAM Xinjie Zhong1, Hua Jin1, Chunpan Zhang2, Yongle Wu2, Dong Zhang2,
integrity by negatively regulating the Parkin-MFN2 axis. This result Guangyong Sun2
provides a new idea for HO-1 to serve as a potential protection against
1
Beijing Chao-yang Hospital, 2Beijing Friendship Hospital
MAM dynamics. Background: Regulatory T cells (Tregs) play a critical role in
Table and Figure:Figure 1.Construction strategy and procedures of immunosuppression and delay the progression of metabolic
HO-1HepKO mice. dysfunction-associated steatotic liver disease (MASLD). CD73, a
Figure 2.Deletion of HO-1 aggravates MAM ultrastructure and functional molecule highly expressed on Tregs, shows increased
mitochondrial calcium disturbance via regulating the Parkin-MFN2 expression in both peripheral blood of MASLD patients and liver tissue
signaling pathway. of MASLD mouse models. However, CD73’s role and its mechanism of
modulating Tregs in MASLD pathogenesis remain unknown.
PP0400 Method: Wild-type (WT) and CD73 knockout (KO) mice, or specifically
transferring WT or CD73 KO Tregs into Rag1-/- mice were fed either
Single-cell and spatial multi-omic profiling implicates the a choline-deficient high-fat diet (CD-HFD) for 16 weeks or choline
senescence-associated CD74+ endothelial cells-mediated deficient diet (MCD) for 4 weeks to establish MASLD model. Liver
metabolic remodeling in MASH progression injury and fat accumulation were evaluated via liver histopathology
Rui Zhang1,2, Yuan Liang3,2, Ling Lu1,2 and serum biochemical parameters. The activation, differentiation, and
1
Jiangsu Key Laboratory of Organ transplantation and transplant cytokine secretion of liver infiltrated immune cells were determined.
immunology; Research Unit of Liver Transplantation and Transplant Transcriptome sequencing of hepatic Tregs from WT or CD73 KO
Immunology, Chinese Academy of Medical Sciences; Hepatobiliary MASLD mice were analyzed. The mechanisms of CD73 regulating
Center, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Tregs survival and immunoregulatory functions were explored in vitro.
China., 2Collaborative Innovation Center for Cancer Personalized Result: CD73 expression increased significantly in nonparenchymal
Medicine, Nanjing Medical University, Nanjing, China., 3Southeast cells, particularly Tregs, in MASLD mice livers. Both soluble CD73
University concentrations and Treg CD73 expression were elevated in MASLD
patients’ plasma. CD73 KO mice fed CD-HFD or MCD showed more PP0403
severe liver inflammation, fibrosis, and lipid accumulation compared to Mechanism of Genipin 1-gentiobioside Targeting IRAK4 to Inhibit
WT mice, along with impaired Treg survival and immunosuppressive NLRP3 Inflammasome Activity in Liver Macrophages to Alleviate
function. While transferred WT Tregs protected Rag1-/- mice against Metabolic Dysfunction-Associated Steatohepatitis Inflammation
MASLD development, CD73 KO Tregs failed to reduce liver injury,
Zhuoyuan Wang1, QinMei Sun2, Beiyu Cai1, Xin Xin1, Ziming An1, Qian
evidenced by higher plasma ALT, AST, TBIL, and fasting glucose levels,
Huang1, Sheng Lv1, Furong Qiu3, Qin Feng1
with increased proinflammatory monocyte infiltration and cytokine
secretion. Transcriptome analysis revealed that liver free fatty acids in
1
Institute of Liver Diseases, Shuguang Hospital Afflicated to
Shanghai University of Traditional Chinese Medicine, 2Shanghai
MASLD promoted GATA2 transcription factor through p38 signaling,
University of Traditional Chinese Medicine, 3 Laboratory of Clinical
leading to CD73 upregulation on Tregs. CD73 protected Tregs through
Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai
both enzymatic pathways, preventing AMP-induced apoptosis and
University of Traditional Chinese Medicine
exhaustion while generating adenosine (ADO) to enhance cell survival,
and non-enzymatic pathways, by interacting with DR5 to prevent Trail- Background: Genipin 1-gentiobioside, a major active component
induced apoptosis and maintain immunoregulatory function. isolated from Gardenia jasminoides, which is traditionally used in
Conclusion: CD73 downregulates liver inflammation and MASLD Chinese medicine for the treatment of liver-related diseases, has not
pathogenesis by regulating Tregs. Our study reveals a novel had its specific efficacy and mechanism of action against Metabolic
intrinsic mechanism that CD73 is crucial for Tregs homeostasis and Dysfunction-Associated Steatohepatitis (MASH) clearly defined. This
immunosuppressive function in MASLD development, offering a study aims to uncover the therapeutic effects of GG on MASH and its
promising immunotherapy strategy for MASLD treatment with potential underlying mechanisms.
clinical applications. Method: The mouse MASH model was established by feeding with
Table and Figure:Figure 1. The mechanisms of CD73 modulating Tregs high-fat high-carbohydrate diet and high sugar drink for 18 weeks.
in MASLD At the last 6 weeks, mice in the GG group received GG (50/100 mg/
kg/day) by oral gavage. Histopathological examination, biochemical
examination and other methods were used to evaluate the effect of GG
PP0402 on MASH. Molecular docking simulation, cell thermal migration analysis
Genome-wide CRISPR Screening Identifies NOC2L as an (CETSA) and drug affinity reaction target stability (DARTs) were used
Epigenetic Determinant of Hepatocyte Steatosis for prediction and identification. Subsequently, both in vivo and in vitro
Jianxu Chen1,2, Jiandi Chen3, Minzhao Gao1, Chengmin Ma1, Yuan observations were made to assess the impact of GG on IRAK4 activity,
Liu1, Yanzhi Han1, Xiaofeng Li1 NF-κB transcription, and NLRP3 inflammasome activation. The in vitro
1
Department of Gastroenterology, the Fifth Affiliated Hospital, Sun Yat- model utilized LPS + ATP to induce NLRP3 inflammasome activation in
sen University, Zhuhai, Guangdong Province, China., 2Guangdong bone marrow-derived macrophages (BMDM) and Kupffer cells. IRAK4
Provincial Engineering Research Center of Molecular Imaging, The Gene knockout mice were established,with wild-type mice serving as
Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong controls, and a high-fat high-carbohydrate diet and high sugar drink
Province, China., 3Department of Radiology, the Fifth Affiliated was used to verify the impact of GG on the IRAK4/NF-κB/NLRP3
Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, signaling pathway.
China. Result: GG significantly reduced liver fat deposition and inflammation
Background: Alterations of hepatic metabolism is the hallmark of in MASH mice. In line with the suggestion of molecular docking, the
metabolic dysfunction–associated steatotic liver disease (MASLD). results of CETSA and DARTS experiments demonstrated that GG
Lean MASLD, a subset of MASLD patients, with higher risks of liver bound to IRAK4 protein by enhancing its structural stability. Further
cirrhosis, who face a higher risk of developing liver cirrhosis and not research has found that GG decreased the phosphorylation of IRAK4
did not consume excessive amounts of fat. The characteristics of these and the transcriptional activity of NF-κB in the livers of MASH mice,
patients indicate the presence of significant risk factors for MASLD thereby inhibiting the activation of the NLRP3 inflammasome. In
that remain unexplored, beyond lifestyle influences. Recent studies vitro experimental results showed that GG could also significantly
suggested epigenetic remodeling changes cell functional states and reduce macrophage IRAK4 activity, NF-κB transcription, NLRP3 gene
metabolic modulations. Epigenetic remodeling is an important factor transcription, and inflammasome activity. However, when IRAK4 was
contribute to MASLD progression. In our study, we identified NOC2 knocked out, this inhibitory effect was significantly diminished both in
Like Nucleolar Associated Transcriptional Repressor (NOC2L) as vivo and in vitro.
an epigenetic determinant in promoting hepatocyte steatosis. Some Conclusion: GG can improve the liver inflammatory of MASH
studies suggested NOC2L is an inhibitor of histone acetyltransferase. by targeting IRAK4 to inhibit NF-κB transcription and NLRP3
Method: We established Cas9-expressing steatotic hepatocyte inflammasome activity in liver macrophages, providing basic evidence
model (HepG2 cells) models, then transduced with single-guide RNA for its future application.
(sgRNA) libraries, which targets 19,114 genes with four gRNAs per Table and Figure:Figure 1.Schematic of the therapeutic effect of GG
gene. The relatively less lipid accumulation cells were sorted by FACS. in alleviating MASH liver inflammation by targeting IRAK4 to inhibit the
By deep-sequencing and bioinformation analysis, NOC2L was one of NF-κB/NLRP3 signaling pathway
the top-ranking epigenetic regulators in the screening. Furthermore, Figure 2.Illustration of the therapeutic mechanisms of GG in MASH
we established shNOC2L steatotic hepatocytes and validated its level liver inflammation via IRAK4 targeting and NF-κB/NLRP3 signaling
of lipid accumulation. Meanwhile, we explored high-fat diet (HDF) inhibition.
mice with AAV-shNOC2L. H3K27ac CHIP-seq assay were employed
to study the epigenetic remodeling. PP0404
Result: Less lipid was accumulated after NOC2L knockdown in
MELK blunts metabolic dysfunction-associated steatohepatitis
steatotic hepatocyte cells and HFD mice. The epigenetic states
through modulating Lars2-mediated mitochondrial homeostasis
were significantly changed in shNOC2L steatotic hepatocyte and
in hepatocytes
less H3K27ac marks were deposited in the enhancers of lipogenesis
genes. The expression of lipogenesis genes, including FASN, SCD1 Jing Qi1, Jiabin Huang1, Yufei Wang1, Lanqian Li1, Xin Zhang1, Xi
and SREBP1, were suppressed after NOC2L knockdown. Zheng1, Zhengyi Tan1, Xueqing Yan1, Zixiong Zhou1
Conclusion: So, we concluded the NOC2L induces epigenetic
1
Fujian Medical University
remodeling to enhance lipid de novo biosynthesis and exacerbate Background: Maternal embryonic leucine zipper kinase (Melk) is
MASLD progression. a novel oncogene and belongs to an atypical member of the Snfl/
Table and Figure:Figure 1.Graphic Abstract AMPK family of serine/threonine kinase. Metabolic dysfunction-
associated steatohepatitis (MASH) is considered a high-risk factor for
hepatocellular carcinoma (HCC). However, the role of Melk in MASH
has never been explored. Thus, this study is aimed to investigate the (MAFLD) is an escalating global health crisis marked by hepatic
novel role of Melk in the progression of MASH. steatosis, inflammation, and endothelial dysfunction (ED), culminating
Method: MELK/Melk expression patterns were compared in normal in liver failure. Despite its growing prevalence, effective therapeutic
and MASH patients and mouse livers. MASH was established and options remain unavailable. This study explores the preclinical efficacy
compared between Melk knockout, and wild-type mice fed with high- of Picrorhiza kurroa and Boerhaavia diffusa aqueous extracts in
fat diet (HFD) and methionine choline-deficient (MCD) diet. Using reversing hepatic and endothelial damage in MAFLD.
genetic and therapeutic strategies in vitro and in vivo, the downstream Method: A robust diet-induced MAFLD model was developed using
targets of Melk and the associated mechanisms of lipid metabolism in a high-fat diet (HFD) and a 60% sucrose plus 40% fructose water
MASH were established. mix for 24 weeks. After model development, animals were treated
Result: Melk was highly expressed in hepatocytes of MASH liver. In with aqueous extracts of Picrorhiza kurroa and Boerhaavia diffusa for
MASH murine models, deleting Melk aggravated steatohepatitis with 4 weeks. Healthy controls were used as a baseline. Comprehensive
pronounced liver inflammation and fibrosis. Melk deficiency or inhibition assessments included ex-vivo hemodynamic monitoring,
significantly promoted lipid deposition and lipotoxicity in hepatocytes. evaluation of endothelial dysfunction and hepatic microvascular
However, overexpression of Melk showed opposite results. Inhibiting function, measurement of biochemical markers (AST, ALT, ALP),
MELK expression promoted mitochondrial dysfunction. Additionally, histopathological analysis, oxidative stress indices (malondialdehyde
RNA-Seq analysis identified that leucyl-tRNA synthetase 2 (Lars2) is [MDA], glutathione peroxidase [GPX]), and gene expression analysis
one of the downstream targets of Melk. Also, Melk-Lars2 cascade related to inflammation and lipid metabolism was performed in hepatic
has been established in maintaining mitochondrial function including tissue.
oxidation of fatty acids by genetic study in vivo and in vitro. Result: Hemodynamic analysis demonstrated that HFHC-fed rats
Conclusion: Melk regulates hepatocyte mitochondrial homeostasis experienced a significant elevation in portal pressure and MAP,
by targeting Lars2 and disrupting Melk aggravates the progression approximately 40% higher than controls, signifying the onset of
of MASH. portal hypertension and increased hepatic vascular resistance.
Upon treatment with Picrorhiza kurroa and Boerhaavia diffusa, portal
pressure decreased by 20%, and MAP reduced by 15% (p<0.05),
PP0405
reflecting improved vascular resistance. Vasodilatory responses to
INTESTINAL EPITHELIAL CELL OSTEOPONTIN PROTECTS acetylcholine, severely diminished in HFHC-fed rats, were markedly
AGAINST METABOLIC DYSFUNCTION-ASSOCIATED restored in treated animals, highlighting the mitigation of endothelial
STEATOHEPATITIS BY ALTERING THE BILE ACID COMPOSITION dysfunction and enhanced nitric oxide bioavailability. These
AND THE GUT MICROBIOME hemodynamic improvements were complemented by histological
Hui Han1,2, Nithyananthan Subramaniyam1, Xiaodong Ge1, Sai analyses that revealed substantial reductions in hepatic inflammation
Komakula1, Chao Wang1, Jeongwoo Park1, Daniel Lantvit1, Grace (Grade +2 to nearly normal), steatosis (Grade +3 to +1), and necrosis.
Guzman1, Bruno Ramos Molina3, Natalia Nieto1 Biochemical assessments confirmed the normalization of liver enzyme
1
Department of Pathology, University of Illinois Chicago, 2China levels (AST, ALT, ALP) and a significant reduction in oxidative stress, as
Pharmaceutical University, 3Biomedical Research Institute of Murcia evidenced by lower MDA levels and increased GPX activity. Molecular
Background: The gut-liver axis is critical in metabolic dysfunction- profiling further corroborated these findings, showing a pronounced
associated steatohepatitis (MASH). Osteopontin (OPN) is involved in downregulation of pro-inflammatory mediators (IL-1β, IL-6, HMGB1)
chronic liver disease; however, whether it is expressed in intestinal and lipogenic genes (CD36, FASN), coupled with reactivation of
epithelial cells (IECs) and plays a role in MASH is unknown. antioxidant pathways mediated by NRF2 and HO-1.
Method: To investigate this, we evaluated intestinal OPN expression Conclusion: Picrorhiza kurroa and Boerhaavia diffusa aqueous
during MASH progression in patients. To dissect the contribution of extracts exhibit exceptional potential in mitigating MAFLD-induced
IEC-derived OPN to MASH, Spp1 knock-in (Spp1KI IEC) and knock- hepatic and endothelial dysfunctions. By targeting inflammation,
out (Spp1ΔIEC) mice were fed with a high-fat, fructose, and cholesterol oxidative stress, and endothelial health, this phytotherapeutics offer
diet to induce MASH and fed them a high-fat, fructose, and cholesterol a promising avenue for developing integrative approaches in MAFLD
diet to induce MASH. management.
Result: IEC OPN decreased with disease progression to MASH Table and Figure:Figure 1.Graphical abstract
and was associated with liver injury in patients. Ablation of Spp1
in IECs exacerbated MASH, whereas overexpression or oral OPN PP0407
supplementation protected against it. Specifically, Spp1ΔIEC mice
NEDD4 regulates TGF-beta/SMAD signaling pathway through
showed significant hepatic inflammation, displayed clutched IECs,
ubiquinated decorin to ameliorate Metabolic Dysfunction-
had more IEC apoptosis, reduced IEC turnover, increased intestinal
Associated Steatohepatitis
permeability, showed hepatic 16s RNA, and had higher levels of
conjugated BAs in portal serum than WT with MASH. The increase Rui Jin1, Nan Geng1, Shengxia Yin1, Qianwen Zhao1, Jie Li1
in TCA and TDCA caused hepatocyte damage, which activated liver
1
Department of Infectious Disease, Nanjing Drum Tower Hospital,
macrophages to enhance inflammation. In the fecal microbiome, fewer Affiliated Hospital of Medical School, Nanjing University
bacteria were expressing bile salt hydrolase (Bsh), which deconjugates Background: Metabolic dysfunction-associated steatohepatitis
BAs. This was responsible for the increased levels of conjugated BAs (MASH) poses a significant global public health challenge, with
in the portal serum of Spp1ΔIEC mice. its underlying mechanisms yet to be comprehensively elucidated.
Conclusion: IEC OPN protects against MASH by altering the BA NEDD4, as an E3 ubiquitin ligase, is implicated in the regulation of
composition and the gut microbiome. multiple metabolism-associated signaling pathways. However, its role
in MASH remains inadequately clarified.
Method: Hepatocellular NEDD4 were knocked down or over-expressed
PP0406
in mice via the AAV8 system respectively, and male C57BL/6J mice
Picrorhiza kurroa and Boerhaavia diffusa: Potential (six weeks old) were fed either a western diet (WD), or a methionine-
Phytotherapeutics for Hepatic and Endothelial Dysfunction in choline deficient (MCD) diet for 10 weeks to induce MASH. 293T and
Metabolic Associated Fatty Liver Disease AML12 cells were utilized for in vitro studies.
Tahseen Khan1, Akash Mourya2, Vaibhav Tiwari1, Rajni Yadav1, Result: An integrated analysis of human and murine MASH datasets
Himanshi Himanshi1, Aishwarya Bhatnagar1, Shiv Kumar Sarin1, was conduced and NEDD4 was identified as the differentially
Savneet Kaur1, Dinesh Mani Tripathi1 expressed E3 ubiquitin ligase in hepatocytes. Notably, NEDD4 protein
1
Institute of liver and biliary sciences, 2NIPER levels were significantly elevated in both in vivo and in vitro MASH
Background: Metabolic dysfunction-associated fatty liver disease models, with this upregulation predominantly observed in hepatocytes.
Lipid accumulation was markedly exacerbated in MASH mice fed
an MCD or WD diet for 10 weeks in NEDD4-KD mouse.Conversely, Associated Steatohepatitis (MASH). Myokines, bioactive peptides
overexpression of NEDD4 in hepatocytes significantly ameliorated released by skeletal muscle, play a pivotal role in regulating peripheral
hepatic lipid accumulation. RNA-seq analysis revealed an upregulation tissues, including the liver. Among them, myostatin (MSTN) has
of the TGF-β pathway in NEDD4 knockdown AML12 cells, with decorin emerged as a critical regulator of muscle mass and metabolism.
(DCN) exhibiting pronounced transcriptional changes. Additionally, However, its specific role and underlying mechanisms in MASH
predictions from the Ubibrowser website suggested that DCN is a development remain unclear.
potential substrate of NEDD4. Method: MASH was induced in mice using high-fat, high-fructose diet
Conclusion: Collectively, our findings demonstrate that NEDD4 (HFHFD) and choline-deficient, amino acid-restricted, high-fat diet
ameliorates MASH by modulating the TGF-β/SMAD signaling pathway (CDA-HFD). Muscle-specific MSTN knockdown was achieved using
through the ubiquitination of decorin. an adeno-associated virus 8 (AAV8) system. MSTN expression in the
Table and Figure:Figure 1.Graphical Abstract serum of MASH patients was assessed via Elisa. The role of MSTN
in MASH progression was investigated using recombinant MSTN
protein and co-cultures of C2C12 muscle cells and primary mouse
PP0408
hepatocytes. Additionally, RNA sequencing was employed to analyze
Targeted Delivery of IGFBP7 Antisense Oligonucleotide to the the impact of MSTN on the hepatocyte transcriptome.
liver Protects Mice Against MASH Result: MSTN was found to be overexpressed at both the transcriptional
Aiting Yang1, Xuzhen Yan1, Yiwen Wang1, Hong You1 and protein levels in the skeletal muscle tissues of MASH mice. Muscle-
1
Experimental and Translational Research Center, Beijing Friendship specific MSTN suppression significantly inhibited the progression
Hospital, Capital Medical University of HFHFD- and CDAHFD-induced MASH (Figure 1). Recombinant
Background: Metabolic-dysfunction-associated steatohepatitis MSTN protein exacerbated hepatocyte steatosis, inflammation, and
(MASH) is emerging as leading causes of liver disease worldwide. senescence. Transcriptomic analysis identified the cystine transporter
Especially for MASH-related fibrosis, there remains an unmet need SLC7A11 as a key target of MSTN-induced hepatocyte changes
for more effective therapeutic strategies. Therefore, we investigated (Figure 2). Furthermore, MSTN promoted the degradation of SLC7A11
the therapeutic potential of specific IGFBP7 antisense oligonucleotide via the ubiquitination pathway during MASH progression.
(ASO), along with their effect on the inflammatory and fibrotic Conclusion: Reducing muscular myostatin expression may represent
component, in an experimental MASH diet-induced liver fibrosis. a promising therapeutic strategy for treating MASH.
Method: Igfbp7-/- mice were generated to investigate the function and Table and Figure:Figure 1.Muscle-specific MSTN knockdown mitigates
mechanism of IGFBP7 in experimental CDAA diet-induced liver fibrosis. HFHFD-induced MASH
Furthermore, we developed an ASO targeting IGFBP7 and evaluated Figure 2.RNA-seq identifies SLC7A11 as a novel MSTN target in
its effect on NAFLD features in mice fed with CDAA diet. Based on hepatocytes
its efficacy and safety, a dosage regimen of 30 mg/kg intraperitoneal
injection of IGFBP7 ASO 3 times per week was selected for further PP0410
investigation in a therapeutic setting in a CDAA-induced MASH mouse
NPM1 inhibits mitophagy in hepatocytes through hindering ANT2
model. Liver inflammation, steatosis, and fibrosis was measured via
ubiquitination and facilitates metabolic dysfunction-associated
blood metabolic markers, histomorphological evaluation, and mRNA
steatotic liver disease
and protein expression.
Result: In Igfbp7-/- mice, the microenvironment during liver fibrosis Caijun Rao1, Zhipeng Du2
development exhibited reduced inflammation and fibrosis, evidenced
1
Department of Geriatrics, Tongji Hospital, Tongji Medical College,
by decreased monocyte/macrophage infiltration and lower expression Huazhong University of Science and Technology , 2Department of
of proinflammatory factors and fibrogenesis markers. We found that Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong
systemic administration of liver-targeting IGFBP7 ASO in MASH mice University of Science and Technology
effectively ameliorated steatosis, inflammatory infiltration, hepatic Background: Nucleophosmin 1 (NPM1) is multifunctional protein that
stellate cell activation, fibrosis, and hepatocellular damage in the liver participates in the pathogenesis of various cancers, however, the
compared with mice treated with PBS treatment, without any systemic role and underlying mechanisms of NPM1 in metabolic dysfunction-
toxicity or local tolerability concerns. BMDM from Igfbp7-/- mouse associated steatotic liver disease (MASLD) remains unknown. This
exhibited suppressed proinflammatory M1 polarization and in vitro. study aims to examine the expression and roles of NPM1 in MASLD,
Moreover, IGFBP7 ASO suppressed M1-macrophage polarization, and uncover the underlying mechanism.
providing insight into the molecular mechanisms underlying repression Method: Hepatic expression of NPM1 was measured in C57BL/6
of hepatic steatosis and liver fibrosis. mice fed with high fat diet (HFD) and in ob/ob mice. NPM1’s roles and
Conclusion: IGFBP7 ASO significantly reduced hepatic inflammation mechanisms in the pathogenesis of MASLD were explored using gain-
and fibrosis in the HFCDAA mouse model of MASH after 4 weeks of and loss-of-function methods.
therapeutic dosing. This study provides in vivo nonclinical proof-of- Result: NPM1 expression was dramatically upregulated in the fatty
principle for the fibrotic benefit of liver-specific inhibition of IGFBP7 in liver of HFD-fed C57BL/6 mice and ob/ob mice. Hepatocyte-specific
the context of MASH and warrants future investigations to address the knockdown of NPM1 alleviated HFD-induced hepatic steatosis,
therapeutic potential of IGFBP7 ASO in the prevention and treatment attenuated intolerance of glucose and insulin, and ameliorated
of MASH related fibrosis. hepatic inflammation and the degree of fibrosis. Furthermore, we
observed that hepatic knockdown of NPM1 facilitated mitophagy of
the damaged mitochondria, reduced mitochondrial dysfunction, and
PP0409
thus ameliorated energy expenditure. Mechanistically, NPM1 was
Myostatin Regulates the Muscle-Liver Axis by Inducing Hepatocyte found to interact directly with adenine nucleotide translocase 2 (ANT2),
Senescence via SLC7A11 Ubiquitination in Metabolic Dysfunction- inhibited its ubiquitination, and enhanced ANT2 protein expression.
Associated Steatohepatitis Importantly, hepatocyte ANT2 conditional knockout (ANT2 cKO)
Nan Geng1, Qianqian Chen1, Fajuan Rui1, Wenjing Ni1, Yixuan Zhu1, alleviated the NPM1 overexpression induced exacerbation of HFD-
Zhiwen Fan2, Shengxia Yin1, Qianwen Zhao1, Jie Li1 elicited fatty liver disease and re-activated mitophagy. Clinically, NPM1
1
Department of Infectious Diseases, Nanjing Drum Tower Hospital, was significantly upregulated in liver of patients with MASLD, and was
Affiliated Hospital of Medical School, Nanjing University, Nanjing, positively correlated with NAFLD activity score and ANT2 expression.
Jiangsu, China, 2Department of Pathology, Nanjing Drum Tower Conclusion: Hepatic upregulation of NPM1 inhibited ubiquitination of
Hospital, Affiliated Hospital of Medical School, Nanjing University, ANT2, disrupted mitophagy, resulted in mitochondrial dysfunction, and
Nanjing, Jiangsu, China therefore facilitating progression of MASLD. Thus, it may be feasible to
Background: Recent studies suggest that skeletal muscle alterations treat MASLD with drugs that target NPM1.
may contribute to the pathogenesis of Metabolic Dysfunction-
 PP0411 Method: Clinical databases of NAFLD patients at different stages were
HFCF diet alters Klb histone methylation inducing MASLD by analyzed, and various NAFLD mouse models, including high-fat diet
regulating KLB expression (HFD)-induced, genetically obese (db/db), and Gubra-Amylin NASH
diet-induced models, were established to examine GINS2 expression
Yu Hua Ruan1, Fang Ji2
and its correlation with hepatic lipid accumulation.
1
Public Experimental Research Center, Xuzhou Medical University, GINS2 knockdown and overexpression in hepatic cells were
2
Affiliated Hospital of Xuzhou Medical University
performed to explore its effect on hepatic lipid accumulation.
Background: Metabolic-associated steatotic liver disease (MASLD) RNA sequencing, gene set enrichment analysis (GSEA), and
is a prevalent metabolic disorder with increasing global incidence. related molecular experiments were used to identify the key signaling
Emerging evidence highlights the role of epigenetic regulation in pathways and molecular mechanisms by which GINS2 regulates lipid
the pathogenesis of MASLD, particularly histone modifications accumulation.
that modulate gene expression in response to metabolic stress. To Co-immunoprecipitation (Co-IP), mass spectrometry, and
investigate the role of epigenetic mechanisms in MASLD, this study molecular experiments were used to identify downstream targets of
focuses on the beta-Klotho (KLB) gene, a key regulator of lipid GINS2 and elucidate their roles in regulating hepatic lipid accumulation.
metabolism in the liver. Specifically, we investigated how a high- Result: Clinical database analysis revealed significantly upregulated
fat, high-cholesterol, and fructose diet (HFCFD) influences histone GINS2 expression in the liver tissues of NAFLD patients and mouse
modifications at the Klb promoter, with an emphasis on H3K4me3, an models. GINS2 expression was positively correlated with the severity
active histone mark associated with gene activation. We hypothesized of hepatic steatosis and was elevated in lipid-overloaded cell models
that HFCFD alters KLB expression through epigenetic reprogramming, in a dose-dependent manner.
contributing to the development of MASLD. GINS2 knockdown in hepatocytes significantly reduced
Method: C57BL/6 mice were fed either a high-fat, high-cholesterol, oleic acid-induced lipid accumulation, while overexpression of GINS2
and high-fructose (HFCF) diet or a normal (N) diet for 20 weeks to exacerbated HFD-induced lipid accumulation in mice.
establish a MASLD model. Liver-specific overexpression of KLB RNA sequencing and GSEA revealed significant enrichment
was achieved using an adeno-associated virus (AAV) vector (DIO of the autophagy pathway in GINS2 knockdown hepatocytes.
system) via tail vein injection. ChIP-Seq and ChIP-qPCR analyses were GINS2 knockdown increased LC3B expression and decreased p62
performed to examine how histone methylation modifications regulate levels, enhancing autophagolysosome formation and lipid droplet-
KLB expression. autophagolysosome colocalization.
Result: Our research revealed significant differences in histone Co-IP and mass spectrometry identified the autophagy-
modification patterns between dietary groups. HFCFD significantly related transcription factor TFEB as a potential GINS2 binding partner,
reduced H3K4me3 enrichment at the Klb promoter, accompanied by further confirmed by Co-IP. Overexpression of GINS2 reduced TFEB
decreased KLB mRNA and protein levels. Interestingly, in the liver- transcriptional activity in liver tissues and AML12 cells.
specific KLB overexpression model, we observed a negative correlation Conclusion: Lipid stress upregulates GINS2 expression in the liver,
between the enrichment of H3K4me3 and KLB protein expression. suppressing lipophagy activation by regulating TFEB transcriptional
That is, when KLB protein expression is elevated, the activation mark activity, thereby promoting hepatic lipid deposition and NAFLD
H3K4me3 decreases. We speculate that under the condition of KLB progression.
overexpression, a negative feedback regulation mechanism might Table and Figure:Figure 1.GINS2 is significantly upregulated in NAFLD
be activated to reduce the active modification of Klb. This suggests and promots hepatic lipid deposition
a complex self-regulatory pattern in the epigenetic control of Klb Figure 2.GINS2 suppresses lipophagy activation by regulating TFEB
expression during metabolic stress. Additionally, histological analysis transcriptional activity
confirmed that KLB overexpression ameliorated HFCFD-induced liver
steatosis and fibrosis, highlighting the protective role of KLB under
metabolic stress.
PP0413
Conclusion: This study demonstrates that HFCFD induces epigenetic Results of triple therapy for fatty liver disease (NAFLD) in Mongolia
reprogramming at the Klb promoter, characterized by reduced Amarsanaa Jazag1,2,3, Erdenebayar Gonchig4,2, Byambatsetseg
H3K4me3 enrichment and subsequent downregulation of KLB Togtuunbayar4,2, Enkhtuya Damba4,2, Batgerel Zagdragchaa4,2,
expression. The findings suggest that liver-specific KLB overexpression Bolorchimeg Batsaikhan4,2, Davaajav Bavuudorj4, Oidov
mitigates liver damage and steatosis caused by HFCFD, potentially Baatarkhuu5,4,2, Davaajav Bavuudorj4
through a self-regulatory epigenetic mechanism. These insights 1
Mongolian Association for the Study of Liver Diseases, 2Happy
provide a basis for further exploration of histone modifications as Veritas Hospital, 3Otoch Manramba University, 4Mongolian Association
therapeutic targets for MASLD. for the Study of Liver Diseases (MALSD), 5Department of Infection
Table and Figure:Figure 1.Liver-specific overexpression of KLB diseases, Mongolian National University of Medical Sciences
protects against HFCFD-induced hepatic steatosis and improves lipid Background: Although the recent decrease in hepatitis virus infections
metabolism in mice. and viral hepatitis in Mongolia is commendable, it is expected that the
Figure 2.H3K4me3 methylation depletion at Klb promoter reduces KLB increase in fatty liver and cirrhosis related to unhealthy lifestyle will
expression under HFCFD conditions continue. Therefore, we conducted large scale study to determine the
results of triple therapy for NAFLD.
PP0412 Method: Before the start of treatment, the degree of steatosis was
determined using the elastography (Fibrotouch) device, a 1-month
GINS2 Accelerated Non-Alcoholic Fatty Liver Disease via
triple therapy and lifestyle modification regimen were recommended,
Regulating TFEB Mediated Lipophagy
and a second measurement was taken 1 month after, at the end of
Zhaohong Mo1, Mingbei Zhong1, Gangping Feng1, Kai Ke1, Xinghuang
treatment. 687 people who were treated at the Happy Veritas Hospital
Yi1, Guandou Yuan1, Songqing He1, Shuangdi Duan1
outpatient clinic were included in the treatment. Treatment included
1
Division of Hepatobiliary Surgery, the First Affiliated Hospital of atorvastatin 20-40 mg once daily, ursodeoxycholic acid 250 mg
Guangxi Medical University 2-3 times daily, and vitamin E 400 IU 2 capsules daily, all pills were
Background: Non-alcoholic fatty liver disease (NAFLD) has become taken after the meal. Lifestyle recommendations included eliminating
the most prevalent chronic liver disease globally. However, no FDA- alcohol consumption, drastically reducing flour, rice, potato, and sugar
approved specific drugs are currently available for NAFLD treatment consumption, increasing physical activity, and reducing excess weight.
due to its complex pathogenesis. This study investigates the role of Result: Out of 687 people who participated in the treatment, 679 or
GINS2 in hepatic lipid metabolism and NAFLD progression, aiming to 98.8% had reduction in liver steatosis, and 8 or 1.2% had increase in
provide new therapeutic targets and foundations for NAFLD prevention steatosis.
and treatment. When we categorized the patients, n=580 or 84.4% have reduced
steatosis by at least 1 stage, and 99 or 14.4% steatosis reduced within Center, Institute of Chemistry, Chinese Academy of Sciences,
the stage. 4
Department of Pathology, Beijing Ditan Hospital
Conclusion: Decrease of steatosis or return to normal rate was very Background: The incidence and mortality of alcohol-associated
high 98.8%. Liver stiffness decreases with triple therapy in 75% of liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD) are
cases. Increase in stiffness in 24% of patients is difficult to explain, but increasing steadily in decades. ALD and NAFLD are characterized
one possible explanation was due to decrease of fat between fibrotic by large amounts of lipid compositions which accumulate in liver in
tissues. Treatment is safe. None or some very minimal adverse events the early stages of the diseases.However, the method to differentiate
like diarrhea due to Ursodeoxycholic acid was observed between the two diseases is unclear in clinic and pathologic. The study
Table and Figure:Figure 1. aims to differentiate ALD and NFALD in lipid metabolism of animal
models by the high spatial resolution- and high sensitivity-time- of-flight
PP0414 secondary ion mass spectrometry(SIMS-ToF).
Method: Establishing mice ALD and NAFLD animal models.The fresh
CD133 drives MASLD-related hepatocellular carcinoma and is a
live tissue of mice animal models was cut into 4μm-thick sections,and
therapeutic target
embedded with optimal cutting temperature compound(OCT),put it on
Yasi PAN1, Xiang ZHANG1, Chi Chun WONG1, Huarong Chen1, Kai
a conductive glasses. SIMS-ToF mass spectrum can break lipidomic
YUAN1, Jun YU1
profiles into ion fragments, which is high sensitivity and high utilization.
1
The Chinese University of Hong Kong Then we applied the region of interest(ROI) of the liver tissue sections,
Background: Metabolic dysfunction-associated steatotic liver obtaining the total mass spectrum data across the SIMS-ToF imaging.
disease-related hepatocellular carcinoma (MASLD-HCC) is a rising SURFACELAB 6 software was used for analysis the SIMS-ToF spectra
malignancy. However, the identity and role of cancer stem cells (CSCs) and images. The SIMS-ToF data was used a standard processing
in MASLD-HCC remain largely unknown. This study aims to explore by semi-quantitative comparison,principal component analysis(PCA)
the function, mechanisms, and targeted therapies of CSCs in MASLD- .PCA was performed in the lipid region with the mass range of m/z 50-
HCC. 650 to examine the molecular species.The relative intensities of interest
Method: Genetic lineage tracing in mice, along with single-cell peaks in the liver tissue sections were measured and compared
RNA sequencing (scRNA-seq) of CD133+ progeny, was utilized to statistically using Student’s t-test.
characterize cancer stem cells (CSCs) in MASLD-HCC. The functional Result: In the study,we found significant morphological differences in
role of CD133 was assessed using a hepatocyte-specific Cd133 the mice ALD and NAFLD animal models. ALD mice are characterized
overexpression mouse model of MASLD-HCC. RNA sequencing (RNA- by extensive microvesicular steatosis,however, the NAFLD mice
seq) was performed to identify pathways regulated by CD133. Protein are mainly characterized by mixed macrovesicular/mediovesicular
interactions with CD133 were analyzed through pull-down assays, steatosis. Moreover,ALD and NAFLD mice are performed significant
followed by silver staining and mass spectrometry. The effectiveness differences in the lipidomics.In the ALD mice, phosphocholines(PC)
of genetically ablating CD133 in combination with multikinase inhibitors content was significantly higher than in NAFLD(P<0.001),nevertheless,
(Sorafenib and Lenvatinib) was evaluated in MASLD-HCC mouse cholesterols (P<0.001)and glycerids including monoglycerol(MAG)
models. Additionally, targeting CD133 with nanoparticle-siRNA in (P<0.001)and diglycerol(DAG)(P<0.001) were significantly lower than
combination with Sorafenib was tested in both subcutaneous and in NAFLD.
orthotopic MASLD-HCC mouse models. Conclusion: There are differences in the morphology and metabolites
Result: In this study, we used intravital genetic lineage tracing in mice to of hepatic steatosis between ALD and NAFLD. The application of
demonstrate that CD133+ cells in MASLD-HCC exhibit characteristics SIMS-ToF imaging is greatly facilitates the study of tissue section
of cancer stem cells (CSCs), including superior self-renewal capacity components.
in vitro and tumorigenicity in vivo compared to CD133- counterparts.
Single-cell RNA sequencing of CD133+ progeny revealed their clonal
PP0416
expansion into multiple lineages during tumor progression, highlighting
the role of CD133+ CSCs in contributing to cellular plasticity in MASLD- Paeoniflorin ameliorates Metabolic dysfunction-associated
HCC. Additionally, we found that CD133 functionally drives CSC steatohepatitis via inhibiting JAK2/STAT1/CXCL10 pathway
phenotypes in MASLD-HCC, and hepatocyte-specific overexpression QinMei Sun1, Xin Wang1, SiTing Gao1, Xin Xin1, Yiyang Hu1, Qin
of Cd133 in mice aggravated MASLD-HCC formation. Mechanistically, Feng1
CD133 interacts with myosin heavy chain 9 (MYH9) to stabilize active 1
Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai
β-catenin, thereby enhancing Wnt/β-catenin signaling, which is crucial University of Traditional Chinese Medicine
for CSC phenotypes and tumorigenic potential. Notably, knockdown of Background: Paeoniflorin (PAE) has been recognized as a major
MYH9 eliminated the induction of Wnt/β-catenin signaling by CD133. active component of total glycoside of paeony derived from the dried
From a translational perspective, targeted ablation of CD133+ cells root of Paeonia lactiflora Palla, but the detailed efficacy and mechanism
using a selective diphtheria toxin receptor (DTR) system sensitized of PAE on metabolic dysfunction-associated steatohepatitis (MASH)
MASLD-HCC to multikinase inhibitors (Sorafenib and Lenvatinib). remains limited. The aim of this study is to reveal the therapeutic effects
Furthermore, targeting CD133 with nanoparticle-siRNA in combination and potential mechanisms of PAE on MASH.
with Sorafenib resulted in synergistic tumor regression in MASLD- Method: The MASH model in mice was established by feeding with
HCC. Collectively, these findings suggest that CD133 is a promising high-fat high-carbohydrate diet and high sugar drink for 18 weeks. At
therapeutic target in MASLD-HCC, especially in combination with the last 6 weeks, the mice in PAE group received paeoniflorin (77.06
multikinase inhibitors. mg/kg/day) via gavage. The hepatic triglyceride, serum ALT and AST
Conclusion: Our findings indicate that CD133+ cancer stem cells activity were measured, along with the liver pathology assessed by
(CSCs) promote MASLD-HCC by activating Wnt/β-catenin signaling hematoxylin-eosin and oil red O staining. The molecular docking,
through MYH9 and is a therapeutic target, especially in combination Cellular Thermal Shift Assay (CETSA) and Drug Affinity Responsive
with multikinase inhibitors. Target stability (DARTs) were used to further predict and identify.
Following this, the effects of PAE on Janus Kinases 2 (JAK2)/Signal
PP0415 Transducer and Activator of Transcription 1 (STAT1)/CXC chemokine
ligand-10 (CXCL10) pathway were observed in vivo and in vitro (FFA-
The Differential Diagnosis of Lipid Metabolism in Alcohol-
induced hepatocytes and LPS+IFN-γ-induced macrophages). And the
associated liver disease and Non-alcoholic fatty liver disease by
lentiviral siRNA-JAK2 transfection was performed in vitro to prove the
Time-of-Flight Secondary Ion Mass Spectrometry
effects.
Mingxin Qiu1, Yang Wang2, Yao Zhao3, Lei Sun4 Result: PAE could significantly decrease hepatic fat deposition and
1
Department of Pathology, Beijing Ditan Hospital, Capital Medical inflammation in MASH mice. With the hint of molecular docking, CETSA
University, 2Beijing Institute of Infectious Diseases, 3Huairou Research
and DARTS experiments results proved that PAE binds to JAK2 protein PP0418
by enhancing its structural stability. Further study uncovered that PAE Exacerbation of MASH by Nicotine: Insights into Gut Dysbiosis
reduced the hepatic protein expression of p-JAK2 and p-STAT1 and and HIF-1α Regulation
the mRNA expression of CXCL10 in MASH mice. Then, the results in
Fangfang Yi1, Xiaodong Wang1, Yilun Huang2, Dazhi Chen3, Yongping
vitro showed that PAE could significantly decreased the activation of
Chen1
JAK2/STAT1/CXCL10 pathway too. But the effects were significantly
blocked when JAK2 was knockdown.
1
Hepatology Diagnosis and Treatment Center, The First Affiliated
Hospital of Wenzhou Medical University & Zhejiang Provincial Key
Conclusion: PAE could ameliorate hepatic inflammatory response
Laboratory for Accurate Diagnosis and Treatment of Chronic Liver
via inhibiting JAK2/STAT1/CXCL10 pathway in MASH, which providing
Diseases, 2Alberta InstituteWenzhou Medical University, 3The First
foundational evidence for its future use.
People’s Hospital of Lin’an Distract, Hangzhou, Lin’an People’s
Table and Figure:Figure 1.Figure 1
Hospital Affiliated to Hangzhou Medical College, Hangzhou Medical
Figure 2.Graphic Abstrct College
Background: Cigarette smoking exacerbates the progression of
PP0417 metabolic dysfunction-associated steatotic liver disease, although
FGF21 counteracts ERS-induced hepatic steatosis aggravated by the underlying mechanisms remain incompletely understood. Nicotine
loss of Fam172a gene accumulation in the intestine is associated with an exacerbation
Herui Wei1, Fan Xiao2, Hongshan Wei1 of metabolic dysfunction-associated steatohepatitis (MASH). To
1
Beijing Ditan Hospital, Capital Medical University, Beijing 100015, investigate how nicotine impacts intestinal microbiota composition and
China., 2National Center for Infectious Diseases, Beijing Ditan barrier function, we examined the mechanistic role of nicotine in MASH
Hospital, Capital Medical University, Beijing 100015, China. progression.
Method: Male C57BL/6J mice, 8 weeks old, were fed either a control
Background: Inhibition of endoplasmic reticulum stress (ERS)
or choline-deficient high-fat diet for 10 weeks, with daily nicotine
can effectively improve the progression of metabolic dysfunction-
injections. Fecal microbiota analysis was performed by the 16S
associated steatotic liver disease (MASLD). In our previous study, we
rRNA. Transmission electron microscopy was used to examine tissue
have reported for the first time that the deletion of FAM172A promotes
ultrastructure, and various biochemical and molecular techniques,
tunicamycin (Tm)-induced ERS and aggravates hepatic steatosis in
including Western blotting and immunohistochemistry, were employed
mice. But its regulatory mechanism remains unclear. Therefore, it is
to assess gut permeability, inflammation, and gene expression.
necessary to further investigate the mechanism of FAM172A involved
Additionally, antibiotic treatment and HIF-1α silencing using AAV7
in hepatic steatosis.
vectors were involved to explore underlying mechanisms of nicotine-
Method: In this study, we performed RNA-seq and analyse the
induced intestinal dysfunction in MASH.
bioinformatics data from primary hepatocytes of WT and Fam172a-/-
Result: Our study revealed significant intestinal microbiota dysbiosis
mice. We utilized the murine recombinant protein of the target molecule
in a nicotine-exposed MASH mouse model, with substantial
to interfere with tunicamycin (Tm) -induced Fam172a-/- mice. We
changes in bacterial profiles, particularly a marked increase in
evaluated the degree of liver steatosis and key molecules of ERS and
Erysipelatoclostridium. Hypoxia-inducible factor 1-alpha (HIF-1α)
apoptosis.
expression was positively associated with the regulation of several
Result: We performed RNA-sequence (RNA-seq). KEGG analysis
barrier-related genes in the intestine. Notably, nicotine exposure
showed that DEGs enriched in the cancer pathway and calcium
markedly increased HIF-1α levels in MASH mice. Using HIF-1α
signaling pathway (Figure 1B). Among DEGs, we found a target gene
knockdown models, we found that nicotine-exposed MASH mice
associated with NAFLD and obesity: Fgf21 gene (Figure 1A). Some
exhibited more severe intestinal barrier dysfunction in the absence of
studies have shown that FGF21 is closely related to NAFLD and
HIF-1α. This exacerbation resulted from the suppression of MEK/ERK
other metabolism dysfunction diseases. Next, we examined mRNA
signaling pathway phosphorylation in HIF-1α-deficient mice, leading to
expression levels of Fgf21 gene in vivo and vitro. Hepatic mRNA level
the disruption of epithelial tight junction proteins and further aggravating
of Fgf21 in Fam172a-/- mice was higher than WT mice (Figure 1C).
gut microbiota dysbiosis. Increased gut permeability facilitated
Furthermore, hepatic Fgf21 mRNA level of high fat diet(HFD)-induced
bacterial translocation to the liver, intensifying hepatic inflammation
WT mice was higher than that of chow diet-fed WT mice, but there was
and fibrosis in nicotine-exposed MASH mice. Furthermore, treatment
no difference between HFD-induced Fam172a-/- and WT mice (Figure
with Lactobacillus rhamnosus GG supernatant alleviated hepatic injury
1C). In Tm-induced ERS mice model, we also found that Fam172a-/-
in nicotine-exposed MASH mice; however, this protective effect was
mice had higher level of hepatic Fgf21 compared to WT mice (Figure
abolished in the absence of HIF-1α.
1D). In vitro, PA and Tm-induced primary hepatocytes of Fam172a
Conclusion: Taken together, this study highlights the pivotal role
knockout mice showed the most significant increase of Fgf21 mRNA
of nicotine in exacerbating MASH through intestinal microbiota
level (Figure 1E-F). Then, we used FGF21 recombinant protein to
modulation and barrier dysfunction mediated via HIF-1α regulation.
intervene Tm-induced Fam172a-/- mice. Compared with Tm-induced
It also suggests exogenous probiotic supplementation as a potential
Fam172a-/- mice, plasma AST level was slightly decreased after the
therapeutic strategy for mitigating nicotine-induced MASH progression.
intervention of murine FGF21 recombinant protein(Figure 2A-B). We
Table and Figure:Figure 1.
also performed liver H&E staining and inflammation score. The results
showed that hepatic steatosis was significantly reduced after FGF21
treatment (Figure 2C), and the inflammation score was also decreased PP0419
(Figure 2D). Hepatic oil red O staining suggested that the abundance Redefining the noninvasive assessment of liver fibrosis
of lipid droplets after the treatment of FGF21 was reduced (Figure 2E). Zhen Yuan1, Junhua Ma2
After treatment with FGF21, the TG level in Tm-induced Fam172a-/- 1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia
mice was reduced by approximately 50% (Figure 2F). Finally, we found
medical university , 2Department of Endocrinology, Gongli Hospital of
that compared with Tm-induced Fam172a-/- mice, the hepatic ERS Shanghai Pudong New Area
and apotosis molecules protein levels were all obviously decreased
under the intervention of FGF21 (Figure 2G-H). Background: Chronic liver disease (CLD) is a major health problem
Conclusion: We reveal that FGF21 recombinant protein can partly worldwide. In China, the number of patients with chronic liver disease
counteract Fam172a deletion-induced ERS and hepatic steatosis. may exceed 400 million. It is essential to stage the severity of liver
FAM172A may serve as a potential target for the treatment of MASLD. disease. Regardless of the cause, ongoing liver injury and disease
Table and Figure:Figure 1.Figure 1. FGF21 expression can be induced progression lead to liver fibrosis, and liver fibrosis is a very important
by loss of Fam172a gene. consequence of ongoing liver injury. Furthermore, the presence of
Figure 2. Figure 2. FGF21 counteracts ERS-induced hepatic steatosis. fibrosis has prognostic orientation in many different liver diseases.
Therefore, the assessment of liver fibrosis is of great clinical significance
Method: We conducted a comprehensive literature search of the liver steatosis, inflammation and fibrosis than the negative control
Cochrane Library Science Network, Embase, PubMed, and Google group. Furthermore, in FATP5-knockdown cells, we observed an
Scholar for articles related to liver fibrosis published in English up to increase of SCD1, the rate-limiting enzyme of fatty acid desaturation
November 30, 2024 that participates in the de novo synthesis of less oxidizable
1. Assessment of liver fibrosis using blood tests (e.g., APRI and FIB-4) monounsaturated fatty acids (MUFAs). Correspondingly, overexpress-
and imaging studies (e.g., LSM) SCD1 cells show resistance to erastin-induced ferroptosis. Finally,
2To compare the accuracy and reliability of non-invasive detection we clarified that FATP5 effectively regulates SCD1 expression to
methods and liver biopsy, and to explore its application in the diagnosis manipulate ferroptosis.
of liver diseases Conclusion: Our results suggest that FATP5 regulates lipid metabolism
3Analyze the relationship between portal vein pressure and the degree in NASH progression by controlling SCD1 expression. Inhibition of
of liver fibrosis, as well as the correlation between inferior vena cava FATP5 effectively activates SCD1 and reduces lipid peroxidation,
dilation and liver fibrosis thereby preventing ferroptosis and relieving the progression of NASH.
4The combination of non-invasive examination and liver biopsy Overall, our findings might offer a promising target for NASH treatment
is recommended in the diagnosis of liver diseases to improve the in the future.
diagnostic accuracy Table and Figure:Figure 1.fig.1
Result: Through literature search, we found that the application of Figure 2.fig.2
non-invasive detection has developed rapidly in the past 10 years. .
Doctors should routinely use blood tests to evaluate liver fibrosis. It PP0421
is recommended to use FIB-4 as the initial test because it is simple,
inexpensive, and widely available. The best imaging method for Heme oxygenase-1 attenuates nonalcoholic steatohepatitis via
evaluating liver fibrosis is liver hardness measurement. There are inhibiting mitochondrial apoptosis
currently several different devices, but the most widely used is Li Dongdong1, Zhi Jing Wu1, Jia Cen Cao1, Wen Zhao1, Shou Song
instantaneous elastography. At present, the best test for assessing the Zhao1
potential presence of clinically significant portal hypertension (CSPH) 1
First Affiliated Hospital of Bengbu Medical University
is imaging testing Background: Our previous study indicates that HO-1 reduces
Conclusion: 1. NILDA is currently at the forefront and center of liver hepatic necroinflammation and fibrosis in nutritional steatohepatitis by
disease severity assessment. Non invasive blood tests, including suppressing lipid peroxidation. In this research, we further explored
APRI and/or FIB-4, should be the preferred method for assessing the whether and how HO-1 could exert a regulatory effect on mitochondrial
severity of liver fibrosis and/or portal hypertension in all patients with apoptosis in nonalcoholic steatohepatitis (NASH).
known liver diseases. For most patients, imaging evaluation should Method: The effects of HO-1 on mitochondrial apoptosis and the
be performed after these examinations. Frontier technology provides associated molecular pathways were examined by pharmacological
accurate assessment of liver fibrosis through blood and imaging inhibition or induction in NASH models as well as knockout or
examinations, with high predictive prognostic value. overexpression in human hepatocyte.
2. Non invasive detection methods such as ultrasound, MRI, and EMR Result: In the both dietary-induced NASH animal models, hepatic
have high accuracy and reliability in the assessment of liver fibrosis, HO-1 was significantly elevated. Down-regulation of HO-1 by inhibitor
but sensitivity and specificity need to be considered. ZnPP-IX significantly aggravated impaired mitochondrial integrity and
3. Liver biopsy still has important value when the diagnosis is unclear. function, apoptosis, and oxidative mitochondrial DNA damage as
It is recommended to combine non-invasive examination with liver evidenced by ATP and 8-OHdG accumulation and the induction of
biopsy in uncertain situations to exclude or evaluate HVPG DRP1, Cyt c and c-Caspase3. Conversely, induction of HO-1 by hemin
restored these changes in mice. Consistent with these in-vivo results,
PP0420 in comparison to the control, mitochondrial calcium overload and ROS
accumulation increased the frequency of mitochondrial permeability
Inhibition of FATP5 Alleviates the Progression of NASH by
transition pore (mPTP) opening as well as contributed to mitochondrial
Increasing SCD1 Activity thereby Inhibiting Hepatic Ferroptosis
damage and increased membrane permeability in vitro. Furthermore,
Yiran Liu1,2, Jiazhi Liao1,2, Suhong Xia1,2 mechanistic studies demonstrated that HO-1 had the capacity to
1
Department of Gastroenterology, Tongji Hospital, Tongji Medical inhibited mitochondrial calcium overload, ROS accumulation and mPTP
College, Huazhong University of Science and Technology, 2Institute of opening, thereby restored mitochondrial membrane permeability, led
Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato- to ameliorate mitochondrial apoptosis and reverse steatohepatitis in
Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, NASH.
Huazhong University of Science and Technology
Conclusion: Heme oxygenase-1 plays a pivotal role in attenuating
Background: Non-alcoholic steatohepatitis (NASH) is a metabolic nonalcoholic steatohepatitis through the regulation of mitochondrial
liver disease that progresses from simple steatosis to inflammation calcium overload, leading to decrease of mPTP opening, and inhibiting
and fibrosis. Ferroptosis is a programmed cell death characterized by mitochondrial apoptosis. HO-1 holds potential as an innovative
iron accumulation and lipid peroxidation which plays an important role therapeutic approach for the treatment of NASH.
as the trigger for initiating inflammation in NASH. Fatty Acid Transport Table and Figure:Figure 1.HO-1 protects mitochondrial membrane
Protein 5 (FATP5), a liver-specific enzyme that regulates long-chain permeability and inhibits mitochondrial apoptosis through decreasing
fatty acids (LCFAs) uptake and bile acids synthesis, was identified as mPTP opening in the non-alcoholic steatohepatitis
a risk gene for NASH in a previous epigenetic association study. In Figure 2.Schematic illustration of the mechanism of HO-1 in inhibiting
this study, we aim to elucidate the mechanism between FATP5 and ER-Ca2+-mediated mitochondrial apoptosis in steatohepatitis.
ferroptosis in NASH progression.
Method: Oil acid (OA) and palmitic acid (PA) were used to induce
lipid accumulation in HepG2 cells. Plasmid and si-RNA were used to
PP0422
manipulate the expression of FATP5 and Stearoyl-CoA desaturase 1 Chinese medicine Ger-Gen-Chyn-Lian-Tang Mitigates High-
(SCD1) in the HepG2 cell line to explore their crosstalk. NASH mice Fat Diet-Induced Liver Steatosis and Metabolic Dysregulation
models were established by a 6-week methionine choline-deficient Through Multi-Target Mechanisms
(MCD) diet. Erastin treatment in HepG2 cells and daily intraperitoneal Tzung Yan Lee1
injection of ferroptosis inhibitor Ferr-1 for 3 weeks in NASH mice were 1
Chang Gung University
used to control ferroptosis. Background: The traditional Chinese formulation Ger-Gen-Chyn-Lian-
Result: We first observed an upregulation of FATP5 in OA and PA- Tang (GGCLT) has demonstrated therapeutic potential in metabolic
induced lipid accumulation cell models and MCD-induced NASH and liver disorders. However, its molecular targets and mechanisms of
mice. Then we found that Ferr-1 treatment NASH mice show less
action remain poorly understood. This study aims to identify GGCLT’s oxidation, and enhanced fatty acid synthesis.
active constituents and evaluate its protective effects against high- Mouse Models of YAP Knockout and Overexpression:
fat diet (HFD)-induced metabolic dysfunction-associated fatty liver YAP knockout worsened lipid accumulation, increasing triglycerides
disease (MAFLD). (TG) and total cholesterol (TC).
Method: Six major bioactive compounds of GGCLT were identified via Overexpression of YAP improved lipid accumulation and mitigated
HPLC: puerarin, baicalin, berberine, baicalein, glycyrrhizic acid, and MASH progression.
wogonin. Bioinformatics and protein-protein interaction (PPI) network Interaction Between YAP and CPT1A:
analyses identified 26 overlapping genes between GGCLT targets Immunoprecipitation identified CPT1A, a key lipid metabolism
and fatty liver-related genes, including Pparg, Stat3, and Mmp9. regulator, as a YAP target.
HFD-fed mice were treated with varying doses of GGCLT, and its Co-immunoprecipitation confirmed YAP-CPT1A interaction, with
effects on metabolic parameters, liver histology, glucose metabolism, cytoplasmic co-localization and protein docking analysis showing
mitochondrial function, oxidative stress, ferroptosis, and circadian strong molecular binding.
rhythms were assessed. Conclusion: YAP in Hepatocyte plays a vital role in MASH by
Result: GGCLT improved liver-to-body weight ratio, and lipid profiles regulating fatty acid metabolism, inflammation, and fibrosis
in HFD-fed mice, reducing plasma and hepatic triglycerides and Fatty Acid Metabolism: YAP activation promotes fatty acid oxidation
free fatty acids. Histological analyses revealed significant reductions and reduces hepatic fat deposition
in hepatic steatosis and lipogenic markers, including SREBP1, Fas, Inflammation and Fibrosis: YAP modulates inflammatory responses
and Scd1. GGCLT enhanced glucose metabolism through AMPK and inhibits fibrosis by regulating hepatic stellate cells
signaling activation, upregulation of Glut2 and Hk2, and suppression Clinical data confirm a strong correlation between YAP expression
of gluconeogenesis. Additionally, GGCLT restored mitochondrial and MASH pathology (fat deposition, inflammation, and fibrosis),
respiratory chain activity, improved redox balance by modulating the highlighting its potential as a therapeutic target
NAD+/NADH and GSH/GSSG ratios, and attenuated lipid peroxidation
and ferroptosis through the upregulation of GPX4 and xCT.
PP0424
Furthermore, GGCLT corrected HFD-induced circadian rhythm
dysregulation by normalizing PER2, BMAL1, and other circadian gene Deregulation of FTO isoforms correlates with the progression of
expressions, enhancing metabolic flexibility and energy expenditure. metabolic dysfunction associated steatotic liver disease and its
These multi-target effects highlight GGCLT’s ability to modulate lipid amelioration with Entacapone
metabolism, oxidative stress, and circadian rhythms, thereby mitigating Sunita Giri1, Vijay Kumar1
HFD-induced liver injury and systemic metabolic dysfunction. 1
Institute of liver and biliary sciences
Conclusion: GGCLT demonstrates robust hepatoprotective and Background: The mechanisms underlying the progression of
metabolic benefits via multi-faceted mechanisms, including lipid- nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis
lowering, antioxidant, and circadian-modulating effects. These findings (NASH) remain unclear. The increasing incidence of obesity, metabolic
provide a strong foundation for developing GGCLT as a therapeutic syndrome, and NAFLD emphasizes the need for a new approach of
strategy for fatty liver disease and associated metabolic disorders. their management. Fat mass and obesity-associated (FTO) protein is
considered to be a key player in obesity and type 2 diabetes risk. Here,
PP0423 we examined the expression of FTO isoforms 1, 3, 5, and 12, under
different conditions of liver disease and their progression. Further, we
Role and Mechanism of YAP in hepatocyte in the Pathogenesis
repurposed entacapone, a known FTO inhibitor for the amelioration of
of MASH
liver diseases.
Xiaowei Ling1 Method: In this retrospective study, 75 adults (age, 36 ± 19 years;
1
The First Affiliated Hospital with Nanjing Medical University body mass index [BMI], > 28 kg/m2) with biopsy-proven NAFLD
Background: (n=25), NASH (n=25), and cirrhosis (n=25) were recruited according
Metabolic-associated fatty liver disease (MAFLD), includes a spectrum to the AASLD guidelines along with a healthy group (n=5) as a control.
of liver conditions diagnosed based on hepatic steatosis with The severity of fibrosis was determined by measuring liver stiffness,
obesity, type 2 diabetes, or metabolic dysfunction,with 20% of cases whereas steatosis was investigated using a controlled attenuation
progressing to metabolic-associated steatohepatitis (MASH), which parameter. Liver histology was assessed by microscopy, whereas
involves chronic liver and systemic inflammation. Yes-associated serum biochemistry and adipokine (leptin and adiponectin) levels were
protein (YAP), a key effector in the Hippo signaling pathway, regulates measured using ELISA. The expression of FTO isoforms (1, 3, 5, and
cell proliferation, metabolism,and has been implicated in liver 12) in the liver was measured by RT-qPCR, immunohistochemistry, and
development, fibrosis, and hepatocellular carcinoma western blotting. The clinical data and FTO expressions were validated
Method: 1.Mouse Models: MASH was induced in mice using high-fat in an NAFLD model of primary human hepatocytes by treating cells with
(HFD) or Western diets (WD). YAP expression and localization in liver 0.5 mM free fatty acids (palmitic acid and oleic acid) and entecapone.
tissues were analyzed at different stages (4, 8, 12 weeks) using IHC Fat accumulation was assessed by oil red staining, and cell viability
and WB was measured using the MTT assay.
2.YAP Gene Intervention: RNA interference silenced YAP in Result: The expression of FTO isoforms (1,3, and 5) was relatively
hepatocytes, while transgenic models achieved hepatocyte-specific higher in NAFLD and NASH patients (p<0.05) but lower in patients
YAP overexpression. Effects on fat accumulation, inflammation, with cirrhosis. In contrast, FTO-12 expression was higher in patients
oxidative stress, hepatic stellate cell activation, and fibrosis were with cirrhosis. Interestingly, FTO isoforms (1, 3, and 5) positively
evaluated correlated with disease progression. The NAFLD model of hepatocytes
3.Molecular Mechanism Exploration: Techniques like qPCR and corroborated the clinical observations showing elevated expression
Western blotting assessed YAP’s involvement in fatty acid metabolism (p <0.01) of isoforms 1, 3, and 5 decreased expression of isoform
(SREBP-1c, FAS, PPAR-α) and inflammation (TNF-α, IL-6) 12 levels after 18 h of fat treatment. Interestingly, treatment with
Result: YAP Expression and Dynamics in MASH: entacapone down-regulated the expression of FTO isoforms, except
YAP expression was reduced in the liver during MASH.During phases isoform 5, and was found to be non-toxic and safe between 5 -50 µM.
of increased hepatic fat deposition and inflammation, YAP expression Conclusion: The present study suggests that FTO expression is
and nuclear translocation were elevated.YAP levels correlated with deregulated during the progression of NAFLD to NASH. Isoform
hepatic fat deposition, inflammation scores, and fibrosis severity. FTO-12 is selectively overexpressed in cirrhosis, whereas levels of
YAP’s Role in Fatty Acid Metabolism: isoforms 1, 3, and 5 are elevated in NAFLD and NASH. Treatment with
YAP activation reduced fat accumulation by inhibiting fatty acid entacapone normalized the expression of FTO isoforms in the NAFLD
synthesis (SREBP-1c, FAS) and increasing fatty acid oxidation model of primary human hepatocytes suggesting its therapeutic
(PPAR-α).YAP silencing increased fat accumulation, reduced fatty acid potential in mitigating the progression of liver disease.
 PP0425 disease. To date, food and drug administration (FDA) approved only
Preclinical studies of a novel hydrolysis-based prodrug for Rezdiffra (resmetirom) for the treatment of patients with liver scarring
treating metabolic dysfunction associated steatohepatitis due to MASLD. This study aimed to assess various novel biomarkers
related to ED in MASLD patients compared to healthy volunteers
Gongxin He1, Xiubo Tang1, Jia Meng1, Hao Wu1, Kai Hou1, Wenyuan
(HV). Furthermore, we assessed an association between Nostrin and
Fan1, Chunyan Yao1, Xiaowu Chen1
endothelial dysfunction in MASLD patients.
1
Shanghai CureGene Pharmaceutical Co., Ltd Method: This cross-sectional analytical study was conducted on
Background: Approval of resmetirom for treating Metabolic dysfunction MASLD patients (n=40 cases) and HV (n=40 controls). The established
associated steatohepatitis validated thyroid hormone receptor beta ED biomarkers such as asymmetric dimethylarginine (ADMA) and
(THR-b) as an effective therapeutic target. VK-2809, another THR-b- cyclic guanosine monophosphate (cGMP) levels were measured using
targeting drug, showed significant reductions in cholesterol, liver fat commercially available ELISA kits. Flow-mediated dilation (FMD) of
and MASH resolution and fibrosis regression in a phase II study. It is the brachial artery ultrasonography (USG) was also used to measure
a prodrug relying on cytochromes P450 (CYP) for bioactivation to its endothelial function non-invasively. In addition, endothelial nitric oxide
active metabolite (MB07344) in the liver. We designed and synthesized synthase (eNOS) trafficking inducer (Nostrin) and oxidative stress
novel prodrugs based on MB07344 but using fast hydrolysis by marker such as 4- hydroxynonenol (HNE) were assessed by ELISA.
esterases for bioactivation and avoiding CYP related issues. Result: When compared to HV, significantly elevated serum levels of
Method: Our prodrugs were tested in a HepG2 assay for in vitro ADMA and cGMP were observed in MASLD patients. Moreover, serum
activity and evaluated in rats and dogs for pharmacokinetics (PK) and Nostrin and 4-HNE levels were found to be elevated in MASLD patients
distribution. CG-025016 was selected for efficacy testing in a hyper- compared to HV (p<0.0001 for both). FMD of the brachial artery
cholesterolemia rat model. Serum cholesterol levels (TC and LDL-C) was reduced in MASLD patients compared to controls (p<0.0001).
were measured at baseline and 24h post-dose. Moreover, Nostrin level was positively correlated with endothelial
Result: CG-025013 and CG-025016 showed EC50 of 39.3 and 44.5 dysfunction markers and negatively associated with endothelial
nM, respectively, in HepG2 vs 662 nM for VK-2809. For oral PK study in function marker, FMD. A receiver operating characteristic (ROC) curve
rats, both compounds at 1mg/kg dose were barely detectable (Cmax showed the diagnostic proficiency of serum Nostrin concentration and
< 1 nM) in the plasma, liver, and heart. In contrast, Cmax for VK-2809 discriminated MASLD patients from HV.
was around ~100 nM in the same tissues when dosed at the same Conclusion: Our data showed for the first that Nostrin was upregulated
level. For the active metabolite, Cmax was much higher in the liver in MASLD and was negatively associated with FMD and positively
for CG-025013 and CG-025016: 5,000 and 1400 nM, respectively, correlated with other ED markers. Therefore, targeting Nostrin could
vs 464 nM for VK-2809. Area under the curve (AUC) values were be a new potential therapeutic approach in the management of patient
similarly differentiated. Similar results were observed in dogs. Rats with MASLD.
on high-fat diet treated with 1.5 mg/kg CG-025016 led to significantly
greater declines in plasma TC (87.1%) and LDL-C (69.5%), compared
PP0427
to declines in plasma TC (21.3%) and LDL-C (16.6%) with resmetiron
treatment at same dose. At 0.3 mg/kg, CG-025016 resulted in slightly Heme Oxygenase-1 Improve Mitochondrial Function and
higher reductions compared with VK-2809 at same dose in plasma Apoptosis in Non-Alcoholic Steatohepatitis
TC (55.0% vs 45.9%, respectively) and LDL-C (52.0% vs 47.4%, Xiwei Yuan1, Yuemin Nan1
respectively). The dose-dependent reductions were also observed for 1
Department of Traditional and Western Medical Hepatology, Third
CG-025016. CG-025016 was safe and well tolerated in 7-day rat safety Hospital of Hebei Medical University, shijiazhuang, China
study. Background: We aimed to explored the significance of Heme
Conclusion: Our prodrugs showed a ~15-fold in vitro activity increase oxygenase 1 (HO-1) in regulating mitochondrial function and apoptosis
over VK-2809 in HepG2 assay. In vivo PK studies showed that they during NASH development in animal models, cultured hepatocytes
were barely detectable while the active metabolite was preferentially and NASH patients.
concentrated in the liver compared to VK-2809. The ratio of the active Method: The effects of HO-1 on mitochondrial function were evaluated
metabolite AUC between liver and heart was 116 (CG-025013), 158 by genetic knockout in mouse models and in vitro. Meanwhile, NASH
(CG-025016) vs 63 (VK-2809). These findings suggest that our novel patients and healthy controls were enrolled. The mitochondrial
prodrugs based on esterase hydrolysis can indeed enrich the active structure was observed by confocal microscopy. The expression of
metabolite more efficiently in the liver, resulting in higher potency while proteins related to mitochondrial function and apoptosis were detected
reducing the exposure outside the liver. In vivo efficacy in rats was by western blot and immunohistochemical staining. Hepatic levels of
also observed. Overall, CG-025016 is a highly potent THR-b agonist mitochondrial reactive oxygen species (ROS), DNA damage and ATP
with an excellent PK and safety profile, making it a promising clinical were examined. Cell apoptosis were assessed by tunnel staining.
candidate to address the limitations of current treatment options. Result: In mice, HFD and MCD caused lipid accumulation,
Table and Figure:Figure 1.Therapeutic Efficacy in Hypercholesterolemia steatohepatitis injury, and cell apoptosis, which were aggravated
Rat by HO-1HEPKO. Meanwhile, mitochondrial function was impaired
in HFD or MCD HO-1HEPKO mice compared to WT HFD or MCD
PP0426 mice, evidenced by increased protein expression of dynamic-related
protein-1 (DRP1) and decreased protein expression of mitofusin-2
Association of Endothelial Nitric Oxide Synthase Trafficking
(MFN2) and optic atrophy 1 (OPA1). In line with the results in vivo,
Inducer with Endothelial Dysfunction Markers in Patients with
HO-1 knockdown upregulated lipid accumulation, DNA damage, lipid
Metabolic Dysfunction-Associated Steatotic Liver Disease
peroxidation and cell apoptosis, while reduced the ATP level in AML12
Balasubramaniyan Vairappan1, Kalaivani Subramani1, Sunitha V2,
and HepG2 cells, which were in contrast to HO-1 overexpression in
Jayaprakash Sahoo 3
vitro. Likewise, these findings were consistent with the results in liver
1
Department of Biochemistry, Jawaharlal Institute of Postgraduate histopathology of NASH patients.
Medical Education and Research (JIPMER), 2Department of Conclusion: HO-1 could alleviate the NASH progression by mediating
Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical
mitochondrial function and suppressing apoptosis.
Education and Research (JIPMER), 3Department of Endocrinology,
Jawaharlal Institute of Postgraduate Medical Education and Research
(JIPMER) PP0428
Background: Metabolic dysfunction-associated steatotic liver disease Potassium Citrate Monohydrate Alleviates Hepatic Lipid
(MASLD) is a multisystemic disease and the prevalence is exponential Peroxidation in Metabolic Dysfunction-associated Fatty Liver
worldwide. MASLD complications are an expanding health problem Disease via AMPK-autophagy-ferroptosis Axis
concomitant with endothelial dysfunction (ED) at early stages of the Jingyuan Xu1,2, Longyun Wu1, Xiaolan Lu1
Shanghai Pudong Hospital, 2the Affiliated Suzhou Hospital of Nanjing
1
composition in MASLD mice, especially increasing the abundance
Medical University of A. muciniphila and decreased that of Allobaculum. Therefore, we
Background: Lipotoxicity and the resulting oxidative stress is one of further established the MASLD mice model with the treatment of A.
the major driver contributing to metabolic dysfunction-associated fatty muciniphila and WLT gavage. The results showed that A. muciniphila
liver disease (MAFLD), which is characterized by the accumulation of was effective in alleviating MASLD and also synergized the protective
triglycerides in hepatocytes. Potassium citrate monohydrate (PCM), effect of WLT against MASLD such as hepatic steatosis, inflammation
the main active component of Garcinia cambogia, possesses a and liver injury. In addition, serum untargeted metabolomics
hydroxyl structure and exhibits antioxidant activity. Thus, we sought to sequencing suggested that the WLT treatment affected a variety of
investigate the potential for MAFLD improvement by administration of metabolites, including up-regulation of isofucosterol, N2-acetyllysine,
PCM and the underlying mechanisms. and down-regulation of 2-Chlorophenol. In vivo, WLT attenuated M1
Method: In this study, we explore PCM’s preventive effects on MAFLD polarization and increased M2 polarization in MASLD mice. In vitro,
both in vivo and in vitro. We used oleic acid-induced AML12 cells and WLT-containing serum attenuated M1 polarization of mouse bone
high-fat diet (HFD)-induced mice to explore PCM’s preventive effects marrow-derived macrophages.
on MAFLD both in vivo and in vitro. Through hematoxylin and eosin Conclusion: WLT ameliorate MASLD by improving the intestinal
staining, immunohistochemistry, oil red staining, biochemical analysis barrier and regulating the gut microbiota, particularly by increasing
and western blotting, we showed that PCM activates adenosine the abundance of A. muciniphila, and then inhibiting macrophage M1
monophosphate (AMP)-activated protein kinase (AMPK)-autophagy polarization in the liver.
pathway and thus inhibits ferroptosis. Fecal 16S rRNA sequencing Table and Figure:Figure 1.Macrophage polarization levels
and metabolomics were employed to explore the impact of PCM on Figure 2.The feces 16S rRNA sequencing
intestinal microenvironment.
Result: PCM demonstrating a significant reduction in lipid PP0430
accumulation both in oleic acid-induced AML12 cells and hepatocytes
Genipin 1-β-D-gentiobioside alleviates MASH by inhibiting
of MAFLD mice. The in vivo studies revealed that PCM significantly
hepatocyte PP2A enzymatic activity
mitigated intrahepatic steatosis, indicating a therapeutic potential of
Xin Xin1, Feng Qin1, Xie Cen Group, Huang chenggang group, Hu
PCM as an anti-MAFLD agent. Mechanistically, by employing an AMPK
yiyang Group
inhibitor, our findings provided evidence that PCM alleviated hepatic
lipid peroxidation via the AMPK-autophagy-ferroptosis axis. Also,
1
Shuguang Hospital Affiliated to Shanghai University of Traditional
PCM alleviated MAFLD by modulating the gut-liver axis, manifested Chinese Medicine
as increasing gut metabolites which activated AMPK-autophagy Background: Genipin 1-β-D-gentiobioside (GG) is one of the important
pathways and decreasing those inhibited AMPK-autophagy pathways. natural components from the herb Gardenia jasminoides. The aim of
Conclusion: In conclusion, PCM effectively alleviated lipid this study is to explore the potential therapeutic targets of GG against
accumulation and metabolic disorders, reduced intrahepatic lipid metabolic-associated steatohepatitis (MASH) and elucidate its
deposition, and mitigated lipid peroxidation via the AMPK-autophagy- potential pharmacological mechanism.
ferroptosis axis. These beneficial effects of PCM are attributed to its Method: In this study, two MASH mouse models induced by high
unique structural characteristics as well as its ability to modulate gut trans-fatty acid and high-sugar diet (HFHC) and methionine/choline
microbiota and metabolites. deficient diet (MCD) and the rat model induced by high-fat diet (HFD)
Table and Figure:Figure 1.Activation induced by PCM activated were used to investigate the anti-MASH effect of GG. Concurrently,
autophagy and reduced lipid peroxidation in murine liver. we used an FFAs (Free Fatty Acids)-induced THLE2 cell model for in
Figure 2.Correlation analysis of gut microbiota and metabolites. vitro observations. The potential GG-binding proteins were screened
by HuProt protein chip and pull-down mass spectrometry. Surface
Plasmon Resonance (SPR), Drug Affinity Responsive Target Stability
PP0429
(DARTS), and Cell-based Thermal Shift Assay (CETSA) techniques
Wei-Ling-Tang Oral Solution Alleviates Metabolic Dysfunction- were used to verify the interaction between GG and the target protein.
Associated Steatotic Liver Disease by Regulating Gut-Liver Axis Phosphorylated protein chip technology was used to screen the
You Yanying1, Wu Minxia1, Zeng Danyi1, Xing Qingqing1, Xue Hanxin1, downstream substrates of the binding protein. Ultimately, both in vivo
Pan Jinshui1 and in vitro models of liver-specific gene editing were used to ascertain
1
the First Affiliated Hospital of Fujian Medical University the mechanism of effect of GG against MASH.
Background: Wei-Ling-Tang (WLT), a traditional Chinese herbal Result: We demonstrated that GG significantly reduced hepatic lipid
decoction, has been reported to treat metabolic dysfunction- accumulation, inflammation, and early liver fibrosis in the MASH models.
associated steatotic liver disease (MASLD). However, how WLT GG could substantially reverse lipid deposition under metabolic stress
alleviate the progression of MASLD remains unclear. in FFAs-induced cells models. Importantly, the combined analysis
Method: First, the effects of WLT on MASLD was evaluated by results suggested that Protein phosphatase 2 (PP2A) was the direct
biochemical analyzer, qPCR, ELISA, and histopathology. Then, binding proteins of GG, which was strongly verified by SPR (KD=7.99E-
intestinal barrier function was detected by qPCR, ELISA and WB. The 06mol/L). Interestingly, we further observed in liver tissues and
feces 16S rRNA sequencing and serum untargeted metabolomics hepatocytes that GG did not alter PP2A expression but significantly
were performed to investigate the potential mechanism. In addition, inhibited PP2A enzyme activity that was significantly elevated under
the polarizing effect of WLT on macrophages was investigated by metabolic stress. The phosphoprotein screening results showed that
immunohistochemistry and flow cytometry in mice with MASLD. In ACC1, the key enzyme regulating de novo lipid synthesis, was the
vitro, bone marrow macrophages were stimulated with WLT-containing most likely downstream substrate of PP2A, and CO-IP experiments
serum and the polarization of macrophages was detected by ELISA confirmed that the two could interact. With the decrease of PP2A
and flow cytometry. enzyme activity after GG intervention, the phosphate level of ACC1
Result: WLT reduced serum albumin transaminase, serum albumin was significantly increased. Subsequently, hepatocyte-specific gene
transaminase, and hepatic triglyceride content in MASLD mice. Oil deletion of PP2A in vitro and in vivo blunted the therapeutic effect of
Red O staining and HE staining of the liver indicated that hepatic GG in the MASH model.
steatosis and inflammation were improved after WLT treatment. We Conclusion: Our study clearly showed that GG could inhibit de novo
also found the mRNA expressions of occludin and Zo-1 in colon and lipogenesis and improve MASH liver lipid deposition by targeting
small intestine of MASLD mice were significantly increased after WLT hepatocyte PP2A and then up-regulating ACC1 phosphorylation,
treatment, which indicated that the intestinal barrier function of MASLD which provided strong evidence for the clinical practice of natural
mice was improved by WLT. Then, 16S rRNA sequencing showed active ingredients in MASH field.
that WLT partially restored the changes in gut microbial community Table and Figure:Figure 1.
Figure 2.
 PP0431 (LPS). In contrast, exposure of macrophages to DPP-4 reduced M2
Mechanistic Investigation of Sitravatinib’s Therapeutic Potential markers of mRNA expression when incubated with IL-4. However,
in Hepatic Fibrosis: A Comprehensive Analysis of Function and the role of DPP-4 in macrophage-mediated inflammation and insulin
Molecular Pathways resistance remains largely unknown.
Method: We investigated the effects and the mechanism of of
Huan Zhang1,2,3, Fajuan Rui1,2,3, Qianwen Zhao2,3, Jie Li1,2,3
linagliptin, an inhibitor of DPP-4, on macrophage migration and
1
Department of Infectious Diseases, Nanjing Drum Tower Hospital polarization in liver in a lipotoxic model of MASH.
Clinical College of Nanjing University of Chinese Medicine, Nanjing,
Result: Both plasma and liver DPP-4 activity was significantly
Jiangsu, China. , 2Department of Infectious Disease, Nanjing Drum
increased in MASH mice. DPP-4 positive classically activated
Tower Hospital, Affiliated Hospital of Medical School, Nanjing
macrophage (M1 macrophages) were significantly increased in MASH
University, Nanjing, Jiangsu, China. , 3Institute of Viruses and
mice, while DPP-4 positive alternatively activated macrophage (M2
Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.
macrophages) were decreased, when compared with the normal
Background: Background & aims: Liver fibrosis represents a complex mice. Meanwhile, inhibition of DPP-4 activity regulated macrophage
physiological response to sustained hepatocellular injury, primarily polarization and ameliorated MASH in mice. Previous studies showed
triggered by chronic hepatitis conditions. During this process, the that MIP-1α, also known as CCL3, is converted into the most efficient
activation and subsequent transformation of hepatic stellate cells monocyte/macrophage attractant after cleavage by DPP-4. Loss of
(HSCs) into myofibroblasts serves as a fundamental mechanism in the MIP-1a, in MASH mice abrogated M1/M2 macrophage-polarizing and
progression of hepatic fibrosis. Through our extensive research efforts, insulin-sensitizing effects of linagliptin. CCR1/CCR5, as the receptor
we successfully identified Zeb2 as a crucial regulatory factor in liver of MIP1a, their antagonist alleviates MASH-related insulin resistance
fibrosis pathogenesis. Utilizing advanced artificial intelligence (AI) and inflammation by regulating both macrophage recruitment and M1/
screening methodologies, we conducted a comprehensive analysis M2 status.
that identified sitravatinib as the most promising Zeb2 antagonist Conclusion: We clarify the role and mechanism of DPP-4-MIP1a-
candidate. This study aims to thoroughly evaluate sitravatinib’s CCR1/CCR5 in the pathogenesis of MASH by regulating macrophages
therapeutic potential in alleviating liver fibrosis and understanding its polarization, which may contribute to the better understanding and
underlying mechanisms. more scientific approaches for the prevention and treatment of MASH.
Method: Methods: We established comprehensive mouse fibrosis
models through two distinct approaches: administration of a choline-
deficient l-amino acid-defined diet (CDAA) and systematic carbon PP0433
tetrachloride (CCl4) injection in vivo. Parallel to this, we conducted in Blood metabolic Panels for identifying advanced Fibrosis and
vitro experiments using the human hepatic stellate cell line (LX-2), which Inflammation in among patients with MASH
was activated through TGF-β1 stimulation. Both experimental models Yan Huang1, Jiaqi Li2,3, Bingyin Du1, Zhujun Cao1, Xiaozhen Guo2,
were subjected to treatment with carefully calibrated concentrations Cen Xie2,3,4, Qing Xie1
of sitravatinib to assess its therapeutic effects. We examined the 1
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao
expression of pivotal molecules by Western blotting and RT-PCR. Tong University School of Medicine, Shanghai, China, 2State Key
Result: Results: In comparison to the control group, mice receiving Laboratory of Drug Research, Shanghai Institute of Materia Medica,
sitravatinib treatment exhibited significant improvements in multiple Chinese Academy of Sciences, Shanghai 201203, China, 3University
parameters. We observed marked reduction in fibrotic tissue of Chinese Academy of Sciences, Beijing 100049, P.R. China, 4School
development, accompanied by substantial enhancement in key of Chinese Materia Medica, Nanjing University of Chinese Medicine,
biochemical indicators, particularly notable decreases in serum TG Nanjing 210023, China
and TC levels. In addition, sitravatinib attenuated CDAA and CCl4- Background: Metabolic dysfunction-associated fatty liver disease
induced fibrosis by decreasing the expression of α-SMA, COL1A1 (MAFLD) has become one of the most prevalent chronic liver diseases,
and other markers of HSCs activation in mice liver tissue. Our in vitro yet its diagnosis and treatment remain limited. This study aimed to
investigations revealed that sitravatinib treatment led to pronounced construct diagnostic models based on serum metabolomics and
reductions in both the contractile capabilities and migratory potential investigate the therapeutic potential of guanidoacetic acid (GAA) and
of LX-2 cells, indicating significant impacts on cellular function. sebacic acid (SA) in MAFLD and its more severe form, metabolic-
Conclusion: Conclusions: Our comprehensive investigation provides associated steatohepatitis (MASH).
compelling evidence that sitravatinib demonstrates significant efficacy Method: A total of 255 participants were recruited and divided into a
in alleviating liver fibrosis. These findings strongly support its potential discovery cohort (n=87) and a validation cohort (n=168). The discovery
as a promising therapeutic intervention for the treatment of hepatic cohort included 24 healthy controls and 63 MAFLD patients confirmed
fibrosis, warranting further investigation in clinical settings. by liver biopsy, while the validation cohort included 26 healthy
Table and Figure:Figure 1.Figure 1. Sitravatinib activated human controls and 142 MAFLD patients diagnosed by MRI-PDFF (≥5%).
hepatic stellate cell line (LX-2) with TGF-β1 in vitro. (A) Collagen gel Serum metabolites were analyzed using machine learning methods,
contraction. (B) Transwell. including random forest, Lasso regression, AdaBoost, and support
Figure 2.Figure 2. Sitravatinib mitigated choline-deficient l-amino acid vector machines, to develop diagnostic panels for significant fibrosis
defined diet (CDAA)-induced liver fibrosis. (A) Paraffin sections were (Kleiner score ≥F2) and significant inflammation (lobular inflammation
stained with H&E and sirius red. (B) Plasma TG and TC levels. Data score ≥I2). The diagnostic performance of these panels was validated.
are expressed as the mean±SD. *p<0.05, two-tailed Student’s t-test. Furthermore, therapeutic effects of two metabolites, GAA and SA were
evaluated in C57BL/6 and Db/db mouse models of MASH.
PP0432 Result: The fibrosis diagnostic panel, consisting of 10 metabolites
(including four organic acids, such as reduced GAA; two bile acids;
DPP-4 inhibition by linagliptin attenuates lipotoxicity-induced
one carnitine; two fatty acids; and one indole derivative), achieved an
metabolic associated fatty liver disease by regulating M1/M2
AUROC of 0.928 (95% CI: 0.835–0.978) in the validation cohort. The
macrophage polarization
inflammation diagnostic panel, comprising 10 metabolites (including
Fen Zhuge1
four fatty acids, one organic acid such as reduced GAA, and three
1
The Affiliated Hospital of Hangzhou Normal University bile acids), demonstrated an AUROC of 0.894 (95% CI: 0.791–0.957).
Background: The activation of Kupffer cells (KCs) was confirmed to In therapeutic studies, both GAA and SA significantly reduced
play a central role in the development of metabolic associated fatty liver weight, liver-to-body weight ratio, serum liver injury markers
liver disease (MASH). Dipeptidyl peptidase-4 (DPP-4), also known (ALT and AST), and hepatic triglyceride content in MASH mouse
as CD26, is widely expressed, including immune cells. Exposure models. Histological analysis showed alleviation of hepatic steatosis,
of cultured peritoneal macrophages to DPP-4 increased mRNA inflammation, and fibrosis in treated mice. The fibrosis diagnostic panel
expression for M1 markers upon stimulating with lipopolysaccharide also demonstrated robust performance in identifying high-risk MAFLD
(LSM ≥12 kPa) in the validation cohort, with an AUROC of 0.910 (95% This study aims to explore the therapeutic and preventive effects of
CI: 0.844–0.954). homocysteine carbon dots (HeyCD) in a MASH, focusing on their
Conclusion: The fibrosis diagnostic panel demonstrated excellent mechanisms in alleviating liver damage.
diagnostic accuracy in distinguishing patients with significant fibrosis Method: In this study, we utilized a diet-induced MASH mouse model,
among the MAFLD population. Additionally, GAA and SA exhibited wherein mice were randomly assigned to four groups: a control group,
significant anti-steatotic, anti-inflammatory, and anti-fibrotic effects, a high-fat diet group (HFD), a HeyCD prevention group (HFD+CD(2))
providing novel therapeutic strategies for MAFLD management. in which HeyCD was applied two weeks after HFD, and a HeyCD
Table and Figure:Figure 1. treatment group(HFD+CD(16)) in which HeyCD was treated 16 weeks
after the HFD. Mice in the prevention and treatment groups were
administered specific doses of HeyCD via intraperitoneal injection.
PP0434
We assessed liver lipid accumulation, liver function markers, and
Suppression of Baicalein on Myeloid-Derived Suppressor Cells in inflammation-related biomarkers through biochemical assays and
Nonalcoholic Steatohepatitis through m6A Modification of NRF2 histological analyses. Additionally, expression levels of key genes
Huilian Shi1, Yuanyuan Chen2 and proteins involved in metabolic and inflammatory pathways were
1
Affiliated Hospital of Nanjing University of Chinese Medicine, evaluated by RT-PCR and immunohistochemistry.
Department of Infectious Diseases, Nanjing, Jiangsu, China, 21. Result: The experimental results demonstrated that, compared to
Department of Biochemistry and Molecular Biology, Nanjing Medical mice on a high-fat diet alone, the HeyCD prevention and treatment
University, Nanjing, Jiangsu, China groups exhibited a significant reduction in liver lipid accumulation
Background: Myeloid-derived suppressor cells (MDSCs) are a accompanied with lower weights. Liver function markers, such as
heterogeneous population of myeloid progenitor cells that play a serum ALT and AST levels, were also significantly improved in the
critical role in dampening adaptive immune responses through various treatment groups. Histological analysis confirmed that liver steatosis
mechanisms. They have been recognized as significant contributors to and inflammation were markedly reduced in the HeyCD groups. In vitro
the malignant prognosis of nonalcoholic steatohepatitis (NASH), which experiments using cells treated with sodium palmitate and oleic acid
can progress to cirrhosis and liver cancer. Baicalein, an important alone demonstrated significant lipid droplet formation, whereas the
natural flavonoid, has been reported to improve NASH; however, the HeyCD treatment significantly reduced this phenomenon.
underlying mechanism remains unclear. Conclusion: This study demonstrates the potential therapeutic and
Method: In this study, we utilized a high-fat diet-induced NASH preventive effects of HeyCD in mitigating MASH, highlighting their
mouse model and free fatty acid-incubated HepG2 cells as in vivo ability to reduce liver lipid accumulation, improve liver function, and
and in vitro models, respectively. The effects of Baicalein treatment modulate the inflammatory response. These findings suggest that
were assessed through histopathological analysis and blood factor HeyCD could be a promising candidate for the clinical management of
measurements to evaluate the degree of NASH. The aggregation MAFLD and MASH. However, further studies are needed to assess the
of MDSCs was confirmed via immunohistochemistry of liver tissues. safety, long-term efficacy, and potential toxicity of these nanoparticles
Additionally, the molecular mechanisms were investigated through co- in larger, more diverse animal models and trials.
culture experiments with hepatocytes and MDSCs. Gene-sequencing
analysis was performed to identify the specific molecular pathways PP0436
involved, which were further verified by qPCR and Western blotting,
Intracellular C3 Alleviates Hepatic Lipid Accumulation via
ultimately focusing on Nrf2. To explore the mechanism of Baicalein on
Interacting with USP4
Nrf2, bioinformatics analysis, meRIP-qPCR, and luciferase reporter
gene assays were employed. Yinling Li1, Binbin Zhang1, Haitao Wang2, Junping Shi1
Result: Our findings revealed that Baicalein effectively inhibits the
1
Center for Translational Medicine, 2Queen Mary University of London
aggregation of liver MDSCs induced by interleukin-18 (IL-18) and IL-1β Background: Non-alcoholic fatty liver disease (NAFLD) is a complex
released from hepatocytes, thus preventing the progression of NASH pathological state involving multiple factors and mechanisms.
to cirrhosis. Additionally, we determined that Baicalein enhances Numerous studies have confirmed that NAFLD patients have elevated
the stability of Nrf2 mRNA by down-regulating its m6A modification, C3 level in serum, although the causal relationship remains unclear.
leading to the inhibition of NLRP3/GSDMD-mediated release of IL-18 Besides, NAFLD patients also have increased transcription level of C3,
and IL-1β. suggesting that complement C3 play a significant role in the regulation
Conclusion: This study provides compelling evidence that Baicalein of hepatic lipid metabolism. After production, complement C3 is
exerts a therapeutic effect on MDSCs accumulation in NASH through secreted into the peripheral blood to exert various immune functions.
the modulation of Nrf2 stability and its associated signaling pathways. In recent years, researchers have discovered that intracellular
These findings not only elucidate the underlying mechanisms of complement components exhibit many physiological functions that are
Baicalein in the context of NASH but also offer new insights and distinct from traditional perceptions. As the most important organ for
strategies for clinical treatment. the production of complement C3, we hypothesize that intracellular
complement C3 also plays a crucial role in lipid metabolism within
PP0435 hepatic tissue.
Method: Male C3−/− mice and wild type (WT) control mice, with a
Homocysteine Carbon Dot as a Novel Therapeutic Strategy for
C57BL/6J background and wild type (WT) control mice with BALB/c
MAFLD and MASH
backgroud aged 8–16 weeks, were obtained from Jackson Laboratory
Junda Li1,2, Yongquan Chi1,2, Wenzhu Li1,2, Haipeng Jiang1,2, Wei Xu1,2, (Bar Harbor, ME, USA). The C5a like receptor 2 (C5L2)−/− mice with
Shanke Sun1,2, Jianhua Rao1,2 a C57BL/6J background and C3aR-/- mice with a BALB/c backgroud
1
Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical aged 8–10 weeks were gifted by Dr. Weiguo Hu (School of Medicine,
University, 2 Research Unit of Liver Transplantation and Transplant Fudan University, Shanghai, China). Using Oil Red O staining and TG
Immunology, Chinese Academy of Medical Sciences detection kit to observe lipid accumulation level in liver tissues. Using
Background: Metabolic associated fatty liver disease (MAFLD) and Co-IP/MS to explore interaction between C3 and proteins.
its progression, metabolic dysfunction-associated steatohepatitis Result: To explore the role of complement C3 in hepatic lipid
(MASH) are associated with inflammation, hepatocellular injury, and metabolism, we established a NAFLD model using C3-deficient (C3-
fibrosis, significantly increase the risk of cirrhosis and liver cancer. /-) mice and found that the absence of complement C3 exacerbates
Recent research has increasingly focused on the potential therapeutic hepatic lipid accumulation. Subsequently, we confirmed that
applications of novel biomaterials, such as nanoparticles, to treat intracellular pro-C3 participates in the regulation of hepatic lipid
MAFLD and MASH. Homocysteine, a sulfur-containing amino acid, is a metabolism, and this regulation is not at the transcriptional level but
metabolic intermediate that has been implicated in several metabolic rather through protein-protein interactions. Complement C3 directly
disorders, including cardiovascular disease and liver dysfunction. interacts with USP4, and by modulating the deubiquitination function
of USP4 protein, alleviates hepatic lipid accumulation. Ren1,2, Jianni Qi1,2, Zhen Yang1,2
Conclusion: In physiological conditions, complement C3 within 1
Provincial Hospital of Shandong First Medical University, 2National
hepatocytes plays a crucial role in maintaining the homeostasis medical center for infectious diseases, 3The First Hospital of Xinjiang
of hepatic tissues, and its mechanism may be related to the Medical University
deubiquitinating function of USP4. Background: BACKGROUND: The prevalence of metabolic
Table and Figure:Figure 1. Complement C3 deficiency exacerbates dysfunction-associated steatotic liver disease (MASLD) has been
hepatic lipid accumulation increasing year by year. Recent studies discovered that impaired
Figure 2.Intracellular pro-C3 participates in the regulation of hepatic mitochondrial function plays a key role in the pathogenesis of MASLD,
lipid metabolism which may lead to oxidative stress, impaired lipid metabolism, and
inflammation of hepatocytes. Alanine-glyoxylate aminotransferase
PP0437 2 (AGXT2) is a multifunctional mitochondrial aminotransferase
High-fat and high-fructose diet feeding induces MASLD in mice by involved in the metabolism of asymmetric dimethylarginine(ADMA)
affecting the liver-gut axis of lipid metabolism and mitochondrial dysfunction. Our previous study revealed that the
Regulators of G-protein signaling 16(RGS16) significantly upregulated
Xiangyun Zou1, Wenying Qi1, Yue Chen2, Xu Cao1, Qiuyue Wang3,
the expression of AGXT2. Therefore, whether RGS16 interacts with
Xiaobin Zao4,5
AGXT2 in MASLD requires further investigation.
1
Dongzhimen Hospital, Beijing University of Chinese Medicine, Method: METHODS: Liver-specific RGS16 knockdown and RGS16
2
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The
overexpression mouse models were used to establish choline-deficient
University of Hong Kong, 3Dongzhimen Hospital, Beijing University of
high-fat diet and western diet MASLD models. The role of RGS16 in
Chinese Medicine, 4Institute of Liver Diseases, Dongzhimen Hospital,
the pathogenesis of MASLD was assessed using immunofluorescence
Beijing University of Chinese Medicine, 5Key Laboratory of Chinese
assay, immunohistochemical staining, biochemical index test, qRT-
Internal Medicine of Ministry of Education and Beijing, Dongzhimen
Hospital, Beijing University of Chinese Medicine PCR, immunoprecipitation assay, and flow cytometry.Transmission
electron microscopy, mitochondrial membrane potential assay, and
Background: Metabolic Associated Steatohepatitis Like Disease MitoSOX and MitoTracker staining were used to detect mitochondrial
(MASLD) has become the leading chronic liver disease globally. function and its molecular mechanisms. ADMA levels of animal serum
Studies have shown that a diet with high fat and fructose can induce and cell culture supernatants were assessed using ELISA.
a phenotype in mice that closely resembles MASLD patients, which is Result: RESULTS: RGS16 levels were significantly downregulated
suitable for studying MASLD. However, the pathogenesis of MASLD is in human MASH liver samples. RGS16 overexpression ameliorated
complex and the relationship between gut flora and lipid metabolism in hepatic injury and lipid accumulation in mice. Specifically, RGS16
MASLD is not yet elucidated. domin might interact with AGXT2 to maintain hepatic mitochondrial
Method: A model of MASLD in mice was developed by administering a function. It’s known AGXT2 could ADMA to improve mitochondrial
high-fat diet along with 5% fructose water for 16 weeks. The success of function. In our study, RGS16 up-regulates ADMA via AGXT2 in animal
the model was determined by recording the body weight of the mice, serum and cell culture supernatants, suggesting the role of RGS16 IN
testing serum liver function, blood lipids, intrahepatic fat content, and MASLD is associated with the AGXT2 activation.
histopathological examination with hematoxylin-eosin (HE) and oil red Conclusion: CONCLUSION: The current study reveals the critical
(OR) staining. Meanwhile, 16S ribosomal RNA sequencing (16S-seq) role of RGS16 in MASLD. RGS16 interacts with AGXT2 and promotes
of the mice’s fecal and a lipidomic assay of the mice’s livers were restoration of mitochondrial function to ameliorate MASLD. In this
performed and further analyzed. process, AGXT2 activation is necessary for maintaining the function
Result: Compared to the control group, the levels of serum ALT, AST, of RGS16.
TG, CHO, and the levels of liver TC and TG in the model group were Table and Figure:Figure 1.RGS16 promotes restoration of mitochondrial
significantly elevated. HE and OR staining indicated that high-fat and function through activation of AGXT2 in MASLD
fructose intervention increased fat accumulation and inflammatory
responses in the liver of the model group, which was evidenced by
the presence of hepatocyte ballooning, and inflammatory infiltration in PP0439
the liver tissue. Additionally, the villi of the small intestine in the model HBV Does Not Protect Against Steatosis in Adults with Metabolic
group were dispersed, the cells were shedding, and there was an Dysfunction-Associated Fatty Liver Disease
increase in the glands of the small intestine. At the gut microbiota level, Jie Zhou1, Jing Chen2, Yudong Wang3, Yan Liu4, Dong Ji5, George
the Spearman Correlation analysis revealed significant associations LAU3,6
between the gut microbiota of mice and Lee’s index, obesity index, and 1
Department of Infectious Diseases, Xinjiang Uygur Autonomous
serological indicators. In detail, Tuzzerella Lachnoclostridium showed Region Infectious Disease Hospital, Xinjiang, China, 2JC School of
a significant positive correlation with Lee’s index and Obesity index. Public Health and Primary Care, Chinese University of Hong Kong,
Furthermore, norank_f__norank_o__Clostridia_UCG-014 displayed Hong Kong SAR, China, 3Humanity and Health Clinical Trial Center,
significant negative correlations with serum ALT, AST, CHO, LDL, and Humanity and Health Medical Group, Hong Kong SAR, China, 4Senior
TG levels, whereas Colidextribacter exhibited the opposite. Lastly, the Department of Infectious Diseases, the Fifth Medical Center of PLA
Wilcoxon rank-sum test on the 16S-seq indicated that, at the phylum General Hospital, Beijing 100039, China, 5Senior Department of
level, compared to the control group, the gut microbiota of mice in the Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing
model group exhibited a decrease in Bacteroidota (p < 0.01) and an 100039, China , 6Zhongshan Hospital, Fudan University, Shanghai,
increase in Firmicutes (p < 0.05). Finally, the results of fecal lipidomic China
indicated that this dietary intervention led to lipid disturbances in the Background: Metabolic-associated fatty liver disease (MAFLD) is a
mice’s liver, with an increase in the content of lower-carbon triglycerides leading cause of chronic liver disease, driven by obesity, diabetes,
and a decrease in the content of higher-carbon triglycerides. and metabolic dysfunction. Chronic hepatitis B virus (HBV) infection,
Conclusion: The mice MASLD model was successfully established prevalent in the Asia-Pacific, contributes to liver inflammation and
by a high-fat diet combined with 5% fructose water. The mechanism fibrosis, but its role in MASLD-associated steatosis remains unclear.
may be related to affecting the normal function of the gut-liver axis and This study investigates whether HBV is an independent risk factor for
disrupting liver lipid metabolism. steatosis in adults with MAFLD.
Method: Consecutive Adult patients diagnosed with MAFLD at the
PP0438 Fifth Medical Center of PLA General Hospital (Jan 2020–Jul 2024)
were included. MAFLD was defined per 2020 APASL guidelines.
RGS16 Promotes Restoration of Mitochondrial Function through
Chronic HBV infection (CHB) was defined by hepatitis B surface
Activation of AGXT2 in MASLD
antigen positivity for ≥6 months. Steatosis was assessed using
Miaomiao Tian1,2, Huiling Cao1,2, Shujun Ma1,2, XI Zhao3,2, Wanhua Controlled Attenuation Parameter (CAP) via FibroTouch. Generalized
linear models were used to evaluate the impact of HBV on risk of liver potential therapeutic targets for MAFLD
steatosis. Figure 2.Bisphenol A was identified as a activator targeting all four key
Result: Among 5,467 patients (mean age 53.6 ± 13.2 years; 59.6% genes with the strongest interactions
male), 665 had valid CAP data (mean age 50.1 ± 11.4 years; 61.6%
male; CHB prevalence: 42.9%). CHB initially appeared to increase
PP0441
steatosis risk (Coefficient: 8.7, 95% CI: 3.8 to 13.5). However, after
adjusting for age, sex, BMI, and clinical parameters, HBV CHB was Machine Learning-Enhanced Bioinformatics Analysis Identifies
no longer significantly associated with steatosis (-0.28, 95% CI: -5.6 Glycosylation Genes, Immune Cell Infiltration in Non-Alcoholic
to 5.0). Male sex (10.8, 95% CI: 5.6 to 16.1) and higher BMI (3.4 per Steatohepatitis
unit, 95% CI: 2.8 to 4.0) were identified as significant risk factors for Shan Hong1, Lei Sun2
steatosis. 1
Department of Gastroenterology, Beijing Ditan Hospital, Capital
Conclusion: In Chinese adults with MASLD, HBV did not seem to Medical University, 2Department of Pathology, Beijing Ditan Hospital,
protect against steatosis. The interplay between HBV and MAFLD- Capital Medical University
associated steatosis warrants further research to clarify potential Background: As the leading cause of chronic liver disease worldwide,
mechanisms. the prevalence of MAFLD is projected to rise to 55.7% by 2040,
NASH is widely recognized as the primary driver of liver fibrosis, and
PP0440 the assessment of NASH is now an essential requirement for drug
trials. Research have firmly established that NASH is a condition in
IDENTIFICATION OF THE KEY GENES RELATED TO BOTH LIPID
which immune play a pivotal role. Previous studies have found that
METABOLISM AND INFLAMMATION IN MAFLD
glycosylation plays a critical role in NASH pathogenesis. Limited
Xin Dai1,2, Yuhong Hu1, Bangmao Wang1, Samar H Ibrahim2, Hailong research has been conducted on the identification of glycosylation
Cao1 associated diagnostic candidates for NASH.
1
Department of Gastroenterology and Hepatology,Tianjin Medical Method: We first downloaded datasets from the gene expression
University General Hospital , 2Division of Gastroenterology and omnibus (GEO) database and glycosylation-related genes (GRGs)
Hepatology, Mayo Clinic from the MSigDB database, then identified differentially expressed
Background: Both lipid metabolism and inflammation are critical genes (DEGs) between nonalcoholic steatohepatitis (NASH) and
contributors to the progression of Metabolic Associated Fatty Liver control samples and selected important immune genes via xCell
Disease (MAFLD). However,there is a lack of data integrating lipid algorithm. The intersecting genes of immune cell-related and GRGs
metabolism and inflammation to investigate the key genes implicated were identified. Functional enrichment analysis, construction of
in MAFLD progression. This study aims to identify and validate the key protein–protein interaction (PPI) network, Gene Set Enrichment
genes associated with both of them in order to better elucidate the Analysis (GSEA), evaluation of nomogram, and receiver operating
pathogenesis of MAFLD. characteristic (ROC) curve evaluation were subsequently performed
Method: In the current study, GSE135251 from the public database to identify immune related, and glycosylation related diagnostic
was analyzed to identify differentially expressed genes between biomarkers.
MAFLD and control groups.Genes related to lipid metabolism Result: A total of 6360 differentially expressed genes (DEGs) were
and inflammation were retrieved from the MSigDB database. The detected, with 3709 upregulated genes and 2651 downregulated
intersection of these 3 gene sets yielded candidate genes that are genes. Significant differences were observed in macrophages using
associated with both lipid metabolism and inflammation in MAFLD. the xCell algorithm. The integrative analysis of gene expression
The identification of key genes was accomplished through machine was conducted by determining the intersection between the ICR-
learning and validated using the external transcriptome database DEGs with GRGs, identifying 18 genes. The GO and KEGG analysis
GSE89632. Furthermore, the RT-qPCR and Western blot were identified enriched biological pathways. GALNT11, ST6GALNAC2,
employed to validate the expression levels of identified key genes and ST3GAL5 consistently ranked as top hub genes across all three
in mouse models. Subsequently, enrichment analysis, immune algorithms by PPI network. We employed a combination of machine
microenvironment analysis and nomogram were performed to evaluate learning and network analysis techniques. Specifically, GALNT11
the role of the key genes in MAFLD. Moreover, single-cell sequencing demonstrated a robust upregulation. In contrast, ST8SIA2 exhibited
(scRNA-seq) database GSE186328 was analyzed on both MAFLD a significant downregulation in NASH. The area under the curve
and control groups, providing insights into the cellular landscape and (AUC) of GALNT11 was 0.785. Similarly, ST6GALNAC2 exhibited a
heterogeneity. Finally, the comparative toxicogenomics database was commendable AUC of 0.748. A nomogram was developed using hub
employed to predict specific activator targeting these key genes. genes (GALNT11, ST6GALNAC2, and ST8SIA2).
Result: The study identified 4 key genes: fatty acid desaturase Conclusion: This research could lead to the identification of
1(FADS1), atty acid desaturase 1(FADS2), galactosidase beta 1(GLB1) glycosylation related and immune-associated potential diagnostic
and patatin like phospholipase domain containing 3 (PNPLA3). markers for NASH patients.
Compared to the chow groups, the hepatic expression levels of Table and Figure:Figure 1.Flow diagram of the analysis process.
FADS1, FADS2, GLB1 and PNPLA3 are significantly increased in mice Figure 2.Screening for differential genes, PPI, KEGG, nomogram for
with high-fat diet-induced MAFLD. Interestingly, FADS1, FADS2, GLB1 biomarkers and the diagnostic value of glysocylation-immune related
and PNPLA3 were found to be co-enriched in the ‘’ribosome’’ pathway. biomarkers.
Further analysis of immune infiltration revealed a strong correlation
between GLB1 and CD56dim natural killer cells. Additionally, scRNA-
PP0442
seq analysis identified 7 distinct cell types. Notably, the expression of
FADS1, FADS2, and GLB1 was significantly different in both NK cells Alterations of Differential Expressing Genes or Metabolites Were
and T cells between the MAFLD and control groups. The nomogram Associated with MASLD Malignant Transformation
indicated that the constructed model, which utilized these 4 key genes, Min Yao1, Min Xu2, Tiantian Ruan1, Rongfei Fang2, Qun Xie3, Wenli
exhibited excellent disease discrimination ability with an AUC value Sai2, Dengfu Yao2
of 0.98981. Furthermore, bisphenol A was identified as a activator 1
Nantong University, 2Affiliated Hospital of Nantong University, 3Haian
targeting all 4 key genes with the strongest interactions. People‘s Hospital
Conclusion: This study identified that 4 key genes, including FADS1, Background: Differential expressing genes (DEGs) and differential
FADS2, GLB1, and PNPLA3, which integrate both lipid metabolism metabolites (DMs) were related to metabolic dysfunction steatotic
and inflammation, are implicated in the progression of MAFLD. liver disease (MASLD) progression. However, their dynamic alterations
Table and Figure:Figure 1.This study revealed that four key genes remain to be identified. The aims of this study were to investigate the
including FADS1, FADS2, GLB1, and PNPLA3 integrating both lipid levels of LDMs and DEGs during MASLD malignant transformation.
metabolism and inflammation in the progression of MAFLD, providing
Method: Dynamic models of Sprague Dawley (SD) rats were made future of MASLD/MASH treatment may be combination therapy.
with high fat diet (HFD) and added 2-fluorenylacetamide to induce The safety of Resmetirom seems acceptable, with gastrointestinal
MASLD malignant transformation. Livers by Ematoxylin & Eosin (H&E) adverse events being the most common. Unfortunately, GLP-1RA
staining were divided into MASLD, MASH, liver fibrosis/cirrhosis (LF/ also has the disadvantage of gastrointestinal adverse reactions. When
LC), hepatocellular carcinoma (HCC), and healthy rats as normal Resmetirom is used in combination with GLP-1 receptor agonists, the
control (NC) group, with lipid by Oil Red O staining. DMs or DEGs gastrointestinal effects of the drug may be amplified, which is a tricky
were identified by liquid chromatography-mass spectrometry (LC- issue
MS) or whole gene chips. GO term, KEGG pathway and proteinte in Table and Figure:Figure 1. Clinical trial drugs:Resmetirom combined
interaction (PPI) were analyzed by bioinformatics. with GLP-1 RA for MASLD.
Result: Hepatocytes during MASLD progression showed obvious
lipid accumulation, with inflammation, necrosis, LF/LC, nuclear PP0444
pleomorphism and disordered arrangement. The numbers of DEGs
in RNA transcriptomics or DMs in metabonomics were 163 or 131 in Enhanced expression of FTO gene in the liver correlates with
MASLD, 934 or 134 in MASH, 1452 or 127 in LF/LC, and 1738 or 130 progression of Metabolic Dysfunction Associated Steatotic Liver
in HCC group, respectively. Downregulated Cyp51 and Tm7sf2 were Disease
discovered in steroid biosynthesis pathway. CNB1 and CDK1 were Sunita Giri1, Vijay Kumar1
involved in P53 pathway and cell cycle, Cyp51 and Tm7sf2 in the PPI. 1
Institute of liver and biliary sciences
The DMs such as phosphatidyl choline (PC) and sphingomyelin (SM) Background: Metabolic dysfunction associated steatotic liver disease
in steroid biosynthesis were related to HCC, with such as CNB1 or (MASLD) is a metabolic disease, strongly associated with
CDK1 in cell cycle, and Cyp51 and Tm7sf2 in PPI. Biological processes obesity, hyperlipidemia, and type 2 diabetes mellitus. The
were focused on metabolic regulating cell responses to stimulin overexpression of Fat mass and obesity associated
and molecular functions included protein binding, cell apoptosis or (FTO) gene is associated with obesity and metabolic disorders. The
proliferation. aim of our study was to investigate the expression of FTO in the liver
Conclusion: The dynamic alterations of DEGs and DMs were and plasma of a MASLD mouse model. The validation of the study was
associated with MASLD malignant transformation and should be conducted in invitro model of MASLD.
potential targets for MASLD prevention or treatment. Method: MASLD model was developed using high fat and high-
carbohydrate diet (HFHC) for 24 weeks. The biochemical parameters,
PP0443 histological changes, and expression of FTO were monitored in plasma
(ELISA) and in the liver tissue (RT-qPCR and immunohistochemistry)
The application prospects of Resmetirom combined with GLP-1
at 8, 19, and 24 weeks of diet intake.The primary hepatocytes were
receptor agonists in the treatment of MASLD
treated with free fatty acids to induce fat accumulation and were
Zhen Yuan1, Junhua Ma2 analysed by ORO stain and FTO expression was monitored using
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia analytical methods (qPCR and ELISA).
medical university , 2Department of Endocrinology, Gongli Hospital of Result: Body and liver weights significantly increased (p<0.0001)].
Shanghai Pudong New Area In addition, MAS scores progressively increased (p<0.0001) with
Background: The prevalence of metabolic dysfunction associated increased steatosis, ballooning, and lobular inflammation at increased
fatty liver (MASLD) is constantly increasing, posing a significant time points compared to the control. Pericellular/periportal fibrosis was
challenge to global health and affecting over 30% of adults worldwide. observed at weeks 19 and 24. Biochemical parameters, including
Despite the increasing burden of MASLD/MASH, there has been a alanine transaminase, aspartate transaminase, triglyceride, and total
lack of effective drug treatment until recently when the FDA approved cholesterol, were significantly increased (p<0.01). The plasma FTO
Resmetirom. Resmetirom is a thyroid hormone receptor beta selective level increased substantially in HFHC mice compared to that in control
drug targeting the liver, which has shown promise in clinical trials for animals. Immunohistochemical examination confirmed the nuclear
the treatment of moderate to advanced MASH. It has been proven expression of FTO at 8 and 19 weeks, but both cytoplasmic and nuclear
to effectively reduce liver fat content, improve liver histology (MASH expressions were observed at 24 weeks. A progressive increase in
regression and fibrosis improvement), and improve biomarkers of liver the FTO gene expression was observed in the liver and plasma of
injury without significantly affecting body weight or glucose metabolism HFHC mice (p<0.0001), probably the increased steatosis inhibits the
Method: We conducted a comprehensive literature search on the degradation of FTO. Primary hepatocytes showed increased lipid
Cochrane Library Science Network, Embase, PubMed, and Google accumulation (p<0.01) and FTO overexpression which further stabilize
Scholar to search for relevant literature reports on Resmetirom and lipogenic genes and promote lipogenesis.
GLP-1 receptor agonists for the treatment of MASLD published in Conclusion: MASLD mouse model was developed and validated for
English as of November 30, 2024. Summarize existing literature physical and biochemical parameters. A time-dependent increase
reports. Conduct a systematic review of MAFLD new drugs. We aim in FTO gene expression was observed in the HFHC model. The
to collect information on the existing mechanisms of GLP-1RA and biochemical parameters were also elevated, and the MAS score
Resmetirom in MAFLD and evaluate their future clinical use prospects directly correlated with disease progression. Overexpression of FTO
Result: Through literature search, it was found that thyroid hormones in cell culture model of MASLD conclude that it promote lipogenesis
mainly mediate their effects through two receptors, namely thyroid and hepatic steatosis by increasing mRNA stability of lipogenic,
hormone receptor alpha (THR - α) and beta (THR - β). THR - β is gluconeogenic and inflammatory genes.
the dominant receptor subtype in liver cells, playing a crucial role Table and Figure:Figure 1.Histological changes in MASLD mouse with
in reducing cholesterol and triglyceride levels, increasing bile acid time
synthesis, and lipid oxidation. Resmetirom (MGL-3196) is an orally Figure 2.FTO expression in the liver tissues of MASLD and control
active liver targeting compound that selectively activates THR - β. group at respective time points
However, THR - β agonists have almost no effect on other tissues.
GLP-1RA can enhance satiety, reduce appetite, lower body weight,
PP0445
and improve blood glucose control, all of which are important factors
determining the efficacy of GLP-1 in MAFLD. They have also been Relationship Between Serum Vitamin D Levels and Metabolic-
shown to significantly improve liver steatosis Associated Fatty Liver Disease in Hypertensive Adults: Evidence
Conclusion: As we celebrate the milestone of FDA approval for the from the 2017-2018 NHANES Cycle
treatment of adult MASH, there are still significant challenges that Liu Mengmeng1, Fei Yue1, Xu Xiahong1, Li Xue1, Lin Han2, Guo
need to be addressed in order to widely use resmetirom in daily Yonghong1
clinical practice. Based on the evidence that MASLD is a multisystem 1
Department of Infectious Disease,Shanghai Pudong New Area
disease and its strong disease heterogeneity, we believe that the Gongli Hospital,219 Miaopu Road, Shanghai,200135,China, 2School
of Gongli hospital Medical Technology,University of Shanghai for using a SUMO inhibitor, GA. RNA interference of SREBP2 reversed
Science and Techonology, Shanghai 200093, China SENP3-mediated cell steatosis under fatty acid treatment.
Background: While vitamin D deficiency is associated with various Conclusion: Our findings demonstrate that de-SUMOylation is an
metabolic disorders, its role in metabolic-associated fatty liver disease important regulatory mechanism that governs the lipid accumulation
(MAFLD) development and progression among hypertensive adults of SREBP2 in mammalian cells. Also, the critical role of the de-
remains unclear. The relationship of vitamin D with MAFLD and liver SUMOylation of SREBP2 by SENP3 to exacerbate steatosis may be a
fibrosis detected by vibration controlled transient elastography was potential therapeutic target for metabolic diseases like MASLD/MASH.
investigated in US adults. Table and Figure:Figure 1.Graphical abstract
Method: A total of 1,165 hypertensive participants were included after
applying exclusion criteria. Serum vitamin D levels were measured via PP0447
HPLC-MS/MS and categorized as normal (>75 nmol/L), insufficient
Focus on a new perspective of NAFLD: re-understand the
(50~75 nmol/L), or deficient (<50 nmol/L). MAFLD diagnosis was
characteristics of lipid droplets
based on vibration-controlled transient elastography (VCTE), with
Zhen Yuan1, Junhua Ma2
controlled attenuation parameter (CAP) values≥263 dB/m defining
hepatic steatosis. Fibrosis and steatohepatitis severity were assessed
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia
via liver stiffness measurement (LSM) and FibroScan-AST (FAST) medical university , 2Department of Endocrinology, Gongli Hospital of
scores, respectively. Linear and logistic regression analyses were Shanghai Pudong New Area
used to explore the relationships among these variables. Background: Non-alcoholic fatty liver disease (NAFLD) is a typical
Result: Among the 1,165 hypertensive participants, the prevalence chronic liver disorder characterized by the existence of lipid droplets
of MAFLD and liver fibrosis was 49.63% and 15.93% respectively. (LDs) in over 5% of hepatocytes, with simple steatosis as the feature
Compared to participants without MAFLD, no significant difference in in the initial stage. LDs are complex and dynamic metabolically
serum vitamin D was observed in MAFLD participants (74.2 vs. 77.7 active organelles composed of a neutral lipid core surrounded by a
nmol/l; P= 0.08). Using multivariate logistic regression analysis, no monolayer of phospholipids and proteins. The accumulation of LDs in
obvious connection of vitamin D status to MAFLD was discovered in hepatocytes is regarded as a prominent characteristic of NAFLD and
hypertensive participants. However, among MAFLD participants, the is also considered an adaptive response to the increased content of
sufficiency of vitamin D represents a lower liver fibrosis risk. When free fatty acids (FA) derived from diet, adipose tissue, and de novo
evaluated in quartiles, in comparison to the lowest quartile, high lipogenesis in hepatocytes.We aspire to obtain the complex biological
vitamin D represents low liver fibrosis risk (Q2 vs. Q1, OR: 0.54, 95%CI: characteristics of LDs, which will offer critical insights into the
0.31–0.95; Q3 vs. Q1, OR: 0.50, 95%CI: 0.28–0.90; Q4 vs. Q1, OR: heterogeneity of NAFLD and its transformation to NASH and contribute
0.81, 95%CI 0.45–1.43). to the exploration of therapeutic regimens for NAFLD
Conclusion: While serum vitamin D levels did not directly correlate Method: A systematic analysis method was used to evaluate the effect
with MAFLD presence, lower levels were associated with increased of LDs on NAFLD. We conducted a comprehensive literature search
liver fibrosis severity in hypertensive patients. on Cochrane Library Science Network, Embase, PubMed, and Google
Table and Figure:Figure 1.Baseline characteristics of the study Scholar to search for relevant articles on NAFLD and lipid droplets
participants with NAFLD according to serum vitamin D levels published in English up to Nov 30, 2024
Figure 2.Factors associated with significant fibrosis Result: Through the retrieval of literature, we have learned that there
is a significant correlation between the biosynthesis of lipid droplets
and the stress of the endoplasmic reticulum. The intensified stress
PP0446
of the endoplasmic reticulum leads to the accumulation of LDs in the
SENP3 promotes hepatocyte steatosis via de-SUMOylation of liver, causing inflammation and promoting the occurrence of NASH.
SREBP2 The synthesis and storage of lipids in LDs can protect cells from the
Linxi Chen1, Nian Fu2, Qianyu Tang1, Yang Hu2, Xiaohua Jiang2, influence of toxic fatty acids (FAs). Triglycerides (TG) can also be
Wenjing Peng2 catabolized into FAs through lipolysis or autophagy, providing essential
1
School of Basic Medical Sciences, Department of Gastroenterology, lipid raw materials for cell membrane biosynthesis.The balloon-like
the Affiliated Nanhua Hospital, Institute of Pharmacy and changes of lipid droplets and hepatocytes, and the development from
Pharmacology, Hunan Provincial Key Laboratory for Tumor simple steatosis to NASH are marked by the ballooning alterations of
Microenvironment Responsive Drug Research, Hengyang Medical hepatocytes, manifested as the dilation of the endoplasmic reticulum,
School, University of South China, 2The Affiliated Nanhua Hospital, the damage of the cytoskeleton, the parenchymal lesions of cells,
Department of Gastroenterology, Clinical Research Center for and the massive accumulation of LDs. The characteristic of ballooned
Metabolic Associated Fatty Liver Disease in Hunan Province, hepatocytes is the imbalance of lipid metabolism, releasing FAs and
Hengyang Medical School, University of South China cholesterol from the core of LDs, thereby resulting in lipotoxicity and
Background: SENP3, a member of the sentrin-specific protease inflammation
family, plays a pivotal role in lipid metabolism and the pathogenesis of Conclusion: Previous studies on NAFLD have limited their focus
fatty liver disease by regulating the dynamic process of SUMOylation. to the accumulation of TG in hepatocytes, but have not recognized
It has previously been demonstrated that SREBP2 is SUMOylated. that TG is stored in LDs. The biological properties of LDs were found
However, the function and regulatory mechanism of SENP3-mediated through literature search, indicating that LDs play an important role in
SREBP2 de-SUMOylation in hepatocyte steatosis is unclear. the progression of NAFLD to NASH and fibrosis. An understanding of
Method: We used 0.5mM oleic acid in vitro as a model of hepatocyte the biological characteristics of LDs in hepatocytes is critical to the
steatosis. Oil red O staining and triglyceride content were determined molecular mechanisms and heterogeneity of NAFLD
to detect hepatic steatosis. Protein interactions were observed by
using CO-IP, immunofluorescence, and protein structure prediction, PP0448
and molecular targets were screened using transcriptome association
analysis, modification site prediction, and signal peptide prediction. Elevated levels of serum GM3 as a novel diagnostic biomarker for
Result: Treatment with OA increased the level of both whole and nuclear hepatic steatosis
forms of SENP3 in L-02 cells. Multi-transcriptomes, protein structure, Moran Hu1, Ziyu Liu1, Zhenzhen Fu1, Hongwen Zhou1, Yingyun
and interaction analysis suggested that SENP3 bounded to SREBP2. Gong1
Mechanistically, it is observed that the co-localization between SREBP2 1
The First Affiliated Hospital of Nanjing Medical University
and SENP3 is increased. Moreover, SENP3-mediated de-SUMOylation Background: The growth in metabolic steatosis-associated fatty
also decreases ZMIZ1-ligated SUMO3 binding to SREBP2 at K464 liver disease (MASLD) has led to significant global health concerns
in the nucleus. Interfering with the SUMOylation and deSUMOylation and a push for new diagnostic tools. The manifestation of MASLD is
cycle induced hepatocyte steatosis by overexpressing SENP3 and
typified by the accumulation of fat in liver cells, with the potential to for identifying NAFLD.The combined hepatic steatosis index (HSI)
progress to more severe complications, including NASH, cirrhosis, and and fatty liver index also show promising prospects for diagnosing
hepatocellular carcinoma. Recent advances in metabolomics have led NAFLD. We found that it is difficult to identify patients with NASH and
to the identification of numerous lipid biomarkers associated with the liver fibrosis and their fibrosis severity based solely on one or a few
onset and progression of MASLD. biomarkers. By combining imaging features with serum biomarkers, the
Method: The objective of this study is to determine whether success rate of diagnosing NAFLD/NASH has been greatly improved,
glycosphingolipids, particularly ganglioside GM3, can function as and the severity of fatty liver patients can be classified accordingly
early diagnostic indicators of liver steatosis. We conducted lipidomic
analyses in both patients with MASLD and murine models, followed by
PP0450
validation in a cellular model.
Result: Lipidomics analysis of serum samples revealed a significant Investigating heat shock protein dysregulation and immune cell
elevation of ganglioside GM3 and its subclasses in individuals with dynamics in non-alcoholic steatohepatitis by integrated multi-
hepatic steatosis compared to healthy subjects. In a mouse model RNA seq analysis
of metabolic associated fatty liver disease induced by a 60% high- Qian Wang1 , Andrew Dong1
fat diet or a high-fructose, high-fat, high-cholesterol diet for 16 weeks, 1
iLab Research Institute
plasma lipidomic profiling also revealed a marked upregulation of total Background: The development of metabolic dysfunction-associated
GM3 and its subclasses in MAFLD mice, accompanied by a significant steatohepatitis (MASH) imposes various stresses on hepatocytes due
increase in the expression of ST3GAL5 in the liver. In an in vitro model to fatty acid accumulation. Heat shock proteins (HSPs), which play
of oleic acid-induced cellular model, a significant increase in both a key role in alleviating these stresses, are important markers in the
mRNA and protein levels of ST3GAL5 was observed. Furthermore, pathogenesis of MASH.
silencing of ST3GAL5 effectively attenuated oleic acid-induced lipid Method: This study analyzed 3 bulk RNA-seq datasets and 1 single-
accumulation. cell RNA-seq dataset from humans and mice.
Conclusion: These results suggest that serum GM3 levels may serve Result: This study identified dysregulation of HSP families, such as
as a potential biomarker for the diagnosis of hepatic steatosis, and HSP70s and HSP90s, in MASH patients. Notably, a significant shift
targeted intervention of the synthase of GM3, GM3S, may alleviate in immune cell populations from macrophages to monocytes was
hepatic lipid accumulation. observed during the development of MASH. Among the macrophages
in mice liver cells, two distinct groups were identified, namely
PP0449 monocyte-derived macrophages (MDMs) and resident Kupffer cells,
with an increase in the proportion of MDMs in MASH. An upregulation
New Diagnosis of NASH - Imaging Changes Combined with Non
of HSPs was also detected in both monocytes and macrophages in
Invasive Serum Biomarkers
MASH.
Zhen Yuan1, Junhua Ma2 Conclusion: These findings suggest that HSPs and immune cell
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia shifts may play a dual role in either promoting MASH progression
medical university , 2Department of Endocrinology, Gongli Hospital of or providing a compensatory response to cellular stress in MASH
Shanghai Pudong New Area livers. Understanding these cell-specific dynamics offers insights into
Background: Non alcoholic fatty liver disease (NAFLD) is a rapidly the pathogenic mechanisms underlying MASH and may guide the
rising spectrum of liver diseases worldwide,Due to the fact that NAFLD development of targeted therapeutic strategies.
does not show corresponding symptoms until the late stage of liver Table and Figure:Figure 1.Figure 1. Upregulation of HSPs in MASH
disease, many patients are not detected until the middle and late livers compared with normal livers.
stages. Liver biopsy is currently the standard for diagnosing NAFLD Figure 2.Figure 2. UMAP shows four types of sequenced cells from
and prognosis. However, this is an expensive invasive procedure, mouse liver on a normal diet and HFD.
sampling is highly invasive, and there is a risk of various complications
including bleeding and pain.there is an urgent need for reliable and
PP0451
accurate imaging features combined with non-invasive biomarkers for
clinical diagnosis of NASH Let’s Get reacquainted the function of macrophages in NAFLD
Method: 1. Collected 17 articles on the latest literature on non- Zhen Yuan1, Junhua Ma2
alcoholic fatty liver disease (NAFLD), including English reviews of 1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia
serum biomarkers, imaging, genetics and metabolomics, long non medical university , 2Department of Endocrinology, Gongli Hospital of
coding RNA (lncRNA), coding and non coding RNA, gut microbiome, Shanghai Pudong New Area
2. Evaluated liver fat content using magnetic resonance proton density Background: Non-alcoholic fatty liver disease (NAFLD) is an important
fat fraction (MRI-PDFF), assessed liver hardness and fibrosis using public health problem, and the number of NAFLD patients is increasing
transient elastography or point shear wave elastography, assessed worldwide. Clinical studies have provided different perspectives
liver fat content using multi omics biomarkers, and assessed liver fat on the key role of immune cells in the progression of NAFLD. Liver-
content using serum biomarkers resident macrophages, Kupffer cells (KCS) and monocyte-derived
Result: Through searching, we found that liver enzymes (alanine macrophages are key cell types involved in the progression of
aminotransferase, aspartate aminotransferase) themselves are not NAFLD. Their unique polarization contributes to the progression of
reliable and accurate serum biomarkers for predicting NASH. NAFLD NAFLD. Here, we focus on the role of macrophages and describe the
Liver Fat Score (NLFS) for NAFLD evaluates liver fat content and shows pathological mechanism and molecular pathways of kupffer cells . To
satisfactory accuracy in diagnosing NAFLD. the hepatic steatosis summarize the potential therapies targeting KCs and macrophages
index (HSI) and fatty liver index (FLI)have shown promising prospects Method: We conducted a comprehensive literature search on the
for diagnosing NAFLD. Advanced magnetic resonance imaging (MRI) Cochrane Library Science Network, Embase, PubMed, and Google
can accurately and repetitively measure the proton density fat fraction Scholar, searching for articles published in English as of Nov 30, 2024,
(PDFF), which is an objective quantitative indicator for evaluating related to macrophages and NAFLD1. Conduct a comprehensive
liver fat content. Transient elastography (TE) is an ultrasound based analysis of the roles of KCs and macrophages in NAFLD through a
modality that uses transient elastography to measure liver stiffness as systematic review, including their polarization effects and their impact ;
an alternative indicator for evaluating liver fibrosis.We also found that 2. Single cell sequencing technology was used to identify macrophage
the level of Cytokeratin (CK)-18 segment has been widely evaluated subtypes in detail, and their functions in NAFLD and roles in innate
in fatty hepatitis immunity
Conclusion: So far, MRI-PDFFseems to be the most accurate method Result: Through literature search, we found subsets of macrophages,
for diagnosing fatty liver Evaluate emerging biomarkers, such as CK- a: Monocyte-derived liver macrophages(MoMF), b: KCs from yolk sac-
18 fragments and miR-122, which can serve as early diagnostic tools
derived erythromyeloid progenitor cells.Macrophages are also divided risen significantly. The new term MAFLD emphasizes the central role
into two phenotypes: a) classically activated macrophages (M1) and of metabolic disorders in diseases, replacing the traditional definition
b) alternatively activated macrophages (M2), where M1 participates of non-alcoholic fatty liver disease (NAFLD). This disease is not
in Th1 response and M2 participates in polarized Th2 response , only related to the accumulation of liver fat, but also closely related
they participate in the regulation of liver inflammation, fibrosis, and to the occurrence of liver inflammation, fibrosis, even cirrhosis and
hepatocellular carcinoma (HCC). Their activation state and polarization hepatocellular carcinoma. This study aims to systematically review
(M1/M2) affect the progression of NAFLD. Current potential treatment the latest advances in the pathological mechanisms, diagnostic
strategies: focus on the signaling pathways of KC and macrophages, methods, and treatment strategies of MAFLD, in order to provide a
such as macrophage scavenger receptor 1 (MSR1), cAMP PKA ,STAT3 more comprehensive understanding and management strategies for
pathway, etc to develop new therapeutic goal this disease
Conclusion: The pathological process of NAFLD begins with Method: This study used a systematic literature review method
steatosis and may develop into steatohepatitis (NASH), even cirrhosis to collect research papers on MAFLD in recent years by searching
and liver cancer. The innate immune system of the liver, especially databases such as PubMed, Web of Science, and Embase. The
the macrophage network, is precisely involved in this process, but inclusion criteria included studies on the pathological mechanisms,
its exact mechanism remains to be further studied. Non alcoholic diagnostic techniques, and treatment strategies of MAFLD, with
fatty liver disease Immune cells, especially Kupffer cells (KCs) and a focus on pathological mechanisms related to insulin resistance,
macrophages, play a key role in the progression of NAFLD, and their lipid metabolism disorders, gut microbiota dysbiosis, and genetic
polarization state affects the disease progression KCs, as phagocytic susceptibility; The application of non-invasive imaging techniques and
cells in the liver, participate in maintaining liver homeostasis. When serum biomarkers in diagnosis; And the latest developments in lifestyle
damaged, they activate and participate in inflammatory reactions, interventions and drug treatments
promoting the onset of NAFLD Result: The literature review shows that the occurrence of MAFLD
involves multiple factors. Insulin resistance is a key driving factor
.Dysregulation of lipid metabolism, also significantly affects liver fat
PP0452
deposition. Dysbiosis of gut microbiota exacerbates liver inflammation
Evaluation of autoimmune phenomena in patients with and fibrosis through the transport of endotoxins and metabolites.
nonalcoholic fatty liver disease on the basis of liver pathology Genetic susceptibility, especially mutations in the PNPLA3 gene, are
Zhu Yu Jin1, Zhang Yan2, Rao Yao3, Jiang Yong4, Liu Yong Gang5, associated with the severity of MAFLD. Liver biopsy remains the gold
Li Jian Zhou6, Yuan Jia Qi6, Zhao Ying2, Zheng Wen Wen2, Ma Lin2, standard for evaluating the degree of liver inflammation and fibrosis.
Wang Chun Yan3, Li Jia3 Emerging elastography techniques and serum biomarkers, such
1
Xi’an No. 3 Hospital, 2Tianjin Medical University, 3 Clinical School as fibrosis index 4 (FIB-4) and NAFLD fibrosis score (NFS), provide
of the Second People‘s Hospital, 4The Second Hospital of Tianjin more convenient and accurate diagnostic tools.In terms of treatment,
Medical University, 5Clinical School of the Second People‘s Hospital, lifestyle interventions such as dietary control and increased physical
6
Xining Second People‘s Hospital activity are the foundation for managing MAFLD. Recent clinical trials
Background: Autoimmune phenomena can be used in some patients have shown that GLP-1 RA and SGLT2 inhibitors have the potential to
with nonalcoholic fatty liver disease (NAFLD) in the clinic, but these improve fat content and liver enzyme levels
patients are not autoimmune hepatitis patients. Conclusion: MAFLD is a complex multifactorial disease, with its
Method: A total of 104 patients with NAFLD diagnosed by liver biopsy pathogenesis involving insulin resistance, lipid metabolism disorders,
at Tianjin Second People’s Hospital between 2019 and 2023 were gut microbiota dysbiosis, and genetic susceptibility. Although traditional
enrolled. The patients were divided into three groups according to their imaging and liver biopsy techniques still play an important role in
biopsy results: The NAFL (n = 36), nonalcoholic steatohepatitis (n = diagnosis, emerging non-invasive diagnostic techniques provide more
51), and liver cirrhosis groups (n = 17). convenient and accurate alternative methods. In terms of treatment,
Result: The differences in IgA, an immune marker, among the three lifestyle intervention is the foundation, and the research progress of
groups of patients were statistically significant (P = 0.025). In all NAFLD drug therapy provides new hope for the future
patients, antinuclear antibody and anti-smooth muscle antibody
were the most common autoantibodies. The antinuclear antibody PP0454
detection rate was the highest at 48.1%. The cirrhosis group had
Steatotic Liver Disease Associated with Hepatitis C: Analysis of
the highest autoantibody positivity rate (64.7%). Portal enlargement
Determinants and Progression
is also common in NAFLD patients. The rates of positivity for portal
lymphoplasmacytic infiltration, small bile duct hyperplasia and Hajar Elibrahimi1, Maryeme Kadiri2, Fatimazahra Chabib2, Nawal
interfacial hepatitis were highest in the cirrhosis group; the differences Lagdali2, Mohamed Borahma2, Fatimaezzahrae Ajana2
between the cirrhosis group and the other two groups were significant
1
ibn sina university hospital department C, 2ibn sina university
(P < 0.05). Hepatocellular rosettes were identified only in the cirrhosis hospital, department C
group (11.8%). Background: SLD (steatotic liver disease) is a pathology characterized
Conclusion: Autoimmune phenomena occur in NAFLD patients, by the accumulation of fat in the liver in individuals without excessive
especially in patients with NAFLD-related cirrhosis, in whom this alcohol consumption. It encompasses a broad spectrum of diseases
phenomenon may be more pronounced. ranging from steatosis associated with a dysmetabolic context
Table and Figure:Figure 1.Comparison of biochemical indexes among (MASLD) to the presence of inflammation and hepatocyte ballooning
the three groups. on histology e (MASH).
Figure 2.Comparison of autoantibody detection rates in three groups In chronic viral hepatitis C, MASLD is multifactorial, depending on either
the infecting genotype (often genotype 3) or metabolic comorbidities,
PP0453 favoring its appearance.
The aim of our study is to investigate the impact of MASLD in chronic
Metabolic Associated Fatty Liver Disease : latest advances in viral hepatitis C.
pathological mechanisms, diagnostic techniques, and treatment Method: This is a retrospective, preliminary, descriptive study
strategies extending over a 4-year period (between 2021 and 2024), focusing on
Zhen Yuan1, Junhua Ma2 patients with MASLD in whom viral hepatitis C was associated. Patients
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia lost to follow-up were excluded, as were patients in whom the degree
medical university , 2Department of Endocrinology, Gongli Hospital of of steatosis was not assessed.
Shanghai Pudong New Area, All patients were genotyped.
Background: Metabolism related fatty liver disease (MAFLD) is the MASLD was determined by abdominal ultrasound and cardiometabolic
most common liver disease in the world.its global prevalence has profil
Result: Our study included 81 patients with viral hepatitis C. The mean with Stage 3/4 of CKM Syndrome
prevalence of steatosis was 18.5% (n=15), of whom 6.2% were S1
(n=5), 8.6% were S2 (n=7), and 3.7% were S3 (n=3). Mean age was PP0456
60.5% (33-83), with a female predominance, i.e. a sex ratio M/F= 0.3.
Genotype 1 was predominant in 66.66% (n=10), followed by genotype Evaluation of different non-invasive models in assessing lean
2 in 33.33% of cases (n=5). metabolic associated fatty liver disease in people living with HIV
Diabetes, hypertension, obesity and dyslipidemia were described Wei Xu1, Yinzhong Shen1, Chen Jun1, Renfang Zhang1
respectively in 20% of cases (n=3), 26.6% of cases (n=4), 13.3% of 1
Department of Infection and Immunity, Shanghai Public Health
cases (n=2) and 6.6% of cases (n=1). Clinical Center
The degree of fibrosis was variable: 25% (n=6) of patients were F1, Background: This study aimed to investigate the prevalence of lean
22.2% were F2 (n=4), 15.7% were F3 (n=3), and 10% were F4 (n=2). metabolic associated fatty liver disease (lean MAFLD) in people living
13% of patients (n=2) had associated occult viral hepatitis b (n=2) and with HIV(PLWH) and the value of ten diagnostic models in MAFLD
6.6% had a shyphilitic infection (n=1). among PLWH.
53% of patients had PH (n=8). Method: Transient Elastography (Fibroscan), Controlled attenuation
Progression was favorable, with a clear improvement in symptoms in parameter (CAP) and ultrasonography were performed among PLWH.
86.66% of cases (n=13). Hemorrhagic decompensation was described MAFLD was defined by the 2024 revised edition of the Chinese
in 6.6% of cases (n=1), and ascitic and neurological decompensation guidelines for prevention and treatment of MAFLD. Lean MAFLD was
in 6.6% of cases (n=1). However, no cases of HCC were observed. defined as a BMI<24kg/m2 in patients with MAFLD. The SteatoText
Conclusion: In our study, steatosis prevalence in CVH was 18.5%, (ST), fatty liver index (FLI), NAFLD-liver fat score (NAFLD-LFS),
with 10% of patients being cirrhotic (F4) and genotype 1 predominating hepatic steatosis index (HSI), index of NAFLD(ION), ZJU index, NAFL
in 66.7%. Half of the cases were in PH, with most showing favorable screening score (NSS), K-NAFLD, visceral adiposity index (VAI) and
outcomes. Only 13% presented a decompensation. Effective MASLD Lipid Accumulation Product (LAP) were evaluated. The area under the
and hepatitis C management requires a multidisciplinary team of receiver operating characteristic (AUROC) curve was used to evaluate
hepatologists, endocrinologists, and nutritionists the performance of them for diagnosing MAFLD.
Result: Among the 361 PLWH, 141 were diagnosis with MAFLD,
PP0455 with a prevalence of 39.05%. Out of these 361 patients, 111 were
overweight (BMI≥24kg/m2), and 250 were non-overweight(BMI<24kg/
Prevalence of Metabolic Dysfunction-associated Fatty Liver
m2). MAFLD affect 58(23.2%) in 250 lean PLWH. Among the overall
Disease (MAFLD) and Cardiac, Kidney, Metabolic Conditions
population, the NSS had the highest AUROC of 0.887, followed by FLI
(CKM) in Adults: A Community-Based Study
(AUROC =0.880), ZJU (AUROC = 0.873), LAP (AUROC = 0.849), and
Jing Zeng1, Zhen Yang1, Jian Gao Fan1 ST (AUROC = 0.847). ION had the lowest AUROC with value of 0.744.
1
Shanghai Xinhua Hospital In the non-overweight population, the AUROC of NSS was 0.868,
Background: Metabolic dysfunction-associated fatty liver disease suggesting moderate diagnostic value. However, among overweight
(MAFLD) is a liver disease closely associated with metabolic disorders, or obesity population, it showed limited diagnostic value with AUROC
with its global prevalence increasing year by year, becoming a of 0.736.
significant public health issue worldwide. Patients with MAFLD are Conclusion: We found a non-negligible prevalence of MAFLD in lean
often accompanied by various metabolic abnormalities, such as PLWH. Models established on chemical and metabolic indicators
obesity, type 2 diabetes, and insulin resistance, which also increase provide no advantage for MAFLD diagnosis in PLWH, especially for
the risk of cardiovascular and kidney diseases. However, the specific overweight patients.
relationship between MAFLD and cardiac, kidney, and metabolic Table and Figure:Figure 1.Correlation matrix between models and
conditions (CKM) remains unknown. MAFLD in Non-overweight group
Method: This study aimed to assess the relationship between the Figure 2.Correlation matrix between models and MAFLD in Overweight
prevalence of MAFLD and the prevalence of CKM syndrome through group
a community-based study.
Result: A cross-sectional study was conducted from 2011 to 2012 in PP0457
Shanghai, China, utilizing random stratified cluster sampling of 9,980
individuals aged 40 and above. The distribution of CKM stages was Golgi protein 73: Charting new territories in diagnosing significant
as follows: CKM stage 0: 1.1%, CKM stage 1: 15.4%, CKM stage 2: fibrosis in MASLD: A prospective cross-sectional study
79.4%, and CKM stage 3-4: 4.0%. The prevalence of CKM stage 2 Shan Hong1, Hongshan Wei1
was notably high, indicating a higher burden of metabolic risk factors 1
Department of Gastroenterology, Beijing Ditan Hospital, Capital
and a greater prevalence of chronic kidney disease (CKD). Very Medical University
few individuals were classified in CKM stage 0, which had no risk Background: Metabolism-Associated Steatotic Liver Disease
factors. The prevalence of CKM stage 2 was significantly higher in (MASLD), previously known as non-alcoholic fatty liver disease
MAFLD patients (88.3%) compared to non-MAFLD patients (73.4%). (NAFLD), is a major global liver disease. Its prevalence is rising,
Additionally, the prevalence of CKM stage 3-4 was also significantly particularly in China, where many remain undiagnosed due to
higher in MAFLD patients (5.2%) compared to non-MAFLD patients inadequate diagnostic tools.MASLD can progress to inflammation
(3.3%). In CKM stage 2, the prevalence of MAFLD was 45.1%, while (MASH) and fibrosis, leading to cirrhosis. While liver biopsy is the
in CKM stage 3-4, the prevalence of MAFLD increased to 51.6%. standard for staging fibrosis, its risks have spurred the development of
Univariate analysis revealed that MAFLD was an independent risk non-invasive tests (NITs) for better assessment.Guidelines recommend
factor for CKM stage 3-4 (OR 1.592, 95% CI: 1.304–1.045). Multivariate non-invasive panels like the NAFLD Fibrosis Score (NFS) and Fibrosis
analysis further confirmed that MAFLD remained an independent risk Index-4 (FIB-4) for evaluating fibrosis, although they can yield false
factor for CKM stage 3-4 (OR 1.387, 95% CI: 1.127–1.706). positives and negatives. New NITs are needed for effective MASLD
Conclusion: Significant differences in the prevalence of CKM monitoring.Golgi Protein 73 (GP73) is a promising biomarker for HCC,
syndrome were observed across its stages. Both univariate and increasing with chronic liver disease. This study aims to quantify GP73
multivariate analyses identified MAFLD as an independent risk factor levels in biopsy-proven MASLD, assess their correlation with significant
for CKM stage. These findings suggest that MAFLD is not only a fibrosis, and develop a novel algorithm combining GP73 with transient
common comorbidity in CKM syndrome but also plays a key role in the elastography (TE) for diagnosing significant fibrosis.
progression of CKM to more advanced stages. Method: This dual-center, cross-sectional study involved patients
Table and Figure:Figure 1.Prevalence of Each Stage of CKM Syndrome diagnosed with steatotic liver disease at Beijing Ditan Hospital and
and Prevalence of Each Stage in MAFLD Beijing Youan Hospital from May 2018 to January 2024. Inclusion
Figure 2.Univariate and Multivariate Analysis of Risk Factors Associated
criteria included informed consent, ages 18-75, hepatic steatosis Table and Figure:Figure 1.Development of nomogram for predicting
confirmed by imaging and biopsy, and at least one cardiometabolic the probability of chronic DILI.
risk factor (CMRF).Exclusion criteria involved excessive alcohol Figure 2.Validation of the nomogram for predicting the probability of
consumption, known liver diseases, or malignancies.Approved by the chronic DILI in the training cohort and validation cohort.
Ethics Committees, participants provided informed consent. The study
followed the Declaration of Helsinki and is registered with the China
PP0459
Clinical Trials Registry (ChiCTR1800015157).
Result: 379 participants were recruited, with 346 (91.3%) diagnosed PPARs family as a target and regulator of epigenetic mechanism
with MASLD. After excluding those with other conditions, 228 MASLD in NASH
patients were analyzed.Among the MASLD patients, 57.5% were men, Zhen Yuan1, Junhua Ma2
and 37.2% had significant fibrosis. Higher BMI and waist circumference 1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia
were common CMRFs, with 45.7% having three or more risk factors. medical university , 2Department of Endocrinology, Gongli Hospital of
Patients with significant fibrosis were older (45 vs. 38 years) and had Shanghai Pudong New Area
higher GP73 levels (128 ng/mL vs. 46 ng/mL). A correlation (0.269, Background: The pathophysiology of non-alcoholic steatohepatitis
p<0.001) existed between GP73 levels and NAS.Fibrosis was F0-1 in (NASH) includes a complex set of intrahepatic and extrahepatic
62.7% of cases, with significant liver fibrosis (F2-4) in 37.3%. MASH driving mechanisms, involving many metabolic, inflammatory,
was diagnosed in 35.1%, correlating significantly with fibrosis (Pearson vascular, and fibrotic pathways. Peroxisome proliferator activated
0.402, p<0.001).Age, LSM, and GP73 were independent predictors receptors (PPARs) α, β, and γ belong to the nuclear receptor family
of significant fibrosis. A non-invasive diagnostic algorithm (GFA) was of ligand activated transcription factors. Activated PPAR regulates
developed using these variables.The GFA model had an AUC of 0.860, the transcriptome profile of target tissues, enabling the body to
outperforming traditional algorithms like FIB-4 and NFS (p<0.001). This adapt to constantly changing nutritional, metabolic, and inflammatory
was consistent in the validation group. environments. Therefore, PPAR regulates several pathways involved in
Conclusion: Serum GP73 is an independent risk factor for significant the pathogenesis of NASH。The targeted research of PPARs provides
liver fibrosis in MASLD, and the GFA model based on GP73 combined new ideas for the treatment of NAFLD and related diseases, and its
with LSM has good diagnostic efficacy for significant liver fibrosis. importance in medical research and drug discovery is increasingly
Table and Figure:Figure 1.Serum GP73 levels were markedly higher in prominent
patients with significant fibrosis than in those without (128 ng/mL v.s 46 Method: we conducted a comprehensive literature searh in the
ng/mL, p<0.001) cochrane library science network ,embase and pubmed,google
Figure 2.ROC Curves of Different Non-Invasive Diagnostic Models for scholar for relevant articles on PPARα in the NASH published in English
Diagnosing Significant Liver Fibrosis in the Validation Group (n=92) up to 22.dec 2024.the existing literature reports were summarized
Result: The literature review shows that PPAR family includes three
PP0458 subtypes, alpha, beta/delta, and gamma, which have different
expression patterns in different organs and cell types, thus playing
Development and Validation of a comorbidity burden based model
complementary roles in the pathogenesis of NASH. PPAR α is highly
for predicting chronicity following acute drug-induced liver injury
expressed in the liver, heart, and skeletal muscle, regulating fatty acid
Shuo Zhang1, Zhijing Wang1, Lu Xia1, Bing Ji2, Yang Li1, Changqing oxidation and transport, and helping to adapt to fasting conditions.
Yang1 PPAR γ is highly expressed in adipose tissue, promoting fat storage
1
Department of Gastroenterology and Hepatology, Tongji Hospital, and insulin sensitivity, and improving systemic glucose tolerance.
School of Medicine, Tongji University, Shanghai, China, 2General PPAR δ is expressed in multiple tissues and protects mice from obesity
Medical Ward, Jiangning Road Community Health Service Center, and diabetes by promoting energy consumption and improving
Jing’an District, Shanghai 200041, China insulin sensitivity .Clinical use of PPAR agonists: PPARα agonists
Background: Patients with drug-induced liver injury (DILI) could (fibrates) are used to treat hypertriglyceridemia, and PPARγ agonists
experience persistent liver injury, referred as chronic DILI, leading (thiazolidinediones) are used to improve insulin sensitivity in patients
to several complications. This study investigated the risk factors with diabetes
associated with chronic DILI and developed a combined predictive Conclusion: PPARs, as members of the nuclear receptor family,
model. play a crucial role in regulating lipid and glucose metabolism as well
Method: Patients with DILI were retrospectively collected and as inflammatory responses, and are promising drug targets for the
randomized into the training and validation cohorts, of whom chronicity treatment of NASH. Although individual PPAR agonists have shown
was characterized by persistent abnormalities in liver biochemistry, some efficacy in clinical trials, full PPAR activation is necessary to
imaging assessments, or histology one year after DILI. The least achieve significant effects at histological endpoints. The chemical
absolute shrinkage and selection operator (LASSO) regression differences and pharmacological properties of PPAR agonists require
analysis was applied to select the predictive features. Logistic individualized evaluation to ensure their effectiveness and safety in
regression analysis was used to identify independent risk factors and NASH treatment
further developed a predictive model of chronic DILI. The predictive Table and Figure:Figure 1.The function and Mechanism of PPARs
performance of the model was evaluated by receiver-operating Representative Agonists.
characteristic (ROC) curve, calibration curve and decision curve
analysis (DCA).
PP0460
Result: A total of 380 patients were included and randomized into
the training (n=219) and validation (n=161) cohorts, with 56 (14.7%) Additive effect of SAMM50 and MBOAT7 variants on the histological
of them experienced chronic DILI. LASSO and logistic regression severity of metabolic-associated steatotic liver disease
analyses identified that gender (P=0.004), HbA1c (P=0.001), γ-GT Jinhan Zhao1,2, Jing Zhang1, Yang Zhang2, Fanqiang Meng3, Xiaodie
(P=0.006), uric acid (P=0.002) and extra-hepatic solid tumor (P=0.013) Wei1, Qiqige WuYun4
were the independent predictors of chronic DILI. The area under the 1
The Third Unit, Department of Hepatology, Beijing Youan Hospital,
ROC curves indicated good discrimination, with 79.7% and 88.2% of Capital Medical University, 2Beijing Institute of Hepatology, 3China
internal and external validation, respectively. The calibration curves Japan Friendship Hospital, 4Department of Surgery, Capital Medical
confirmed high consistency. The DCA determined that 0.1-0.7 was the University Affiliated Beijing Shijitan Hospital
optimal decision range of threshold probabilities of the model. Background: The polygenic risk score (PRS) has been proved to
Conclusion: This study confirmed that gender, clinical burden of be associated with the development and progression of metabolic-
comorbidity and other host factors were independent predictors associated steatotic liver disease (MASLD), but few studies were
chronic DILI, based on which the combined predictive model could be targeting Asian patients. This study explores the impact of SAMM50
conveniently applied for clinical decision-making. rs3761472 and MBOAT7 rs641738 variants on MASLD susceptibility
and histological severity in a Chinese cohort. Diagnostic performance of ultrasound-derived fat fraction (UDFF)
Method: A total of 269 patients with biopsy-confirmed MASLD to quantify hepatic steatosis in a biopsy-proven cohort
were enrolled, including 117 patients with metabolic dysfunction- Yi Dong MD1, Yunlin Huang1, Ying Wang1, Li Wei1, Juan Cheng1,
associated steatotic liver (MASL) and 152 with metabolic-associated Xiuyun Lu1, Rui Cheng1
steatohepatitis (MASH). A TaqMan probe assay was used to genotype 1
Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai
the SAMM50 and MBOAT7 variants. PRS was calculated based on Jiao Tong University School of Medicine, Shanghai, 200092, China
these two variants.
Background: To evaluate the diagnostic performance of ultrasound-
Result: The prevalence of SAMM50 G allele carriers was signicantly
derived fat fraction (UDFF) for diagnosing and grading hepatic
higher in MASH group than MASL, whereas there was no significant
steatosis using liver biopsy as the reference.
difference in MBOAT7 variants between the two groups. The
Method: Patients who had steatosis liver disease and were referred
prevalence of NAS≥5, severe steatosis, inflammation, and advanced
to undergo liver biopsy were enrolled in this prospective study. All
fibrosis was significantly increased with the elevation of PRS. Carriers
patients underwent UDFF measurements. The histologic hepatic
of the SAMM50 G allele exhibited a higher risk of MASH (OR, 1.99;
steatosis was graded (S0, < 5 %; S1, 5 - 33 %; S2, 33 - 66 %; S3, > 66
P=0.014). MBOAT7 exhibited an additive effect, conferring significant
%). The Kruskal-Wallis tests were performed to compare UDFF
vulnerability to MASH when combined with SAMM50 (OR per risk
values between different degrees of hepatic steatosis. The Pearson
allele, 1.4; 95% CI, 1.03–1.97). The risk of significant liver fibrosis (F≥2)
correlation was performed to compare UDFF to histopathological
was markedly higher when PRS≥3.
results. Univariate and multivariate linear regression analyses were
Conclusion: The SAMM50 rs3761472 and MBOAT7 rs641738 variants
used to evaluate significant associated factors for UDFF. The area
significantly contribute to the histological severity in patients with
under the receiver operating characteristic curve (AUC) was used
MASLD, demonstrating notable additive effects on susceptibility to
to evaluate the diagnostic performances of UDFF in the detection of
MASH and liver fibrosis. These findings underscore the critical role of
hepatic steatosis grade.
genetic profiles in managing and predicting the prognosis of MASLD.
Result: From February 2023 to April 2024, a total of 56 patients (44.6
Table and Figure:Figure 1.Cumulative incidence of different degrees
% [25/56] men and 55.4 % [31/56] women) were included. The median
of steaotosis, ballooning, inflammation, fibrosis in patients with MASLD
age and body mass index were 46 years (interquartile range [IQR]: 33,
stratified by genetic risk score
64) and 24 kg/m2 (IQR: 22, 26), respectively. Among the 41 patients,
Figure 2.The additive effect of mutation sites (PRS) of SAMM50 and
46.3 % (19/41), 31.7 % (13/41), 9.7 % (4/41), and 12.1 % (5/41) of
MBOAT7 on the risk of MASH
them were steatosis graded S0, S1, S2, and S3, respectively. The
success rate of the UDFF and CAP measurements were 100 % and
PP0461 97.6 %, respectively. The median UDFF value of all patients was 6.0
Association of Sarcopenia and Physical Activity on the Severity % (IQR: 3.3 – 12.0). The median UDFF values of patients with S0, S1,
of MASLD S2, and S3 were 4.0 % (IQR: 3.0 – 6.5), 10.0 % (IQR: 4.0 – 11.5),
Xiaodie Wei1, Jing Zhang1, Xiaohui Liu1, Jinhan Zhao1 10.3 % (IQR: 5.0 – 20.4), and 18.5 % (IQR: 16.5 – 31.8), respectively.
There were significant differences in UDFF values between S0 and S2,
1
The Third Unit, Department of Hepatology, Beijing Youan Hospital,
Capital Medical University S0 and S3, S1 and S3, and S2 and S3 (P < 0.05). The cut-off value
of UDFF for detecting hepatic steatosis was 9.5 %. Both UDFF and
Background: Sarcopenia, physical activity (PA), and sedentary CAP had good diagnostic performance in detecting hepatic steatosis,
behavior are associated with metabolic dysfunction-associated with AUCs of 0.81 (95% confidence intervals [CI]: 0.68 – 0.94) and
steatotic liver disease (MASLD). The study aimed to evaluate the 0.87 (95% CI: 0.76 – 0.98), sensitivity of 63.6 % (95% CI: 43.0 – 80.3)
effects of sarcopenia and PA on the presence and severity of MASLD. and 81.8 % (95% CI: 61.5 – 92.7), and specificity of 94.7 % (95% CI:
Method: This cross-sectional study analyzed data from the 2017-2018 75.4 – 99.7) and 78.9 % (95% CI: 56.7 – 91.5), respectively. However,
National Health and Nutrition Examination Survey (NHANES). Hepatic The diagnostic performance showed no significant difference between
steatosis and liver fibrosis were assessed by vibration-controlled UDFF and CAP (P > 0.05). UDFF values had a significant positive
transient elastography (VCTE). Sarcopenia was defined based on correlation with CAP values (R = 0.77, P < 0.001).
the Foundation for the National Institutes of Health criteria. PA and Conclusion: UDFF showed good diagnostic performance in the
sedentary behavior were evaluated using the Global Physical Activity evaluation of hepatic steatosis. Especially when patients fail to obtain
Questionnaire (GPAQ). valid CAP values, UDFF measurement could be a potential alternative
Result: Among 1,831 participants, 664 were diagnosed with MASLD, tool in clinical practice.
including 482 with severe steatosis and 89 with significant fibrosis. The Table and Figure:Figure 1.Representative UDFF image (a).
prevalence of sarcopenia in the MASLD and non-MASLD populations Distribution of UDFF values according to hepatic steatosis grade (b).
was 11.7% and 3.8%, respectively. Multivariable-adjusted models Representative CAP result (c). The diagnostic performance of UDFF
demonstrated that sarcopenia significantly increased the risk of and CAP for diagnosing hepatic steatosis (d). Correlation between
MASLD, severe steatosis, and significant fibrosis, with odds ratios UGAP and CAP (e).
(ORs) of 2.45 (95% CI: 1.33, 4.52), 2.56 (95% CI: 1.40, 4.66), and 6.10
(95% CI: 2.08, 17.84), respectively. Individuals with sarcopenia and
low PA had a 7.91-fold increased risk of developing significant fibrosis PP0463
(OR, 7.91; 95% CI: 1.42–44.16, P = 0.022). Additionally, individuals with Machine learning model using R2* radiomics for predicting
both sarcopenia and prolonged sedentary behavior had significantly metabolic dysfunction-associated steatohepatitis
higher risks of MASLD, severe steatosis, and significant fibrosis, with Xiaodie Wei1, Jing Zhang1, Chen Shao2, Shi Qi3, Jinhan Zhao1, Jing
ORs of 3.75 (95% CI: 1.60,8.76), 17.58 (95% CI: 1.93,159.79), and Zhao4
4.32 (95% CI: 1.31,14.31), respectively. 1
The Third Unit, Department of Hepatology, Beijing Youan Hospital,
Conclusion: Patients with sarcopenia should increase physical activity Capital Medical University, 2Department of Pathology, Beijing Youan
and reduce sedentary time to decrease the risk and progression of Hospital, Capital Medical University, 3BEIJING FENGTAI HOSPITAL,
MASLD. 4
Department of Radiology, Beijing Youan Hospital, Capital Medical
Table and Figure:Figure 1.Multivariate ORs of sarcopenia and physical University
activity for MASLD, severe steatosis, and significant fibrosis. Background: Non-invasive diagnosis of metabolic dysfunction-
Figure 2.Forest plot showing the multivariable-adjusted risk of associated steatohepatitis (MASH) remains a challenge. R2* mapping
sarcopenia and physical activity for MASLD, severe steatosis, and is an imaging technique derived from the Dixon sequence. This study
significant fibrosis. aimed to develop a machine learning-based radiomics and clinical
model using R2* images for the diagnosis of MASH.
PP0462 Method: This study enrolled 151 patients with biopsy-proven metabolic
dysfunction-associated steatotic liver disease (MASLD) who underwent did not show an association with all-cause mortality in MASLD patients
MRI examinations. MASH was defined by the presence of steatosis, (all P >.05). However, MASLD individuals with moderate and poor
lobular inflammation, and hepatocyte ballooning, with a total NAS LE8 health behavior scores exhibited an increased risk of all-cause
score ≥4. A total of 993 radiomic features were extracted from the right mortality (moderate: HR, 1.51; 95% CI, 1.05–2.17; and poor: HR,
liver lobe region of interest (ROI) in R2* images and then filtered by the 2.32; 95% CI, 1.64–3.30), particularly among patients with advanced
least absolute shrinkage and selection operator combined with cross- fibrosis (moderate: HR, 1.77; 95% CI, 1.07–2.92 and poor: HR, 2.43;
validation (LASSO-CV). Five machine learning models were evaluated: 95% CI, 1.23–4.78). PAF estimates suggested that 35.0% of all-cause
Random Forest (RF), Extreme Gradient Boosting (XGBoost), Extra Tree mortality attributed to poor or moderate health behaviors score could
(ET), Adaptive Boosting (AdaBoost), and Gradient Boosting (GB). be avoided if ideal CVH metrics were achieved by all MASLD patients,
Result: Among the participants, 37 had MAFL and 114 had MASH. which increased to 41.8% among those with advanced fibrosis.
After selecting radiomics features, 15 features were input into the Conclusion: These findings demonstrate a significant association
machine learning models. The areas under the receiver operating between the LE8 health behaviors score and all-cause mortality in
characteristic curve [AUCs (95% CI)] for MASH diagnosis were as patients with MASLD, highlighting the usefulness of this score in
follows: GB 0.74 (0.56–0.92), RF 0.71 (0.52–0.91), ET 0.66 (0.45–0.86), optimizing risk management strategies for MASLD in future clinical
AdaBoost 0.66 (0.45–0.86), and XGBoost 0.65 (0.44–0.85). Clinical practice.
variables identified by the RF classifier (ALT, TC, BMI, Sex, and GGT) Table and Figure:Figure 1.Graphic Abstract
were incorporated into the models. The AUCs (95%CI) for diagnosing
MASH using clinical features were as follows: GB, 0.69 (0.45-0.92); RF,
PP0465
0.69 (0.46-0.92); ET, 0.70 (0.49-0.92); AdaBoost, 0.72 (0.52-0.91); and
XGBoost, 0.66 (0.41-0.90). The combined clinical-radiomics models Appraising the causal role of depression in the risk of multiple
achieved AUCs (95% CI) of GB, RF, ET, AdaBoost, and XGBoost were chronic liver diseases: A Meta-analysis and bi-directional
0.70 (0.51-0.90), 0.77 (0.58-0.96), 0.79 (0.61-0.98), 0.72 (0.53-0.91) Mendelian randomization study
and 0.75 (0.54-0.96), respectively. Huan Wu1, Long Wu1, Can Li1, Quan Zhang1, Mao Mu1
Conclusion: The R2*-based radiomics-clinical model demonstrated 1
No. 28 Guiyi Street
promising diagnostic performance for MASH, providing a potential Background: Depression has been reported to be associated with
non-invasive tool for its diagnosis. some types of chronic liver diseases in observational studies. However,
Table and Figure:Figure 1.Diagnostic performance of radiomics,clinical the causality of the association between depression and chronic liver
and clinical-radiomics models for MASH. diseases is undetermined. We applied Mendelian randomization
Figure 2.Radiomics feature selection using the LASSO-CV method. approach and Meta-analysis to systematically explore the associations
(A) Identification of the optimal penalization coefficient lambda (λ) of depression with 9 Chronic liver diseases.
(B) LASSO coefficient profiles of the radiomics features.Important Method: We performed the two-sample bi-directional mendelian
coefficient of selected radiomics features of LASSO randomization with the publicly available genome-wide association
studies summary statistics to investigate the causal relationship
PP0464 between the genetically predicted depression and the risk of multiple
types of liver diseases. Causal estimate was calculated by five
Association between the Life’s Essential 8 Health Behavior Score
methods, which included inverse variance weighted method. We also
and All-cause Mortality in Patients with Metabolic Dysfunction-
performed additional sensitivity tests to evaluate the validity of the
associated Steatotic Liver Disease
causal relationship. Thereafter, Meta-analysis was applied to combine
Yan Han1, Jing Tang1, Na Wu1, Zhao Li2, Hong Ren1, Peng Hu3,1, study-specific estimates.
Zhiwei Chen1 Result: After correction for heterogeneity and horizontal pleiotropy,
1
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry we only detected suggestive evidence for the causality of genetically
of Education), Institute for Viral Hepatitis, Department of Infectious predicted depression on non-alcohol fatty liver disease (NAFLD).
Diseases, the Second Affiliated Hospital of Chongqing Medical Autoimmune hepatitis increases genetic risk for depression. No
University, Chongqing, China., 2Department of Gastroenterology,
evidence of causal effects of depression on other types of chronic liver
the Seventh People‘s Hospital of Chongqing, Chongqing, China.,
diseases and reverse causality was detected. In addition, the results
3
Department of Infectious Diseases, the First Affiliated Hospital of
of the meta-analysis also showed that there is causal relationship
Chongqing Medical University, Chongqing, China.
between depression and non-alcoholic fatty liver disease.
Background: Metabolic dysfunction-associated steatotic liver disease Conclusion: The result of this study suggests genetic predisposition
(MASLD) has emerged as the most prevalent chronic liver disorder to depression may have positive causal roles on specific type of
globally, affecting approximately 30% of the world’s population. chronic liver disease. Genetic susceptibility to self-awareness of mood
Therefore, any endeavors aimed at optimizing the management of problems may be a strong causal risk factor of NAFLD. Prevention and
patients with MASLD while reducing their mortality are highly warranted. early diagnosis of depression are important in management of NAFLD.
The association between Life’s Essential 8 (LE8), a recently updated Table and Figure:Figure 1.
measure of cardiovascular health (CVH), and all-cause mortality in
patients with metabolic dysfunction-associated steatotic liver disease
(MASLD) remains unknown. PP0466
Method: This population-based prospective cohort study analyzed Could Targeted Reduction of Liver Fat Reduce Blood Glucose
data from participants aged 20 to 79 years in the National Health Levels in Patients with Non-alcoholic Fatty Liver Disease (NAFLD)
and Nutrition Examination Survey from 2005 to 2018, with mortality : A Meta-analysis
information linked until 2019. The USFLI score was employed to Zhaoqian Xu1, Xinlei Zhang1, Linong Ji1, Xiantong Zou1
determine the presence of liver steatosis, while NFS, APRI, and FIB4 1
Peking University People‘s Hospital
scores were utilized for assessing advanced liver fibrosis. Multivariable
Background: There was strong correlation between liver fat content
Cox proportional hazards regression was used to estimate hazard
and blood glucose levels. Recent advancements in NAFLD treatment
ratios (HRs) and 95% confidence intervals (CIs) for the associations
have introduced drugs with various mechanisms and most drugs
of different CVH scores with all-cause mortality in participants with
targeting body-weight lowering and glycemic control had strong
MASLD. Population-attributable fraction (PAF) estimates were used to
effects in reducing hepatic fat content. However, it remains unclear
determine the proportion of all-cause mortality that could be prevented
whether reducing liver fat alone could directly affect blood glucose
by improving the health behaviors CVH score.
levels.
Result: Among 11,988 participants, 4,109 participants (34.3%) were
Method: This meta-analysis aimed to investigate the effect of drugs
classified as having MASLD. During the median 7.8 years follow-up,
targeting hepatic steatosis on glucose levels. We selected drugs
912 deaths were recorded. Unexpectedly, the total LE8 CVH score
based on the following criteria: (1) primarily targeting the liver with all-cause mortality in US adults with MASLD, particularly below the
minimal effects on other organs, and (2) having reached at least phase threshold of 1.669 µg/dL. These findings underscore the need to
2 trials demonstrating efficacy in reducing hepatic fat in patients with minimize lead exposure in vulnerable populations with MASLD.
NAFLD. A systematic literature search was conducted in PubMed, Table and Figure:Figure 1.Linear relationship between blood lead and
Embase and Clinical Trial.gov to identify relevant randomized clinical all-cause mortality in patients with MASLD
trials involving the selected drugs published up to July 2024. The Figure 2.Threshold effect analysis of blood lead on all-cause mortality
primary outcomes were changes in the mean values of blood glucose in patients with MASLD
and glycated hemoglobin (HbA1c) levels between treatment and
placebo groups. The risk of bias assessment in all included studies
PP0468
was performed using the Cochrane Risk of Bias version 2 (RoB2).
Meta-regression analysis was conducted to examine the relationship Semaglutide reduced hepatic steatosis assessed by ultrasound-
between liver fat reduction and glucose decrease. derived fat fraction in metabolic dysfunction-associated steatotic
Result: There were 14 eligible studies with 2513 patients. The average liver disease patients
study duration was 27 weeks. There were no significant differences in Yunlin Huang1, Yi Dong1, Ying Wang1, Li Wei1, Rui Cheng1, Juan
fasting blood glucose (SMD: -0.09, 95% CI: -0.18 to 0.01) or HbA1c Cheng1, Yijie Qiu1
levels (SMD: -0.26, 95% CI: -0.63 to 0.12) between drug-treated 1
Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai
patients and controls. Additionally, no notable improvements were Jiao Tong University School of Medicine, Shanghai, 200092, China
observed in insulin levels (SMD: 0.04, 95% CI: -0.06 to 0.13), HOMA- Background: To investigate the effects of ultrasound-derived fat
IR (SMD: -0.05, 95% CI: -0.15 to 0.05), or ALT levels (SMD: -0.21, 95% fraction (UDFF) for monitoring semaglutide treatment response in
CI: -0.45 to 0.04).Body weight (SMD = -0.32, 95% CI: -0.49, -0.14) metabolic dysfunction-associated steatotic liver disease (MASLD)
and AST levels (SMD = -0.26, 95% CI: -0.49, -0.01) were significantly patients.
decreased in the treatment group compared to the placebo group. Method: In this prospective study, patients with MASLD were enrolled.
Meta-regression analysis revealed no statistically significant linear All patients received 0.5 mg of once-weekly subcutaneous semaglutide
relationship between liver fat reduction and changes in blood glucose treatment. At baseline and follow-up (more than 14 weeks of therapy),
or HbA1c levels (n=8). UDFF measurements (Acuson Sequoia ultrasound system [Siemens
Conclusion: These findings suggest that hepatic-targeting drugs Healthineers], equipped with a DAX transducer [1.0 – 5.7 MHz]) and
have minimal impact on systemic metabolic status, highlighting the body composition assessment (InBody 770 device [BioSpace]) were
intrinsic link between hepatic fat and blood glucose in NAFLD. This performed; clinical and laboratory data were also recorded.
underscores the need for comprehensive therapeutic strategies that Result: From July 2023 to June 2024, 22 patients were included. The
address both hepatic and systemic metabolic dysfunction in NAFLD patients were mainly female (77.3 % [17/22]), with a median age of 36
management. Further studies with larger sample sizes and longer years (interquartile range [IQR]: 31.5, 41.0) and a median body mass
durations are needed to explore this relationship in more depth. index (BMI) of 31.4 kg/m2 (IQR: 28.9, 35.8). Semaglutide treatment led
Table and Figure:Figure 1.Forest plot of the effects of liver targeted to a mean change in waist-hip ratio, waist circumference, body weight,
drugs on blood glucose. BMI, percent body fat, and visceral fat area were -4.1 %, -7.4 %, -7.8
Figure 2.Forest plot of the effects of liver targeted drugs on glycosylated %, -8.5 %, -10.9 %, and -17.7 %, respectively. However, no significant
hemoglobin (HbA1c) levels. changes were found between baseline and follow-up (all P > 0.05).
UDFF measurements yielded valid measurements in all patients at
PP0467 baseline and follow-up. Semaglutide induced a significant reduction
in UDFF values at follow-up (9.4 %, IQR: 5.0, 12.3) compared with the
Association of blood lead concentrations and all-cause mortality
baseline (21.8 %, IQR: 9.3, 24.5) (P = 0.001). At baseline, UDFF values
in US adults with MASLD: a prospective cohort study
were positively correlated with weight, waist circumference, γ-glutamyl
Jinhan Zhao1,2, Jing Zhang1, Yang Zhang2, Xiaodie Wei1 transpeptidase (GGT), fasting plasma glucose (FPG), BMI, aspartate
1
The Third Unit, Department of Hepatology, Beijing Youan Hospital, aminotransferase (AST), visceral fat area, alanine aminotransferase
Capital Medical University, 2Beijing Institute of Hepatology (ALT), hemoglobin A1c (HbA1c), and hepatic steatosis index (HSI) (P
Background: Metabolic dysfunction-associated steatotic liver disease < 0.05). At follow-up, UDFF values were positively correlated with BMI,
(MASLD) is a major public health issue, particularly among individuals weight, waist circumference, visceral fat area, insulin, waist-hip ratio,
exposed to environmental toxins. Limited epidemiological evidence C-Peptide, and HSI (P < 0.05).
exists on the relationship between lead exposure and mortality in Conclusion: Repeating UDFF measurement enables hepatic steatosis
MASLD populations. This study aimed to examine the association assessment to semaglutide treatment response in MASLD patients.
between blood lead concentrations and all-cause mortality in US Table and Figure:Figure 1.The flowchart of the population
adults with MASLD using a prospective cohort design. Figure 2.Ultrasound-derived fat fraction (UDFF) values (b) at baseline
Method: A total of 2,879 MASLD patients were analyzed. Blood lead and follow-up
levels were categorized into quartiles, and all-cause mortality served
as the primary outcome. Hazard ratios (HRs) were calculated using
PP0469
Cox proportional hazards models, adjusting for demographic factors,
health behaviors, and comorbidities. Restricted cubic spline models The Relationship Between Quantitative Fibrosis Parameters and
evaluated nonlinear associations, and threshold effect analyses Non-Invasive Fibrosis Tests in MASLD
identified critical turning points in blood lead levels. Xiaodie Wei1, Jing Zhang1, Chen Shao2, Qiang Yang3, Shi Qi4, Jinhan
Result: During a median follow-up of 93 months, 398 deaths were Zhao1, Jing Zhao5
recorded. Patients in the highest blood lead quartile had significantly 1
The Third Unit, Department of Hepatology, Beijing Youan Hospital,
reduced survival rates ( P < 0.05). Higher blood lead levels were Capital Medical University, 2Department of Pathology, Beijing Youan
associated with increased mortality risk, showing a dose-response Hospital, Capital Medical University, 3Hangzhou Choutu Technology
relationship ( P for trend = 0.004). A significant nonlinear relationship Co., Ltd, 4BEIJING FENGTAI HOSPITAL, 5Department of Radiology,
was observed ( P < 0.001), with a critical threshold of 1.669 µg/dL. Beijing Youan Hospital, Capital Medical University
Below this threshold, blood lead levels were strongly associated with Background: Fibrosis stage is crucial for the prognosis of patients with
increased mortality risk (HR: 2.722, 95% CI: 1.814–4.084), whereas metabolic dysfunction-associated steatotic liver disease (MASLD).
above the threshold, the association weakened (HR: 1.166, 95% CI: Dual-photon microscopy offers an automated, quantitative analysis
1.024–1.327). Subgroup analyses indicated that blood lead levels of fibrosis by quantifying collagen fiber structures. As noninvasive
were significantly linked to mortality in Mexican Americans, individuals tests are necessary to monitor histological changes, this study aimed
with BMI >30 kg/m², and hypertensive patients. to explore the relationship between quantitative fibrosis parameters
Conclusion: Blood lead concentration is positively associated with (q-FPs) and noninvasive liver fibrosis scores.
Method: This study involved 99 patients with MASLD, who underwent significant threat to human health. It is anticipated to become a major
liver biopsy, second-harmonic generation/two-photon excitation burden in the realm of liver diseases. MAFLD has the potential to
fluorescence microscopy (SHG/TPEF), magnetic resonance progress to more severe conditions such as hepatitis, liver fibrosis,
elastography (MRE), and vibration-controlled transient elastography and cirrhosis; In the initial stages of MAFLD, particularly when the
(VCTE). The diagnostic accuracy of q-FPs for determining fibrosis condition is characterized solely by steatosis and not accompanied by
stages was assessed using the METAVIR fibrosis staging system as severe fibrosis, it appears that disease progression may be mitigated
the gold standard. Additionally, the correlation between noninvasive or even partially reversed through lifestyle modifications and weight
fibrosis scores and q-FPs was analyzed. loss. Therefore, the accurate and straightforward identification of early-
Result: The area under the receiver operating characteristic curve stage MAFLD is of considerable importance.
(AUC) for q-FP values across fibrosis stages ranged from 0.924 to Method: Data from the Department of Endocrinology at Jiangsu
0.967. Notably, the parameters strwidth and strlength showed the Provincial Hospital of Traditional Chinese Medicine, covering the
strongest association with fibrosis. Among the eight noninvasive tests, period from January 1, 2022, to December 31, 2022, were collected.
MRE exhibited the highest correlation with q-FP values, particularly in The parameters from Fiberscan equipment were utilized as the gold
the periportal (PT) and perisinusoidal (PeriPT) areas. MRE was closely standard, with early MAFLD defined by a controlled attenuation
related to strlength, strwidth, and the number of longstr in the PT region. parameter (CAP) of ≥ 244 dB/m and a liver stiffness measurement
Conclusion: q-FPs provide a highly accurate method for diagnosing (LSM) of ≤ 10 kPa. R programming language were used to build
liver fibrosis stages in MASLD, and MRE showed a significant nomogram.
correlation with q-FPs. Result: In the context of training and validation, it was observed that
Table and Figure:Figure 1.Diagnostic performance of qFibrosis and 71.2% and 73.2% of the population exhibited early stages of MAFLD.
NITs for liver fibrosis Through rigorous statistical analysis and consideration of clinical
Figure 2.The correlation between eight noninvasive markers and all significance, eight clinically relevant variables were initially identified:
parameters of qFibrosis age, type 2 diabetes mellitus, metabolic risk factors, hemoglobin
(Hb), alanine aminotransferase (ALT), serum cholesterol (TG),
serum triglycerides (TC), and serum high-density lipoprotein (HDL).
PP0470
Nomogram was subsequently constructed, achieving an area under
Focus on cardiometabolic risk factors on the risk of cholelithiasis the curve (AUC) of 0.847 (ranging from 0.8104 to 0.8838)
in patients with MASLD However, considering the heterogeneity of MAFLD, upon incorporating
YuanYing Zhao1,2, TianYuan Yang3, Qi Wang3,4, Yue Li1,4 the overall bioelectrical impedance parameters (InBody), the analysis
1
Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, revealed an additional four indicators associated with early MAFLD:
Beijing, China., 2Capital Medical University, Beijing, China., 3Center body mass index (BMI), waist-to-hip ratio (WHR), visceral fat area
of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, (VFA), and skeletal muscle index (SMI). Ultimately, we integrated the
Beijing, China., 4Beijing Key Laboratory of Emerging Infectious aforementioned eight easily obtainable variables with the four body
Diseases, Institute of infectious diseases, Beijing Ditan Hospital, composition indicators to reformulate the array, resulting in an AUC
Capital Medical University, Beijing, China. of 0.893 (ranging from 0.8625 to 0.9242), which exhibited excellent
Background: Cholelithiasis is one of the common extrahepatic predictive performance in the validation set.
comorbidities. At present, the relationship between metabolic Conclusion: Lifestyle modifications and weight reduction have the
dysfunction-associated steatotic liver disease and the prevalence of potential to mitigate and even reverse early stages of MAFLD to a
cholelithiasis is rarely investigated. Therefore, we aimed to investigate certain degree. Following a comprehensive screening and analysis
the impact of metabolic dysfunction-associated steatotic liver disease of early MAFLD patients. The first array comprises only eight easily
and its cardiometabolic risk factors on the development of cholelithiasis. obtainable variables, thereby facilitating straightforward identification
Method: Data from the cycle NHANES 2017-2020 were used to analyze of early MAFLD. The second array builds upon the first by incorporating
the relationship between the prevalence of cholelithiasis in the non- additional body composition parameters, thereby improving the
alcoholic fatty liver disease population and the metabolic dysfunction- accuracy of the predictive model.
associated steatotic liver disease population. Subgroup analyses and Table and Figure:Figure 1.Nomgram 1
weighted multifactorial regression analyses were used to examine the Figure 2.Nomgram 2
relationship between different subgroups of the population and the
prevalence of cholelithiasis in patients with metabolic dysfunction- PP0472
associated steatotic liver disease.
Result: The difference in the prevalence of cholelithiasis between Application of IMB Model-Based Self-Management Interventions
patients with metabolic dysfunction-associated steatotic liver disease in Non-Alcoholic Fatty Liver Disease
after the name change and patients with non-alcoholic fatty liver Run Zhou1, Wei Zhang2, Ting Ting Kong1, Jie Fu1, Lan Chun Liu1, Jie
disease was not statistically significant. There were differences Li3, Ping Jun Shi4
in the prevalence of cholelithiasis between subgroups of patients 1
School of Nursing, Hangzhou Normal University, Hangzhou,
with different cardiometabolic risk factors. And in After adjustment, Zhejiang, China, 2Department of Teaching, The Affiliated Hospital
hypertension (OR: 1.41, 95% CI: 1.02-1.94), dyslipidemia (OR: 1.41, of Hangzhou Normal University, Hangzhou, Zhejiang, China,
95% CI: 1.08-1.84) and diabetes (OR: 1.81, 95% CI: 1.24-2.64) were
3
Department of Infectious Diseases, Nanjing Drum Tower Hospital,
risk factors for the prevalence of cholelithiasis. Affiliated Hospital of Medical School, Nanjing University, Nanjing,
Conclusion: Attention to different cardiometabolic risk factors is Jiangsu, China, 4The Department of Infectious disease and
important for the prevention of cholelithiasis in patients with metabolic Hepatology, the Affiliated Hospital & Institute of Hepatology and
dysfunction-associated steatotic liver disease. Metabolic Disease, Hangzhou Normal University, Hangzhou,
Zhejiang, China
Background: Non-alcoholic fatty liver disease (NAFLD) is the
PP0471 most common chronic liver disease, affecting 32.4% of the global
Single machine nomogram for risk estimation of early Metabolic population. It is a metabolic disorder linked to insulin resistance and
dysfunction-Associated Fatty Liver Disease (MAFLD)) genetic predisposition, characterized by hepatic fat accumulation
Tiansu Lv1,2, Xiqiao Zhou1,2 without significant alcohol intake. Its progression, from simple steatosis
1
Department of Endocrinology, Jiangsu Province Hospital of Chinese to cirrhosis and hepatocellular carcinoma (HCC), involves metabolic
Medicine, Afffliated Hospital of Nanjing University of Chinese imbalances, inflammation, and fibrosis, leading to complications
Medicine, Nanjing, China, 2The First Clinical Medical College of such as cardiovascular disease and type 2 diabetes, along with
Nanjing University of Chinese Medicine, Nanjing, China rising healthcare costs. NAFLD also impacts quality of life, causing
Background: MAFLD is a chronic liver condition that poses a fatigue, emotional distress, and abdominal discomfort. However, self-
management is often hindered by low disease awareness, lack of Conclusion: Several new drugs currently in clinical trials have shown
motivation, and insufficient skills for lifestyle changes. The Information- potential therapeutic effects for fibrosis improvement in MAFLD
Motivation-Behavioral Skills (IMB) model offers a structured approach patients, especially those targeting Fibroblast growth factor 21(FGF21).
to enhance self-management, helping patients make sustainable More definitive efficacy will depend on the results of Phase III clinical
lifestyle changes. This study evaluates the effectiveness of an IMB trials. This study may assist clinicians in therapy selection and support
model-based self-management intervention, aiming to address gaps future clinical trial designs.
in NAFLD care and improve clinical and psychosocial outcomes.
Method: This study evaluated an IMB model-based self-management
PP0474
intervention for NAFLD patients. A total of 126 patients were randomized
into an intervention group (n=63) or control group (n=63). The control Risk stratification for patients with MASLD based on
group received standard care, while the intervention group participated cardiometabolic risk factors
in an IMB-based program to enhance knowledge, motivation, and Yiheng Zhang1, Yan Wang1, Tao Li, Yundong Qu
skills. Outcomes, including self-management, self-efficacy, quality of 1
the second hospital of shandong university
life, and clinical parameters, were assessed at baseline and 12 weeks. Background: There is a lack of evidence regarding the mortality risk
Data were analyzed using SPSS 26.0 with statistical tests for group associated with cardiometabolic risk factors (CMRFs) in patients with
comparisons. metabolic dysfunction-associated steatotic liver disease (MASLD). We
Result: This study assessed the effectiveness of an IMB model- explored the association of mortality with CMRFs and developed a
based self-management program for NAFLD patients. Of 126 enrolled practical risk stratification method for MASLD patients.
participants, 16 withdrew, leaving 110 for analysis (intervention: Method: MASLD patients from the National Health and Nutrition
n=56; control: n=54). After 12 weeks, within-group analysis showed Examination Survey (NHANES III) database were included as the
significant improvements in self-management, self-efficacy, health- evaluation cohort, while the validation cohort was based on NHANES
related quality of life, waist circumference, skeletal muscle mass, CAP, 2003-2018. The observational endpoints of the current study were all-
ALT, AST, HDL-C, and LDL-C. Between-group comparisons revealed cause and cardiac-specific mortality. Univariate and multivariate Cox
greater improvements in self-management, self-efficacy, quality of life, proportional hazards regression models were employed to investigate
BMI, hip circumference, and LDL-C in the intervention group (P < 0.05). the association of CMRFs with long-term mortality.
Conclusion: The IMB model-based self-management intervention Result: A total of 3,545 MASLD patients were included in the evaluation
effectively improved clinical outcomes in NAFLD patients. These cohort. During a median follow-up period of 26 years, 1,344 subjects
findings highlight the value of theory-driven, structured approaches died, of which 347 were due to cardiac-specific causes. Multivariate
in addressing NAFLD’s challenges. Integrating behavioral and Cox regression models revealed elevated glucose and hypertension as
motivational components is crucial for sustainable self-management significant predictors for both all-cause and cardiac-specific mortality.
strategies. Future research should explore digital and remote platforms Based on the type and number of CMRFs, we stratified the MASLD
to enhance accessibility and scalability, ensuring more comprehensive patients into three risk groups. After risk stratification, the cumulative
care. Long-term studies are needed to confirm the durability and incidence of all-cause and cardiac-specific mortality at 20 years was
broader application of these interventions. 11.5% and 2.6% in low-risk group, 25.5% and 9.3% in medium-risk
Table and Figure:Figure 1.Promoting Physical and Mental Health in group, and 44.2% and 16.0% in high-risk group, respectively. Sensitivity
NAFLD Patients: An Intervention Based on the IMB Skills Model analysis and the validation cohort reached similar conclusions.
Conclusion: Based on the type and number of CMRFs, we developed
PP0473 a practical risk stratification method for MASLD patients, enabling
clinicians to identify patients at higher mortality risk and tailor follow-up
Comparative efficacy of pharmacologic therapies for MAFLD in
and intervention plans accordingly.
improving fibrosis: Systematic review and network meta-analysis
Table and Figure:Figure 1. Kaplan-Meier survival curves for all-cause
Xiao Han1, Xiaowei Ai, Yameng Sun, Shuyan Chen, Xinyu Zhao,
mortality in the (A) evaluation cohort, (B) sensitivity analysis and (C)
Hong You
validation cohort and cardiac-specific mortality in the (D) evaluation
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical cohort, (E) sensitivity analysis and (F) validation cohort.
University, State Key Lab of Digestive Health, National Clinical Figure 2.Risk stratification according to the type and number of CMRFs
Research Center of Digestive Diseases, Beijing Key Laboratory of for MASLD.
Translational Medicine on Liver Cirrhosis, No. 95 Yong-an Road,
Beijing, 100050, China.
Background: Fibrosis is a key predictor of the long-term prognosis PP0475
in metabolic dysfunction-associated with fatty liver disease (MAFLD). Associations between Skeletal Muscle Strength and Chronic
Numerous clinical trials in drug development for MAFLD have used Kidney Disease in Patients with MAFLD: a large-scale study
fibrosis improvement as an efficacy endpoint. We aim to compare the involving four separate cohorts
efficacy of pharmacologic therapies for MAFLD in improving fibrosis Xinlei Zhang1, Yeqing Gu2, Jing Zhao3, Peiwu Zhu4, Wenying Chen1,
using histopathological and noninvasive assessments. Gang Li1, Wenyue Li5, Wen Zheng1, Ni Zhang1, Lili Chen1, Giovanni
Method: A comprehensive search for randomized controlled trials Targher6, Christopher D Byrne7, Kaijun Niu8, Danqin Sun3, Minghua
(RCTs) was conducted across multiple databases, focusing on drug Zheng1
therapy in adult patients with MAFLD. The primary outcome was 1
MAFLD Research Center, Department of Hepatology, the First
1-stage fibrosis improvement. The secondary outcomes included Affiliated Hospital of Wenzhou Medical University, 2Institute of
changes in liver stiffness measurement (LSM) via vibration-controlled Radiation Medicine, Chinese Academy of Medical Sciences & Peking
transient elastography (VCTE) and magnetic resonance elastography Union Medical College, 3Urologic Nephrology Center, Jiangnan
(MRE). Each intervention’s ranking probability was assessed using the University Medical Center, 4Department of Laboratory Medicine, The
surface under the cumulative ranking curve (SUCRA). First Affiliated Hospital of Wenzhou Medical University, 5Department
Result: Fouty-eight RCTs involving 10,119 participants were included. of Endocrinology, The First Affiliated Hospital of Wenzhou Medical
For the primary outcome, Obeticholic acid (OCA) was superior to University, 6Department of Medicine, University of Verona, Verona,
placebo in the 1.5-year analysis. In the F1-3 analysis, Pegozafermin,
7
Southampton National Institute for Health and Care Research,
OCA, and Resmetirom all outperformed placebo. OCA at 1.5-year Biomedical Research Centre, University Hospital Southampton
(SUCRA 81.64%), Pegbelfermin (SUCRA 77.11%), and Pegozafermin and University of Southampton, Southampton General Hospital,
(SUCRA 74.91%) at F1-3 were ranked as the most effective treatments. Southampton, 8School of Public Health of Tianjin University of
For the secondary outcome, Pegozafermin significantly outperformed Traditional Chinese Medicine
placebo for decreasing LSM via VCTE in 0.5-year analysis, ranking as Background: A decline in skeletal muscle strength (SMS) is closely
the most effective treatment for this outcome (SUCRA 96.98%). associated with metabolic diseases, but whether SMS declines
with chronic kidney disease (CKD) in individuals with metabolic was assessed by change in estimated glomerular filtration rate (eGFR).
dysfunction-associated fatty liver disease (MAFLD) is uncertain. This Result: In patients with MASLD, the eGFR decline in the QLF+ group
study examined the cross-sectional and longitudinal associations was greater than that in the QLF- group. In addition, liver fibrosis
between SMS and risk of CKD in MAFLD population changes in the central vein and peri-central regions were more
Method: We performed a large-scale study with four cohorts, including strongly associated with eGFR decline than in peri-portal, zone 2 and
14,079 participants. The PERSONS and NHANES 2011-2014 cohorts portal tract regions. We combined these parameters to construct a
were used for the cross-sectional investigation, and the TCLSIH and prediction model, which better differentiated eGFR decline [training
UK Biobank cohorts were used for the longitudinal investigation. A AUROC=0.87 (95% CI: 0.77, 0.95), validation AUROC=0.82 (0.69,
handgrip dynamometer measured handgrip strength as a proxy for 0.91), p<0.001].
overall SMS. Subjects were stratified according to CKD status [non- Conclusion: A decline in renal function is significantly related to
CKD or CKD (stages 1-5)] liver fibrosis progression in MASLD. Regional qFibrosis assessment
Result: The CKD group had a lower handgrip strength than the non- can efficiently predict eGFR decline, highlighting the importance of
CKD group (27.14 ± 9.19 vs. 33.59 ± 11.92 kg, P<0.05) in the PERSONS assessing renal function in patients with worsening liver fibrosis.
cohort. Higher handgrip strength was associated with lower odds of Table and Figure:Figure 1.Digital assessment of liver fibrosis and
abnormal albuminuria or CKD (OR: 0.96 and 0.95, respectively). The quantified fibrosis parameters in different liver regions demonstrated
highest handgrip strength tertile was associated with the lowest risk changes in fibrosis
of having abnormal albuminuria or CKD (compared with the lowest or
middle tertile). Results were similar in the NHANES cohort. Furthermore,
PP0477
the highest handgrip strength was an independent protective factor for
incident CKD in MAFLD (HR: 0.95 and 0.99 in TCLSIH and UK Biobank Lower Plasma Lipoprotein(a) Threshold in MASLD Patients with
cohorts). In Kaplan-Meier curve analysis, the cumulative incidence of Advanced Fibrosis
CKD was lowest in the highest handgrip strength tertile compared to Tie Xiao1, Huihui Liu2, Na Tian1, Liyou Lian1, Kaiwen Miao1, Yuting
the lowest or the middle tertile Li1, Lili Chen1, Haiyang Yuan1, Mulong Du3, Shanshan Wu4, Giovanni
Conclusion: Higher handgrip/muscle strength is independently Targher5,6, Christopher D Byrne7, Michael D Shapiro8, Gregory YH
associated with a lower risk of abnormal albuminuria and CKD in Lip9,10, Xiaodong Zhou11, Jianjun Li2, Minghua Zheng1,12,13
MAFLD patients 1
MASLD Research Center, Department of Hepatology, the First
Table and Figure:Figure 1.Associations between handgrip strength Affiliated Hospital of Wenzhou Medical University, Wenzhou, China,
and the risk of abnormal albuminuria in cross-sectional analyses
2
Department of Cardiology, Cardiometabolic Center, State Key
Figure 2.Kaplan-Meier curves for the analysis between handgrip Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National
strength and the risk of developing incident CKD in MAFLD Center for Cardiovascular Diseases, Chinese Academy of Medical
Sciences and Peking Union Medical College, Beijing, China,
3
Department of Biostatistics, Center for Global Health, School
PP0476 of Public Health, Nanjing Medical University, Nanjing, China,
Regional liver fibrosis progression analyzed by digital pathology 4
Department of Gastroenterology, Beijing Friendship Hospital, Capital
with artificial intelligence is associated with renal function decline Medical University; State Key Laboratory for Digestive Health;
Danqin Sun1, Jiaqi Shen1, Xiaofei Tong2, Yayun Ren3, Haiyang Yuan4, National Clinical Research Center for Digestive Diseases, Beijing,
Yangyang Li5, Xinlei Wang3, Suidan Chen5, Peiwu Zhu4, Xiaodong China, 5Department of Medicine, University of Verona, Verona, Italy,
Wang6, Christopher D Byrne7, Giovanni Targher8, Lai Wei9, Vincent
6
Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don
Calabria Hospital, Negrar di Valpolicella, Italy, 7Southampton National
WS Wong10, Dean Tai3, Arun J Sanyal11, You Hong2, Minghua Zheng4
Institute for Health and Care Research Biomedical Research Centre,
1
Department of Nephrology, Jiangnan University Medical Center, University Hospital Southampton, and University of Southampton,
2
Liver Research Center, Beijing Friendship Hospital, Beijing Key Southampton General Hospital, Southampton, UK, 8Center for
Laboratory of Translational Medicine on Liver Cirrhosis, National Prevention of Cardiovascular Disease, Section on Cardiovascular
Clinical Research Center of Digestive Diseases, Capital Medical Medicine, Wake Forest University School of Medicine, Winston-Salem,
University, 3HistoIndex Pte Ltd, Singapore, 4MAFLD Research Center, NC, US, 9Liverpool Centre for Cardiovascular Science at University
Department of Hepatology, the First Affiliated Hospiof Wenzhou of Liverpool, Liverpool John Moores University and Liverpool Heart
Medical University, 5Department of Pathology, The First Affiliated & Chest Hospital, Liverpool, United Kingdom, 10Danish Center for
Hospital of Wenzhou Medical University, 6Key Laboratory of Diagnosis Health Services Research, Department of Clinical Medicine, Aalborg
and Treatment for the Development of Chronic Liver Disease in University, Aalborg, Denmark, 11Department of Cardiovascular
Zhejiang Province, 7Southampton National Institute for Health and Medicine, the Heart Center, the First Affiliated Hospital of Wenzhou
Care Research Biomedical Research Centre, University Hospital Medical University, Wenzhou, China, 12Institute of Hepatology,
Southampton and University of Southampton, Southampton General Wenzhou Medical University, Wenzhou, China, 13Key Laboratory
Hospital, Southampton, 8Department of Medicine, University of of Diagnosis and Treatment for the Development of Chronic Liver
Verona, 9Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Disease in Zhejiang Province, Wenzhou, China
Hospital, Tsinghua University, 10Department of Medicine and
Therapeutics, Chinese University of Hong Kong, Hong Kong Special Background: Whether Lp(a) is associated with increased
Administrative Region, 11Stravitz-Sanyal Institute for Liver Disease cardiovascular risk in metabolic dysfunction-associated steatotic
and Metabolic Health, Virginia Commonwealth University School of liver disease (MASLD) patients is unknown. We aimed to investigate
Medicine, Richmond the association between plasma Lp(a) levels and major adverse
cardiovascular events (MACE) in MASLD patients.
Background: The relationship between biopsy-proven liver fibrosis
Method: In this retrospective study, We enrolled 55,357 Chinese
progression and renal function decline in patients with metabolic
patients with ultrasound-defined MASLD from Wenzhou and 4,130
dysfunction-associated steatotic liver disease (MASLD) has not been
patients with MASLD from Beijing. MACEs were defined as incident
fully elucidated. We used an automated quantitative liver fibrosis
nonfatal myocardial infarction, nonfatal ischemic stroke and all-cause
assessment (qFibrosis) to investigate changes in regional liver fibrosis.
mortality. Lp(a) percentile groups were generated with the reference
Method: This longitudinal study included formalin-fixed sections from
group set at the 1st to 50th Lp(a) percentiles. Cox proportional hazards
136 paired liver biopsy slides. A total of 184 fibrosis parameters were
modeling was used to assess the
quantified in five different liver regions, including portal tract, peri-
association between the Lp(a) percentile groups and MACE. Advanced
portal, zone 2, peri-central and central vein regions, and qFibrosis
liver fibrosis was defined as fibrosis (FIB)-4 index >2.67.
continuous values were generated for all samples based on 10 fibrosis
Result: Overall, 59,487 patients with MASLD (mean age 60.9, SD 12.3;
parameters using qFibrosis assessment. Liver fibrosis progression
44.8% female) were analyzed with a median follow-up of 4.8 years
(QLF+) and regression (QLF-) was defined as at least a 20% relative
(IQR: 2.0-8.3 years), and 8,631 patients had incident MACE morbidity
change in qFibrosis over 23-month follow-up. Renal function decline
or mortality. There was a significant inverse association between Lp(a)
percentiles and advanced liver fibrosis. In patients with advanced liver pathology suggested early cirrhosis after necrosis and liver cells
fibrosis, there was a lower proportion (3.2% lower) in the 91st-100th showed large vesicular steatosis. Although the patient’s diagnosis of
percentile group of Lp(a) NAFLD-related cirrhosis and Gilbert was clear, unfortunately he was
concentration (chi-squared test P <0.001), although the incidence of unable to adjust their BMI. Three years later, the patient experienced
MACE remained high. MASLD patients with advanced liver fibrosis upper gastrointestinal bleeding again, accompanied by congenital non
and high Lp(a) levels (71st to 90th percentile) had a significantly higher hemolytic jaundice. Symptomatic hemostasis was given to stabilize
risk of MACEs (adjusted HR: 1.37, 95%CI 1.20-1.57; P <0.001) than the condition. Currently, the patient is receiving oral treatment with
those with low Lp(a) levels (1st to 50th percentile). In MASLD patients phenobarbital and carvedilol, as well as lifestyle improvement therapy.
without advanced liver fibrosis, those with high Lp(a) levels (71st to There has been no further gastrointestinal bleeding.
90th percentile) had a significantly higher risk of MACEs (adjusted CONCLUSION
HR: 1.25, 95%CI 1.18-1.32; P <0.001) than those with low Lp(a) levels The diagnosis of NAFLD-related cirrhosis in adolescents is relatively
(1st to 50th percentile).when considering the same HR, patients with rare and difficult, and its characteristics and prognosis are different
advanced liver fibrosis had lower Lp(a) levels. These results were also from those of adults. Improving lifestyle and weight loss are treatment
found in sensitivity analysis. options, nevertheless there are still some individuals who require liver
Conclusion: The plasma Lp(a) levels associated with increased CVD transplantation.
risk were lower for MASLD patients according to the presence of
advanced liver fibrosis.
PP0480
Table and Figure:Figure 1.Figure 1
Figure 2.Figure 2 Clinical characteristics of MASLD/MetALD/MAFLD/NAFLD and the
relative risk analysis on metabolic disorders
Hongye Peng1,2, Chunli Lu3,2, Mo Zhao1,2, Xiaoqiang Huang3, Shuxia
PP0478 Huang2, Ziwen Zhuo2, Jing Liu2, Wenliang Lv2
A case of liver disease with complex causes 1
Beijing University of Chinese Medicine, 2Guang’anmen Hospital,
JIE WEN LUO1, RONG YUE ZHANG1 China Academy of Chinese Medical Sciences, 3Guangdong
1
University-Town Hospital of Chongqing Medical University Pharmaceutical University
Objective: To explore the real pathogenic factors and interaction of Background: NAFLD has become the number one chronic liver
liver injury caused by complex causes. The diagnosis and treatment disease worldwide, with a prevalence rate of 32.4%. MAFLD, MASLD,
of chronic viral hepatitis B (CHB) , metabolic associated fatty liver and MetALD are novel concepts proposed in recent years. Our
disease (MAFLD), and autoimmune liver disease (AIH) have been objective was to compare the clinical features of MASLD/MetALD/
reported, but the cases of hepatitis mixed with multiple factors have MAFLD/NAFLD and the relative risk analysis of metabolic disorders
been rarely reported. Patient: A 39-year-old female was found to have (hypertension, T2DM, hyperlipidemia).
abnormal liver function during physical examination. She had a history Method: The NHANES for the 2017–2018 cycle was used to screen
of hepatitis B surface antigen carrying and was complicated with the participants. Multivariate-adjusted logistic regression models were
fatty liver disease. Blood examination in hospital suggested Sjogren’s applied to explore the difference in relative risk analysis between
syndrome. The patient was discharged from the hospital after antiviral NAFLD/MAFLD/MASLD/MetALD and metabolic disorders.
and hepatoprotective treatment. Sjogren’s syndrome was diagnosed Result: 1 Characteristics of the participants
by lip gland biopsy in another hospital, and the patient was treated There were 835 patients with MASLD (44.84%) and 213 with MetALD
regularly for half a year. Subsequently, liver function returned to normal, (11.44%) among the 1,862 participants. Participants with MASLD
but liver function injury occurred again one year after drug withdrawal, had a greater likelihood of being older, having hypertension/T2DM/
and autoimmune liver disease was considered as a complication. hyperlipidemia, and having higher FIPR/BMI/WC/FBG/Hb1Ac/SBP/
Diagnosis: Liver biopsy showed CHB complicated with MAFLD, and TG/HOMA-IR levels than those without it. Compared to participants
AIH was considered in clinical diagnosis and treatment. Results: without MetALD, those with MetALD had a higher likelihood of being
After antiviral therapy and liver protection therapy, the transaminase male, younger, smokers, and having higher BMI/WC/FBG/DBP/TG/
returned to normal. Lessons: When cases of liver function injury are HOMA-IR levels, and lower PIR/education/HDL-C levels. There were
associated with multiple causative factors, careful screening of the 841 individuals with NAFLD (45.17%) and 1,125 with MAFLD (60.42%).
cause and long-term follow-up observation are required. Individuals with NAFLD/MAFLD tended to be older, have hypertension/
T2DM/hyperlipidemia, and have higher BMI/WC/FBG/Hb1Ac/SBP/TG/
HOMA-IR levels.
PP0479
2 The association between MASLD/MetALD/MAFLD/NAFLD and the
A 15-years-old of Gilbert and non-alcoholic fatty liver associated risk of hypertension/T2DM/ hyperlipidemia
cirrhosis with esophagogastric variceal bleeding Positive associations with the risk of hypertension were discovered for
Hua Liu1, Fushuang Ha1, Zhao De Song1, Jun Jun Cai1, Min Hong Lv1 MASLD (OR = 2.892, 95% CI = 2.226–3.756), MetALD (OR = 1.802,
1
The Third Central Hospital of Tianjin 95% CI = 1.355–2.398), MAFLD (OR = 3.455, 95% CI = 2.741–4.354)
BACKGROUND and NAFLD (OR = 1.983, 95% CI = 1.584–2.484). Also, positive
The incidence of non-alcoholic fatty liver disease (NAFLD) in associations with the risk of T2DM were discovered for MASLD (OR
adolescents is on the rise, but it is rare for the progression to cirrhosis = 6.360, 95% CI = 4.440–9.109), MAFLD (OR = 7.026, 95% CI =
with esophagogastric variceal bleeding. 4.893–10.090) and NAFLD (OR = 3.372, 95% CI = 2.511–4.528). We
CASE SUMMARY discovered similar results for hyperlipidemia.
This report was about a 15-year-old teenager with BMI index of 33 3 Relationship of steatosis grade and hypertension/T2DM/
who was admitted due to intermittent tarry stool for 2 months. The hyperlipidemia
clinical laboratory findings showed that hemoglobin 49g/L, GGT69U/L, For MASLD/MAFLD/NAFLD, the degree of liver steatosis was strongly
hepatitis B surface antibodies(+), ANA 1:320, Other etiological and independently correlated with the existence of T2DM in all models.
examinations, tumor markers and hemolysis tests were negative. And Compared to mild steatosis, the moderate to severe steatosis in
ultrasound showed fatty liver, abdominal enhanced CT showed liver patients with MASLD (OR = 3.924, 95% CI = 2.399–6.419), MAFLD
and spleen enlargement, gene testing showed two heterozygous (OR = 3.814, 95% CI = 2.367–6.144), NAFLD (OR = 4.910, 95% CI =
mutations in UGT1A1. After hemostatic treatment, no active bleeding 2.983–8.080) have higher risk for T2DM. However, the grade of liver
was observed. Moreover, gastroscopy showed severe esophagogastric steatosis for MetALD was not associated with the presence of T2DM.
varices. Colonoscopy and capsule endoscopy did not reveal any Conclusion: We found that participants with MASLD or MetALD have
other lesions. To clarify the cause of portal hypertension, transjugular a higher BMI and metabolic level. As the degree of steatosis increases,
liver biopsy was performed. The results were HVPG17mmHg, and patients with MASLD are at progressively higher risk of developing
T2DM. The proposed definitions of MASLD and MetALD are valuable
and deserve further exploration. Our findings suggest that MAFLD is bidirectional Mendelian randomization (MR) was conducted to analyze
a more effective indicator for identifying patients at increased risk for the causal relationships between general obesity (indexed by BMI),
metabolic disorders. central obesity (indexed by WHR), and NAFLD. Multivariable MR was
Table and Figure:Figure 1.Graphical Abstract and Schematic diagram then used to analyze the synergistic effects of general obesity, central
of the relationship between MASLD, MetALD, MAFLD and NAFLD obesity, and NAFLD on outcomes, including CVD, cirrhosis, and HCC.
Figure 2. Basic characteristics of participants by MASLD, All causal effects were estimated using inverse variance–weighted
MetALD,NAFLD and MAFLD in NHANES 2017–2018. (IVW) method.
Result: Genetic predisposition to higher BMI (odds ratio (OR) = 2.06,
95% confidence interval (CI) = 1.78–2.38, P = 7.45e-22) and higher
PP0481
WHR (OR = 1.74, 95% CI = 1.48–2.05, P = 1.12e-11) increased the risk
Glycometabolism-based prediction of metabolic associated fatty of NAFLD. Genetically predicted NAFLD was positively associated with
liver disease in patients with type 2 diabetes mellitus higher WHR (beta = 0.05, 95% CI = 0.03–0.08, P = 1.98e-05), but not
Zhenjun Yu1, Mengdie Chen1, Jie Chen1, Yuetao Zhang1, Ping Feng1, with BMI (beta = -0.01, 95% CI = -0.06–0.03, P = 0.486). Multivariable
Xiaosheng Teng1 MR showed that only genetic predisposition to higher WHR increased
1
Taizhou Central Hospital (Taizhou University Hospital) CVD risk (OR = 1.07, 95% CI = 1.05–1.09, P = 1.00e-18), whereas
Background: Metabolic associated fatty liver disease (MAFLD) higher BMI and NAFLD showed no association with CVD. Genetically
stands as one of the most prevalent chronic liver conditions globally, predicted NAFLD was correlated with an increased risk of cirrhosis
particularly among individuals with type 2 diabetes mellitus (T2DM). (OR = 1.33, 95% CI = 1.20–1.46, P = 1.46e-08) and HCC (OR = 1.24,
Its progression is intricately linked to an elevated risk of extrahepatic 95% CI = 1.12–1.40, P = 1.07e-04), while higher BMI and WHR were
comorbidities, underscoring the paramount importance of conducting not associated with liver-related outcomes.
systematic, non-invasive assessments among the T2DM population. Conclusion: Both general obesity and central obesity causally
Method: We screened patients with T2DM from the Metabolic promote the development of NAFLD, while NAFLD causally promotes
Management Center of Taizhou University Hospital and categorized central obesity rather than general obesity. Central obesity is causally
them into MAFLD and non-MAFLD groups based on liver associated with CVD, independent of the presence of NAFLD or
ultrasonography findings. Additionally, we utilized the NHANES data obesity. NAFLD is causally associated with cirrhosis and HCC, and
spanning from 2017 to 2023 as a validation set. General information this association is impacted by neither general obesity nor central
and clinical parameters were gathered to evaluate the association and obesity. These findings highlight the importance of targeting central
predictive value with MAFLD using logistic regression. obesity for preventing CVD, alongside managing NAFLD to reduce
Result: A total of 3,305 patients with T2DM were enrolled in the study, the risk of hepatic outcomes. Tailored interventions addressing central
including 1,074 patients (28.4%) with MAFLD. Notably, patients in the obesity may provide dual benefits in reducing CVD and liver-related
MAFLD group exhibited significantly higher BMI, head, neck, waist, complications, the latter through the indirect improvement of NAFLD.
and hip circumference compared to the non-MAFLD group (p<0.001).
Sugary drinks emerged as an independent risk factor for MAFLD, PP0483
with a trend indicating that increased intake further elevates the
Association between newly consensus defined metabolic
risk of MAFLD (p value for trend <0.001). Among T2DM patients, a
hyperferritinemia criteria and mortality in patients with MAFLD:
notable increase in the OR value for MAFLD was observed as serum
evidence from a nationwide population-based study
C-peptide and glucose levels rose (p<0.01). The MAFLD model based
on glycometabolism (MMBG) demonstrated superior performance in Jia Li1, Jie Zhang1, Chao Sun1
terms of AUC value and DCA curve compared to individual parameters.
1
Tianjin Medical University General Hospital
Furthermore, analysis of NHANES data corroborated the independent Background: Hyperferritinemia is firmly linked to fibrosis, but its
influence of BMI, waist, hip, sugar intake, and hyperglycemia on incremental value on predicting incident hard outcomes remains
MAFLD in diabetic patients. elusive in the context of metabolic dysfunction-associated fatty liver
Conclusion: The sugary drinks served as an independent risk factor disease (MAFLD). We sought to investigate the association between
for the MAFLD in patients with T2DM. A positive correlation existed modified definition and a provisional staging system concerning
between MAFLD and the abnormal glycometabolism, based on which metabolic hyperferritinemia (MHF) and mortality among subjects with
the MMBG model was formulated. The model effectively anticipates the MAFLD.
risk of MAFLD in T2DM, holding significant value in patient evaluation Method: Data from NHANES 1999-2010 and 2015-2018 including
and personalized interventional strategies. 6,286 participants were analyzed. MHF was diagnosed according
Table and Figure:Figure 1.The multi-model logistic regression analysis to increased circulating ferritin levels with concomitant metabolic
for MAFLD exploring consumption of sugary drinks in T2DM. dysfunction, further categorized into distinct stages (stage 0: within
Figure 2.RCS curve analysis between clinical parameters and the OR upper limit of normal; stage 1: female 200-/male 300-550 ng/mL;
value of MAFLD in T2DM. combined stages 2/3: ≥550 ng/mL). Multivariable survey-weighted
Cox model was performed to explore all-cause mortality and cause-
specific mortality between all addressed stages, adjusted for known
PP0482
risk factors.
Bidirectional relationship between obesity and NAFLD and their Result: The proportions of stage 1 and stages 2/3 MHF were 9.3%
Effects on Cardiovascular and Hepatic Outcomes: A Mendelian (585/6286) and 1.9% (121/6286), respectively. MAFLD participants
Randomized Study with aggravated stages exhibited worse survival status during a
Qi Huang1, Linong Ji1, Xiantong Zou1 median follow-up of 46 months (log-rank: P <0.001). Although no
1
Peking University People‘s Hospital significant differences were noted in all-cause mortality, stages 2/3
Background: Non-alcoholic fatty liver disease (NAFLD) and obesity/ of MHF were associated with a higher risk of diabetes mellitus (DM)-
central obesity both increased the risk for cardiovascular disease and specific mortality (hazard ratio [HR] 7.107; 95% CI 1.775, 28.46).
hepatic fibrosis, but how the impact of their inter-relationships on final Furthermore, subgroup analyses implicated a significantly negative
outcomes remains unclear. This study aimed to investigate the causal impact of higher MHF stages on all-cause mortality in non-Hispanic
bidirectional relationship between obesity/central obesity and NAFLD, race, less educational level, BMI ≥30 kg/m2, current drinker, never/
and their effects on cardiovascular and hepatic outcomes. current smoker, comorbid DM and dyslipidemia, where these
Method: We collected phenotypic data on NAFLD, body mass associations were more pronounced in the female (P-interaction
index (BMI), waist-to-hip ratio (WHR), cardiovascular diseases <0.001) and MAFLD participants with FIB-4 index <1.30 (P-interaction
(CVD), cirrhosis, and hepatocellular carcinoma (HCC) from publicly = 0.008). Restricted cubic spline revealed a linear dose-response
available genome-wide association study summary data. Two-sample relationship between circulating ferritin levels and mortality risk.
Conclusion: In this nationwide population-based study, updated
diagnostic and staging criteria concerning MHF were associated with Background: To understand the pathological characteristics
increased risk of DM-specific mortality in the entire populations, and of nonalcoholic fatty liver disease (NAFLD) with normal alanine
all-cause mortality among female and MAFLD participants with less aminotransferase (ALT) levels, and the diagnostic value of FibroScan
advanced fibrosis. and NAFLD fibrosis score (NFS) in patients with normal ALT (NALT)
Table and Figure:Figure 1.Table 1. Survey-weighted Cox proportional levels.
hazards results examining the association of serum ferritin levels with Method: A total of 151 patients with NAFLD who underwent liver
all-cause mortality in population with MAFLD from NHANES 1999-2010 biopsy between August 2006 and December 2021 were enrolled,
and 2015-2018 (follow-up to 2019). Table 2. Survey-weighted Cox including 32 and 119 patients with NALT and elevated ALT (EALT)
proportional hazards results examining the association of serum ferritin levels, respectively. Clinical and pathological data were collected,
levels with cause-specific mortality in population with MAFLD from NFS values were calculated, and the area under the receiver operating
NHANES 1999-2010 and 2015-2018 (follow-up to 2019) characteristic (ROC) curve was used to evaluate the diagnostic effect
Figure 2.Figure 1. Kaplan Meier survival estimates for all-cause of FibroScan and NFS models for liver fibrosis.
mortality in MAFLD with three distinct MHF stages Figure 2. Restricted Result: There were significant differences in ALT, aspartate
cubic spline fitting for the association between circulating ferritin levels aminotransferase (AST), NFS, and liver stiffness measurement (LSM)
and all-cause mortality between the two groups (P<0.05). Nonalcoholic steatohepatitis (NASH)
was scored using two methods. There were 12 cases of NASH in the
PP0484 NALT level group based on the NAFLD activity score (NAS), but only six
cases in the NALT level group were judged by SAF (Steatosis, Activity,
Clinical and pathological features and prognostic analysis of and Fibrosis) score. The two scoring systems showed differences in
progressive liver fibrosis in metabolic dysfunction associated NASH diagnosis (P=0.01). A total of five and 11 cases of severe liver
steatotic liver disease fibrosis were found in the NALT and EALT groups, respectively, and
Liuyi Chang1, Yafen Dong1, Moli Shao1, Zikun Ma2, Xinyan Zhao2 there was a difference in lobular inflammation between the two groups
1
Yuncheng Central Hospital,Gastroenterology Department,Shanxi (P=0.01). The area under the curve (AUC) of NFS in the NALT and
Medical University,YunCheng,044000,China, 2Beijing Friendship EALT groups was 0.685 and 0.865 (all P <0.05), respectively. AUC of
Hospital, Capital Medical University LSM in the NALT and EALT groups was 0.873 and 0.826 (all P <0.05),
Background: To compare the clinical and pathological features as well respectively. The AUC was statistically significant NFS compared with
as the clinical outcomes of patients with advanced liver fibrosis (F3) LSM in the NALT group (P=0.038).
and cirrhosis (F4) due to Metabolic Dysfunction-Associated Steatotic Conclusion: NAFLD with NALT still has a high proportion of NASH and
Liver Disease (MASLD). progressive liver fibrosis. FibroScan has a better diagnostic value for
Method: A retrospective study included 65 patients with MASLD fibrosis in the NALT level with NAFLD.
advanced liver fibrosis diagnosed by liver biopsy, divided into Table and Figure:Figure 1.Case screening flow chart.
two groups, F3 and F4, to compare the differences in clinical and Figure 2.Comparison of the diagnostic value of NFS and LSM in NAFLD
pathological features and outcomes between the two groups. A Cox with different ALT levels
regression model was used to analyze the influencing factors of
decompensation in cirrhosis for patients with advanced liver fibrosis. PP0486
Result: In terms of clinical characteristics, there were no statistical
Longitudinal changes in alanine aminotransferase (ALT) enhance
differences between F3 and F4 stages in gender, age, body mass
risk assessment for liver-related events in patients with type 2
index, and comorbidities (P>0.05); Prothrombin activity and ferritin in
diabetes (T2D) with different ALT levels at diagnosis
F4 patients were lower than those in F3 (P<0.05), while International
Normalized Ratio (INR) and Liver Stiffness Measurement (LSM) were Nana Peng1,2,3, Sherlot Juan Song1,2,3, Mary Yue Wang1,2,3, Jimmy CT
higher in F4 than in F3 (P<0.05). In terms of pathological characteristics, Lai1,2,3, Grace LH Wong1,2,3, Vincent WS Wong1,2,3, Terry CF Yip1,2,3
there was no statistical significance in the extent of steatosis and the
1
Medical Data Analytics Centre, 2Department of Medicine and
degree of ballooning degeneration between the two groups (P>0.05), Therapeutics, 3Institute of Digestive Disease, The Chinese University
but in F4, the distribution of steatosis was more irregular, the degree of of Hong Kong, Hong Kong SAR, China
lobular inflammation was significantly reduced, while the inflammatory Background: As a routine blood test during regular follow-up, serial
activity in the portal areas, interface hepatitis, and ductular reaction ALT measurements are typically available in patients with T2D. We
significantly increased (P<0.05). In terms of clinical outcomes, there examined whether ALT trajectory adds value beyond ALT level in
were no statistical differences in the occurrence of decompensated identifying patients with T2D who are at risk of liver-related events
cirrhosis, liver cancer, death/transplantation between the two groups including hepatic decompensation, hepatocellular carcinoma, and
(P>0.05). Univariate Cox regression analysis was performed on the liver-related death.
occurrence of decompensated cirrhosis in patients with advanced Method: This was a territory-wide retrospective cohort study of
liver fibrosis, and age, body mass index, fasting blood glucose, patients with T2D from 2000-2016 in Hong Kong. Patients with type 1
γ-glutamyl transferase, and Controlled Attenuation Parameter (CAP) diabetes, chronic viral hepatitis, excessive alcohol use, or liver-related
were selected for multivariate Cox regression analysis. The results events before T2D diagnosis (i.e., baseline), or follow-up <5 years
showed that age and fasting blood glucose were independent risk were excluded. Unsupervised machine learning clustering was used
factors for the occurrence of decompensated cirrhosis in patients with to detect up to 6 distinct trajectories. Distance functions with centroid
advanced liver fibrosis. estimation including Euclidean distance, dynamic time wrapping
Conclusion: There are certain differences in clinical and pathological (DTW) and move-split-merge (MSM) with arithmetic mean, DTW with
characteristics between F3 and F4 stages of MASLD advanced liver DTW barycenter averaging, and MSM with MSM barycenter averaging
fibrosis, but there is no significant difference in clinical outcomes. (MBA) were tested. Cluster validity indices were summarized to select
Patients with advanced liver fibrosis who are younger and have higher the best algorithm and the optimal number of clusters. Association
fasting blood glucose are more likely to develop decompensated between ALT trajectories with liver-related events given different
cirrhosis, which should be given clinical attention. baseline ALT levels were examined using cause-specific hazard
models, with non-liver-related death as competing risk.
PP0485 Result: Among 240,076 patients with T2D (age 61 ± 13 years, 51.3%
males, 1.9% cirrhosis, haemoglobin A1c [HbA1c] 8.0 ± 2.2%, ALT 23
Diagnostic value of FibroScan and nonalcoholic fatty liver [17 - 35] U/L), 2,859 (1.2%) developed liver-related events at a median
fibrosis score in nonalcoholic fatty liver with normal alanine follow-up of 12.0 (9.3 - 15.0) years. MSM-MBA detected 3 distinct ALT
aminotransferase trajectories in the first 5 years after T2D diagnosis: stable (n=149,520
Youwen En Tan1 [62.3%]), increasing (n=54,593 [22.7%]), and decreasing (n=35,963
1
The Third Hospital of Zhenjiang Affiliated Jiangsu University [15.0%]). Similar ALT trajectories were observed in patients with
baseline ALT below the upper limit of normal (ULN: 25 U/L for women acid metabolism and multiple amino acid metabolism pathways. The
and 35 U/L for men), ALT 1-2×ULN, and ≥2×ULN (Figure 1). Figure 1 group of MAFLD-CHB showed significant abundance in fatty acid and
shows the annual change of ALT in each ALT trajectory. Compared to multiple amino acid metabolism.
patients with baseline ALT <ULN and a stable ALT trend, those with Conclusion: Compared with pure MAFLD, those with concurrent
baseline ALT <ULN but increasing ALT trend (aHR 1.12, 95% CI 1.01 HBV infection exhibit significant differences in their oral microbiota.
- 1.24), those with ALT 1-2×ULN and a stable (1.36 [1.22 - 1.51]) or Correlation and functional analysis suggest that these bacterial
increasing ALT trend (1.84 [1.49 - 2.28]), and those with baseline ALT differences may be associated with better blood lipid metabolism
≥2×ULN regardless of ALT trajectories showed higher risks of liver- status and a lower degree of fatty liver diagnosed by ultrasound in the
related events (Figure 2). Patients with baseline ALT 1-2×ULN but MAFLD+CHB group.
decreasing ALT trend had a comparable risk (aHR 0.91, 95% CI 0.77 Table and Figure:Figure 1.Fig 1 1A, 1B, and 1C respectively display
- 1.08) to those with baseline ALT <ULN and a stable ALT trend. Older the Alpha diversity analyses using the Chao1, Shannon, and Simpson
age, presence of cirrhosis, hypertension, lower albumin and platelets, methods; 1D presents the Beta diversity analysis using the Principal
and higher total bilirubin, HbA1c and creatinine, were associated with Coordinates Analysis (PCoA) method; 1E and 1F are heatmaps
higher risk of liver-related events. annotating species abundance at the phylum level, with a gradient
Conclusion: ALT trajectory adds value to risk stratification in T2D. In from blue to red indicating a change in abundance from low to high,
patients with elevated ALT, decreasing ALT trajectory is associated where bluer colors represent lower abundance and redder colors
with a reduced risk of liver-related complications. represent higher abundance.
Table and Figure:Figure 1.Figure 1. Linear mixed models on the annual Figure 2.Fig 2. 2A shows the correlation analysis between phylum-level
change of ALT in the ALT trajectories stratified by baseline ALT level in bacteria and blood indicators; 2B displays the correlation analysis
patients with type 2 diabetes. between genus-level bacteria and biochemical indicators; 2C presents
Figure 2.Figure 2. Multivariable cause-specific hazard model on the LEfSe analysis at all levels; 2D presents the correlation analysis among
association of baseline ALT level and ALT trajectory with the risk of differentially abundant genus-level bacteria. Group A: MAFLD; Group
liver-related events in patients with type 2 diabetes. B: MAFLD+CHB

PP0487 PP0488
Analysis of the impact of concurrent HBV infection on the oral An Accurate Race and Ethnic-specific Novel Index for the
microbiota of patients with MAFLD based on 16S rDNA sequencing Diagnosis of Metabolic Dysfunction-associated Steatotic Liver
Jingjing Zhang1, Song Feng2, Dali Zhang1, Jian Xue3, Pengcheng Liu1, Disease: A population-based study
Shuangnan Fu1, Man Gong1, Hui Feng2, Ning Zhang1 Xinyuan He1, Zhiluo Yang1, Takanori Ito2, Hideyuki Hyogo3, Masafumi
1
Senior Department of Liver Disease, The Fifth Medical Center Ono4, Kentaro Oniki5, Tetsuhito Kojima6, Zhanpeng Yang7, Sally Tran8,
of Chinese PLA General Hospital, Beijing, China, 2Department of Zixuan Xing1, Yi Liu1, Naoyoshi Kariya6, Shinya Yokoyama2, MingHua
Ultrasound, Senior Department of Oncology, , The Fifth Medical Zheng9,10, Junji Saruwatari5, Hirokazu Takahashi11, Lei Zhang12,13,
Center of Chinese PLA General Hospital, Beijing, China, 3Senior Takashi Honda2, Mindie H Nguyen14, Fanpu Ji1,15
Department of Cardiology, Sixth Medical Center of Chinese PLA 1
the Second Affiliated Hospital of Xi’an Jiaotong University, 2Nagoya
General Hospital, Beijing, China University Graduate School of Medicine, 3Hyogo Life Care Clinic
Background: Metabolic dysfunction-associated fatty liver disease Hiroshima, 4Kagawa University, 5Kumamoto University, 6Aichi Health
(MAFLD) has surpassed HBV as the primary cause of chronic liver Promotion Foundation, 7Xi’an Jiaotong University, 8Stanford University
disease in China, with an increasing incidence rate. The impact of HBV Medical Center, 9The First Affiliated Hospital of Wenzhou Medical
co-infection on MAFLD is currently a topic of great concern. University, 10Key Laboratory of Diagnosis and Treatment for the
Method: Patients diagnosed with MAFLD at the outpatient clinics Development of Chronic Liver Disease in Zhejiang Province, 11Saga
between November 2023 and January 2024, were enrolled. Patients University Hospital, 12Xi‘an Jiaotong University Health Science Centre,
1
3Monash University, 14Stanford University School of Medicine, 15Xi‘an
were categorized into the MAFLD+CHB group and the pure MAFLD
Jiaotong University
group. Tongue coating samples were collected from patients in the
morning fasting state and subjected to high-throughput sequencing Background: Metabolic dysfunction-associated steatotic liver disease
analysis of 16S rDNA. The characteristics and differences in microbial (MASLD) is a newly adopted term to replace NAFLD as a more inclusive
distribution between the two groups were profiled, and potential and positive term that also better reflects the underlying mechanism of
signaling pathways involved were analyzed. Correlation analysis the disease. We aimed to develop a novel noninvasive assessment
between the microbiota and clinical indicators was also conducted. index to characterize MASLD with its new diagnostic criteria.
Result: The two groups were comparable in terms of age, gender, BMI, Method: Using data from National Health and Nutrition Examination
waist circumference, and comorbidities. Notably, the MAFLD+CHB Surveys 2017-2020 (NHANES), we included participants aged 20-74
group exhibited lower levels of fasting blood glucose, gamma glutamyl years old who met the diagnostic criteria of MASLD. Participants were
transferase, total cholesterol (TC), and TyG index. Ultrasound diagnosis randomly grouped into a training cohort and an internal validation
further revealed a relatively lower degree of fatty liver in this group. cohort, with an over-sampling technique to balance the training cohort.
The results of 16S rDNA sequencing indicated there was a significant We performed a forward stepwise logistic regression to create a MASLD
difference in beta diversity. Differential analysis and LEfSe analysis both index in the training cohort. Area under the curves (AUC), sensitivity
revealed that Patescibacteria exhibited the most significant difference analysis, Delong test and Brier Score were performed and compared
at the phylum level, with higher expression in the MAFLD+CHB group. with previous diagnostic indices including the Hepatic Steatosis Index
At the genus level, Hydrogenophaga and Absconditabacteriales (HSI), Fatty Liver Index (FLI), US FLI, and the Metabolic Dysfunction
were overexpressed in the MAFLD+CHB group, while Megasphaera Associated Fibrosis 5 score (MAF-5) in the internal validation cohort as
was underexpressed. Further correlation analysis indicates that well as two external validation cohorts from 5 centers from Japan and
Patescibacteria exhibits a negative correlation with TC, γ-GGT, alanine UK Biobank.
aminotransferase (ALT), and alkaline phosphatase (ALP). Similarly, Result: The study included 1,853 eligible participants from NHANES
Absolutibacteriales also demonstrates a negative association with TC, (MASLD prevalence 40.9%) and external validation cohorts of 33,466
γ-GGT, and ALP. Conversely, Megasphaera shows a positive correlation patients from 5 Japan centers (MASLD prevalence 28.2%), 774
with low-density lipoprotein and TC. Functional analysis indicated that participants from UK Biobank (MASLD prevalence 19.6%). Using data
the differential bacteria in both groups were primarily involved in fatty derived from the NHANES cohort, we developed a forecast formula
acid metabolism and multiple amino acid metabolism pathways, with named MASLD index with four variables (waist circumference [WC],
the MAFLD+CHB group showing significant abundance in fatty acid triglyceride [TG]s, fasting glucose [FG], and race and ethnicity), which
and multiple amino acid metabolism. Functional analysis suggested performed well in both the training (n=1,062) and internal validation
that the two groups of differential bacteria were mainly involved in fatty cohort (n=556), with AUCs of 0.87 (95%CI 0.84-0.89) and 0.84,
respectively. The AUCs in the training and internal validation cohorts for MASLD risk stratification, the high-risk group (HR 13.69, 95% CI
for the US FLI for MASLD were (0.84, 0.85), followed by the FLI (0.84, 7.00–26.48) and intermediate-risk group (HR 3.53, 95% CI 1.52–8.17)
0.83), HSI (0.82, 0.79) and MAF-5 (0.81, 0.80), respectively. In both had significantly increased risks of liver-related events compared to
the training and internal validation cohorts, the curve of MASLD index the low-risk group (Figure 2D).
was closest to the reference line, with the lowest Brier Score, indicating Conclusion: In patients with CHB and concurrent MASLD receiving
best agreement between the predicted and observed probabilities antiviral therapy, the Agile 3+ score effectively identifies advanced
and with superior performance over other indices across subgroups fibrosis and predicts liver-related events.
by sex, age, race and ethnicity, and abdominal obesity subgroups. Table and Figure:Figure 1.Figure 1. Participant selection flow chart.
The MASLD index also achieved AUCs of 0.88 (95%CI 0.87-0.88) and Figure 2.Figure 2. Comparison of non-Invasive tests for diagnosing and
0.84 (95%CI 0.80 - 0.87) for the two external validation cohorts in the predicting outcomes in in chronic hepatitis B and concurrent MASLD
Japan and UK Biobank, respectively.
Conclusion: Using data derived from a large population-based U.S.
PP0490
cohort and two large multicenter external validation cohorts from 5
centers in Japan and UK Biobank, we proposed a simple yet accurate Evaluation of the Clinical Effect of High-Protein Low-Glycemic
novel diagnostic index for MASLD outperforming traditional indices. (HPLG) Diet Intervention on the Rehabilitation of Patients with
Table and Figure:Figure 1.Figure 1. Area Under Receiver Operating MAFLD and T2DM
Characteristic curves (AUROCs) of MASLD index, MAF-5, US FLI, FLI Taolong Zhou1, Xiaoliang Li 1, Kefeng Li2, Mingxing Huang1
and HSI for identifying MASLD in the population of U.S. population from 1
Zhuhai Third People’s Hospital, Zhuhai, Guangdong, China, 2Centre
2017 to 2020 pre-pandemic, by ethnicity. (A) Non-Hispanic white, (B) for Artificial Intelligence Driven Drug Discovery, Faculty of Applied
Non-Hispanic black, (C) Non-Hispanic Asian, (D) Mexican American, Sciences, Macao Polytechnic University, Macau SAR, China
(E) Others. Background: Metabolic associated fatty liver disease (MAFLD) has
Figure 2.Table 1. Comparison for Area Under Receiver Operating become the most common liver disease globally and is a major cause
Characteristic curves (AUROCs) of MASLD index, MAF-5, US FLI, FLI of liver-related morbidity and mortality. The progression of MAFLD
and HSI in a population-based U.S. cohort from 2017 to 2020 pre- is closely related to insulin resistance and type 2 diabetes mellitus
pandemic, by age, sex, race/ethnicity, and waist circumference. (T2DM). There is a bidirectional association between the two, with
each serving as a risk factor for the other. Lifestyle changes such as
PP0489 calorie restriction and exercise have been proven to provide significant
therapeutic benefits for both diseases. However, limited attention
Diagnostic and prognostic performance of the Agile 3+ score in
has been paid to the role of diet types and nutritional components.
chronic hepatitis B and concurrent MASLD after complete viral
Therefore, there is an urgent need for scientific and effective dietary
suppression with nucleos(t)ide analogues
interventions.This trial aims to assess whether a high-protein low-
Hongsheng Yu1, Yuexiang Ren2, Mingkai Li3, Hu Can1, Hao Jiang1, glycemic (HPLG) diet intervention improves the controlled attenuation
Yinan Huang1, Bin Wu1, Jianning Chen2, Yidong Yang1 parameter (CAP) and related metabolic markers such as blood
1
Department of Gastroenterology, the Third Affiliated Hospital of Sun glucose in patients with MAFLD combined with T2DM (MAFLD/T2DM).
Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, P. R. Method: A 12-week dietary intervention trial was conducted.
China., 2Department of Pathology, The First Affiliated Hospital, Jiangxi Seventeen patients with MAFLD/T2DM were recruited and provided
Medical College, Nanchang University, Nanchang, Jiangxi, China., with a scientific HPLG diet (40-45% protein, 20-25% carbohydrates,
3
Department of Gastroenterology, Shenzhen Hospital, Southern 30-35% fat) with energy restriction (initial body weight × 25 kcal/kg
Medical University, Shenzhen, People‘s Republic of China.
× 0.7). During the treatment period, lunch and dinner staples were
Background: The prevalence of chronic hepatitis B (CHB) concomitant replaced with nutritional meal replacement bars (Table 1), and
with metabolic dysfunction-associated steatotic liver disease (MASLD) individual adjustments were made to other HPLG supplementary
has been increasing, with patients at elevated risk for disease diets within the limit of energy intake. After 12 weeks, the improvement
progression and advanced fibrosis (F≥3). The Agile 3+ is a non- in relevant indicators in MAFLD/T2DM patients before and after the
invasive test (NIT) with high accuracy in predicting advanced fibrosis intervention was compared. The primary outcome measures were
in MASLD patients. This study investigates whether the Agile 3+ score CAP, liver function, and metabolic markers such as blood glucose and
can be generalized to patients with CHB and concurrent MASLD lipids. Secondary outcome measures included BMI, blood pressure,
undergoing antiviral therapy.The prevalence of chronic hepatitis B renal function, and other indicators.
(CHB) concomitant with metabolic dysfunction-associated steatotic Result: All 17 participants completed the intervention and were
liver disease (MASLD) has been increasing, with patients at elevated included in the final analysis (Table 2), with an average age of
risk for disease progression and advanced fibrosis (F≥3). The Agile 3+ 40.5±12.4 years and 58.8% being male. In this trial, 1. compared to
is a non-invasive test (NIT) with high accuracy in predicting advanced with the physical examination and laboratory test indicators before the
fibrosis in MASLD patients. This study investigates whether the Agile intervention, after the HPLG diet intervention treatment for patients,
3+ score can be generalized to patients with CHB and concurrent their CAP and LSM were significantly improved (both P-values <
MASLD undergoing antiviral therapy. 0.001), especially with a notable alleviation in the degree of hepatic
Method: This two-part study included patients with CHB and MASLD steatosis (88.2% liver steatosis before treatment vs. 0% liver steatosis
recruited consecutively from 2017 to 2020. In Part 1, we evaluated after treatment); 2.FPG and HbA1c also improved significantly (both
the performance of Agile 3+ in predicting advanced fibrosis. In Part P-values < 0.001); 3.patient’s BMI decreased significantly (P-value
2, the Agile 3+ score was applied to a follow-up cohort to assess its < 0.001); 4.AST, ALT, GGT and blood lipid-related indicators such as
correlation with liver-related events (Figure 1). TC,TG, and LDL-C were significantly reduced (all P-values < 0.001);
Result: Among 2,492 patients evaluated by VCTE, 103 patients with 5.BP, UA, and CR levels decreased but were not statistically significant.
CHB and hepatic steatosis were included in the biopsy cohort, and Conclusion: HPLG diet intervention in MAFLD/T2DM may improve
716 patients were included in the follow-up cohort (Figure 1). The Agile liver steatosis and fibrosis, while also exhibiting glucose-lowering,
3+ score demonstrated the highest area under the curve (AUC) of lipid-regulating, and liver enzyme-modulating effects.
0.916 for predicting advanced fibrosis, outperforming FIB-4 (0.845), Table and Figure:Figure 1.Table 1: The energy composltion of the
NFS (0.838), and APRI (0.726) (Figure 2A). Using the recommended nutrltious meal replacement bar is as follows
cut-offs for ruling in and out advanced fibrosis, Agile 3+ identified more Figure 2.Table 2 Comparation of changes in physical examination or
patients while reducing the number of patients in the gray zone (15.5%) laboratory tests variables in patients with type 2 diabetes mellitus with
(Figure 2B). In predicting liver-related events at 3, 5, and 8 years, the or without meal replacement
Agile 3+ score showed significantly higher AUCs (0.795 at 3 years,
0.809 at 5 years, and 0.834 at 8 years) compared to other NITs (Figure
PP0491
2C). When applying the recommended cut-offs (0.451 and 0.679)
Prevalence of Metabolic Dysfunction-associated Fatty Liver levels, but lower HDL-C and ApoA1 levels than lean patients. However,
Disease (MAFLD) and Cardiac, Renal, Metabolic Conditions (CRM) TC, LDL-C, nonHDL-C, LP(a) levels show no significant differences
in Adults: A Community-Based Study between these two groups. Obese group had significantly higher
Jing Zeng1, Zhen Yang1, Jian Gao Fan1 HbA1c, METS-IR, FINS, and HOMA-IR levels compared to lean group.
1
Shanghai Xinhua Hospital Obese group had significantly higher CAP values (288.46 vs. 254.91
dB/m), liver MRI-PDFF values (10.2% vs. 7.7%), visceral fat area,
Background: Metabolic dysfunction-associated fatty liver disease
abdominal subcutaneous fat area, and body fat percentage compared
(MAFLD) is a liver disease closely associated with metabolic disorders,
to lean group (P<0.05). Obese group showed significantly higher NAS
with its global prevalence increasing year by year, becoming a
score than lean group. Their average hepatic steatosis and ballooning
significant public health issue worldwide. Patients with MAFLD are
scores are also higher, but there is no significant difference in lobular
often accompanied by various metabolic abnormalities, such as
inflammation scores between these two groups. Although the liver fat
obesity, type 2 diabetes, and insulin resistance, which also increase
content and MRI-PDFF in the obese group were higher than those in
the risk of cardiovascular and renal diseases. However, the specific
the lean group, the ratio of liver fat content/BMI and PDFF/BMI in the
relationship between MAFLD and cardiac, renal, and metabolic (CRM)
lean group was higher than that in the obese group. But there was no
diseases remains unknown.
significant difference in fibrosis stage between lean and obese group,
Method: This study aimed to assess the relationship between the
with similar proportions having S ≥ 2 (60.0% vs. 57.9%) (P>0.05). Lean
prevalence of MAFLD and the prevalence of CKM syndrome through
group showed higher rates of cirrhosis than obese group.
a community-based study.
Conclusion: Obese MAFLD patients showed higher glucose and lipid
Result: A cross-sectional study was conducted from 2011 to 2012 in
metabolism, more liver fat. But the ratio of liver fat content/BMI and
Shanghai, China, utilizing random stratified cluster sampling of 9,980
PDFF/BMI in the lean group seemed to be higher than that in the obese
individuals aged 40 and above. The distribution of CKM stages was
group; no significant difference was found in fibrosis stage between
as follows: CKM stage 0: 1.1%, CKM stage 1: 15.4%, CKM stage 2:
lean and obese groups. Thus, more attention should be paid on lean
79.4%, and CKM stage 3-4: 4.0%. The prevalence of CKM stage 2
MAFLD patients in the future.
was notably high, indicating a higher burden of metabolic risk factors
Table and Figure:Figure 1.Differences in liver fat between lean and
and a greater prevalence of chronic kidney disease (CKD). Very
obese group
few individuals were classified in CKM stage 0, which had no risk
Figure 2.Differences Liver fibrosis stage between lean and obese
factors. The prevalence of CKM stage 2 was significantly higher in
group
MAFLD patients (88.3%) compared to non-MAFLD patients (73.4%).
Additionally, the prevalence of CKM stage 3-4 was also significantly
higher in MAFLD patients (5.2%) compared to non-MAFLD patients PP0493
(3.3%). In CKM stage 2, the prevalence of MAFLD was 45.1%, while Identifying Heterogeneity in Newly Diagnosed Metabolic
in CKM stage 3-4, the prevalence of MAFLD increased to 51.6%. Dysfunction-associated Steatotic Liver Disease Using Group-
Univariate analysis revealed that MAFLD was an independent risk Based Multi-trajectory Models
factor for CKM stage 3-4 (OR 1.592, 95% CI: 1.304–1.045). Multivariate Chenlu Yang1, Yang Zhou1, Shutong Wu1, Shuohua Chen2, Shouling
analysis further confirmed that MAFLD remained an independent risk Wu2, Li Wang1
factor for CKM stage 3-4 (OR 1.387, 95% CI: 1.127–1.706). 1
Institute of Basic Medical Sciences Chinese Academy of Medical
Conclusion: Significant differences in the prevalence of CKM Sciences, 2Kailuan General Hospital
syndrome were observed across its stages. Both univariate and
multivariate analyses identified MAFLD as an independent risk factor Background: Given the complex etiology of metabolic dysfunction-
for CKM stage. These findings suggest that MAFLD is not only a associated steatotic liver disease (MASLD), individuals exhibit distinct
common comorbidity in CKM syndrome but also plays a key role in the histological and metabolic phenotypes. Research highlights the crucial
progression of CKM to more advanced stages. role of these phenotypes and their changes in MASLD progression to
Table and Figure:Figure 1.Prevalence of Each Stage of CKM Syndrome adverse outcomes. However, identifying high-risk MASLD populations
and Prevalence of Each Stage in MAFLD remains unresolved.
Figure 2.Univariate and Multivariate Analysis of Risk Factors Associated Method: This study enrolled 17,455 individuals aged 18-65 with newly
with Stage 3/4 of CKM Syndrome diagnosed MASLD from the Kailuan cohort (2006-2013). Group-based
multi-trajectory models were built using metabolic and nutritional
phenotype variables from pre-onset, onset, and post-onset periods.
PP0492 Goodness-of-fit indices determined the final variables and subgroup
Differences in Glucose and Lipid metabolism Characteristics numbers. Risks of all-cause of mortality, cancer, cardiovascular
between Lean and Obese patients with Metabolic Associated Fatty disease (CVD), chronic kidney disease (CKD), and intrahepatic
Liver Disease adverse outcomes, as well as MASLD-related single nucleotide
Huanming Xiao1, Meijie Shi1, Zhiheng Chen2, Yubao Xie1, Yousheng polymorphisms (SNPs), were compared across subgroups. A
Mo1, Chaozhen Zhang1, Ming Lin1, Xiaoling Chi1 validation was conducted on 8,923 incident NAFLD enrolled between
1
The Second Affiliated Hospital of Guangzhou University of Chinese 2014 and 2017 in the same cohort.
Medicine, Guangdong Provincial Hospital of Chinese Medicine, 2The Result: The trajectory of six variables (body mass index, systolic blood
Affiliated TCM Hospital of Guangzhou Medical University pressure, fasting blood glucose, triglycerides, high-density lipoprotein
cholesterol, and alanine aminotransferase) was finally selected to
Background: It is well known that Metabolic Associated Fatty Liver
distinguish five subgroups: persistently elevated blood pressure
Disease (MAFLD) Patients often experience abnormal regulation of
(PEBP), steatotic liver-only (SL), metabolically healthy obese (MHO),
glucose and lipid metabolism. However, it is still not very clear whether
persistently severe hypertriglycerides (PSHTG), and persistently
the glucose and lipid metabolism characteristics were different
hyperglycemic (PHG) group. SL group had the lowest risk of all events.
between lean and obese patients. So, the aim of this study is to
Compared to the SL, the PHG group had the highest risk of all-cause
investigate the metabolic differences in glucose and lipids between
mortality (hazard ratio (HR)=4.55, 95% confidence interval (CI): 3.59-
lean and obese patients.
5.75), CVD (HR=4.30, 95% CI: 3.51-5.26), and CKD (HR=5.62, 95%
Method: In this retrospective cohort study, 1007 patients with MAFLD
CI: 3.99-7.93). The PEBP group also had a higher risk of extrahepatic
were enrolled from January 2018 to Sep 2023 in Guangdong Provincial
adverse outcomes (mortality: HR=2.40, 95% CI: 1.99-2.90; cancer:
Hospital of Chinese Medicine. According to BMI<24 or ≥ 24kg/m2,
HR=1.33, 95%CI: 1.04-1.69; CVD: HR=1.94, 95% CI: 1.66-2.26;
they are divided into obese group (n=668) and lean group(n=339).
CKD: HR=2.44, 95% CI: 1.82-3.29). The MHO and PSHTG shared
Result: Of these 1007 patients studied, 81.0% had lipid metabolism
a higher risk of CVD, CKD and intrahepatic adverse outcomes. The
abnormalities and 52.8% had glucose metabolism abnormalities, 540
subtypes were confirmed in the validation cohorts. The five subgroups
patients underwent liver biopsy. Obese group had higher TG and ApoB
exhibited differences in the frequency of loci associated with glucolipid
metabolism-related genes such as TM6SF2, GCKR, MTARC1, HFE, he correlation between Hepatic Controlled Attenuation Parameter
APOA5, and others. (CAP) value and Insulin Resistance (IR) was stronger than that
Conclusion: Dynamic changes of multiple metabolism-related between Body Mass Index, Visceral Fat Area and IR
indexes before and after the occurrence of MASLD offer the potential Zhouhuiling Li1
to distinct subtypes of MASLD. This novel grouping may improve the 1
tianjin university of traditional chinese medicine
precision-targeted therapies for MASLD.
Background: Hepatic controlled attenuation parameter (CAP) value
is a novel marker for quantifying hepatic fat accumulation. Insulin
PP0494 resistance (IR) plays a major role in the pathogenesis and natural
Reduction in Liver Stiffness after One-Year Intervention Is history of hepatic steatosis. This study aimed to investigate the possible
Associated with Improvement in Glucose and AST Levels: A relationship between CAP value and IR.
Longitudinal Chinese Cohort Study of Biopsy-Proven MASLD Method: This study included a total of 420 patients with overweight
Patients or obesity who came to the obesity clinic at Tianjin Union Medical
Meng Lu1, Mingyu Zhu1, Mingjie Wang1, Hu Li2, Qingling Wang3, Li Center. Vibration-controlled transient elastography examination was
Chen1 conducted to detect CAP and liver stiffness measurement (LSM)
1
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong values. Body composition, including visceral fat area (VFA), and body
University School of Medicine, 2Department of Infectious Disease, fat mass (BFM), was evaluated by the direct segmental multi-frequency
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, bioelectrical impedance analysis (BIA). The associations between
3
Department of Infectious Disease, Mianyang Central Hospital, School CAP value, body mass index (BMI), VFA, BFM and homeostasis model
of Medicine, University of Electronic Science and Technology of China assessment of insulin resistance (HOMA-IR) were analyzed.
Result: CAP value was positively associated with HOMA-IR (r=0.568,
Background: In metabolic dysfunction-associated steatotic liver
P < 0.001), the strength of which was much stronger than BMI, VFA,
disease (MASLD), the response to comprehensive interventions varies
and BFM. In multivariate linear regression, CAP value and HOMA-IR
among patients. We aimed to identify factors associated with reduction
showed a significant positive association (adjusted β=0.015, 95% CI:
in liver stiffness(LS) after one-year interventions in a Chinese biopsy-
0.007-0.022, P < 0.001). Subgroup analysis suggested no significant
proven MASLD cohort.
interaction between CAP value and HOMA-IR across age, BMI, LSM,
Method: Baseline liver biopsy-proven MASLD patients were
hypertension, and sex groups (all P for interaction > 0.05).
enrolled retrospectively and followed up for one year. Patients
Conclusion: Hepatic CAP value is more remarkably than other obesity
received interventions including dietary modification, exercise and
markers associated with HOMA-IR in individuals with overweight or
pharmacotherapy. The clinical features were collected, including LSM
obesity, regardless of age, BMI, LSM, hypertension, and sex.
by VCTE, biochemical and demographic data. LS improvement was
Table and Figure:Figure 1.Correlation between HOMA-IR and obesity
defined as a ≥20% reduction in LSM at one year. The baseline and
markers.
follow-up clinical characteristics between the responder(R) group and
Figure 2.Multivariable-adjust β and 95%CI of the CAP value associated
non-responder(NR) group were compared. Univariate and multivariate
with HOMA-IR
Cox regression analysis were used to identify independent factors
associated with LS reduction.
Result: A total of 82 eligible patients were included with a median PP0496
age of 41.0years [IQR 33.25, 58.00] and a median BMI of 28.46 kg/ Impact of Lowering ALT Upper Limit of Normal on Reducing
m²[IQR 26.55,31.44]. Thirty-one patients (37.8%) were diagnosed Missed Diagnosis of MASH and Significant Fibrosis in MAFLD
as diabetes mellitus with a mean fasting glucose 6.63±1.31mmol/L. Patients
Baseline fibrosis distribution according to SAF score: F1 6.1%(n=5), Jie Liu1, Hang Yang1, Jia Li1
F2 42.7% (n=35), F3 36.6%(n=30), and F4 14.6%(n=12). Baseline 1
Tianjin Second People‘s Hospital
median LSM was 11.65 kPa [IQR 9.22, 13.80], with 12.40 kPa [IQR
9.60,14.00] in the R group and 10.00 kPa [IQR 8.80,12.40] in the NR Background: Metabolic Dysfunction-Associated Fatty Liver Disease
group(P=0.056). After one year, median LSM decreased to 7.25 kPa (MAFLD) patients with elevated alanine aminotransferase (ALT)
[IQR 5.53,9.65], with 6.20 kPa [IQR 5.30,8.40] in the R group and are typically recommended for liver biopsy to assess for Metabolic
9.50 kPa [IQR 7.75, 12.10] in the NR group(P<0.001). Responders dysfunction-Associated SteatoHepatitis (MASH) or significant fibrosis.
demonstrated significantly weight loss compared to non-responders, However, MAFLD patients with ALT within normal range may also have
with a median weight change of -5.00% [IQR -11.60,-1.86] in the R MASH or significant fibrosis, often leading to missed diagnosis. In
group, versus -1.79%[IQR -7.06,3.20] in the NR group(P=0.025). the field of hepatitis B, the ALT reference values have been lowered,
Additionally, AST levels decreased more substantially in the R group, with the upper limit of normal (ULN) now set at 30 for men and 19
with a median reduction of -37.05U/L [IQR -63.86, -12.83], compared for women, to minimize missed diagnosis of disease progression. This
to -17.86 U/L[IQR -45.45,6.80] in the NR group(P=0.021). The fasting study aimed to investigate whether lowering the ULN for ALT could
glucose at one year was significantly lower in the R group (5.50mmol/L similarly reduce missed diagnosis of MASH or significant fibrosis in
[IQR 5.20,6.10]) compared to the NR group(5.90mmol/L[IQR MAFLD patients.
5.45,6.75](P=0.042). Univariate Cox regression analysis indicated Method: This cross-sectional study included 404 MAFLD patients
that lower glucose at one year(P=0.018) and greater reduction in who underwent liver biopsy at Tianjin Second People’s Hospital from
AST(P=0.008), not weight reduction, were significantly associated October 2012 to July 2024. Patients were divided into two groups. One
with LS reduction. Further multivariable analysis confirmed that lower used commonly used ALT ULN (50 U/L for men, 40 U/L for women)
glucose at one year (HR:0.709,95%CI:0.5218–0.9634,P=0.0279) and , while the other used lower ALT ULN (30 U/L for men, 19 U/L for
greater AST reduction (HR:0.989,95%CI:0.9805–0.9962,P=0.0036) women). Sensitivity, specificity, positive predictive value, negative
were independently associated with LS reduction. predictive value, positive likelihood ratio, and negative likelihood
Conclusion: In biopsy-proven MASLD patients, LS reduction after ratio were calculated for both ALT ULNs in predicting MASH, and for
one year interventions was significantly associated with lower follow- both ALT ULNs, APRI, FIB-4, and Liver Stiffness Measurement (LSM)
up fasting glucose and greater AST reduction. These findings provide in predicting significant fibrosis. Significant fibrosis was defined as
insights into metabolic factors of fibrosis regression and may inform stages ≥ S2 in pathology reports. Use APRI > 1.5, FIB-4 > 3.25, and
personalized therapeutic strategies for MASLD management. LSM > 8.0 kPa to detect significant fibrosis.
Result: Among the 404 MAFLD patients, 284 (70.3%) had MASH,
and 271 (67.1%) had significant fibrosis. Patients with concurrent
PP0495 MASH were younger and exhibited higher levels of BMI, CAP, LSM,
ALT, AST, ALB, TG, Ferritin, and APRI. Those with significant fibrosis
demonstrated increased proportions of IFG/DM, as well as elevated
levels of BMI, CAP, LSM, ALT, AST, FGB, Ferritin, APRI, and FIB-4 Synergic Effect of Pancreatic Steatosis and MASLD on Risk of
(Table 1). Using the commonly used ALT ULN resulted in a 17.3% New-onset Heart Failure in the General Population: A Prospective
false negative rate for MASH, which decreased to 3.5% when using Analysis of the UK Biobank
the lower ALT ULN. For significant fibrosis, the false negative rate was Liyou Lian1,2,3, Tianyi Xia4, Zhongwei Chen5, Caiyun Wen5, Xiaodong
17.7% using the commonly used ALT ULN, decreasing to 4.4% with Zhou1,2,3, Tie Xiao1,2,3, Giovanni Targher6,7, Christopher D Byrne8, Yee
the lower ALT ULN. The false negative rates for APRI, FIB-4, and LSM Hui Yeo9, Shenghong Ju4, Wenyue Liu10, Minghua Zheng1,2,3
were 89.7%, 91.5%, and 60.7%, respectively (Table 2). 1
MAFLD Research Center, Department of Hepatology, the First
Conclusion: By employing a lower ALT ULN (30 U/L for men, 19 U/L Affiliated Hospital of Wenzhou Medical University, Wenzhou,
for women) in MAFLD patients could reduce missed diagnosis of China, 2Institute of Hepatology, Wenzhou Medical University,
MASH and significant fibrosis. However, the specificity of using ALT to Wenzhou, China, 3Key Laboratory of Diagnosis and Treatment for
predict MASH or significant fibrosis remains low. Patients still require the Development of Chronic Liver Disease in Zhejiang Province,
further evaluation, including liver biopsy, for accurate assessment of Wenzhou, China, 4Nurturing Center of Jiangsu Province for State
disease severity. Laboratory of AI Imaging & Interventional Radiology (Southeast
Table and Figure:Figure 1.Table 1. General characteristics of subjects University), Department of Radiology, Zhongda Hospital, Medical
by MASH or significant fibrosis. School of Southeast University, Nanjing, Jiangsu, 210009, China,
Figure 2.Table 2. Comparison of ALT ULNs, APRI, FIB-4, and LSM 5
Department of Radiology, the First Affiliated Hospital of Wenzhou
Values for Predicting MASH and Significant Fibrosis Medical University, Wenzhou, China, 6Department of Medicine,
University of Verona, Verona, Italy, 7Metabolic Diseases Research
Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Negrar di
PP0497 Valpolicella, Italy, 8Southampton National Institute for Health and
Lower cerebral blood flow in the right median cingulum is Care Research, Biomedical Research Centre, University Hospital
associated with liver fat fraction in metabolic dysfunction- Southampton, and University of Southampton, Southampton General
associated fatty liver disease (MAFLD) Hospital, Southampton, UK, 9Karsh Division of Gastroenterology and
Jingjie Zhao1, Hao Wang1, Chaoru Han1, Di Cao1, Ruimin Jiao1, Hong Hepatology, Cedars-Sinai Medical Center, Los Angeles, California,
You1 USA, 10Department of Endocrinology, the First Affiliated Hospital of
Wenzhou Medical University, Wenzhou, China
1
Beijing Friendship Hospital, Capital Medical University
Background: Metabolic dysfunction-associated steatotic liver disease
Background: Metabolic dysfunction-associated fatty liver disease
(MASLD) frequently occurs with pancreatic steatosis (PS). It is unclear
(MAFLD) has become the most prevalent chronic liver disease. The
whether these two metabolic conditions have a synergic effect on the
morbidity and mortality of patients with MAFLD are primarily associated
risk of new-onset heart failure (HF). We aimed to explore the combined
with cerebrovascular disease (CVD) and non-hepatic malignancies.
effect of MASLD and PS on cardiac structure/function measures and
Recently, more evidence showed the association between the brain
the risk of new-onset HF.
and the liver. One study suggested that subjects with histologically
Method: We studied UK Biobank participants undergoing magnetic
proven non-alcoholic fatty liver disease (NAFLD) show reduced
resonance imaging (MRI) assessments of the heart, liver, and
cerebral perfusion confined to limited brain areas even before the
pancreas. PS was defined as pancreatic MRI-proton density fat
extrahepatic manifestations of MetS can be detected. We explored the
fraction values exceeding the 95th percentile of a healthy reference
liver-brain associations using liver fat fraction and cerebral blood flow
population, stratified by sex and age. Fine-Gray sub-distribution
(CBF).
hazard models were used to examine the combined effects of MASLD
Method: We recruited 30 MAFLD patients and 30 healthy controls
and PS on the risk of new-onset HF. Generalized linear regression
(HCs) with age and sex-matched(Figure 1), on which we performed
models were also used to explore the interaction between pancreatic
normal arterial spin labeling (ASL) sequences on the brain and the
fat content and cardiac structural and functional changes within the
axial IDEAL IQ sequences on the liver. Then, we collected the physical
MASLD population.
and biochemical examinations. Finally, we compared the differences
Result: Of 15,794 participants with a median 5.6-year follow-up,
between the two groups in CBF value and the association of proton
126 developed new-onset HF. Compared to those without either
density fat fraction (PDFF).
condition, subjects with MASLD and PS had a threefold risk of new-
Result: In demographic and clinical characteristics, there are body
onset HF when considering death or coronary heart disease (CHD)
mass index (BMI), MRI-PDFF, alanine aminotransferase (ALT), and
as competing events (HR [95% CI] =3.007 [1.342-6.740], P=0.007;
gamma-glutamyl transferase (GGT) differences between the MAFLD
HR=2.996 [1.337-6.714], P=0.008, respectively) after adjusting
and HCs groups.
covariates. In MASLD participants, the highest pancreatic fat content
Compared to HCs, the MAFLD group had significantly lower CBF in
quartile was associated with poorer left ventricular function and greater
the bilateral median cingulate and paracingulate gyri (DCG) (p < 0.05,
left ventricular structural remodeling (both P<0.05) after adjusting
FDR corrected).
covariates.
Particularly, the CBF in the right median cingulate is negatively
Conclusion: Co-occurrence of MASLD and PS markedly increased
correlated with MRI-PDFF (r = -0.655, p < 0.001).
the risk of new-onset HF. In individuals with MASLD, higher pancreatic
Lower CBF in the right median cingulate was significantly associated
fat content was associated with cardiac structural and functional
with high serum GGT levels by univariate analysis (p = 0.033) and
abnormalities.
multivariate analysis (p = 0.006).
Table and Figure:Figure 1.Graphical abstract
For lower CBF in the right median cingulate, MRI-PDFF and GGT were
an independent predictor.
Conclusion: The lower CBF in the bilateral DCG in MAFLD patients. PP0499
Particularly, the CBF in the right median cingulate is decreased by Is hepatic steatosis an independent risk factor for advanced
increased liver fat accumulation and abnormal liver function. One study fibrosis in Chronic hepatitis B patients with metabolic dysfunction-
indicated that DCG had been attributed to inhibitory function and self- associated steatotic liver disease?
control. So we speculate that MAFLD is associated with uncontrolled
Ming Lin1, Meijie Shi1, Huanming Xiao1, Yubao Xie1, Chaozhen
behavior (such as eating and exercise).
Zhang1, Yousheng Mo1, Folai Zeng1, Mengling Han1, Xiaoling Chi1
Table and Figure:Figure 1.table1-3 1
Department of Hepatology, Guangdong Provincial Hospital of
Figure 2.figure1-3
Chinese Medicine, The Second Affiliated Hospital of Guangzhou
University of Chinese Medicine
PP0498 Background: The annual incidence of chronic hepatitis B (CHB) with
metabolic dysfunction-associated steatotic liver disease (MASLD) is
rising. The impact of hepatic steatosis (HS) on the progression of liver
fibrosis or cirrhosis remains uncertain. This study seeks to pinpoint syndrome (OR: 2.69, 95% CI: 2.21-3.28), severe depression (OR: 1.69,
risk factors for liver fibrosis progression in CHB-MASLD patients and 95% CI: 1.37-2.09), obesity (OR: 2.78, 95% CI: 2.29-3.38), and alcohol
assess the role of HS in this process. consumption (OR: 1.43, 95% CI: 1.05-1.96).
Method: The study analyzed patients with CHB and MASLD who Conclusion: Depression in MASLD can increase the risk of adverse
underwent liver biopsies at Guangdong Provincial Hospital of Chinese outcomes and early screening of depression is needed in MASLD
Medicine from 2013 to 2020. It examined the relationship between subjects.
clinical characteristics, such as the HS score, and advanced fibrosis Table and Figure:Figure 1.Fig 1. Odds ratio plot for risk
to identify independent risk factors.
Result: In this study of 598 CHB and MASLD patients who had
PP0501
liver biopsies, 34.4% had moderate to severe HS, 20.1% had
advanced fibrosis, and 31.4% had metabolic dysfunction-associated Liver histology and Non invasive tests (NITs) for hepatic fibrosis
steatohepatitis (MASH). Fewer patients with moderate to severe HS had in a large cohort of metabolic dysfunction-associated steatotic
advanced fibrosis compared to those with mild HS (13.9% vs. 23.0%, liver disease (MASLD)in Kerala, S India
P = 0.015). MASH patients had a higher rate of advanced fibrosis than Shenoy T Kotacherry1,2, Leena B3
those without MASH (48.9% vs. 6.8%, P < 0.001). There was a strong 1
Sree Gokulam Medical College and Research Foundation ,Dept. of
positive correlation between lobular inflammation and fibrosis stage Gastroenterology , 2Population Health and Research Institute , 3Senior
(R² = 0.738, P < 0.001), a weak positive correlation between ballooning Tesearch Scientist Population Health and Research Institute
degeneration and fibrosis stage (R² = 0.314, P < 0.001), and a very weak Background: Non invasive tests (NITs) have been evaluated as
negative correlation between HS and fibrosis stage (R² = -0.099, P = screening tests for liver fibrosis in metabolic dysfunction associated
0.015). Univariate logistic regression analysis identified several factors steatotic liver disease (MASLD). The clinical utility of liver biopsy along
influencing advanced fibrosis, including age, diabetes, hypertension, with NITs has been studied in a large prospective study in Kerala,
HS score, lobular inflammation score, ballooning score, MASH, and INDIA
elevated levels of alpha-fetoprotein, platelet count (PLT), aspartate Method: We have two population cohorts of MASLD in,2012-
aminotransferase, gamma-glutamyl transferase, total bilirubin, 2016 (Trivandrum NAFLD Cohort) and 2017-2023 (Scarred liver
albumin, triglycerides, low-density lipoprotein cholesterol, hepatitis B in Trivandrum: SLIT cohort) in the urban and rural population of
e-antigen positivity, and hepatitis B virus DNA (≥6 log10). Multivariate Trivandrum. We reviewed the data of 391 liver biopsies as per the CRN
logistic regression analysis revealed that lobular inflammation score criteria and compared for its utility along with NITs (FIB 4 (fibrosis-4),
(adjusted odds ratio [OR], 8.426; P < 0.001), hypertension (adjusted NFS (NAFLD fibrosis score), AST to Platelet Ratio Index (APRI). AST
OR, 5.903; P < 0.001), and MASH (adjusted OR, 8.818; P < 0.001) and ALT were also determined.
were independent risk factors for advanced fibrosis. Conversely, HS Result: Mean age (SD) was 43.2 (10.1) and 55.5% were males. 56.3%
score (adjusted OR, 0.252; P < 0.001) and PLT (adjusted OR, 0.991; were males and mean (SD) BMI was 27.4 (4.5). Waist circumference was
P = 0.006) emerged as independent protective factors. In a subgroup abnormal in 76.5%. Morbidities were: diabetes (81.3%); hypertension
analysis of 453 patients who underwent FibroScan, the controlled (34.6%); abnormal triglyceride (52.4%); low HDL (53.4%). AST and
attenuation parameter did not demonstrate a protective effect against ALT were abnormal in 67 and 65% of subjects. Mean liver stiffness was
advanced fibrosis (adjusted OR, 0.998; P = 0.461). 7.6Kpa (SD 2.3). LSM was >10.2Kpa. Fib-4 was >2.67 in 49 subjects
Conclusion: In patients with CHB and MASLD, inflammation may CRN stage was 1c and above in 35 subjects. 41 subjects had NAS
intensify fibrotic processes, whereas HS might confer a protective score of 4 and above. APRI score was high in 41 subjects and 32 had
effect. Nevertheless, these protective effects are not readily discernible stage 1c and above. NFS was intermediate in 113 and high in 6 and 82
through routine FibroScan evaluations or serum biomarker analyses. subjects has NAS score of 4 and above.
Conclusion: FIB-4 score had comparable utility with CRN stage and
PP0500 NAS score and results highlight the potential of FIB-4 as a reliable
screening tool for MASLD. APRI had had a similar performance
Depression in Metabolic dysfunction-associated steatotic liver
compared to CRN. These two NITs can be utilised in clinical practice
disease (MASLD) in a population cohort in S India
Leena K B1, Shenoy T Kotacherry2,3, Jayakumar P Pillai4, Guruprasad
P Aithal5 PP0502
1
Senior Research Scientist Population Health and Research Institute, Non-alcoholic fatty liver disease increased the risk of subclinical
2
Sree Gokulam Medical College and Research Foundation ,Dept. of carotid atherosclerosis
Gastroenterology , 3Director, Population Health and Research Institute, Xintian Ren1, Pegnfei Sun2, Yu Wang3, Yanfang Tan4, Xinyan Zhao5,
4
Senior Biostatistician Population Health and Research Institute, 5 Min Li6
Nottingham Digestive Diseases Centre Nottingham, NG7 2UH 1
Department of Clinical Epidemiology and EBM Unit, Beijing
Background: Prevalence of Metabolic dysfunction-associated Friendship Hospital, Capital Medical University, Beijing, 100050,
steatotic liver disease (MASLD) is a major public health issue in the China , 2 Department of Ultrasound, Beijing Friendship Hospital,
state of Kerala, S India. Depression is a major risk for MASLD and we Capital Medical University, Beijing 100050, China , 3Liver Research
examined the prevalence and other risk factors in a population cohort Center, Beijing Friendship Hospital, Capital Medical University,
Method: Population cohort with a nested case control design in Beijing, 100050, China, 4Beijing Friendship Hospital, Capital Medical
Trivandrum, S India. We noted demographic, clinical, and biochemical University, Beijing, 100050, China, 5Liver Research Center, Beijing
and Metabolic Associated Steatotic Liver Disease (MASLD) in 2,161 Friendship Hospital, Capital Medical University, No. 95 Yong-an
individuals. Duke Anxiety-Depression Scale (DUKE-AD), a 7 item scale Road, Beijing 100050, China. E-mail: [email protected],
was used. Univariate and multivariate models with odds ratios (ORs)
6
Department of Clinical Epidemiology and EBM, Beijing Friendship
and 95% confidence intervals (CIs) were done using “jamovi 2.5.3” Hospital, Capital Medical University, No. 95 Yong-an Road, Beijing
100050, China. E-mail: [email protected]
Result: Among 2,161 subjects, 59.4% were females; urban domicile
was 53.8%. Education was up to the 10th grade in 64.3% and marital Background: Non-alcoholic fatty liver disease (NAFLD) exerts a
status was in 91.1%. BMI was 37.0% overweight and 13.7% are obese. notable influence on cardiovascular disease (CVD). In the development
42.9% had hypertension and 25.5% had diabetes mellitus. 45.7% had of CVD, subclinical carotid atherosclerosis (SCA) is mostly formatted
higher waist circumference and metabolic syndrome was in 39.1%. at an early stage. However, the evidence exploring the association
MASLD was noted in 48.1%. Duke anxiety depression scale identified between NAFLD and SCA was limited. Thus, this study is performed to
26.9% with abnormality and 73.1% had normal scores. Mean Duke A evaluate this association in a routine checkup cohort.
D score significantly higher in individuals with MASLD (20.0 ± 20.9) Method: Adult individuals, who underwent health check-ups at Beijing
compared to those without (15.9 ± 19.8, p<0.0001), Predictors of friendship hospital between Jan, 2015 and Sep, 2022, were included.
MASLD were male gender (OR: 2.09, 95% CI: 1.68-2.61), metabolic As the marker of SCA, carotid intima-media thickness (CIMT) and
carotid plaque were assessed via carotid artery ultrasound imaging; PP0504
while NAFLD was identified by abdominal ultrasonography. The Real-World Assessment of Saroglitazar for improving FAST
annual incident rates of CIMT and carotid plaque in individuals with Score and Fibroscan Parameters (LSM and CAP) in Metabolic
NAFLD and healthy controls were calculated and compared with Cox Dysfunction-Associated Steatotic Liver Disease (MASLD): An
proportional hazards regression model. Open-Label, Prospective Study
Result: A total of 28,921 individuals were included, with 9,325 NAFLDs
Sunil B Daschakraborty1, Arnabja Ghosh2
and 19,596 healthy controls. The prevalence rates of CIMT and carotid
plaque in NAFLD were 47.64% and 29.84%, which were significantly
1
Consultant Gastroenterologist, Hepatologist and Interventional
Endoscopist, Ruby General Hospital, E M Bypass, Kolkata, West
higher than that in healthy controls (34.89% and 21.70%). Moreover,
Bengal, India. , 2Resident, Ruby General Hospital, E M Bypass,
the proportion of hypoechoic and mixed echoic plaques (unstable
Kolkata, West Bengal, India
type), and the proportion of multiple plaques in NAFLD patients were
higher than that in healthy controls (both P value<0.01). Notably, Background: Metabolic dysfunction-associated steatotic liver disease
among individuals who were free of SCA at initial checkup, 6725 (MASLD) is estimated to affect approximately 30% of the global adult
individuals with more than once health check-up data were identified. population. The FAST (FibroScan-AST) score serves as a critical
During a median follow-up of 25 months, the annual incident rates of diagnostic tool for assessing the severity of MASLD by identifying
CIMT and carotid plaque in NAFLD individuals were 7.76% and 4.10%, significant fibrosis and steatohepatitis, aiding in disease management.
respectively. NAFLD was significantly associated with increased risk Clinical evidence highlights the efficacy of Saroglitazar (Bilypsa®) in
of developing CIMT and carotid plaque, with hazard ratios with 95% improving liver histology and biochemical markers in MASLD. This
confidence intervals being 1.23 (1.09-1.38) and 1.34(1.12-1.59), study aimed to evaluate the safety and effectiveness of Saroglitazar in
respectively. improving FAST scores in patients with MASLD under routine clinical
Conclusion: Individuals with NAFLD are predisposed to a heightened practice conditions.
risk of SCA. It is imperative to direct increased attention to the arterial Method: In this open-label, prospective, real-world, single-center
condition of these individuals. study, 133 MASLD patients (70% male, 58.5% non-diabetic) with
Table and Figure:Figure 1.Fig 1. Association of NAFLD with CIMT and median(IQR) age 45.5(23.8)years and BMI of 27.3(6.9)kg/m² satisfying
carotid plaque the study inclusion criteria and treated with Saroglitazar, were included
for assessment. The primary objective was to assess improvements in
liver steatosis and stiffness after 24 weeks of treatment by evaluating
PP0503 changes in the controlled attenuation parameter(CAP) and liver
The Relationship Between Body Fat Distribution and the stiffness measurement(LSM) using transient elastography. Changes
Progression of MASLD in the FAST score were analyzed to evaluate disease severity and
Xiaodie Wei1, Jing Zhang2, Jinhan Zhao2, Sitong Chen2 treatment efficacy. Secondary endpoints included improvements
1
The Third Unit, Department of Hepatology, Beijing Youan Hospital, in liver enzymes, like aspartate aminotransferase (AST) and alanine
Capital Medical University., 2The Third Unit, Department of aminotransferase (ALT), and lipid profile parameters. Paired sample
Hepatology, Beijing Youan Hospital, Capital Medical University t-tests were performed to assess differences in these variables over
Background: Metabolic dysfunction-associated fatty liver disease the study period.
(MASLD) is strongly associated with obesity and metabolic syndrome. Result: A total of 52 patients who completed the follow-up assessment
Although some studies have explored the effects of visceral adipose after 24 weeks of Saroglitazar treatment showed significant
tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle improvements in parameters related to MASLD severity. The mean
mass (SMI) on MASLD, a comprehensive evaluation of their relationship LSM, decreased by 1.9 kPa (15.5%, p<0.05), from 12.3±5.01 to
with disease progression remains lacking. This study used MRI to 10.4±4.5 (Fig. 1). Similarly, the CAP showed a mean reduction of 36.8
evaluate the impact of body fat and muscle distribution on hepatic dB/m (13.7%, p<0.001), from 269.5±51.9 to 232.7±46.2 (Fig. 2). The
steatosis and fibrosis in MASLD patients, and analyzed the differences mean FAST score improved by 0.23 (38.5%, p<0.001), from 0.61±0.2
in BMI and metabolic phenotypes. to 0.37±0.2. Additionally, the number of patients with an intermediate
Method: This study retrospectively analyzed adult patients with or high FAST score (≥0.35) decreased from 44 to 26 after 6 months.
MASLD diagnosed by MRI examination between 2020 and 2022. Also, the AST decreased by 33.7(43.5%, p<0.001), from 77.6±44.4
Moderate/severe steatosis was defined as MRI-PDFF ≥17.4%, and to 43.9±21.5, ALT by 58.2(54.9%, p<0.001), from 105.9±54.6 to
significant fibrosis was defined as MRE ≥3.14 kPa. The volumes of 47.8±32.6 and triglycerides(TG) by 54.2(31%, p<0.001), from
VAT, SAT, and SMI at the L3 level were measured, and a multivariate 175±73.4 to 120.8±44.9. There was a non significant improvement in
analysis was conducted to investigate the relationship between body mean BMI by 0.49(1.86%) over the study period.
fat distribution and the progression of MASLD, and the differences in Conclusion: Saroglitazar shows significant benefits in managing
BMI and metabolic phenotypes. MASLD in the Indian population over 24 weeks, improving liver
Result: Among 225 patients, 104 (40.8%) had moderate/severe biomarkers, metabolic parameters, and imaging outcomes, and
steatosis and 51 (20.0%) had significant fibrosis. In the multivariate reducing MASLD severity as indicated by a lower FAST score.
analysis, an increase in SATI increased the risk of moderate to severe Further studies with a larger sample size and extended duration are
steatosis (highest quartile vs lowest quartile [OR], 2.73; 95% CI, 1.06- recommended to validate and strengthen these findings, providing
7.07, P =0.038); Similarly, an increase in VATI (highest quartile vs lowest a more comprehensive understanding of Saroglitazar’s long-term
quartile [OR], 3.36; 95%CI, 1.16 ~ 9.74, P =0.026), and SATI (highest efficacy and safety in MASLD management.
quartile vs lowest quartile [OR], 3.58; 95% CI, 1.05-12.17, P =0.041), Table and Figure:Figure 1.Fig 1: Changes in Liver Stiffness
as well as a decrease in SVR (highest quartile vs lowest quartile [OR], Measurement
0.14; 95% CI, 0.04-0.54, P =0.004) significantly increased the risk of Figure 2.Fig 2: Changes in Steatosis
significant fibrosis, especially in the obese and metabolically unhealthy
subgroups. PP0505
Conclusion: SAT is closely related to hepatic steatosis, whereas Characterizing Nonalcoholic Fatty Liver Disease (NAFLD) in Lean
VAT and SVR are more crucial for the progression of significant individuals in a tertiary care hospital: A cross-sectional study
fibrosis, especially in obese and metabolically unhealthy populations.
Shamim Nazir1, Zaigham Abbas1
Therefore, it is important to focus on monitoring and intervening in the 1
Dr Ziauddin Hospital Karachi
abnormal increase of adipose tissue and the decline of muscle mass.
Table and Figure:Figure 1.Multivariate analysis of adipose tissue and Background: Background: Non-alcoholic fatty liver disease
muscle tissue on the risk of moderate to severe steatosis in MASLD. (NAFLD) is widespread, affecting up to 38% of the global population.
Figure 2.Multivariate analysis of adipose tissue and muscle tissue on Traditionally linked to obesity, NAFLD is increasingly observed in lean
the risk of significant fibrosis in MASLD. individuals, termed lean NAFLD.
Objectives: This study aims to characterize lean NAFLD in a tertiary (1.68–4.06) after further adjusting for CAP scores.
care hospital and compare the effectiveness of Asian and Western Conclusion: This large, population-based study highlights that
body mass index (BMI) criteria, as well as the diagnostic criteria for chronic HBV infection significantly increases the risk of cirrhosis
metabolic dysfunction-associated fatty liver disease (MAFLD) and the among patients with MAFLD.
metabolic dysfunction-associated steatotic liver disease (MASLD).
Method: Methods: This cross-sectional study, conducted from January
PP0507
2023 to March 2024, included 111 patients diagnosed with lean NAFLD
using ultrasound or Fibroscan. Data on anthropometrics, laboratory Cross-Sectional Survey and Analysis of the Prevalence of MAFLD
parameters, and non-invasive liver fibrosis tests were collected. The in HIV-1 Infected Individuals in Zhejiang Province
study applied MAFLD and MASLD diagnostic criteria and compared Yongzheng Guo1, Biao Zhu1
clinical characteristics and metabolic risk factors of patients with BMI ≤ 1
The First Affiliated Hospital, School of Medicine, Zhejiang University
23 kg/m² and BMI ≥ 23 ≤ 25 kg/m². Background: HIV-1-infected individuals have a higher risk of
Result: Results: The cohort consisted of 111 NAFLD cases, developing metabolic associated fatty liver disease (MAFLD). The
diagnosed using ultrasonography 37 (33%) or Fibroscan 74 (67%), objective of this study is to investigate the prevalence and risk factors
with a mean age of 43.3 ± 13.2 years. The majority were male 92 of MAFLD among HIV-1-infected individuals in Zhejiang Province in
(83%), with 19 females (17%). The mean BMI was 23.0 ± 1.5 kg/ order to optimize its management.
m², with 43 (39%) having a BMI ≤ 23 kg/m² and 68 (61%) having a Method: Between 2020 and 2021, a multicenter cross-sectional survey,
BMI between 23 and ≤ 25 kg/m², meeting the lean NAFLD criteria for encompassing questionnaires and liver fat attenuation coefficient
Asia and the West, respectively. The prevalence of diabetes was 18 assessments, was conducted among HIV-1 infected individuals in
(16%), hypertension 12 (11%), and ischemic heart disease 2 (2%). Out Zhejiang Province.MAFLD was diagnosed based on a controlled
of 111 participants, 92 met MASLD-MAFLD criteria, while 18 did not attenuation parameter (CAP) ≥ 238 dB/m, combined with a body mass
qualify for MAFLD diagnostic criteria and grouped as MASLD-Alone. index (BMI) ≥ 23 kg/m² or diabetes, or a BMI ≤ 23 kg/m² with two or
Elevated triglycerides, insulin resistance (HOMA-IR ≥ 2), and three or more metabolic risks (waist circumference ≥ 90 cm for men/80 cm for
more cardiometabolic risk factors (CMRF) were significantly higher in women, blood pressure ≥ 130/85 mmHg or use of antihypertensive
the MASLD-MAFLD group compared to the MASLD-Alone group (p < drugs, triglycerides (TG) ≥ 1.7 mmol/L or use of lipid-lowering drugs,
0.05). Comparing BMI criteria, no significant differences were found in high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/L for men/1.3
terms of fibrosis between BMI ≤ 25 kg/m² (Western) and BMI ≤ 23 kg/ mmol/L for women or use of lipid-lowering drugs, fasting blood glucose
m² (Asian) (p=0.243). 5.6-6.9 mmol/L). The prevalence of HIV-1 combined with MAFLD was
Conclusion: Conclusion: Lean NAFLD is a significant global health calculated, and risk factors for MAFLD in HIV-1 infected individuals
issue. Using non-Asian BMI criteria (BMI ≤ 25 kg/m²) for lean Asians were analyzed. Variables with P < 0.05 in univariate analysis and
enhances early detection and intervention for at-risk individuals. those considered clinically significant by physicians were included
Proper application of MAFLD and MASLD criteria is crucial to avoid in multivariate analysis. Data analysis was performed using SPSS 21,
confusion in the diagnosis of lean NAFLD patients. Further multicenter with statistical significance set at P < 0.05.
studies with larger sample size required to validate these results for Result: A total of 1496 patients from eight centers were included in the
lean NAFLD in our population. study, with 461(30.82%) meeting the diagnostic criteria for MAFLD. No
statistically significant differences were found between the MAFLD and
PP0506 non-MAFLD groups in terms of gender, ethnicity, place of origin, long-
term residence, waist-to-hip ratio, marital status, living alone, education
HBV increases the risk of cirrhosis in adult patients with metabolic
level, economic status, hyperuricemia, previous liver transaminase
dysfunction-associated fatty liver disease
elevation, history of cardiovascular disease, HIV infection stage, HIV
Jianjun Wang1, Jing Chen2, Lei Li3, DONG JI1, Yudong Wang4, George transmission route, hepatitis B co-infection, and CD4+ T lymphocyte
LAU4,5, Yan Liu3 levels. However, statistically significant differences were observed
1
Senior Department of Hepatology, the Fifth Medical Center of PLA between the two groups in terms of age (P=0.0005) , occupation
General Hospital, Beijing 100039, China , 2JC School of Public Health (P=0.0009) , hepatitis C co-infection (P=0.0321) , antiretroviral therapy
and Primary Care, Chinese University of Hong Kong, Hong Kong (ART) regimen type (P<0.0001) , ART duration (P=0.0272) , history
SAR, China, 3Senior Department of Infectious Diseases, the Fifth
of chronic kidney disease (P=0.0382) , and hypercholesterolemia
Medical Center of PLA General Hospital, Beijing 100039, China,
(P<0.0001) . Multivariate analysis revealed that age (P=0.0007)
4
Humanity and Health Clinical Trial Center, Humanity and Health
, the type of core drug in the initial ART regimen (P=0.0295) , and
Medical Group, Hong Kong SAR, China, 5Zhongshan Hospital, Fudan
hypercholesterolemia (P=0.0024) were statistically significant factors
University, Shanghai, China
differentiating the two groups.
Background: The term metabolic-associated fatty liver disease Conclusion: The prevalence of MAFLD among HIV-1 infected
(MAFLD) and its diagnostic criteria were introduced in 2020. Although individuals in Zhejiang Province is similar to that in the non-HIV-1
chronic HBV infection has protective effects on lipid profiles and infected population. Advanced age, hypercholesterolemia, and an
hepatic steatosis, its interaction with MAFLD and the resulting clinical initial ART regimen containing protease inhibitors are associated risk
outcomes, particularly cirrhosis, remain unclear. factors for MAFLD in HIV-1 infected individuals in Zhejiang Province.
Method: We included adult MAFLD patients from the Fifth Medical
Center of PLA General Hospital (Jan 2020–Jul 2024). Chronic HBV
infection was defined by hepatitis B surface antigen positivity for at PP0508
least 6 months. Cirrhosis was assessed using ultrasonography or CT Non-invasive tests for advanced fibrosis in metabolic-dysfunction
scan. Generalized linear models evaluated the effect of dual MAFLD- associated steatotic liver disease and other comorbidities
HBV etiology on cirrhosis risk. Mingkai Li1, Hongsheng Yu1, Jianning Chen1, Yidong Yang1
Result: A total of 5,467 patients (mean age 53.6 ± 13.2 years; 59.6% 1
The Third Affiliated Hospital of Sun Yat-sen University
male) were analyzed. Chronic HBV infection was present in 21.0% of
Background: Non-invasive tests (NITs) were recommended to
patients, with prevalence varying by age group: 22.4% (18–44), 24.4%
assess advanced fibrosis (fibrosis stage ≥3) in metabolic-dysfunction
(45–64), and 11.1% (≥65; p < 0.001). Cirrhosis was present in 60%
associated steatotic liver disease (MASLD) but lack exploration in
of MAFLD patients with HBV, compared to 12% without (p < 0.001).
other combination etiologies. We aimed to explore the performance of
Patients with dual etiology had higher CAP scores (251.3 ± 32.4 vs.
NITs in MASLD and other comorbidities.
242.6 ± 31.1, p = 0.001) and a higher tumor rate (39.0% vs. 27.2%,
Method: This retrospective study included 1029 biopsy-proven
p < 0.001). Chronic HBV infection increased cirrhosis risk tenfold
steatotic liver disease (SLD) subjects with risky cardiometabolic
(OR = 10.6, 95% CI 9.1–12.3), with an adjusted OR of 4.6 (3.6-5.9)
profile [356 MASLD, 522 MASLD with viral hepatitis, 82 MetALD, and
for demographics and clinical parameters, which decreased to 2.61
69 MASLD with other etiologies (including autoimmnue liver disease, FLI (2.270 [2.085,2.470]), FLI (1.899 [1.748,2.062]) and HSI (1.160
drug-induced liver disease and genetic liver disease and hepatic [1.067,1.262]), respectively. The MASLD index demonstrates the
vascular disease)] undergoing contemporaneous fibrosis score 4 best capacity to detect high risk patients, offering a more precise
(FIB-4), NAFLD fibrosis score (NFS) and aspartate aminotransferase prediction of individual survival outcomes compared to other indices.
to platelet ratio index (APRI). Diagnostic performances of NITs for Furthermore, the Kaplan-Meier survival curves indicate that MASLD
advanced fibrosis were evaluated by area under the receiver operating index better distinction between distinguishes survival outcomes
characteristic (AUROC). between MASLD and non-MASLD populations (Figure 1).
Result: The prevalence of advanced fibrosis were 20.8%, 27.6%, Conclusion: MASLD index demonstrates a superior ability to
54.9% and 31.9% in MASLD, MASLD with viral hepatitis, MetALD and distinguish survival differences among MASLD at high risk of mortality,
MASLD with other etiologies, respectively. FIB-4 and NFS showed enhancing the timely treatment and prognostication.
comparable AUROCs across all the include SLD sub-types. Compared Table and Figure:Figure 1.Figure 1. Kaplan-Meier survival curves were
with APRI, FIB-4 displayed higher AUROCs in MASLD (0.819 vs. 0.738, plotted based on the MASLD gold standard, MASLD INDEX, MAF-5,
P < 0.01) and MetALD (0.758 vs. 0.660, P < 0.01), while exhibiting US FLI, FLI, and HSI scores, with data from NHANES III (1988-1994).
similar AUROCs in other sub-types. Using the standard cutoffs to rule-
in/out, modest positive predictive values (PPVs) were observed in all
PP0510
the included disease spectrum. Negative predictive values (NPVs) of
all the NITs exceeded 90% (93.6%, 91.5%, and 92.2% respectively) in Risk factors of atherosclerotic plaque formation in metabolic
MASLD but not in other sub-types. dysfunction-associated steatotic liver disease
Conclusion: Established NITs can effectively exclude advanced Weihao Peng1
fibrosis in MASLD but require modification for MetALD and other 1
13951170827
combination etiologies. Background: The renaming of NAFLD to MASLD puts more emphasis
Table and Figure:Figure 1.Figure 1. Diagnostic performance of FIB- on metabolically related risk factors for steatotic liver disease. At
4, NFS, and APRI for staging advanced fibrosis (S ≥3) in steatotic present, the relationship between MASLD and the prognostic factors
liver disease with metabolic profile. (A) AUCs of non-invasive tests of dyslipidemia is still limited. Atherosclerosis is the manifestation of
in MASLD. (B) AUCs of non-invasive tests in MASLD-viral hepatitis lipid metabolism disorder in the arterial wall. The objective of this study
(including chronic hepatitis B and hepatitis C). (C) AUCs of non- was to assess the association of MASLD with atherosclerosis and its
invasive tests in MetALD. (D) AUCs of non-invasive tests in MASLD risk factors.
overlapped with other eitologies (including drug-induced liver injury, Method: A total of 5372 individuals who underwent carotid and
generic, hepatic vascular disease, and autoimmune liver disease). liver ultrasound were included at a single medical checkup center.
Figure 2.Figure 2. Clinical utility of the non-invasive tests for assessing Clinical data of the subjects were collected. Meanwhile, mendelian
advanced fibrosis (S ≥3) in MASLD, MASLD with viral hepatitis and randomization was used to verify the causal relationship between
MetALD using the standard cutoff points (≥2.67 for FIB-4, ≥0.676 for MASLD and cardiovascular and cerebrovascular vascular disease.
NFS, ≥1 for APRI to rule in advanced fibrosis; <1.3 for FIB-4, <-1.455 Result: MASLD was positively correlated with carotid artery plaque
for NFS, < 0.5 for APRI to rule out advanced fibrosis). (A) Performance (P<0.001, r=0.106), and the risk factors for MASLD patients to
of non-invasive tests in MASLD. (B) Performance of non-invasive tests develop carotid artery plaque were: AGE, GENDER, FPG, SBP. The
in MASLD-viral hepatitis. (C) Performance of non-invasive tests in logistic regression equation was: Logit(P)=1.067 * GENDER+0.103
staging advanced fibrosis in MetALD. * AGE+0.197 * FPG+0.008 * SBP-8.831. The area under the curve
(AUC) was 0.801 [95% CI = (0.782, 0.821)]. Mendelian randomization
PP0509 showed that MASLD was positively associated with coronary heart
disease (OR = 1.12, 95% CI = (1.01, 1.26), P = 0.04), between MASLD
Comparison of the efficacy of different non-invasive assessments
and heart failure [OR = 1.08, 95% CI = (1.03, 1.14), P = 0.002], as well
in identifying MASLD at high risk of mortality: A population-based
as between MASLD and cerebral infarction[OR = 1.0004, 95% CI =
study from NHANES III
(0.9996, 1.0012), P = 0.287]
Yajing Bo1, Xinyuan He1, Yunyu Zhao1, Ming Chen1, Yichen Yang1, Conclusion: MASLD is associated with carotid atherosclerotic plaque
Xubing Zhou1, Xiao Yuan1, Zhiluo Yang1, Fanpu Ji1,2, Ning Gao1 formation. And then, Patients with abnormal glucose metabolism in
1
the Second Affiliated Hospital of Xi’an Jiaotong University, 2Xi’an MASLD have a higher risk of atherosclerotic plaque. The incidence
Jiaotong University of atherosclerotic plaque in MASLD patients increased with age.
Background: Metabolic dysfunction-associated steatotic liver Meanwhile, there is a causal correlation between MASLD and
disease (MASLD) is the leading cause of chronic liver disease and cardiovascular disease.
contributes greatly to liver-related morbidity and mortality. Non- Table and Figure:Figure 1.Model performance in discrimination and
invasive assessment to identify the MASLD at early stage can facilitate calibration for predicting the risk of carotid plaque in population with
the prognostic evaluation, enhancing early detection, timely treatment, MASLD evaluated by ROC curves
and targeted care for affected individuals. Our study aims to compare Figure 2.The incidence of carotid plaque changes with age in MASLD
the efficacy of previous five indices, including the MASLD index, patients.
metabolic dysfunction-associated fibrosis (MAF-5), ultrasound fatty
liver index (US FLI), fatty liver index (FLI) and hepatic steatosis index
PP0511
(HSI) in identifying individuals at high risk of mortality from MASLD.
Method: Our study included participants aged 20 to 74 years from Incidence and Characterization of Small Intestinal Bacterial
National Health and Nutrition Examination Survey (NHANES) III (1988- Overgrowth (SIBO) in Non-Alcoholic Fatty Liver Disease (NAFLD)
1994) without heavy alcohol use. Abdominal ultrasound was used to Patients
identify the participants with MASLD. We plotted and compared the Shamim Nazir1, Zaigham Abbas2
cox proportional hazards model (Cox) and Kaplan-Meier survival 1
Dr Ziauddin Hospital Karachi Pakistan, 2Dr. Ziauddin University
curves of five indices above for assessing prognosis. Hospital Clifton Karachi
Result: A total of 7,942 participants were included in the study, 1,645 Background: The correlation between Small Intestinal Bacterial
of them were classified as MASLD, with 630 deaths during follow-up Overgrowth (SIBO) and Fatty Liver Disease has gained heightened
(38.30%). Cox regression analysis was conducted to evaluate the acknowledgment, especially in the late phases of liver disease. Despite
performance of MASLD index, MAF-5, US FLI, FLI, HSI in identifying this, studies focusing on the prevalence and specific characteristics of
the patients at high risk of mortality during the follow-up period. The SIBO within the NAFLD patient population in Pakistan remain sparse.
results showed that the Hazard Ratio (HR) for MASLD index was This research seeks to investigate the prevalence and characteristics
the highest among five indices (2.393 [2.203, 2.599], P < 0.001, of SIBO in patients with fatty liver disease in a tertiary healthcare facility
concordance = 0.606), followed by MAF-5 (2.336 [2.142,2.547]), US
in Karachi. Duration of AUD [F=18.6, CI(11.68-12.6), p<0.00)] and BDI (F=3.4,
Method: Conducted from July 2023 to March 2024 at Ziauddin Medical p=0.03) were found to be significantly associated with the early onset
University Hospital’s Clifton Campus, this prospective cross-sectional of Alcohol-associated related liver disease. Age at first drink [CI(17.90-
study included 65 adults aged 18 to 80 diagnosed with NAFLD via 18.63) p=0.170] and age at AUD diagnosis[CI( 29.16-29.83) p=0.102]
FibroScan®. SIBO diagnosis was determined by a Glucose Hydrogen however could not reach statistical significance for our sample.
Breath Test (GHBT), with an increase in hydrogen concentration Conclusion: Nearly one in 10 Met-ALD patients in India is below
of ≥20 ppm from the baseline within two hours indicating a positive 32 years of age, and 60% are associated with metabolic traits (Met-
result. Participant demographics, comorbid conditions, and clinical ALD). Beck’s depression inventory score positively correlated with the
symptoms were documented. development of Met-ALD. Addressing AUD and associated psychiatric
Result: Of the 65 individuals, 46 were male, with an average age conditions can provide essential insights for developing preventive
of 44.88 ± 12.30 years, a mean BMI of 26.45 ± 6.45 kg/m², and an strategies and focused interventions to mitigate the onset of Met-ALD.
average waist circumference of 95.20 ± 15.17 cm. Lean NAFLD was Table and Figure:Figure 1.Correlation table
observed in 40% of the participants. Frequent comorbidities included Figure 2.ANOVA table
diabetes (40%), hypertension (38%), and dyslipidemia (38%). SIBO
was identified in 37% of the subjects, 28% of whom were asymptomatic.
PP0513
Symptoms prevalent in SIBO-positive individuals were bloating (41%),
belching (26%), and abdominal pain (28%). Liver stiffness indicated Associations Between Sensitivity to Thyroid Hormones and
that 23% had F2 fibrosis, 28% had F3, and 49% had F4. CAP scores Hepatic Steatosis in People with Obesity
showed S1 steatosis in 37% of patients, S2 in 29%, and S3 in 34%. Yifang Zhang1
The presence of SIBO correlated with increasing fibrosis and steatosis 1
Tianjin Hongqiao District Wuyuan Road People‘s Hospital
levels. SIBO positivity was more prevalent in high Child-Pugh class Background: This study aimed to investigate the association between
and in more severe liver dysfunction. With post-treatment giving liver steatosis and fibrosis, which were evaluated by transient
Lactobacillus reuteri and Rifaximin for two weeks, only 4% remained elastography (TE), and thyroid hormone (TH) sensitivity in obese
SIBO-positive. Significant associations of SIBO were also noted with adults with normal thyroid function, so as to provide a basis for the
dyslipidemia, hyperuricemia, and irritable bowel syndrome. screening and management policies of fatty liver disease and liver
Conclusion: This research highlights a significant incidence of SIBO fibrosis in obese populations.
in NAFLD individuals, particularly those with severe liver damage and Method: This study included 453 obese outpatients from the Health
comorbidities. It stresses the importance of regular screening for SIBO Management Center of Tianjin People’s Hospital. General information,
in such patients, suggesting that timely detection and intervention body composition, and biochemical indicators were collected. Thyroid
could enhance patient outcomes. sensitivity indices were calculated, including the ratio of FT3 to FT4, the
thyroxine feedback quantile index for FT4 (TFQI-FT4), and the thyroxine
PP0512 feedback quantile-based index for FT3 (TFQI-FT3). The ratio of FT3 to
FT4 represented peripheral thyroid hormone sensitivity, while TFQI-FT4
Development of Metabolic dysfunction and Alcohol-associated
and TFQI-FT3 were used to indicate central thyroid hormone sensitivity.
Liver Disease(Met-ALD) in Young Indian Adults : An Observational
The vibration-controlled transient elastography (VCTE) technique was
Study of Clinical and Socio-Demographic Correlates and
used to diagnose and quantify liver steatosis and fibrosis. The degrees
opportunities for Integrated and early intervention
of liver steatosis and fibrosis were evaluated through CAP (Controlled
Mohit Kumar Varshney1, Shiv Kumar SARIN1 Attenuation Parameter) and LAM (Liver Stiffness Measurement).
1
Institute of liver and biliary sciences According to the quartiles of the thyroid hormone sensitivity index
Background: The global trend indicates a decreasing age of onset TFQI-FT3, the study subjects were divided into four groups (Q1,
for Alcohol Use Disorder (AUD) and Metabolic Dysfunction associated Q2, Q3, Q4). Logistic regression and linear regression were used to
Liver Disease (Met-ALD). This study aims to analyse the clinical and explore the relevant correlations.
socio-demographic factors correlating with AUD in Indian patients Result: Compared with the lowest quartile group of TFQI-FT3, there
with Met-ALD under 35 years of age. Special efforts were done to were statistically significant differences in gender, age, BMI, HOMA-
determine the at our tertiary care liver hospital. IR, GGT, ALT, AST, TG, HDL-C, CAP, and LSM in the highest quartile
Method: Altogether, 888(10.06% of total Met-ALD) patients diagnosed group of TFQI-FT3.Spearman correlation analysis indicated that liver
with Met-ALD were under 32 years of age in the past decade (2015- steatosis was positively correlated with BMI (r = 0.276, P < 0.001),
2024) at our centre. We included retrospective data of patients of young positively correlated with FT3 (r = 0.17, P < 0.001), positively correlated
ALD with recent relapse, presenting to our centre, currently following with TFQI-FT3 (r = 0.166, P < 0.001), and positively correlated with the
up in Hepatology OPDs until 35 years of age(n=62). Additionally, we ratio of FT3 to FT4 (r = 0.097, P = 0.04).After adjusting for confounding
also prospectively included youngMet- ALD attending the AUD clinic factors, logistic regression showed that the risk of liver steatosis was
for six months(n=144). Young Met-ALD was defined as Met-ALD first positively correlated with the levels of FT3 (OR= 2.16, 95%CI,1.16 -
diagnosed under 32 years of age (histological/radiological/endoscopic 4.02) and TFQI-FT3 (OR = 3.38, 95% CI 1.01 - 11.35).The results of the
evidence). Informed consent was obtained from prospective patients receiver operating characteristic (ROC) curve analysis for predicting
Result: Two hundred six patients with AUD, 31.39 ± 2.8 years, 202 liver steatosis by FT3, TFQI-FT3, and the ratio of FT3 to FT4 (area under
males, 98.1% with some form of decompensation, MELD (25.13 ± the curve) were 0.643, 0.639, and 0.581 (P < 0.05), respectively, and
6.83), CTP (10.13 ± 1.9) who presented with to our centre at various the cut-off values were 4.2, 0.061, and 0.269, respectively.
stages of ALD were evaluated. There were 45.6% CLD-MetALD, Conclusion: Reduced central TH sensitivity was associated with
39.8% ACLF (APASL definition) with AARC score of (9.35± 2.3) and abnormally elevated liver steatosis in obese patients and can be
14.56% SAH. Metabolic traits were present in 61.6% patients and used for the early screening of Metabolic Associated Steatohepatitis
had Metabolic traits & 59.7% had BMI ≥23. A positive correlation of Disease (MASLD). Our research findings have supplemented the
Beck’s Depression Inventory Score, BDI (r=0.207, p=0.009) was evidence regarding the importance of thyroid hormone (TH) sensitivity
found with the quantity of alcohol consumed in grams/week. Binge to MASLD.
drinking (df=2, p<0.01) and Daytime drinking (df=2, p<0.01) were
significant across the three diagnoses. Group-wise analysis revealed
PP0514
a positive correlation of quantity of alcohol intake (1000±54.2) grams/
week) with MELD (r=0.239, p=0.030), CTP (r=0.346, p=0.001) and Prediabetes (PreDM) and diabetes mellitus type 2 (DM) are strongly
AARC (r=0.259, p=0.019) score in the ACLF group. On the basis of associated with severe liver steatosis and advanced fibrosis in
ANOVA, MELD (F=15.14, p<0.00), CTP (F=13.38, p<0.00) and AARC metabolic dysfunction-associated steatotic liver disease (MASLD)
(F=88929, p<0.00) were found to be significantly correlated with early patients
onset liver disease (F=5.02, p=0.007) across the three diagnoses. Sasunova Armida1, Alexey Goncharov1, Vasily Isakov1
1
Federal Research Centre of Nutrition, Biotechnology and Food safety prevalence of severe liver steatosis.
Background: Metabolic dysfunction-associated steatotic liver disease Table and Figure:Figure 1.Figure. Energy consumption (kcal/ day) of
(MASLD) is considered the most common chronic liver disease. This DM+ and DM- patients from food groups
study aims to clarify the relationship between MASLD and carbohydrate
metabolism disorders, including prediabetes (preDM) and type 2 PP0516
diabetes mellitus (DM). Metabolic dysfunction-associated steatotic
Evaluation of NAS and Fibrosis Stage of Non-Alcoholic
liver disease (MASLD) is considered the most common chronic liver
Steatohepatitis in Pediatric Patients Across Different Age Groups
disease. This study aims to clarify the relationship between MASLD
Peng Xu1, Shuhong Liu1, Yi Dong1, Jianguo Yan1, Lili Cao1, Dong Ji1,
and carbohydrate metabolism disorders, including prediabetes
Jingmin Zhao2, Min Zhang1
(preDM) and type 2 diabetes mellitus (DM).
Method: A retrospective analysis of data of 2075 MASLD patients
1
Department of Senior Infectious Diseases, The Fifth Medical Center
was conducted The stages of liver steatosis and fibrosis were of Chinese PLA General Hospital, 100 Western 4th Ring Middle Road,
Beijing 100039, China, 2The Fifth Medical Center of Chinese PLA
assessed using vibration-controlled transient elastography (VCTE)
General Hospital
with a controlled attenuation parameter (CAP) for ultrasound signal
attenuation. According to clinical guidelines, all patients were Background: Non-alcoholic fatty liver disease (NAFLD) has become
classified as: MASLD without prediabetes or DM (MASLD+/preDM-/ the predominant etiology of chronic liver disease in children and
DM-, n=1334), MASLD with prediabetes (preDM+, n=230), and adolescents, liver biopsy remains the diagnostic golden standard
MASLD with DM (DM+, n=511). The study was funded by the Russian for NAFLD in pediatric populations. NAFLD Activity Score (NAS),
Science Foundation (Project No. 19-76-30014). developed by the U.S. NASH Clinical Research Network (CRN) is a
Result: The prevalence of severe liver steatosis (stage S3) did not differ primary scoring systems used in pediatric NASH diagnosis, which
between the preDM+ and DM+ groups but was lower in the MASLD+/ is commonly employed in clinical trials assessing pharmacological
preDM-/DM- group (Figure 1). The prevalence of liver fibrosis (stages interventions. Thus, the application of the NASH_CRN scoring system
F2-F4) differed among the three groups: the lowest prevalence was to evaluate histopathological changes in pediatric NASH across
observed in the MASLD+/preDM-/DM- group, while the highest was various age groups is critical for enhancing diagnostic accuracy and
in the DM+ group (Figure 2). Absence of liver fibrosis (F0) was found therapeutic decision-making.The aim of this study is to investigate the
in majority (69%) of MASLD+/preDM-/DM- patients. The prevalence characteristics of NASH_CRN scoring in pediatric patients with NASH
of metabolic-associated steatohepatitis (MASH) did not differ between across different age groups.
the preDM+ and DM+ groups (33.9% vs. 35.4%; p=0.7) but was lower Method: A total of 221 children aged 4–18 years with NASH were
in the MASLD+/preDM-/DM- group (26.7% vs. 33.9% and 35.4%; enrolled in this retrospective study, they were divided into three age
p=0.02 and p<0.001, respectively). groups: 4-12 years group(>4 and ≤12), 12-15 years group (>12 and
Conclusion: Carbohydrate metabolism disorders are strongly ≤15), and 15-18 years group (>15 and ≤18). The NAS and fibrosis
associated with advanced liver steatosis and fibrosis in MASLD stages(FS) were assessed using the NASH-CRN scoring system.
patients. Differences in the distribution of NAS and FS across the age groups
Table and Figure:Figure 1.Figure 1. Distribution of the stages of liver were statistically analyzed.
steatosis among studied groups Result: The patients comprised 191 male (86.4%), with 124 in the 4-12
Figure 2.Figure 2. Distribution of the stages of liver fibrosis among years group, 48 in the 12-15 years group, and 49 in the 15-18 years
studied groups group. All subjects had a NAS score ≥4. The NAS distribution in the
4-12 years group, score 4,5,6,7 were 12 (9.7%) , 46 (37%) , 56 (45.2%)
,and 10 (8.1%) cases respectively; In the 12-15 years group, score
PP0515 4,5,6,7 were 5 (10.5%) ,19 (39.6%), 23 (47.9%), and 1 (2.0%) cases
Diabetes mellitus (DM) in patients with metabolic dysfunction- respectively ;In the 15-18 years group, score 4,5,6,7 was 17 (34.7%),
associated steatotic liver disease (MASLD) is associated with an 17 (34.7%), 14 (28.6%), and 1 (2.0%) cases respectively. A significant
increased consumption of saturated fatty acids and higher liver difference in NAS distribution was observed across age groups (P =
steatosis grades. 0.002), with younger patients more frequently exhibiting higher NAS
Vasily Isakov1, Sasunova Armida1, Alexey Goncharov1 scores.
1
Federal Research Centre of Nutrition, Biotechnology and Food safety Fibrosis staging distribution in the 4-12 years group, the FS 0,1,2,3 were
7 (5.7%) ,48 (38.8%) ,29 (23.3%) ,and 40 (32.2%) cases respectively;
Background: MASLD is often associated with DM and is treated with a
In the 12-15 years group, the FS 0,1,2,3 were 1 (2.1%) ,26 (54.2%)
combination of drugs and a low-carbohydrate diet. This study aimed to
,10 (20.8%),and 11 (22.9%) cases respectively; In the 15-18 years
compare the dietary patterns of MASLD patients with and without DM.
group, the FS 0,1,2,3 were 8 (16.4%), 29 (59.2%), 5 (10.2%), and 7
Method: The dietary intake of sex- and age-matched pairs of 158
(14.2%) cases respectively. A significant difference in FS distribution
patients with MASLD (79 DM+ and 79 DM-) was assessed using a
was also noted across the three age groups (P = 0.003), with a higher
semi-quantitative food frequency questionnaire during a personal
proportion of younger children showing advanced stages of fibrosis.
interview, evaluating the consumption of 100 grouped food items. The
Conclusion: The NAS and fibrosis scores of NASH patients aged
stages of liver steatosis and fibrosis were determined using vibration-
4-18 years decreased with age, suggesting that pubertal growth and
controlled transient elastography (VCTE) with a controlled attenuation
development may confer benefits in alleviating NASH.
parameter (CAP). The study was funded by the Russian Science
Table and Figure:Figure 1.NAS distribution in different age groups of
Foundation (Project No. 19-76-30014).
children with NASH
Result: No differences were observed between DM+ and DM- patients
Figure 2.Fibrosis stage distribution in different age groups of children
in terms of daily consumption of energy, protein, fats, or carbohydrates.
with NASH
However, the DM+ group consumed twice as much red meat products
(21.4 [6.7; 62.1] vs. 10.7 [2.1; 32.1] g/day; p=0.003), processed fish
(2.5 [0.2; 13.3] vs. 1.3 [0; 6.7] g/day; p=0.02), and citrus fruits (59.9 PP0517
[10.0; 85.6] vs. 28.5 [6.7; 49.9] g/day; p=0.01), while consuming less Exploring the Relationship Between Serum Ferritin and Metabolic-
added sugar (0 [0; 3.0] vs. 0.1 [0; 6.5] g/day; p=0.03). DM+ patients Associated Fatty Liver Disease in Adolescents Based on NHANES
consumed at least 200 kcal/day more from saturated fats compared Database
to DM- patients (figure). Prevalence of severe liver steatosis (S3) was
Liu Mengmeng1, Fei Yue1, Xu Xiahong1, Li Xue1, Lin Han2, Huang
higher in DM+ patients (82,2% vs 63,2%, p=0,011).
Zhenghaoyu2, Guo Yonghong1
Conclusion: Analysis of dietary patterns of MASLD patients with 1
Department of Infectious Disease,Shanghai Pudong New Area
and without DM revealed a higher consumption of saturated fats by
Gongli Hospital,219 Miaopu Road, Shanghai,200135,China, 2School
patients with DM for their energy balance, which can explain the higher
of Gongli hospital Medical Technology,University of Shanghai for
Science and Techonology, Shanghai 200093, China investigate the influence of MAFLD on the risk of cirrhosis and HCC
Background: Abnormalities in iron metabolism play a critical role in in CHB patients.
the development and progression of metabolic-associated fatty liver Result: At baseline, 76 CHB patients were concurrent with MAFLD
disease (MAFLD). However, the relationship between serum ferritin (40.4%). During a median follow-up of 7.41 years, 4 (5.3%) patients
levels and MAFLD in adolescents remains unclear. This study aims (3 cirrhosis, 1 HCC) in the MAFLD group and 6 (5.4%) patients (5
to investigate the association between serum ferritin levels and cirrhosis, 1 HCC) in the non-MAFLD group developed cirrhosis or
adolescent MAFLD using data from the National Health and Nutrition HCC, respectively (log-rank p=0.94). In our cohort, neither univariate
Examination Survey (NHANES). nor multivariate analyses showed that MAFLD had a significant impact
Method: This study utilized data from the 2017~2020 NHANES the incidence of cirrhosis and HCC. However, in subgroup analysis,
database, ultimately including 559 adolescents aged 12~18 years, MAFLD showed different effects in the overweight and normal weight
divided into the MAFLD group (119 cases) and the non-MAFLD subgroups (p for interaction = 0.001), with a protective effect in the
group (440 cases). Data on demographic characteristics, serum iron overweight subgroup (aHR 0.01, 95% CI 0.0002 – 0.54, p=0.023), and
metabolism indicators, liver function, lipid profiles, glucose levels, and a risk effect in the normal weight subgroup (aHR 8.28, 95% CI 1.06 –
other relevant parameters were collected. Liver steatosis and fibrosis 64.60, p=0.044) (adjusted for gender, age, BMI and waist-to-hip ratio
were assessed using vibration-controlled transient elastography (WHR)). After balancing potential confounding variables using IPTW,
(VCTE). Pearson correlation and logistic regression analysis were MAFLD was associated with a lower risk of cirrhosis and HCC (IPTW-
performed to evaluate the relationship between serum ferritin and aHR 0.11, 95% CI 0.022-0.59, p=0.010) (adjusted for gender, age and
MAFLD. overweight). In addition, IPTW analysis were conducted separately in
Result: Serum ferritin levels were significantly higher in the MAFLD overweight and normal weight patients, which revealed that MAFLD
group compared to the non-MAFLD group (P<0.05). Pearson correlation was associated with a lower risk of cirrhosis and HCC in overweight
analysis indicated that serum ferritin was positively correlated with the subgroup (IPTW-aHR 0.11, 95% CI 0.014-0.82, p=0.032), while was
controlled attenuation parameter (CAP), liver stiffness measurement associated with a higher risk of cirrhosis and HCC in normal weight
(LSM), body Mass Index (BMI), alanine aminotransferase (ALT), subgroup (IPTW-aHR 11.5, 95% CI 1,91 – 68.8, p=0.008) (adjusted for
gamma-glutamyl transferase (GGT), hemoglobin, and uric acid levels gender and age).
(P<0.05), but negatively correlated with high-density lipoprotein Conclusion: The influence of MAFLD on the risk of cirrhosis and HCC
cholesterol levels (P<0.05). Logistic regression analysis revealed in patients with CHB may be distinct in overweight and normal weight
that while the risk of MAFLD significantly increased in the highest subgroups, with a lower risk in overweight patients and a higher risk in
quartile of serum ferritin (Q4) without adjusting for covariates, this normal weight patients.
association disappeared after adjusting for gender, age, race, BMI, Table and Figure:Figure 1.
and other factors. BMI (OR = 1.250, 95% CI = 1.176~1.329), globulin
(OR = 2.991, 95% CI = 1.218~7.343), ALT (OR = 1.052, 95% CI = PP0519
1.003~1.104), and white blood cell count (OR = 1.225, 95% CI =
The Construction of a Combined Predictive Model based on the
1.041~1.441) were identified as independent risk factors for MAFLD.
Association Between Metabolic Associated Fatty Liver Disease
Conclusion: Serum ferritin levels are significantly elevated in
and Hyperglycemia in a Health Examination Cohort
adolescents with MAFLD but are not independently associated with
Sha Wu1,2, Daiyi Zhang3, Jin Li1, Qinkao Xuan4, Xiaodong Qian4,
the occurrence of MAFLD. BMI, globulin, ALT, and white blood cell
Chuanwu Zhu1, Jianhong Pu3, Li Zhu1,2
count are important risk factors for adolescent MAFLD.
Table and Figure:Figure 1.Correlation between SF and covariates
1
Department of Infectious Diseases, The Affiliated Infectious Disease
Figure 2.Multivariate logistic regression analysis of risk factors Hospital of Soochow University (Suzhou Fifth People‘s Hospital),
Suzhou, Jiangsu, China, 2Suzhou Medical College, Soochow
associated with MAFLD
University, Suzhou, Jiangsu, China, 3Health Examination Center, The
First Affiliated Hospital of Soochow University, Suzhou, Jiangsu,
PP0518 China, 4Department of Cardiovascular Medicine, The First Affiliated
The Influence of Metabolic Dysfunction-Associated Fatty Liver Hospital of Soochow University, Suzhou, Jiangsu, China
Disease on the Risk of Cirrhosis and Hepatocellular Carcinoma in Background: The global prevalence and incidence of Metabolic
Patients with Chronic Hepatitis B Associated Fatty Liver Disease (MAFLD) co-occurring with Type 2
Zixiang Huang1, Jilian Fang2, Dan Guo3, Zixing Wang2, Yafan Wang4, Diabetes Mellitus (T2DM) are on the rise, significantly increasing the
Qian Jin2, Danli Ma2, Huiying Rao2, Feng Liu2, Nan Wu2 risk of liver-related adverse outcomes and presenting a major public
1
Peking University People‘s Hospital, Peking University Hepatology health challenge. Despite its importance, the impact of MAFLD
Institute, Infectious Disease and Hepatology Center of Peking combined with hyperglycemia on liver disease progression and the
University People‘s Hospital, Beijing Key Laboratory of Hepatitis associated risk factors remains inadequately understood. This study
C and Immunotherapy for Liver Diseases, Beijing International aims to evaluate the effect of hyperglycemia on hepatic steatosis and
Cooperation Base for Science and Technology on NAFLD Diagnosis, liver fibrosis in MAFLD and identify the key factors influencing the
Peking University Health Science Center, Beijing 100044, China, development of hyperglycemia in MAFLD patients.
2
Peking University People‘s Hospital, Peking University Hepatology Method: Data from 18,286 participants undergoing health
Institute, Infectious Disease and Hepatology Center of Peking examinations. From this cohort, a subgroup of individuals with MAFLD
University People‘s Hospital, Beijing Key Laboratory of Hepatitis was identified and stratified into three categories based on their
C and Immunotherapy for Liver Diseases, Beijing International FIB-4 scores: T1 (FIB-4 < 1.3), T2 (1.3 ≤ FIB-4 ≤ 2.67), and T3 (FIB-
Cooperation Base for Science and Technology on NAFLD Diagnosis, 4 > 2.67). Clinical indicators were compared among these groups.
Beijing 100044, China, 3Peking University Health Science Center, Additionally, the MAFLD cohort was divided into two subgroups:
Beijing 100044, China, 4Peking University People‘s Hospital, Beijing MAFLD with hyperglycemia and MAFLD without hyperglycemia, and
100044, China differences in hepatic steatosis and liver fibrosis-related indicators
Background: Chronic hepatitis B (CHB) concurrent with metabolic were analyzed. Univariate and multivariate logistic regression analyses
dysfunction-associated fatty liver disease (MAFLD) is common in were performed to identify key factors associated with hyperglycemia
clinic. However, the influence of MAFLD on the risk of cirrhosis and in MAFLD patients. The predictive performance of a combined model
hepatocellular carcinoma (HCC) in CHB patients remains inconclusive. for hyperglycemia in MAFLD was evaluated using receiver operating
Method: In this longitudinal cohort study, 188 CHB patients receiving characteristic (ROC) curve analysis.
continuous anti-viral therapy were enrolled from August 2014 to July Result: Among the T1, T2, and T3 groups, clinical indicators such as
2016 and followed up until July 2024. Kaplan-Meier analysis, univariate hypertension, age, FBG, HbA1c, PLT, RBC, and estimated glucose
and multivariate Cox regression analysis, subgroup analysis and disposal rate (eGDR) exhibited highly significant differences (P <
inverse probability treatment weighting (IPTW) were performed to 1.00E-35). Comparisons between the MAFLD with hyperglycemia
group and the MAFLD without hyperglycemia group revealed Time trends in Trivandrum Cohorts of Metabolic dysfunction
significantly higher levels of hepatic steatosis and liver fibrosis Associated Steatotic Liver Disease
indices in the hyperglycemia group (P < 0.01). Logistic regression Shenoy T Kotacherry1,2, Leena K B3, Jayakumar P Pillai4, Guruprasad
analyses identified smoking, hypertension, hyperlipidemia, age, WC, Aithal P5
RBC, NEUT, ALT, TG, HDL-C, UA, Cr, BUN, and ALP as key factors 1
Sree Gokulam Medical College and Research Foundation Dept. of
influencing hyperglycemia in MAFLD (P < 0.05). ROC curve analysis Gastroenterology , 2Director Population Health and Research Institute
demonstrated that age, hyperlipidemia, WC, TG, and HDL-C had , 3Population Health and Research Institute , 4Senior Biostastician
moderate predictive accuracy for hyperglycemia in MAFLD (0.7 ≤ AUC Population Health and Research Institute, 5Nottingham Digestive
≤ 0.85). A predictive model incorporating these five factors achieved Diseases Centre
an area under the curve (AUC) of 0.898 (95% CI: 0.886–0.911), with a Background: MAFLD shows a high prevalence over time. We are
sensitivity of 87% and specificity of 70.5%. reporting three cohorts of MASLD from southern Kerala in India
Conclusion: Hyperglycemia exacerbates hepatic steatosis and liver Method: We evaluated thre population cohorts : Cohort 1 : 2005-2006
fibrosis in patients with MAFLD. Furthermore, age, hyperlipidemia, (484 subjects) ; Cohort II : 2013-2016 ( 2222 subjects) and Cohort III
WC, TG, and HDL-C were identified as significant risk factors for : May 2022 to September 2023 , 2846 participants . All were recruited
hyperglycemia in MAFLD. The predictive model combining these five through multistage cluster sampling. Using the recent criteria for
indicators demonstrated high accuracy, offering a valuable tool for the MAFLD, we reanalysed the data.
early identification of hyperglycemia in MAFLD patients and providing Result: Cohort 1: 52.9% males and 47.1% females. Metabolic
a reference for clinical decision-making. risk factors included diabetes (24.8%), hypertension (50.8%) and
prevalence of NAFLD (39.9%) and MASLD (38.0%);increased waist
PP0520 circumference (64.9%), elevated triglycerides (23.1%), low HDL
MAFLD and IBD: A Crossroad of Metabolic Risk and Disease Flare (23.1%).
Cohort II: MASLD prevalence was 48.2 % ( males 45.7 and females
Pulkit Mehrotra1, Punit Mehrotra2, Vengadakrishnan K3
54.3%) and the NAFLD prevalence was 49.8% .MASLD Odds ratios
1
Ramachandra Medical Center, Chennai, 2Lucknow gastro-gynae
after adjusting for age, sex, domicile, BMI category (with normal
center , Lucknow, 3Sri Ramachandra Medical Center, Chennai
weight as baseline), diabetes and metabolic syndrome are in Table 1.
Background: The convergence of Metabolic-Associated Fatty Liver Cohort III: MASLD prevalence was 65.8% (95% CI 64-67.52 %%).
Disease (MAFLD) and inflammatory bowel disease (IBD) represents Mean age was 51.71 years. Median Stiffness of liver >10.2 was seen in
a nuanced and insufficiently explored area within gastroenterology. 20.5% in MASLD compared to those without MASLD (13.2%: p<0.001)
Although international studies indicate a rising prevalence of MAFLD MASLD 65.8% (95% CI 64-67.52 %%). Age (Ref- <50 years) Ad OR
among IBD patients, comprehensive data addressing this overlap ( 95% CI) 1.23(1.1 - 1.46);Gender (Ref- Female)Ad OR ( 95% CI)
in the Indian population remain sparse. This study investigates the 2.14(1.63 - 2.47);Domicile (Ref- Rural)Ad OR ( 95% CI) 1.2(0.99 - 1.45;
prevalence of MAFLD and liver fibrosis in Indian IBD patients, evaluates Diabetes Adj OR ( 95% CI) 1.77(1.41 - 2.19)Metabolic syndrome : Ad
its associations with metabolic and clinical factors, and examines its OR ( 95% CI) 1.57(1.23 - 1.98) Conclusion MASLD is prevalent in 66%
implications for disease relapse, adhering to the 2023 Asian Pacific of general population and the main risk factors are obesity, diabetes
Association for the Study of the Liver (APASL) guidelines for MAFLD. and metabolic syndrome. Population based life style interventions are
Method: A retrospective cohort study was conducted involving 281 needed
IBD patients (ulcerative colitis and Crohn’s disease) presenting to a Conclusion: MASLD is prevalent in 66% of general population in
tertiary care center between January 2022 and December 2023. a recent cohort and the main risk factors are obesity, diabetes and
MAFLD was diagnosed in accordance with APASL 2023 guidelines, metabolic syndrome. Population based life style interventions are
incorporating metabolic dysregulation criteria and hepatic steatosis needed
assessed via FibroScan-based controlled attenuation parameter Table and Figure:Figure 1.Table 1: Risk factors for MASLD in Cohort II
(CAP). Liver fibrosis was evaluated using liver stiffness measurement
(LSM). Disease severity was classified using the Mayo scoring system
for ulcerative colitis and the Montreal classification for Crohn’s disease. PP0522
Patients with other chronic liver diseases were excluded. Data included Accuracy of non-invasive tools for diagnosis of metabolic
demographics, metabolic profiles, disease phenotypes, and clinical disfunction associated steatotic liver disease (MASLD) in primary
outcomes, with a focus on relapse rates. care settings: Russian experience
Result: MAFLD was identified in 35% of the cohort, with significant Alexey Goncharov1, Vasily Isakov1, Sasunova Armida1, Camilat
fibrosis observed in 1.5% of cases. Patients with MAFLD had a median Gapparova1, Yulia Chekhonina1
age of 45 years, exhibited a higher body mass index (BMI), and were 1
Federal Research Centre of Nutrition, Biotechnology and Food safety
more frequently diagnosed with metabolic comorbidities, including
Background: Metabolic dysfunction-associated steatotic liver disease
type 2 diabetes mellitus and dyslipidemia (p < 0.05). Elevated BMI
(MASLD) is the most common chronic liver disease; therefore, accurate
(OR 1.42, 95% CI 1.18–1.76) and older age at IBD diagnosis (OR 1.09,
and early diagnosis is important in primary care settings. The aim of
95% CI 1.03–1.14) emerged as independent predictors of MAFLD.
this study was to assess the diagnostic accuracy of non-invasive tools
Notably, the presence of hepatic steatosis correlated significantly with
for detecting liver steatosis [fatty liver index (FLI), hepatic steatosis
increased rates of clinical relapse, whereas advanced fibrosis did not
index (HSI), NAFLD liver fat score (NAFLD-LFS)] and fibrosis [fibrosis-4
independently contribute to relapse risk.
(Fib4), fibrosis-8 (Fib8), NAFLD fibrosis score (NFS)].
Conclusion: MAFLD, as defined by APASL 2023 criteria, is a frequent
Method: Steatosis (FLI, HSI, NAFLD-LFS) and fibrosis (Fib4, Fib8,
comorbidity among Indian IBD patients, particularly in those with
NFS) indices were calculated based on anthropometric and blood
higher BMI and metabolic risk factors. Hepatic steatosis notably
analysis data of 3470 patients in whom vibration-controlled transient
increases the risk of disease relapse, emphasizing the importance
elastography (VCTE) with a controlled attenuation parameter (CAP) for
of early detection and integrated management of MAFLD within this
ultrasound signal attenuation was performed. For each test, sensitivity,
population. These findings underscore the need for a multidisciplinary
specificity and accuracy were calculated, and AUROCs were
approach to optimize care and outcomes for patients managing
constructed considering the VCTE and CAP measurement values (7,2
both IBD and MAFLD. Further research is essential to elucidate the
kPa and 248 dB/m) as a diagnostic threshold. The study was funded
underlying pathophysiological mechanisms and to explore targeted
by the Russian Science Foundation (Project No. 19-76-30014).
therapeutic strategies.
Result: After excluding patients with other liver diseases, data from
the MASLD (n=2075) and control (n=1350) groups were analyzed. The
PP0521 sensitivity, specificity and accuracy for detecting of liver steatosis and
fibrosis are shown in the table. The FLI index showed the best AUROC
(0.93) compared with the HSI (0.89) and NAFLD-LFS index (0.85). The liver disease (MASLD). Pemafibrate, a PPARα modulator developed
NFS index demonstrated the best AUROC (0.92) compared to the Fib4 in Japan, reduces neutral fat synthesis. PPARα is abundant in the liver
index (0.91) and Fib8 index (0.88). and crucial for lipid homeostasis. Few reports exist about pemafibrate’s
Conclusion: Among the studied non-invasive tools, the FLI index effect on steatotic liver disease (SLD) patients and predictive factors
showed the best sensitivity and specificity for diagnosing liver for treatment efficacy.
steatosis, whereas the NFS index performed best for diagnosing liver Method: We analyzed changes over time (before administration, and
fibrosis at stage F2 and above. at 3, 6, and 12 months after administration) in liver and biliary enzymes,
Table and Figure:Figure 1.Table. Sensitivity, specificity and accuracy of lipid tests, Fib-4 index, ALBI score, and liver fibrosis markers in 57
liver steatosis and fibrosis indices SLD patients treated with pemafibrate for over 3 months at our hospital
between February 2019 and December 2023. Statistical analyses
included chi-square test, Mann-Whitney U test, repeated ANOVA, and
PP0523
binary logistic regression.
Estiamted glucose disposal rate as a novel index in diabetic Result: The average observation period was 17.8 months, with patients
patients with metabolic syndrome for estimation of liver fat averaging 62.8 years old (40 men, and 17 women). Average alcohol
content index consumption was 160.3 g/week, with 45/6/6 cases of MASLD/MetALD/
Hanieh Radkhah1, Diar Zooravar1 ALD. Pemafibrate significantly improved triglyceride (TG) levels
1
Departement of internal medicine sina hospital (386.1>220.8>211.3>205.2 mg/dL, p<0.01) and gamma-glutamyl
Background: The estimated glucose disposal rate (eGDR), an transferase (γGT) levels (75.7>49.3>45.3>47.7 U/L, p<0.01). The
effective indicator of insulin resistance, has been related to differrent levels of γGT at 3 and 6 months post-administration were significantly
Insulin resistance related syndromes like diabetic microvascular higher in the MetALD group than in the MASLD group (p<0.01). TG
complications . To our knowlege there is not any study for estimation levels at 6 months post-administration were also higher in the MetALD
of liver fat content by this novel score in patients with and without group (p<0.05). After 12 months, the MetALD+ALD group had
Non Alcoholic Fatty liver disease and metabolic syndrome. This significantly higher TG and γGT levels than the MASLD group (TG:
retrospective crosssectional study aims to explore the relationship 300.1 vs 180.6 mg/dL, γGT: 74.2 vs 41.4 U/L, p<0.05).
between eGDR and Liver fat content score in diabetic patients with Conclusion: In the MetALD/ALD group, TG and liver damage
metabolic syndrome . persisted after pemafibrate administration compared to the MASLD
Method: patients who visited in a metabolic clinic in IRAN ,with group. Evaluating alcohol consumption before treatment may help
metabolic syndrome and diabetes mellitus were included in the study. prediction of the therapeutic effect.
excluding cirhosis ,viral hepaitis and alcohol insumption.
Demographic and metabolic datas were collected from database. The PP0525
diagnosis of non-alcoholic fatty liver disease (NAFLD) was established
The Relationship Between the Recently Renamed“Metabolic-
based on relevant clinical criteria. The estimated glucose disposal rate
Associated Fatty Liver Disease ” and Colorectal Cancer
(eGDR), expressed in mg/kg/min, was calculated as: 21.158 - (0.09
× waist circumference in cm)- (3.407 × hypertension, 1=yes 0=no) - Liyue Hu1, Suyi Wang1, Quanwei Xu2, Wei Ni3
(0.551 × HbA1c%). The normality of numeric variables was evaluated
1
School of Clinical Medicine,Hangzhou Normal University, 2The First
using the Kolmogorov-Smirnov test. The Mann-Whitney U test was People‘s Hospital of Yuhang District, Hangzhou, 3Affiliated Hospital of
applied to compare variables with non-normal distributions between Hangzhou Normal University
patients with and without NAFLD. Nominal variables were analyzed Background: “Non-alcoholic fatty liver disease (NAFLD)” has been
using the chi-square test. Multivariate linear regression was performed proposed since 1980 for more than 40 years.NAFLD is defined as
to assess the relationship between eGDR and liver fat content ( using fatty degeneration of more than 5% of liver cells, excluding long-term
NAFLD liver fat score) in patients with and without NAFLD. Three heavy drinking and other known causes of liver injury. The exclusive
models were utilized: Model 1 (unadjusted), Model 2 (adjusted for age diagnostic criteria for NAFLD do not reflect the complex etiology of the
and gender), and Model 3 (adjusted for age, gender, current smoking disease. NAFLD is closely related to metabolic factors, such as obesity,
status, TG, LDL, Chol, HDL, AST, ALT, and ALP). Restricted cubic spline hypertension, type 2 diabetes mellitus (T2DM), insulin resistance (IR),
(RCS) regression was employed to evaluate potential nonlinearity. and dyslipidemia.
Result: A total of 160 patients were included, comprising 73 patients In 2020, the international fatty liver expert panel issued a consensus
with NAFLD and 87 patients without NAFLD.There were no significant statement recommending that NAFLD be renamed“Metabolic
differences between the two groups in WC (p = 0.730), BMI (p = associated fatty liver disease (MAFLD)” and MAFLD adopt positive
0.848), or gender distribution (p = 0.255). disease diagnostic criteria. The statement emphasized the importance
Linear regression analysis revealed a significant inverse relationship of metabolic dysfunction in the pathogenesis of MAFLD, and the name
between eGDR and liver fat content (B = -1.012, SE = 0.120, p < change was supported by the Chinese Medical Association.
0.001) in Model 3. The relationship remained significant when stratified In 2023, Several international liver disease associations announced a
by NAFLD status: for patients with NAFLD (B = -1.553, SE = 0.190, p < multi-society Delphi consensus statement on a new nomenclature for
0.001) and those without NAFLD (B = -0.986, SE = 0.650, p < 0.001). fatty liver disease, recommending that NAFLD be renamed “metabolic
Conclusion: dysfunction associated fatty liver disease (MASLD)”. MASLD also
Low eGDR (an indicator of insulin resistance) levels are corolated to an confirmed the importance of metabolic abnormalities .
increased liver fat content scores in NAFLD patients ini IRAN. further In May 2024, the Chinese Society of Hepatology of the Chinese
prospective studies are still needed to reveal their relationship and its Medical Association suggested that the diagnosis and treatment of
relation to adverse outcomes. NAFLD should follow the actual situation in our country. It indicated
Table and Figure:Figure 1.eGDR crolation With liver fat content the English terms MASLD and MAFLD could be used together, and
MAFLD should be used first.
Colorectal Cancer (CRC) is a common gastrointestinal malignancy, and
PP0524
the International Agency for Research on Cancer (IARC) calculated the
Predictive Factors for the Therapeutic Effect of Pemafibrate in incidence and mortality of cancer worldwide in 2022, which showed
MASLD Patients that CRC ranked third in incidence, the second deadliest. In the 2022
Tomohide Kurahashi1, Atsushi Hosui1, Naoki Hiramatsu1 malignant tumor data of our country showed that CRC incidence rate
1
Department of Gastroenterology and Hepatology, Osaka Rosai ranks second and is the fourth leading cause of cancer death. The
Hospital high incidence and mortality of CRC pose a serious threat to the life
Background: Hypertriglyceridemia is a metabolic disorder meeting and safety of the people and cause a heavy disease burden.
the diagnostic criteria of metabolic dysfunction-associated steatotic Method: The relevant articles were searched by using the
keywords“NAFLD”, “MAFLD”, “MASLD”, and “CRC” in PubMed and
Cnki Advanced Search interface. Metabolic Associated Fatty Liver Disease from a Mechanobiology
Result: MAFLD/MASLD is closely related to obesity, hypertension, type Perspective: Cellular Responses and Disease Evolution
2 diabetes mellitus (T2DM), insulin resistance (IR), and dyslipidemia. At Yushan Li1, Haibo Zhang2, Junzhe Jiao1, Ning Wang1, Zhanjie Chang1,
the same time, CRC is related to abnormal metabolic factors, including Ruijuan Yan1, Jingtao Li1
fatty liver, obesity, diabetes, hypertension, dyslipidemia, and etc. 1
Hepatology Hospital, Affiliated Hospital of Shaanxi University of
Conclusion: Both MAFLD/MASLD and CRC are associated with Chinese Medicine, 2Basic medicine college of Shaanxi University of
abnormal metabolic factors. MAFLD and CRC share common risk Chinese Medicine
factors. The association between MAFLD/MASLD and its components
Background: Mechanobiology studies the effects of mechanical
and the development of CRC further exploration by relevant disciplines.
stimuli on the health, disease, and injury of organisms, as well as
By studying the relationship between MAFLD/MASLD and CRC, we
the mechanisms by which organisms perceive and respond to
can get the clinical regularity of CRC.
mechanical signals. Metabolic Associated Fatty Liver Disease(MAFLD)
encompasses the spectrum from simple steatosis to metabolic
PP0526 dysfunction-associated steatohepatitis (MASH) with interlobular
Histone Methylation as a Biomarker for MASH Progression to inflammation and ballooning hepatocytes, as well as cirrhosis and
Hepatocellular Carcinoma hepatocellular carcinoma. The effects of imbalances in the homeostasis
Xinlei Qi1, Anna Li1, Xi Guan1, Junzhe Jiao1, Ruijuan Yan1, Zhanjie of the mechanistic microenvironment on liver cells are present
Chang1, Haibo Zhang2, Jingtao Li1 throughout MAFLD. This imbalance is crucial for the development of
MAFLD. Liver cells can sense mechanical stimuli and convert them
1
Hepatology Hospital affiliated Hospital of Shaanxi University of
into biochemical signals through mechanotransduction. This study
Chinese Medicine, 2Basic medicine college of Shaanxi University of
Chinese Medicine aimed to systematically analyze the mechanobiological mechanisms
during the development of MAFLD at the cellular level to reveal the
Background: Histone methylation is a dynamic, reversible epigenetic current status of its growth and future evolutionary trends.
modification regulated by readers, writers, and erasers. It’s closely Method: This study reviews literature on classical cell
linked to HCC occurrence and progression, and is a potential mechanotransduction pathways. It analyzes cellular mechanistic
biomarker and intervention target for MAFLD/MASH to HCC transition. microenvironment changes and effects on liver cell processes
This article analyzes histone methylation’s mechanism in this transition in MAFLD. It also summarizes recent mechanodiagnosis and
and HCC progression, offering potential intervention and treatment mechanotherapy advances, aiming to provide a comprehensive and
targets for HCC. in - depth understanding of the field.
Method: A systematic review on histone methylation’s role in MAFLD/ Result: Alterations in the mechanistic microenvironment are key factors
MASH to HCC progression, covering its manifestations in MASH, liver driving MAFLD progression. Lipid droplet growth in hepatocytes
fibrosis/cirrhosis, and HCC, focusing on the link between H3K4, H3K9, and increased extracellular collagen fiber production lead to
H3K27 methylation and HCC transformation risk. altered extracellular matrix stiffness, which drives gene expression,
Result: (1) During the MASH phase, histone methylation accelerates proliferation, differentiation, and hepatic stellate cell activation in
disease progression by regulating lipid metabolism, inflammatory hepatocytes. Portal hypertension and the formation of collateral
responses, and apoptosis. Abnormal H3K4 methylation, caused by circulation can lead to hemodynamic changes within the hepatic
the activation of KMT2D and SET7/9, promotes lipid accumulation sinusoids, and the shift in the mechanical environment has a profound
and TNF-α-mediated inflammatory responses. KDM7A demethylates impact on a wide range of biological behaviors of hepatocytes
H3K9me2/27me2, activating lipid metabolism-related genes (such (including cell proliferation, differentiation, migration, etc.), which
as DGAT2) and inflammatory signaling pathways (such as NF-κB), affects the functional and pathological processes of the liver to varying
exacerbating hepatic steatosis and inflammation. EZH2 amplifies degrees. For example, it induced the activation of the Notch pathway,
inflammatory signals by catalyzing H3K27me3, leading to gene and the expression levels of eNOs and Kruppel-like factor 2 (KLF2)
silencing and chromatin condensation. were significantly increased, as well as negatively regulated the Hippo
(2) In the liver fibrosis/cirrhosis phase, methylation of H3K4, H3K9, and signaling pathway.
H3K27 regulates the activation of hepatic stellate cells (HSCs) and the Conclusion: The biological behavior of liver cells is influenced by
expression of fibrotic genes, promoting disease development. EZH2 the microenvironment in which the cells reside, and there is growing
suppresses the expression of anti-fibrotic genes like Dkk1 through evidence of the important role of the mechanistic microenvironment
H3K27me3, activating the Wnt/β-catenin signaling, which promotes in the development of MAFLD. Therefore, an improved understanding
HSC activation. Changes in H3K9 methylation levels, regulated by of the mechanobiology in the mechanisms of MAFLD development
MECP2 and KDM4C, affect PPARγ and related pathways, thus driving can help us to deepen our understanding of disease prevention and
the acquisition of fibrotic phenotypes. treatment, and contribute to our search for new targets for drug and
(3) In the HCC phase, abnormalities in H3K4, H3K9, and H3K27 physical therapy.
methylation accelerate tumor progression by silencing tumor
suppressor genes and activating oncogenes, significantly affecting
patient prognosis. EZH2/H3K27me3 enhances tumor invasiveness by PP0528
silencing tumor suppressor genes such as p16INK4a. SMYD3 and G9a SGLT2 Inhibitors And Nonalcoholic Fatty Liver Disease (NAFLD):
promote the abnormal expression of tumor-related genes by regulating Meta-Analysis of Randomized Trials Evaluating Hepatic Steatosis
H3K4 and H3K9 methylation, thus accelerating tumor proliferation and Fibrosis
and metastasis. In addition, cumulative methylation changes, in Demver Plamenco Gomez1, Wilmyr Francisco Hababag1, Celeste
conjunction with gene mutations and chronic inflammation, constitute Ong-Ramos1
the mechanisms of HCC development. Elevated levels of H3K9me2 1
De Los Santos Medical Center
and H3K27me3 exacerbate tumor malignancy while regulating the
Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly
tumor microenvironment (TME) and immune response, affecting
recognized as a prevalent hepatic disorder, affecting approximately
treatment sensitivity.
12.2% of individuals in the Philippines and between 10% to 30%
Conclusion: Histone methylation changes are crucial in MASH to
of the U.S. population. Its development is closely associated with
HCC progression, underpinning epigenetic biomarker and intervention
metabolic conditions such as obesity, type 2 diabetes mellitus (T2DM),
research. Yet, the complex methylation-phenotype causal link depends
hypertension, and dyslipidemia. Sodium-Glucose Cotransporter 2
on environment and cell traits. Future studies must probe molecular
(SGLT2) inhibitors, a class of glucose-lowering medications, have
mechanisms and personalized treatment potential.
shown cardiovascular benefits beyond glycemic control, raising
interest in their potential impact on NAFLD. This meta-analysis aims to
PP0527 evaluate the efficacy of SGLT2 inhibitors in improving hepatic steatosis
and fibrosis in NAFLD patients utilizing imaging biomarkers. axis perturbations and systemic metabolic dysregulation in MASLD
Method: A comprehensive electronic database search was conducted progression. The significant associations validate its potential as
to identify studies published from inception through December 2024, a promising non-invasive biomarker for comprehensive MASLD
with no language restrictions applied. Randomized controlled trials assessment in clinical settings.
(RCTs) that assessed the effects of SGLT2 inhibitors on NAFLD were
included. Primary outcomes included the Controlled Attenuation
PP0530
Parameter (CAP) and Liver Stiffness Measurement (LSM). Data were
extracted, and study quality was evaluated using the Cochrane Bias The mevalonate pathway regulates double negative regulatory T
tool 2.0. Statistical analysis was conducted using RevMan 5.4, with cells immunoregulatory function in MASLD
results presented as weighted mean differences (WMD) and 95% Wang Xiyu1, Jin Hua1, Sun Guangyong1, Zhang Dong1
confidence intervals (CI). 1
Medical Research Center, Beijing Chao-Yang Hospital, Capital
Result: A total of ten studies were included, comprising 616 patients. Medical University, Beijing 100020, China
The analysis revealed that SGLT2 inhibitors significantly reduced CAP, Background: Metabolic dysfunction-associated steatotic liver
with a mean difference of −11.35 dB/m (95% CI: −18.54 to −4.16, p = disease (MASLD) is the most common chronic liver disease worldwide.
0.002) and decreased LSM, with a mean difference of −0.82 kPa (95% CD3+TCR+NK1.1-(CD56-)CD4-CD8- double negative immune-
CI: −1.35 to −0.30, p = 0.002). regulatory T cells (DNTregs) are important for maintaining liver
Conclusion: SGLT2 inhibitors effectively reduce hepatic steatosis and immune homeostasis. Our previous findings indicated that DNTregs
may positively influence liver fibrosis in patients with NAFLD. highly expressed enzymes of the mevalonate pathway, which were
Table and Figure:Figure 1. significantly down-regulated in MASLD. However, the role of the
Figure 2. mevalonate pathway and the mechanism by which it modulates
DNTregs in the pathogenesis of MASLD remain unknown.
PP0529 Method: Transcriptome sequencing and flow cytometric analysis were
used to determine the changes of key enzymes and metabolites of
Fecal Angptl4 as a non-invasive diagnostic indicator for gut-liver
mevalonate pathway in liver DNTregs in MASLD mice. Then, stimulation
health in MASLD
with inhibitors or agonist and supplemention of mevalonate pathway
Damien Chua1, Hong Sheng Cheng1, Rattanaporn Kiatbumrung2, metabolites were used to verify the important role and underlying
Pornjira Somnark2, Yin Hao Lee3,4, Natthaya Chuaypen2, Pisit mechanism of mevalonate pathway in regulating the survival and
Tangkijvanich2, Nguan Soon Tan1,5 immunoregulatory function of DNTregs in vitro. Finally, specifically
1
Lee Kong Chian School of Medicine, Nanyang Technological transferring WT or Pggt1b KO DNTregs into CD45.1 mice which were
University Singapore, Singapore, 2Center of Excellence in Hepatitis fed a choline-deficient high-fat diet (CDHFD) for 16 weeks to establish
and Liver Cancer, Department of Biochemistry, Faculty of Medicine, MASLD model in vivo.
Chulalongkorn University, Bangkok, Thailand, 3Department of Result: In this study, we found that the mevalonate pathway of
Microbiology, Faculty of Medicine, Chulalongkorn University,
DNTregs in MASLD was significantly downregualted, and the
Bangkok, Thailand, 4Center of Excellence in Antimicrobial Resistance
expression of Hmgcr (a key metabolic enzyme) had positive correlation
and Stewardship, Faculty of Medicine, Chulalongkorn University,
with the immunoregulatory function of DNTreg. Simvastatin (a inhibitor
Bangkok, Thailand, 5School of Biological Sciences, Nanyang
of Hmgcr) significantly inhibited the survival and function of DNTreg,
Technological University Singapore, Singapore
while the effect could be abolished by geranylgeranyl pyrophosphate
Background: MASLD affects 34% of the Asian population and is often (GGPP), which was the downstream metabolite of Hmgcr, indicated
underdiagnosed due to its asymptomatic nature and heterogeneity. that GGPP was the key metabolite affecting the survival and function of
Current screening methods, like FibroScan transient elastography DNTregs. And Rac1, the Rho family GTPases, was the pivotal molecule
(TE), are costly and detects delayed phenotypic manifestation and which was markedly modulated by GGPP. The activation of Rac1(Rac1-
treatment response. MASLD progression is influenced by disrupted GTP) was closely correlated with the mitochondrial function. Mass
gut-liver communication through complex metabolic and inflammatory spectrometry analysis and co-immunoprecipitation suggested that
pathways. Hence, the fecal exfoliome provides a non-invasive insight Rac1-GTP regulated the mitochondrial and immunoregulatory function
into gut-liver dynamics, offering potential for biomarker discovery. of DNTregs by affecting the mitochondrial protein CLPX. Furthermore,
Given Angiopoietin-like 4 (Angptl4)’s role in inflammation, regulated we knocked out Pggt1b (a key enzyme generating GGPP), and
by microbiome and diet, we hypothesize that fecal exfoliome-derived found that the survival and mitochondrial function of DNTregs were
Angptl4 levels correlate with gut-liver health in MASLD patients. suppressed, implying that mevalonate pathway regulated DNTregs
Method: We recruited 294 adult Thai participants (203 MASLD patients, survival and function by Pggt1b/GGPP/Rac1-GTP/CLPX signaling
61 HCC patients, 30 healthy controls) from King Chulalongkorn pathway mediated mitochondrial function.
Hospital, Bangkok. MASLD diagnosis was confirmed using controlled Conclusion: Mevalonate pathway in DNTregs were significantly
attenuation parameter (CAP, >248 dB/m) with FibroScan® M or XL downregulated in MASLD, which resulted in the reduced Pggt1b/
probes. Fresh fecal samples were collected in DNA/RNA Shield™ GGPP/Rac1-GTP/CLPX and thus impaired mitochondrial function.
solution for RNA extraction (RT-qPCR) and DNA extraction (16S rRNA These findings reveal the mechanism of impaired survival and
sequencing). Clinical parameters were integrated with microbiome immunoregulatory function of DNTregs in MASLD from the perspective
analysis outcomes for multivariate analysis. of metabolism, which provide an important theoretical foundation for
Result: In our MASLD cohort, the proportion of pre-diabetics (11% to the prevention and treatment of MASLD.
40%) and diabetics (0% to 49%) increased with disease progression. Table and Figure:Figure 1.Intrinsic mechanisms of mevalonate pathway
These patients exhibited gut dysbiosis, characterized by decreased regulation on DNTreg during MASLD development
alpha diversity (p<0.001) and reduced gram-positive-to-gram-negative
bacterial ratio (p<0.001). Notably, fecal exfoliome-derived Angptl4
levels showed progressive elevation corresponding to both MASLD PP0531
severity and diabetic status. Multivariate analysis positioned fecal Single-cell proteomics and spatial proteomics revealing unique
exfoliome-derived Angptl4 at the intersection of metabolic parameters new pathogenesis of metabolic dysfunction-associated steatotic
(Diabetes, BMI, plasma TG, CAP) and liver severity markers (FIB-4, TE, liver disease (MASLD)
NAFLD fibrosis score (NFS), and AST to Platelet Ratio Index (APRI). Tiansu Lv1,2, Xiqiao Zhou1,2
Further analysis showed that fecal Angptl4 is significantly correlated 1
Department of Endocrinology, Jiangsu Province Hospital of Chinese
with TE (r=0.17, p=0.01), FIB-4 (r=0.16, p=0.001), and NFS (R=0.15, Medicine, Afffliated Hospital of Nanjing University of Chinese
p=0.039). Medicine, Nanjing,China, 2The First Clinical Medical College of
Conclusion: Our findings demonstrate that fecal exfoliome-derived Nanjing University of Chinese Medicine, Nanjing, China
Angptl4 effectively captures the complex interplay between gut-liver
Background: The incidence of MASLD is experiencing upward trend. insulin, HbA1c, liver and renal function tests, and FibroTouch test
MASLD subsequently leads to MASH and fibrosis. However, there is before and after a 3-month administration of JPTZ in MAFLD patients
no specific pharmacological treatment. Lifestyle modifications and to assess its efficacy and safety in treating MAFLD. For basic research,
weight loss can mitigate or even partially reverse. The advancements MAFLD mouse model was established by administering a high-fat diet.
in proteomics and spatial proteomics together with post-translational The treatment group of mice received JPTZ to evaluate its effects on
modifications (PTMs) offer promising prospects for MASLD. MAFLD using morphological, pathological, and molecular biological
Method: We collected fresh liver tissues from patients undergoing techniques. Network pharmacology and UHPLC-MS/MS analysis were
surgical procedures at multiple centers (Jiangsu Province Traditional used to identify the main components and key targets of JPTZ, which
Chinese Medicine Hospital and Jiangsu Provincial People’s Hospital), were subsequently validated in vivo via ELISA, western blot, qPCR and
with evidence confirmed by imaging or pathology. The samples molecular docking to elucidate the mechanisms of action.
were analyzed using Cytometry by Time Of Flight (CyTOF), mass Result: JPTZ effectively improved hepatic dysfunction and metabolic
spectrometry (MS) identification of proteomics and PTMs, and Imaging disorder in MAFLD patients, as evidenced by reduced serum levels of
Mass Cytometry (IMC). Bioinformatics analysis was performed on the AST, GGT, TG and LDL-c, and increased HDL-c levels. Furthermore, it
data using R language. improved FibroTouch test parameters in these patients.
Result: Initially, we employed CyTOF to characterize celltypes within the Animal experiments showed that JPTZ significantly reduced body and
MASLD. Our analysis successfully identified 22 specific cell subtypes. liver weight, mitigated hepatic pathological damage, improved blood
Notably, we observed significant increase of M2 macrophages lipid and liver enzymes in MAFLD mice. Moreover, JPTZ effectively
within MASLD. Together, we evaluated the overall levels of four improved glucose tolerance and insulin sensitivity in MAFLD mice.
PTMs—phosphorylation, ubiquitination, acetylation, and lactylation— Network pharmacology predicted that JPTZ contains 120 active
across each celltype. It showed that phosphorylation was elevated ingredients targeting 220 targets associated with MAFLD. Enrichment
in myeloid-derived cells associated with MASLD. We then isolated analysis revealed the AGE/RAGE axis as the most significantly enriched
myeloid-derived cells for MS of proteomics and phosphoproteomics. It pathway. In vivo studies further validated that JPTZ markedly reduced
demonstrated downregulation of amino acid metabolism and activation circulating advanced glycation end products (AGEs) levels and RAGE
of inflammatory responses, and we thus constructed of molecular expression in MAFLD mice livers, and normalized gene targets and
mechanism map. We subsequently employing IMC to spatially analyze protein expressions involved in AGE/RAGE axis, including TNF, AKT1
the interactions among phenotypes, cells, and molecules, ultimately and IL-6. These findings suggest that JPTZ regulates the AGE/RAGE
identifying a distinct cell type characterized as M2 macrophages axis to improve MAFLD.
negative for both AGXT2 and PYCR3. The expression of immune The integration of JPTZ-ingredients-target-pathway network analysis
inflammatory cells and proliferative molecules in proximity to such M2 with UHPLC-MS/MS detection revealed atractylenolide, isorhamnetin,
macrophages were significantly elevated, and also the data indicates kaempferol and alisol B as key constituents of JPTZ. Molecular docking
a spatial association of fibroblasts or activated hepatic stellate cells confirmed that these active components had good binding ability with
with such M2 macrophages. This suggests that these cells may play key targets like TNF and AKT1, further supporting the effect of JPTZ on
an active role in the onset and progression of MASLD, positioning them the AGE/RAGE pathway.
as potential therapeutic targets. Conclusion: This study comprehensively revealed the biological
Conclusion: Utilizing CyTOF technology, we effectively clustered compounds, potential targets, and molecular mechanisms of JPTZ in
and categorized the cell subpopulations, revealing notable increase treating MAFLD, providing a reference basis for the promotion of JPTZ
in M2 macrophages of MASLD. Through comprehensive analysis of in clinic.
proteomics and phosphoproteomics, we elucidated the biological
functions of myeloid-derived cells in MASLD. Finally, through the PP0533
integration of spatial proteomic analysis via IMC, we confirmed that
M2 macrophages that are double negative for AGXT2 and PYCR3 play Phase 2 Studies of a Novel Pulsatile FXR Ligand for MASH
a significant role in the onset and progression of MASLD, suggesting Gaihong Wang1, Jingjing Shi1, Guanguan Zhao1, Hualing Pan1,
their potential as therapeutic targets. Shengsheng Yang1, Rong Deng1, Zhenwei Zhang1, Eric H Xu1,2,
Table and Figure:Figure 1.CyTOF revealing the unique cell composition Robert W Barish3, Mark Todd Leibowitz4, Idalia A Acosta5, Carmen E
of MASLD and biological function of myeloid derived cells within Landaverde6, Eric J Lawitz7, Mark Todd Leibowitz8, Stanley H Hsia9,
MASLD William E Sanchez10, Douglas S Denham11, Robert A Jenders12, Gary
Figure 2.MASLD Spatial Proteomics Analysis Michael Reiss13, Francisco Velazquez14, Kathryn Jean Lucas15, Raja
Mohi-Ud-Din16, Manuel E Rodriguez17, Robert W Barish18
1
Cascade Pharmaceutic, 2 Shanghai Institute of Materia Medica,
PP0532
Chinese Academy of Sciences, 3Ocala GI Research, 4Velocity Clinical
Study on the action mechanism of the spleen-strengthening and Research - Santa Ana, 5San Marcus Research Clinic, Inc - Miami,
lipid-regulating herbal formula on MAFLD, based on network 6
Texas Liver Institute (TLI) - Austin, 7The Texas Liver Institute, Inc.,
pharmacology and experimental validation 8
National Research Institute - Gardena, 9Velocity Clinical Research,
Da Wang1, Dan Zhang2, Mengwei Li1, Yingxue Shen1, Rongting Zhao1, Huntington Park, 10Floridian Clinical Research, LLC - Miami
Jinxiu Li1, Jianjun Liu3, Lanqing Ma1 Lakes, 11Clinical Trials of Texas, LLC, 12Velocity Clinical Research
1
The First Affiliated Hospital, Yunnan Institute of Digestive Disease, - Panorama City, 13Metropolitan Gastroenterology Associates -
Yunnan Clinical Research Center for Digestive Diseases, Kunming Westbank Office and Endoscopy, 14Pioneer Research Solutions
Medical University, 2Department of Gastroenterology, First Affiliated Inc - Houston - Stancliff Rd, 15Lucas Research, 16Raja M. Din MD,
Hospital of Dali University, 3Yunnan Key Laboratory of Stem Cell and PLLC - Gastroenterology & Hepatology, 17Florida Research Institute,
Regenerative Medicine, Institute of Biomedical Engineering, Kunming
1
8Gastroenterology Associates of Ocala
Medical University Background: Metabolic Dysfunction-Associated Steatohepatitis
Background: The spleen-strengthening and lipid-regulating formula (MASH) is a severe liver disease with limited treatment options. Linafexor
(JPTZ), derived from master of traditional Chinese medicine Zhang (CS0159), a pulse FXR ligand with a short half-life, is designed to align
Zhen, is designed to target the core pathogenesis of metabolic with the metabolic cycle of bile acids, providing optimized efficacy and
dysfunction-associated fatty liver disease (MAFLD). It is commonly safety. Circadian rhythm and metabolic up-and-down regulation are
used in clinical for treating MAFLD. However, the pharmacodynamic fundamental aspects of animal physiology, and incorporating these
mechanism underlying JPTZ remains unclear. Therefore, this study principles into drug design ensures superior therapeutic potential.
aims to identify its main constituents and elucidate its anti-MAFLD This Phase 2 study investigates the efficacy and safety of Linafexor in
mechanism. MASH patients using doses of 1.4 mg and 2.0 mg.
Method: Clinically, we collected data on various indicators, including Method: A randomized, double-blind, placebo-controlled Phase 2
body weight, waist circumference, plasma lipids, fasting glucose and trial enrolled patients with biopsy-confirmed MASH. Linafexor was
administered daily at doses of 1.4 mg or 2.0 mg for 12 weeks. Efficacy Nageswara Rao Yeluchuri12, Sanjay Hadigal12, Amit Ravindra
assessments included changes in liver histology, serum bile acid Birajdar12
levels, and key metabolic biomarkers. Safety evaluations focused on 1
Khon Kaen University, 2Chulalongkorn University, 3West Visayas State
hepatic function tests and adverse event monitoring. University Medical Center, 4Universiti Teknologi MARA, 5De La Salle
Result: Linafexor treatment resulted in significant dose-dependent Medical and Health Sciences Institute, 6Manial Doctors Hospital,
reductions in liver steatosis, inflammation, and fibrosis. The 2.0 mg 7
Cebu Doctor‘s University Hospital, 8Naresuan University , 9Makati
dose demonstrated superior efficacy compared to the 1.4 mg dose, Medical Center 2, 10Phramongkutklao Hospital, 11Chaiang Mai
with greater reductions in histological markers of disease severity. University, 12viatris
Both doses were well tolerated throughout the study. The circadian- Background: There is limited data on the use of Legalon® in the
dependent modulation of bile acid metabolism by Linafexor’s short management of NAFLD patients with concomitant metabolic syndrome
half-life contributed to its enhanced efficacy and safety profile. (MetS) in real-life settings. We have conducted a non-interventional
Conclusion: Linafexor (CS0159) demonstrates robust efficacy and a study (CT.gov ID: NCT05051527) aimed to evaluate the effectiveness
remarkable safety profile in patients with MASH, with dose-dependent of a medical-grade formulation of silymarin for managing non-alcoholic
improvements in liver histology and metabolic markers. The alignment fatty liver disease (NAFLD) in patients with concomitant metabolic
of Linafexor’s pharmacokinetics with circadian bile acid rhythms syndrome (MetS).
underscores its potential as a new class therapeutic for MASH. Further Method: This study was conducted at 12 sites across Thailand, the
studies are warranted to confirm these promising findings. Philippines, and Malaysia, enrolling adult NAFLD patients with at
least one elevated liver enzyme at baseline and confirmed MetS. At
PP0534 baseline, patients received the standard of care for NAFLD, including
dietary and exercise recommendations, along with 140 mg of silymarin
Association of triglyceride-glucose related indices with mortality
administered three times daily, in line with local clinical practice. The
among individuals with MASLD combined with prediabetes or
patients received treatment for 6 months. Patients were assessed
diabetes
at Baseline, T1 visit (3-months), and T2/End of Study (EOS) visit
Yiheng Zhang1, Yan Wang, Juanli Wu, Tao Li, Yundong Qu (6-months). The primary objective of the study was to measure the
1
the second hospital of shandong university effectiveness of silymarin in lowering the plasma levels of at least one
Background: The prognostic significance of triglyceride-glucose parameter among ALT, AST, and GGT.
(TyG) related indices in individuals with metabolic-associated steatotic Result: Of the enrolled 360 NAFLD patients, 56% (201/360) were
liver disease (MASLD) combined with prediabetes or diabetes is not male. The average age, weight, and BMI were 49.6 (SD ±12.8) years,
yet fully understood. In this study, we explored their predictive value 78.7 (SD ±16.0) kg, and 29.7 (±4.9) kg/m2 respectively. Most frequent
for mortality in this specific population. comorbidities in the study population include overweight/obesity (66%,
Method: Patients with MASLD were identified from the national health 239/360), hypertension (62%, 223/360), and diabetes (43%, 153/360).
and nutrition examination survey (NHANES III) database. The study At baseline, the proportion of patients with abnormal (>1 upper limit
focused on two primary endpoints: all-cause mortality and mortality normal, ULN) AST, ALT, and GGT levels were 45% (161/360), 90%
specifically related to cardiac conditions and diabetes. To examine (324/360), and 47% (170/360), respectively.
the association between TyG-related indices and mortality risk, Cox At EOS, 46% of patients achieved normalization in at least one liver
regression models was utilized. Furthermore, we employed restricted enzyme. Specifically, 42% showed normalization of AST, 34% showed
cubic spline (RCS) analysis to investigate potential dose-response normalization of ALT, and 28% showed normalization of GGT (Figure
relationships. The predictive ability of the TyG indices for mortality 1A).
was assessed by analyzing the time-dependent area under the curve At EOS, 78% of patients achieved a reduction of at least 1 U/L of
(AUC). the concentration of any liver enzyme. Particularly, 75% showed a
Result: In the cohort of patients with diabetes or prediabetes, 46.5% reduction of AST, 71% showed a reduction of ALT, and 71% showed a
were diagnosed with MASLD. During the follow-up period, 994 patients reduction of GGT (Figure 1B).
(46.1%) died, with 329 deaths attributed to heart disease and 78 (3.6%) Further, a clinically meaningful reduction of >30% of enzyme level was
to diabetes. Multivariate cox regression models showed that TyG, TyG- observed in 42% of patients for AST, 40% for ALT, and 34% for GGT
BMI, TyG-WHtR, and TyG-WWI indices were associated with all-cause (Figure 1C).
and cardiovascular/diabetes-specific cause mortality. Furthermore, The mean and median percentage reductions of enzyme level from
RCS analysis revealed a positive linear relationship between the TyG baseline were 17% and 25% for AST, 16% and 23% for ALT, and 13%
and TyG-WWI indices and all-cause mortality, ( p for nonlinear = 0.920; and 17% for GGT, respectively.
= 0.525, respectively). In contrast, the TyG-BMI and TyG-WHtR indices Conclusion: Patients with NAFLD and metabolic syndrome benefit
exhibited a positive nonlinear association with all-cause mortality, (p for from treatment with silymarin, in addition to standard of care. Silymarin
nonlinear = 0.003; = 0.007, respectively). Time-dependen AUC curves can potentially help in normalization and reduction of the elevated
demonstrated that the TyG-WWI index was the most robust predictor liver enzyme levels. Additionally, a considerable proportion of patients
of both all-cause and cardiovascular mortality. experienced at least a 30% reduction in abnormal liver enzyme levels
Conclusion: Elevated levels of TyG, TyG-BMI, TyG-WHtR, and TyG- from baseline, demonstrating clinical relevance.
WWI indices were associated with a poorer prognosis in MASLD Table and Figure:Figure 1.Figure 1
combined with DM or PreDM, with TyG-WWI being the strongest
predictor.
PP0536
Table and Figure:Figure 1.Association between TyG-relate indices and
mortality in patients with MASLD combined with PreDM or DM Comparative Efficacy and Safety of Drugs for non-cirrhotic
Figure 2.Time-dependent AUC for mortality NAFLD: A Systematic Review and Network Meta-Analysis
Yuanming Chen1, XInyu Yang1, Wei Shen1, Peiru Zhang2, Xudong
Yang3, Qianrang Lu4, Qi Ling4, Xiao Xu5, Di Lu5
PP0535 1
Zhejiang University School of Medicine, 2Zhejiang Chinese Medical
Effectiveness of Silymarin Combined with Diet and Exercise in University, 3Hangzhou Normal University School of Medicine, 4The First
Normalizing and Reducing Liver Enzymes in Patients with NAFLD Affiliated Hospital, Zhejiang University school of Medicine, 5Zhejiang
and Metabolic Syndrome. Provincial People‘s Hospital
Wattana Sukeepaisarnjaroen1, Roongruedee Chaiteerakij2, Background: Nonalcoholic fatty liver disease (NAFLD) is a global
Elvie Victonette B. Razon Gonzalez3, Rafiz Abdul Rani4, Maria health issue, yet few pharmacological therapies have been approved
Teresita R Andal Gamutan5, Marie Michelle Simbol Cloa6, Leilanie for treatment. We aimed to compare the relative effects of drugs for
Salgado7, Ekawee Sripariwuth8, Madalinee Eternity Labio9, Sakkarin non-cirrhotic NAFLD.
Chirapongsathorn10, Taned Chitapanarux11, Laura Colombo12,
Method: Studies were searched in PubMed, Embase, Web of Science, AST, ALT, and GGT levels were 45%, 90%, and 47%, respectively.
and ClinicalTrials.gov until June 30, 2024. Randomized controlled At EOS, normalization of at least one liver enzyme was achieved by 44%
trials (RCTs) exploring the efficacy and safety of drugs for biopsy- of T2D subjects, with AST normalized in 43%, ALT in 36%, and GGT in
proven NAFLD were included. Summary data were extracted and 24% of patients compared to BSL. In HTN subjects, normalization in
appraised. The primary outcomes were liver histologic improvements. at least one liver enzyme occurred in 45% of patients (AST: 43%; ALT:
A random effects model was used to calculate the odds ratios with 35%; GGT: 2%). Among overweight/obese subjects, normalization in
95% confidence interval. at least one liver enzyme occurred in 44% of patients (AST: 37%; ALT:
Result: We enrolled 36 RCTs (9309 participants) in this work. 34%; GGT: 28%)
Vitamin E plus pioglitazone and fibroblast growth factor (FGF)-19 At EOS, a reduction of at least 1 U/L in liver enzymes was observed in a
analogs ranked top in reducing NAFLD activity score. For detailed significant proportion of patients: by 79% of T2D patients overall (AST:
features, FGF-19 analogs ranked highest in reducing steatosis and 75%; ALT: 75%; GGT: 71%), by 78% of HTN patients (AST: 77%; ALT:
ballooning, while Vitamin E plus pioglitazone was most likely to resolve 71%; GGT: 68%) and by 78% of overweight or obese patients (AST:
lobular inflammation. NASH resolution, an inflammation comparator 74%; ALT: 73%; GGT: 72%).
recommended by FDA, was reached by FGF-21 analogs and thyroid The proportion of patients that achieved normalization or reduction of
hormone receptor beta (THR-β) agonist as high rank. Improvement of liver enzymes varied depending on the number of UCs: respectively,
fibrosis stage, another FDA suggested outcome, was observed with normalization and reduction of liver enzymes levels were achieved by
pegozafermin (FGF-21 analog), obeticholic acid (FXR agonist), and 62% and 79% patients with one UC, 51% and 83% among those with
resmetirom (THR-β agonist). FXR agonists had higher dropout rates. two UCs, and 42% and 76% among patients with three or more UCs
Conclusion: FGF-21 analogs (especially pegozafermin) and THR-β (Figure 1A and 1B).
agonist (resmetirom), both resolving steatohepatitis and reducing Conclusion: Silymarin help normalize and reduce elevated liver
fibrosis, were recommended for non-cirrhotic NAFLD. Obeticholic acid enzyme levels in patients with UCs; however, its effectiveness tends
demonstrated efficacy but its tolerability should be fully considered. to decrease as the number of UCs increases, suggesting that the
FGF-19 analogs seemed more suitable for reducing ballooning and treatment is more effective in the early stages of metabolic dysfunction.
steatosis, while Vitamin E plus pioglitazone performed well in resolving Table and Figure:Figure 1.Figure 1
lobular inflammation.
Table and Figure:Figure 1.Visual Abstract PP0538
Figure 2.Summary of Vitruvian plots for the overall profile of each
active treatment and placebo across the nine primary and secondary Evaluating the utility of Noninvasive Markers (FLI, LAP, FIB-4,
outcomes HSI, and NFS) for Diagnosing Early Liver Disease: baseline data
from an observational study with NAFLD patients with Metabolic
Syndrome
PP0537 Wattana Sukeepaisarnjaroen1, Roongruedee Chaiteerakij2,
Effectiveness of Silymarin Combined with Diet and Exercise in Elvie Victonette B. Razon Gonzalez3, Rafiz Abdul Rani4, Maria
Normalizing and Reducing Liver Enzymes in NAFLD and Metabolic Teresita R. Andal Gamutan5, Marie Michelle Simbol Cloa6, Leilanie
Syndrome Patients with Underlying Medical Conditions Salgado7, Ekawee Sripariwuth8, Madalinee Eternity Labio9, Sakkarin
Wattana Sukeepaisarnjaroen1, Roongruedee Chaiteerakij2, Chirapongsathorn10, Taned Chitapanarux11, Laura Colombo12,
Elvie Victonette B. Razon Gonzalez3, Rafiz Abdul Rani4, Maria Nageswara Rao Yeluchuri12, Sanjay Hadigal12, Amit Ravindra
Teresita R. Andal Gamutan5, Marie Michelle Simbol Cloa6, Leilanie Birajdar12
Salgado7, Ekawee Sripariwuth8, Madalinee Eternity Labio9, Sakkarin 1
Khon Kaen University, 2Chulalongkorn University, 3West Visayas State
Chirapongsathorn10, Taned Chitapanarux11, Laura Colombo12, University Medical Center, 4Universiti Teknologi MARA, 5De La Salle
Nageswara Rao Yeluchuri12, Sanjay Hadigal12, Amit Ravindra Medical and Health Sciences Institute, 6Manial Doctors Hospital,
Birajdar12 7
Cebu Doctor‘s University Hospital, 8Naresuan University , 9Makati
1
Khon Kaen University, 2Chulalongkorn University, 3West Visayas State Medical Center 2, 10Phramongkutklao Hospital, 11Chaiang Mai
University Medical Center, 4Universiti Teknologi MARA, 5De La Salle University, 12viatris
Medical and Health Sciences Institute, 6Manial Doctors Hospital, Background: Chronic liver diseases (CLDs) are increasingly
7
Cebu Doctor‘s University Hospital, 8Naresuan University , 9Makati prevalent globally, necessitating accessible and accurate screening
Medical Center 2, 10Phramongkutklao Hospital, 11Chaiang Mai tools. Traditional diagnostic methods like liver biopsy remain the gold
University, 12viatris standard but are invasive, costly, and carry procedural risks. Further,
Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent they require trained personnel for execution and interpretation,
chronic liver disorder linked to multiple metabolic abnormalities, and usually are prescribed by the liver specialist after examination.
including metabolic syndrome (MetS), type 2 diabetes mellitus Noninvasive markers such as the Fatty Liver Index (FLI), Lipid
(T2DM), obesity, and cardiovascular disease. These conditions Accumulation Product (LAP), Fibrosis-4 (FIB-4), Hepatic Steatosis
increase the risk of liver fibrosis, cirrhosis, and cardiovascular events Index (HSI), and NAFLD Fibrosis Score (NFS) offer an alternative,
in NAFLD patients. Given the increasing prevalence of NAFLD globally, accessible method for assessing liver health and potential fibrosis in
identifying the high-risk populations and providing treatment is critical. at-risk populations.
Method: NIS3327 is an observational study (CT.gov ID: NCT05051527) Method: We ran an observational study (NIS3327) in Thailand,
conducted across 12 sites in Thailand, the Philippines and Malaysia, Malaysia and Philippines, enrolling adult NAFLD patients with
enrolling adult NAFLD patients with confirmed MetS and at least one Metabolic Syndrome and at least one elevated plasma liver enzyme
elevated liver enzyme at baseline. All patients received standard at baseline. At baseline, biochemical and biometric parameters
NAFLD care (dietary and exercise recommendations) along with 140 have been captured to assess noninvasive markers (FLI, LAP, FIB-
mg silymarin three times daily for 6 months. Patient assessments 4, HSI, and NFS). In addition, at baseline qualitative ultrasonography
occurred at Baseline (BSL), the T1 visit (3 months) and the T2/End assessment was conducted by a trained ultrasonographist, checking
of Study (EOS) visit (6 months). The primary study endpoint was the the presence/absence 4 features: diffuse liver hyperechogenicity,
proportion of patients who achieved at least one normalized liver heterogeneous structure of the liver, indistinctness vascular pattern,
enzyme level (ALT, AST, GGT) at EOS compared to BSL. This subgroup distal echo signal attenuation.
analysis check for normalization or reduction of at least one liver Result: The study enrolled 360 adult NAFLD patients with a mean age
enzyme in patients with one or more underlying medical conditions of 49.6 years, weight of 78.7 kg, and BMI of 29.7 kg/m2. All the non-
(UCs). invasive markers assessed in the study qualify the patients’ populations
Result: The study enrolled N=360 patients. The most common UCs having early-stage liver disease i.e., presence of steatosis or low-risk
were overweight/obesity in 66%, hypertension (HTN) in 62%, and T2D of advanced fibrosis (Figure 1). Ultrasonography assessment showed
in 43% of patients. At BSL, the proportion of patients with abnormal that diffuse liver hyperechogenicity is the most frequent finding (86% of
patients) followed by indistinctness vascular pattern (Figure 2). Salgado7, Ekawee Sripariwuth8, Madalinee Eternity Labio9, Sakkarin
Conclusion: Noninvasive tests are a promising approach for facilitating Chirapongsathorn10, Taned Chitapanarux11, Laura Colombo12,
the identification of patients at risk of FLD and/or ruling out risk of severe Nageswara Rao Yeluchuri12, Sanjay Hadigal12, Amit Ravindra
fibrosis. In our study population, risk assessment conducted with the Birajdar12
support on noninvasive tests correlates with the ultrasonography 1
Khon Kaen University, 2Chulalongkorn University, 3West Visayas State
findings. Use of noninvasive tests could be integrated into non-liver University Medical Center, 4Universiti Teknologi MARA, 5De La Salle
specialist practice as screening and diagnostic tool, increasing early Medical and Health Sciences Institute, 6Manial Doctors Hospital,
diagnosis and facilitating multidisciplinary management of CLDs in at- 7
Cebu Doctor‘s University Hospital, 8Naresuan University , 9Makati
risk populations. Medical Center 2, 10Phramongkutklao Hospital, 11Chaiang Mai
Table and Figure:Figure 1.Figure 1 University, 12viatris
Figure 2.Figure 2 Background: A recent observational study (CT.gov ID: NCT05051527)
investigated the use of a medical grade silymarin, a polyphenolic
PP0539 flavonoid extracted from Silybum marianum seeds for the management
of non-alcoholic fatty liver disease (NAFLD) in patients with metabolic
Pediococcus acidilactici (PA53) Ameliorates MAFLD by Regulating
syndrome (MetS). Chronic liver diseases, including NAFLD, also affect
the Gut-Liver Axis
health—related quality of life (QoL), leading to mental, physical, and
Yue Niu1, Shurui Bu1 social decline as the disease progresses. Here, we present the effects
1
Jinshan Hospital affiliated to Fudan University of silymarin on QoL patients’ reported outcomes.
Background: Pediococcus acidilactici (PA53) shows potential in Method: The study was carried out at 12 locations across Thailand, the
improving gut health and regulating metabolism. However, its effects Philippines, and Malaysia, involving adult NAFLD patients with at least
and optimal dosing time for the treatment of MAFLD remain to be one elevated liver enzyme and confirmed MetS at baseline. Patients
further investigated. This study aims to evaluate the therapeutic and received standard NAFLD care (dietary and exercise advice), along
preventive effects of PA53 in a mouse model of MAFLD and explore with a 140 mg dose of silymarin three times daily for 6 months. The
the underlying mechanisms. impact of Silymarin, along with diet and exercise, on Health-related
Method: A mouse model of MAFLD was induced by subjecting QoL was assessed using a specific questionnaire at baseline (BSL), at
the mice to a high-fat diet for 12 weeks. Subsequently, PA53 was three months (T1) and the end-of-study (EOS) visit (T2). QoL domains,
administered via gavage at a dose of 10^9 CFU/day. The mice were such as physical activity, role limitations due to physical health, role
categorized into a control group, a model group, a PA53 prevention limitations due to emotional problems, energy/fatigue, emotional
group, and a PA53 treatment group, with a curcumin group serving well-being, social functioning, pain/symptoms, and liver health were
as a positive control. The entire experimental period spanned 24 considered.
weeks. In the initial 12 weeks, the mice were fed a high-fat diet for Result: Among the 360 patients enrolled in the study, the Effectiveness
model establishment. From week 13 to week 16, all groups except the Population (N=360) includes those who received treatment and
model group were switched to a normal diet. In the final 8 weeks, all completed the study as per the protocol, regardless of their compliance
groups reverted to the high-fat diet. This feeding protocol was devised and adherence to treatment. The Treatment Compliant Population
to mimic the dietary conditions of clinical patients who have difficulty (N=72) consists of patients who strictly followed the prescribed regimen
in fully controlling their diet, thereby enhancing the practical relevance (diet, exercise, drug treatment), allowing for a controlled evaluation of
of the experimental outcomes and facilitating future clinical research the treatment’s impact. For both the overall and treatment-compliant
and applications. The severity of MAFLD was evaluated based on populations, baseline scores across each domain indicate a mild
body weight, histological analysis, serum inflammatory markers, and impact of the disease on QoL with baseline scores between 60 and 80
related biochemical markers. Fecal samples were collected at Week (Figure 1 and Figure 2).
0, Week 12, and Week 24, and 16S rRNA sequencing was carried out For both the overall and treatment-compliant populations, there is a
for metagenomic analysis of the gut microbiome. In vivo experiments statistically significant increase in the scores across all the domains
were performed to explore the therapeutic and preventive effects of except social functioning. Most of the improvement occurs during the
PA53 on MAFLD, and correlation analysis was conducted between the first months of treatment and stabilizes by the EOS visit (Figure 1 and
gut microbiota and serum markers. Figure 2).
Result: A high-fat diet led to gut microbiota dysbiosis, impaired Generally, the treatment-compliant population achieved better final
intestinal barrier permeability, activated the immune system, and scores in each domain compared to the overall population, despite
increased serum levels of inflammatory cytokines such as IL-6, IL- having similar baseline values (Figure 1 and Figure 2).
1β, and TNF-α. These inflammatory cytokines can directly injured Conclusion: Our results showed a mild impact of NAFLD on QoL at
hepatocytes, resulting in enhanced hepatic lipid accumulation. The baseline in the NAFLD patients with MetS. Over time, scores improved
chronic inflammatory condition could give rise to an imbalance in the across all domains, with significant progress by the EOS visit. The
gut microbiota, aggravate intestinal barrier dysfunction, and create a treatment compliant patients achieved better final scores than the
vicious cycle that further deteriorates MAFLD. The supplementation of overall population.
PA53 effectively restored body weight, hepatic lipid deposition, serum Table and Figure:Figure 1.Figure 1
inflammatory cytokine levels, and the gut microbiota composition to Figure 2.Figure 2
normal. Notably, the PA53 prevention group exhibited more significant
improvements in MAFLD compared to the late-stage treatment group.
PP0541
Conclusion: PA53 demonstrates a robust therapeutic efficacy against
MAFLD triggered by a high-fat diet in mice, and early preventive Integrative metabolomics and network pharmacology analysis
administration proves to be more efficacious. This discovery reveals the therapeutic effect of Jiangan-Jiangzhi Pill on non-
holds significant clinical ramifications for the early prevention and alcoholic steatohepatitis
management of MAFLD. Lianxin Xu1, Yuekui Wang1, Wentao Kuai1,2,3, Shuangjie Yu4, Minghui
Table and Figure:Figure 1. Zeng1, Jiaxin Han1, Xuemei Tao5, Lifeng Han6, Liming Wang6, Rui
Su1,2,3, Liang Xu1,2,3, Yuqiang Mi1,2,3
1
Clinical School of the Second People’s Hospital, Tianjin Medical
PP0540
University, Tianjin 300192, China, 2Department of Hepatology, Tianjin
Impact of Silymarin on Quality of Life in Patients with NAFLD and Second People’s Hospital, Tianjin 300192, China , 3Department of
Metabolic Syndrome Hepatology, Tianjin Research Institute of Liver Diseases, Tianjin
Wattana Sukeepaisarnjaroen1, Roongruedee Chaiteerakij2, 300192, China, 4Phase I Clinical Trial Ward, The Fifth Medical Center
Elvie Victonette B. Razon Gonzalez3, Rafiz Abdul Rani4, Maria of the People‘s Liberation Army General Hospital, Beijing 100039,
Teresita R. Andal Gamutan5, Marie Michelle Simbol Cloa6, Leilanie China, 5Center of Infectious Diseases, West China Hospital of Sichuan
University, Chengdu, China, 6Tianjin State Key Laboratory of Modern fibrosis was defined as liver stiffness measurement (LSM) > 7.3 kPa
Chinese Medicine, Tianjin University of Traditional Chinese Medicine, (F0-F1: ≤7.3 kPa, F2: 7.4-9.7 kPa, F3 and above: ≥9.8 kPa), and liver
Tianjin 301617, China steatosis was defined as controlled attenuation parameter (CAP) >
Background: Non-alcoholic steatohepatitis (NASH) is a progression of 250 dB/m (S0: ≤250 dB/m, S1: 251-290 dB/m, S2 and above: ≥290
non-alcoholic fatty liver disease (NAFLD) and has become one of the dB/m). Receiver operating characteristic curve (ROC) was conducted
leading causes of cirrhosis and hepatocellular carcinoma. Jiangan- to assess their predictive abilities.
Jiangzhi Pill (JJP) has significant advantages in treating NASH and has Result: In the Q4 groups of each parameter, among patients grouped
been used in our hospital for over a decade. However, the mechanism by BMI, 8.9% showed liver fibrosis F2, 1.7% showed F3 or higher,
of JJP intervening in NASH remains unclear. 28.5% showed liver steatosis S1, and 47.7% showed S2 or higher,
Method: First, UHPLC-MS/MS was used to identify the chemical slightly higher than those grouped by WC (F2: 7.7%, F3: 1.3%, S1:
composition of JJP. Second, clinical data and serum samples were 32.2%, S2 or higher: 45.0%), and significantly higher than those
collected from NAFLD patients who regularly took JJP or polyene grouped by WWI (F2: 4.6%, F3: 1.0%, S1: 28.8%, S2 or higher: 32.5%).
phosphatidylcholine capsules (PPC). Methionine-choline-deficient ROC analysis showed that BMI had an area under the curve (AUC) of
(MCD) diet to establish a liver stagnation and spleen deficiency NASH 0.73 (95% CI: 0.65–0.81) for liver fibrosis and an AUC of 0.68 (95% CI:
model, followed by a 4-week treatment with JJP. Finally, metabolomics 0.65–0.71) for liver steatosis, with no statistically significant difference
combined with network pharmacology was utilized to investigate compared to WC (AUC for fibrosis: 0.70 [95% CI: 0.63-0.78], p=0.154,
metabolic pathways and underlying therapeutic targets of JJP in AUC for steatosis: 0.67 [95% CI: 0.64-0.70], p=0.482), but significantly
curing NASH, and validation was performed using molecular docking, higher than WWI (AUC for fibrosis: 0.61 [95% CI: 0.54-0.68], p=0.008,
Western blot, and quantitative real-time polymerase chain reaction AUC for steatosis: 0.57 [95% CI: 0.53–0.60], p<0.001).
(qRT-PCR). Conclusion: Compared to waist circumference and weight-adjusted
Result: A total of 102 components of JJP were identified. JJP alleviated waist index, body mass index is more effective as an evaluation metric
metabolic disorders, oxidative stress, obesity, and inflammation in for liver fibrosis and steatosis in MAFLD patients.
NASH mice, and improved the degree of hepatic steatosis in patients Table and Figure:Figure 1.Distributions of Liver Fibrosis and Steatosis
with NAFLD. Metabolomics combined with network pharmacology in Groups Divided by BMI, WC and WWI.
analysis indicated that the primary metabolic pathways involved were Figure 2.ROC Analysis for Liver Fibrosis and Steatosis
purine metabolism, steroid biosynthesis, and tyrosine metabolism. Key
targets included AKT1, TP53, TNF, IL6, TLR4, and IL1B. PP0543
Conclusion: This study revealed that JJP can reduce inflammation
To Determine Risk Factors in the Development of MASLD/MASH
and maintain serum metabolic homeostasis in liver stagnation and
in “Isolated Anti-HBc IgG Positive” Immunosuppressive Patients
spleen deficiency NASH mice. The mechanism may be related to
Using Antiviral Prophylaxis (IMMUNASH Study)
the regulation of purine metabolism and TLR4/MyD88/NF-κBpathway.
Furthermore, it provides a scientific basis for the treatment of fatty liver Cigdem Mermutluoglu1, Mustafa Kemal Celen1, Yasar Bayındır2,
with Traditional Chinese Medicine formulas. Fethiye Akgul3, Pinar Çakmak4, Tuba Damar Çakırca5, Yusuf Arslan6,
Table and Figure:Figure 1.Pharmacodynamic evaluation of JJP on Ismail Yıldız7, Yesim Tasova8
NASH mice
1
Dicle University, Faculty of Medicine, Department of Infectious
Figure 2.Molecular docking and the effects of JJP on the TLR4/MyD88/ Diseases and Clinical Microbiology, 2Ankara Güven Hospital,
NF-κB signaling pathway. Department of Infectious Diseases and Clinical Microbiology, 3Batman
Training and Research Hospital, Clinic of Infectious Diseases and
Clinical Microbiology,, 4Mardin Training and Research Hospital,
PP0542 Clinic of Infectious Diseases and Clinical Microbiology, 5Sanlıurfa
Body Mass Index is More Effective than Waist Circumference as Training and Research Hospital, Clinic of Infectious Diseases and
an Evaluation Metric for Liver Fibrosis and Steatosis in MAFLD Clinical Microbiology, 6Batman Training and Research Hospital, Clinic
Patients of Infectious Diseases and Clinical Microbiology, 7Dicle University,
Faculty of Medicine, Department of Biostatistics, 8Çukurova University,
Zhengzhao Lu1, Cheng Huang2,3, Xinyu Zhao2,4, Wei Ji5, Jingjie
Faculty of Medicine, Department of Infectious Diseases and Clinical
Zhao6,7, Tingting Xiao8, Dongxu Wang8, Dong Xu8, Hong You1
Microbiology
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
University; State Key Lab of Digestive Health, National Clinical Background: The aim of this study was to investigate the status
Research Center for Digestive Diseases, Beijing, China., 2Clinical and development of Metabolic Dysfunction Associated Steatotic
Epidemiology and EBM Unit, Beijing Clinical Research Institute, Liver Disease (MASLD) and Metabolic Dysfunction Associated
Beijing Friendship Hospital, Capital Medical University, Beijing, Steatohepatitis (MASH) in isolated Anti-HBc IgG positive hepatitis B
China., 3Department of Clinical Epidemiology and Clinical Trial, patients who were initiated immunosuppressive treatment for various
Capital Medical University, Beijing, China., 4National Clinical Research reasons and started antiviral prophylaxis.
Center for Digestive Diseases, State Key Lab of Digestive Health, Method: The presence of MASLD/MASH was investigated
Beijing Friendship Hospital, Capital Medical University, Beijing, prospectively before treatment in 150 patients with isolated Anti-HBc
China., 5Nursing department, Beijing Friendship Hospital, Capital IgG positivity and who needed immunosuppressive treatment for
Medical University; National Clinical Research Center for Digestive any reason. Simultaneous oral antiviral prophylaxis was started in all
Diseases, Beijing, China., 6Department of Traditional Chinese patients to prevent hepatitis B virus reactivation. Vibration controlled
Medicine, Beijing Friendship Hospital, Capital Medical University, transient elastography (VCTE) was measured with Fibroscan®
Beijing, China., 7Clinical Center for Metabolic Associated Fatty M530 in all patients before immunosuppressive treatment and at
Liver Disease, Capital Medical University, Beijing, China., 8Beijing the 6th month of treatment. Liver stiffness measurement (LSM) and
Friendship Hospital, Capital Medical University; National Clinical Controlled Attenuation Parameter (CAP) values were determined in
Research Center for Digestive Diseases, Beijing, China. all measurements. Blood lipid levels, HOMA score, fasting insulin and
Background: Abdominal obesity, indicated by increased waist blood glucose were measured, simultaneously.
circumference (WC), is a predictor of liver fibrosis and steatosis. This Result: Of the 150 patients included in this study, 54.8% were male and
study aims to compare the predictive ability of body mass index (BMI), the average age of the patients was 46.4 years. There was alcohol use
WC and weight-adjusted waist index (WWI), a WC-based metric for in 14% of the patients and statin use in 9.3%. All patients were started
obesity assessment, for liver fibrosis and steatosis in patients with on oral antiviral prophylaxis include Tenofovir Disoproxil Fumarate 36%,
metabolic-associated fatty liver disease (MAFLD). Tenofovir Alafenamide Fumarate 20%, Entecavir 44%. LSM and CAP
Method: Based on the Friendship Community Cohort, we recruited values of all patients were measured by VCTE before and 6th month
3536 participants in 2023. BMI, WC and WWI were calculated in those of treatment. Before the treatment, MASLD was detected in 29.4% of
with MAFLD, divided them into four groups based on quartiles. Liver the patients and MASH in 5.1%. At the 6th month of treatment, MASLD
was detected in 31.4% and MASH in 8.5% of the patients. At the 6th AI-based digital pathology shows that denifanstat improves
month of treatment, it was observed that the MASLD/MASH increase multiple parameters of fibrosis and reduces progression to
was significantly higher in patients receiving TAF prophylaxis (MASLD cirrhosis in MASH patients with F2/F3 fibrosis - results of the
46.2% (p=0.034), MASH 15.4% (P=0.023)) compared to patients FASCINATE-2 study
receiving other antiviral prophylaxis. No significant difference was Mary Rinella1, WenWei Tsai2, Julie Dubourg2, Katharine Grimmer2,
observed between ETV and TDF (Table 1). Eduardo Martins2, Pierre Bedossa3, Kutbuddin Akbary4, Dean Tai4,
Conclusion: According to our knowledge, this is the first study in Marie OFarrell2, George Kemble2, Rohit Loomba5
isolated Anti-HBc positive patients receiving antiviral prophylaxis in our 1
University of Chicago, 2Sagimet Biosciences, 3Liverpat, 4HistoIndex
region. In this study, the use of oral antiviral prophylaxis was shown Pte Ltd, 5MASLD Research Center, University of California San Diego
to cause an upward trend in MASLD/MASH rates. MASH was more
Background: AI-based digital pathology is an advanced tool that
common in patients receiving TAF prophylaxis. We believe that longer
complements conventional histopathology by allowing precise and
follow-up data of these patients will contribute to the literature.
quantitative analysis of histological changes. Denifanstat (TVB-2640),
Table and Figure:Figure 1.Table1.Frequency of Oral Antiviral
an oral fatty acid synthase (FASN) inhibitor, demonstrated significant
Prophylaxis in Patients Diagnosed with MASLD/MASH at the begin and
MASH resolution and fibrosis improvement in the Ph2b study
6th month of treatment.
FASCINATE-2, and decreased liver fat and biomarkers of inflammation
and fibrosis. To further investigate how denifanstat improved liver
PP0544 histology, second harmonic generation (SHG) AI-based digital
The effects of target positioning repetitive Transcranial Magnetic pathology was used to evaluate pre- and post-treatment liver biopsies.
Stimulation on weight and appetite craving levels in patients with Method: 168 patients with biopsy-confirmed MASH and F2/F3 fibrosis
nonalcoholic fatty liver disease: A randomized controlled study were randomized 2:1 to once daily oral denifanstat 50 mg or placebo
Lei Sun1, Jianin Kong2, Junping Shi3,4 (PBO) for 52 weeks. Pre- and post-treatment liver biopsy slides were
read by an expert central pathologist using NASH CRN criteria. A
1
Department of Emergency Medicine, Sir Run-Run Shaw Hospital,
Zhejiang University School of Medicine, Hangzhou, 2Clinical Medicine separate unstained slide was evaluated by SHG AI digital pathology
College, Hangzhou Normal University, Hangzhou, China, 3Department (HistoIndex). All analyses were blinded (PBO n=45 total, F2:22, F3:23;
of Infectious Diseases and Hepatology, The Affiliated Hospital of denifanstat n=81 total, F2:34, F3:47).
Hangzhou Normal University, 4Institute of Hepatology and Metabolic Result: Denifanstat significantly improved liver fibrosis by both
Diseases, Hangzhou Normal University, Hangzhou 310015, China conventional and AI approaches (p<0.05 vs PBO). Significant
correlations were shown between central pathologist and AI-generated
Background: Maintaining long-term weight loss is challenging for
results (steatosis pathologist grade vs. qSteatosis continuous value,
patients with nonalcoholic fatty liver disease (NAFLD). The functional
r=0.82, p<0.001; fibrosis pathologist stage vs. qFibrosis continuous
changes in brain regions may be the reason that contribute to the
value, r=0.67, p<0.001). Denifanstat significantly regressed qFibrosis
difficulty in controlling their eating behaviors.
stage in patients with baseline F3 fibrosis (43% vs. 13% PBO, p<0.05).
This study aimed to evaluate the effects of repetitive transcranial
In baseline F3 patients, denifanstat significantly reduced septa area,
magnetic stimulation (rTMS) on body weight and food craving in
length and width (p<0.05), confirming improvement in liver fibrosis.
overweight and obese patients with NAFLD, and to investigate
Denifanstat reduced qSteatosis stage (69% vs. 29% PBO, p<0.001).
potential neural mechanisms.
Notably, using steatosis-corrected qFibrosis stage, denifanstat
Method: Thirty overweight/obese patients with NAFLD were randomly
improved fibrosis in patients with baseline F2 (53% vs. 18% PBO,
assigned to either the rTMS group (n=15) or the sham stimulation
p<0.05) or F3 (62% vs. 26% PBO, p<0.05). Fibrosis zonal analysis
group (n=15). Both groups received 8 sessions of rTMS targeting the
(steatosis-corrected) revealed significant peri-sinusoidal (Zone 2) and
left dorsolateral prefrontal cortex (DLPFC) over 4 weeks, with follow-
peri-portal fibrosis reduction with denifanstat treatment in patients
up until week 16. Primary outcomes included changes in body weight
with baseline F2 or F3. In denifanstat treated patients, 5% (4 of 81)
from baseline to follow-up. Secondary outcomes included changes
progressed from qF3 to qF4 during 52 weeks compared to 13% (6 of
in food craving levels, body composition, metabolic markers, and
45) PBO patients from qF2/3 to qF4.
functional MRI (fMRI).
Conclusion: AI digital pathology results support denifanstat’s
Result: At week 16, the rTMS group showed significantly weight loss
demonstrated efficacy reducing liver fibrosis and steatosis in MASH.
[-4.58±2.96 vs -0.55 (-1.08, 0.75)kg, P = 0.001] and lower food craving
Denifanstat improved fibrosis in peri-sinusoidal and peri-portal zones,
levels (P < 0.05) compared to sham stimulation group. Additionally,
consistent with FASN inhibition. The steatosis-corrected algorithm
after the 4-week intervention, the rTMS group had significant reductions
provides further insight into histological effect on liver fibrosis and
in HOMA-IR and visceral fat area compared to the sham stimulation
denifanstat therapeutic benefit.
group (P < 0.05). fMRI results revealed a significant decrease in
Table and Figure:Figure 1.
spontaneous activity in the left subparietal lobule and an increase in
functional connectivity between the left ventral striatum and the left
parahippocampal gyrus in the rTMS group. PP0546
Conclusion: 4 weeks of high-frequency (HF) rTMS significantly Efficacy of Saroglitazar in treatment of Metabolic associated fatty
reduced body weight, improved food cravings, decreased visceral liver disease (MAFLD
fat content, and improved HOMA-IR in NAFLD patients. The observed Abdullah Al Mukit1
changes in the left subparietal lobule and functional connectivity 1
Department of Hepatology, Rajshahi Medical College & Hospital
between the left ventral striatum and the left parahippocampal gyrus
may underlie the mechanisms by which rTMS influences food craving Background: Metabolic associated fatty liver disease (MAFLD) is the
in NAFLD patients. most common cause of liverd isease all over the world. Saroglitazar a
Table and Figure:Figure 1.Flow chart of patients through each stage of dual peroxisome proliferator-activatedr eceptor (PPAR) inhibitor. It has
the randomized, controlled trial. been used for the treatment of MAFLD recently.
Figure 2.G-FCQ-S scores, G-FCQ-T scores and the VAS measures for Method: Patients with MAFLD, attending the outpatient department
subjective appetite in the rTMS group and the sham stimulation group. of a tertiary care centre in Bangladesh, were enrolled. MAFLD was
diagnosed by fibroscan (controlled attenuation parameter >248 dB/m).
Patients with cirrhosis and having another concomitant liver disease
PP0545 (alcohol, viral, autoimmune, wilson etc.) were excluded.All patients
received saroglitazar 4 mg/day. Moreover, they were counselled
regarding diet, exercise, and weight reduction. Follow-up was done
after 12 weeks. Patients were categorized into two groups, those who
were able to reduce ≥5% body weight and those who couldn’t. Then,
both these groups were compared. PP0548
Result: A total of 61 patients were included in the study. Among them, The Role of Nutritional Status in Post-Transplant Dysglycemia
median age was38.4 years [range 18– 65 years] and male predominant Among Liver Transplant Recipients
(54%). The median BMI was 27.6 kg/m2 (range 24.7–38.4 kg/m2).
Nguyen Thu Ha1, Dao Thi Hao1, Chu Thi Phuong Nam1, Nguyen Thi
The baseline median (range) alanine transaminase (ALT), aspartate
Huong1
transaminase (AST), Liver stiffness measurement (LSM) and controlled
attenuation parameter (CAP) values were 68 IU/dL (range 38– 132 IU/
1
The 108 Military Central Hospital
dL), 41 IU/dL (range 23–86 IU/dL), 7.2 kPa (range 5.7–12.7 kPa), and Background: Malnutrition prior to liver transplantation increases the
312 dB/m (range 242–380 dB/m). Saroglitazar was tolerated well and risk of postoperative complications and adversely affects recovery.
no major adverse effect was seen. At 12 weeks, 37 patients (60.66%) Dysglycemia, a common metabolic complication post-transplant,
were able to reduce ≥5% weight, whereas remaining 24 patients significantly diminishes recipients’ quality of life. This study aimed
(39.34%) couldn’t. Transaminases and CAP values improved in both to evaluate changes in dysglycemia after liver transplantation and
groups. But, LSM improved only in patients who reduced weight identify nutrition-related risk factors that contribute to elevated blood
Conclusion: In patients with MAFLD, a 12 weeks therapy with sugar levels.
saroglitazar can improve transaminases and CAP values irrespective Method: This retrospective cohort study analyzed adult liver transplant
of weight reduction. But weight reduction along with saroglitazar are recipients with at least 12 months of follow-up who had no history of
needed to improve LSM value diabetes before transplantation. Data were collected from patients
undergoing transplantation between July 2017 and June 2024 at the
Department of Hepatobiliary Surgery, 108 Military Central Hospital.
PP0547
Nutritional status was assessed using the Subjective Global Assessment
Non alcoholic fatty liver - advances in treatment breakthroughs (SGA), Body Mass Index (BMI), and biochemical parameters. Weight
Zhen Yuan1, Junhua Ma2 changes were measured preoperatively (one day before surgery) and
1
Postgraduate training base at Shanghai Gongli Hospital ,Ningxia postoperatively (one month after surgery). Dysglycemia was defined
medical university , 2Department of Endocrinology, Gongli Hospital of per the American Diabetes Association (2022) criteria. Binary logistic
Shanghai Pudong New Area regression was employed to identify nutrition-related predictors of
Background: Nonalcoholic fatty liver refers to a series of diseases post-transplant dysglycemia.
with excessive lipid deposition in the liver.Changes in diet and lifestyle Result: A total of 123 liver transplant recipients (87.4% male; mean
are considered to be the basic strategy of non drug treatment. In age 54.6 ± 10.6 years) were included. Dysglycemia post-transplant
April 2024, the FDA granted Resmetirom breakthrough therapy was prevalent in 65.9% of patients, underscoring its significance as
certification for the treatment of non-alcoholic steatohepatitis (NASH) a major complication. Pre-transplant nutritional assessment revealed
patients with liver fibrosis, making it the only FDA approved drug for that 79.8% of patients were at risk of malnutrition, with severe
treating NASH in recent years. Common treatments for NAFLD include malnutrition (SGA-C) affecting 43.7%. Postoperatively, nutritional
regulating glucose and lipid metabolism, protecting the liver, and anti- improvements were observed, with SGA-C decreasing to 28.6% and
inflammatory effects. In addition, NAFLD treatment methods targeting a corresponding increase in moderate malnutrition (SGA-B) to 71.4%.
gut microbiota based on the gut liver axis are emerging, and various Binary logistic regression identified unintended weight loss (B = 0.9, p
new drugs are also being developed < 0.01), loss of subcutaneous fat (B = 0.8, p < 0.001), and older age
Method: We conducted a comprehensive literature search on the (p < 0.01) as significant predictors of post-transplant dysglycemia.
Cochrane Library Science Network, Embase, PubMed, and Google Notably, recipients with postoperative nutritional improvement (shift to
Scholar, searching for relevant literature reports published in English SGA-B) demonstrated a 30% reduction in glycemic complications (p
as of November 30, 2024, the development of new drugs for NAFLD. < 0.05). These findings highlight the critical role of preoperative and
1. Research non pharmacological treatments (including specific diet postoperative nutritional optimization in mitigating dysglycemia and
and exercise) and pharmacological treatments for NAFLD. improving metabolic outcomes.
2. To explore the application of various drugs for type 2 diabetes (such Conclusion: This is the first study in Vietnam to systematically
as GLP-1 receptor agonist and SGLT2i) in the treatment of NAFLD. investigate nutrition-related predictors of dysglycemia in liver
3. Evaluate the latest clinical trial results of novel drugs (such as thyroid transplant recipients. Unintended weight loss and subcutaneous fat
hormone receptor beta agonists, FGF analogs, and other candidate loss were identified as key contributors to increased blood sugar
drugs) levels. These results emphasize the urgent need for preoperative
Result: Through literature search, we found that non drug treatment nutritional optimization as an integral part of liver transplantation care
programs such as diet change and caloric restriction (CR) are the to improve metabolic outcomes and patient quality of life.
most common dietary intervention programs . T2DM drugs found
that most of the clinical studies using GLP-RA and SGLT2 drugs to PP0549
treat T2DM combined with NASH found that these drugs are safe and
Plasma FSTL-1 accurately assesses MASH-associated liver
effective, and the peroxisome proliferator activated gamma receptor
fibrosis stage
agonist pioglitazone as an example is the only diabetes drug included
in the NASH treatment guidelines. Liver protective drugs, such as Yongquan Chi1,2, Wenzhu Li1,2, Junda Li1,2, Haipeng Jiang1,2, Wei Xu1,2,
ursodeoxycholic acid (UDCA), are synthetic bile acids in the human Shanke Sun1,2, Xiaoguo Li3, Xiaolong Qi3, Jianhua Rao1,2
body that have specific protective effects on the liver. Farnesol X
1
Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical
receptor (FXR) agonist-OCA has been found to significantly improve University, 2Research Unit of Liver Transplantation and Transplant
fibrosis in NASH patients. The gut microbiota has also emerged as a Immunology, Chinese Academy of Medical Sciences, 3Liver Disease
Center of Integrated Traditional Chinese and Western Medicine,
hot topic in clinical trials targeting NASH treatment
Department of Radiology, Zhongda Hospital, Medical School,
Conclusion: NAFLD is a multi system metabolic disease. The
Southeast University, Nurturing Center of Jiangsu Province for State
intervention of lifestyle is the basis of treatment for this disease, and
Laboratory of AI Imaging & Interventional Radiology (Southeast
regulating glucose and lipid metabolism remains the focus of NAFLD
University), Nanjing, China; Basic Medicine Research and Innovation
treatment. Regarding the treatment of gut microbiota, new metabolic Center of Ministry of Education, Zhongda Hospital, Southeast
drugs represented by PPAR agonists, FXR agonists, and THR-β University; State Key Laboratory of Digital Medical Engineering,
agonists are being developed. However, many drugs in clinical trials Nanjing, China
have not reached the endpoint of liver histology due to unsatisfactory
Background: Many emerging drugs for MASH target at liver fibrosis,
trial results. This may be related to the complexity, heterogeneity, and
especially alleviating F2/F3 liver fibrosis, while their efficacy remains
limitations of therapeutic targets in the pathogenesis of NAFLD.
uncertain. Reliable non-invasive biomarkers for assessing MASH-
Table and Figure:Figure 1.TABLE 1 Partial drug clinical trials in progress
associated fibrosis are crucial for clinical assessment and drug
or in preparation for NASH
development. This study aimed at evaluating the accuracy of plasma Met group compared with Mod group, and decreased in Cor + LY
Follistatin-like protein 1 (FSTL-1) in assessing MASH-associated group compared to Cor group.
fibrosis stages and its potential as a guide for drug development. Conclusion: Cordycepin can treat IR and lipid deposition in FFA-
Method: Clinical data, plasma and liver biopsy tissues from 115 induced HepG2 cells and in high-fat diet-induced MAFLD mice by
patients were collected including healthy controls (n = 37) and MASH regulating the PI3K-AKT pathway.
(n = 78) from 2023 March to 2024 May in the First Affiliated Hospital Table and Figure:Figure 1.Figure 1. The Effects and Mechanisms of
with Nanjing Medical University. The plasma FSTL-1 levels were Cordycepin on Glucose and Lipid Metabolism in HepG2 Cells Induced
measured along with the steatosis levels and fibrosis stages based on by Free Fatty Acids
liver biopsy tissues. Figure 2.Figure 2 The Therapeutic Effects and Mechanisms of
Result: Plasma FSTL-1 levels were significantly higher in MASH Cordycepin in Mice with MAFLD
patients (0.47, IQR 0.30–0.60) than controls (0.32, IQR 0.16–0.43),
showing a 1.5-fold increase. FSTL-1 levels positively correlated with
PP0551
steatosis and fibrosis stages. Among the MASH cohort, 36 patients
(46%) had F2 and more, 22 (28%) had F3 and more. Plasma FSTL-1 Association between coffee consumption habits and Non-
distinguished fibrosis stages with high accuracy, achieving area under alcoholic fatty liver disease in community-dwelling populations:
the receiver operating characteristic curve (AUROCs) of 0.82 (95% data from the National Health and Nutrition Examination Survey
confidence interval [CI], 0.72–0.91) for F ≥ 2 and 0.93 (95% CI, 0.84– 2013–2018
1.00) for F ≥ 3., indicating that plasma FSTL-1 can accurately assess Penglin Chen1, Shiyan Wang1, Tao Zhang1, Enqiang Chen2
the MASH-associated liver fibrosis and distinguish participants from 1
Department of Pharmacy, West China Hospital, Sichuan University,
F2 and F3 highlighting its relevance in evaluating drug efficacy and 2
Center of Infectious Diseases, West China Hospital of Sichuan
facilitating drug discovery for MASH-associated fibrosis. University
Conclusion: Plasma FSTL-1 can accurately assess the MASH- Background: Certain evidence has emerged suggesting a potential
associated liver fibrosis and distinguishing liver fibrosis stages in MASH association between coffee and Non-alcoholic fatty liver disease
patients, offering a potential drug discovery for MASH-associated (NAFLD), yet the nature of this relationship remains elusive. The
fibrosis. Further studies incorporating additional parameters are present study was designed to investigate the correlation therein
warranted. Method: A cross-sectional study was conducted, leveraging the
data from the National Health and Nutrition Examination Survey
PP0550 (NHANES) that was amassed during the period from 2013 to 2018.
Weighted univariate and multivariate logistic regression analyses were
The Effect and Mechanism of Cordycepin on Metabolic-associated
implemented to dissect the relationship between coffee consumption
Fatty Liver Disease
and NAFLD. Moreover, restricted cubic spline (RCS) analysis was
Yu Zhang1, Xiaoxiong Hu2 deployed to probe into any potential nonlinear associations between
1
School of Chemistry and Bioengineering, Yichun University, Yichun, coffee consumption and NAFLD.
China., 2Department of Infectious Diseases and Hepatology Unit, Result: The study ultimately incorporated 8062 subjects who were 20
Yichun People’s Hospital affiliated to Yichun University, Yichun, China. years of age or older. The median age was 46 years, with the proportion
Background: To investigate the effect and mechanism of cordycepin of males being 48.30% and non-Hispanic Whites accounting for
on Metabolic-associated fatty liver disease (MAFLD) based on PI3K- 62.91%. The weighted prevalence of NAFLD was determined to
AKT pathway. be 44.18%. After duly controlling for confounding variables, coffee
Method: FFA-induced HepG2 fatty liver cell model was established, consumption was found to be inversely correlated with the risk of
and the experimental groupings were Control (Con) group, Model NAFLD (OR = 0.96, 95%CI: 0.94, 0.99). The RCS analysis indicated
(Mod) group, Cordycepin (Cor) group, Positive control metformin (Met) that coffee consumption was linearly related to NAFLD (P for nonlinear
group, and pathway inhibitor (Cor+LY) group. The glucose (GLU) and > 0.05).
triglyceride (TG) of cell lysis fluid were detected, and oil red O was Conclusion: Appropriate augmentation in coffee intake might
used to observe the lipid droplets. RT-qPCR and WB were used to potentially confer benefits in the context of NAFLD. To sum it up, it
detect the changes in mRNA and protein of PI3K, AKT, GSK3 in cells. seems that incrementing coffee consumption could constitute one of
A total of 40 C57BL6/J male mice were divided into 5 groups (groupings the highly efficacious non-pharmaceutical strategies for the prevention
rules were as above) on average. They were fed with high-fat chow to and management of NAFLD.
build a fatty liver disease model, except for the Con group which was
fed with normal chow. Serum ALT and AST indexes were detected;
PP0552
hepatic lipid droplets were observed by oil red O. RT-qPCR and WB
were used to detect PI3K, AKT, GSK3 in the groups. Serum Metabolomics Uncovers the Mechanisms of QinghuaFang
Result: 1.The area of red lipid droplets in Cor group and Met group in Preventing Non-Alcoholic Fatty Liver Disease
were decreased compared with Mod group. The GLU and TG showed Le Wang1, Chunyan Wang2, Ying Li2
a decreasing trend in Cor group and Met group compared to Mod 1
Shanghai University of Traditional Chinese Medicine, 2Longhua
group. Compared with Mod group, the mRNA changes of PI3K, AKT, Hospital Affiliated to Shanghai University of Traditional Chinese
and GSK3 were increased in Cor group and Met group. PI3K mRNA Medicine
was decreased in Cor+LY group compared with Cor group. The Background: Non-alcoholic fatty liver disease (NAFLD) is the most
protein expression of p-PI3K/PI3K, p-AKT/AKT, and p-GSK3/GSK3 common chronic liver disease, with an estimated global prevalence
were decreased in Mod group compared with Con group, but Cor of 25%. The spectrum of NAFLD ranges from the benign form of
group and Met group were increased compare with Mod group. non-alcoholic fatty liver disease to the severe form of non-alcoholic
2. The Fasting blood glucose, Fasting insulin and Insulin Resistance steatohepatitis (NASH), which may progress to fibrosis, cirrhosis, and
Index increased in Mod group compared to Con group, and decreased even liver cancer. The estimated annual medical costs directly attributed
in Cor group and Met group compared with Mod group. The TG, TC to NAFLD treatment exceed USD 100 billion in the United States;
and LDL-C increased in Mod group compared with Con group, and moreover, the prevalence of NAFLD has been increasing in children
decreased in Cor group and Met group compared with Mod group. and young adolescents . Because of its widespread prevalence and
The ALT and AST increased in Mod group compared with Con group, increased economic burden, NAFLD has become a critical public
and decreased in Cor group and Met group compare with Mod group. health issue globally; therefore, it is crucial to investigate and develop
The expression of PI3K, AKT and GSK3 mRNA were increased in Cor efficient therapeutic strategies for NAFLD.Through previous clinical
group and Met group when compared with Mod group. The protein trials, it was found that QinghuaFang(QHF) significantly alleviates Non-
expression of p-PI3K/PI3K, p-AKT/AKT and p-GSK3/GSK3 decreased Alcoholic Fatty Liver Disease(NAFLD), reduces the degree of hepatic
in Mod group compared with Con group, increased in Cor group and
steatosis and hepatocyte inflammation. And yet, we are not fully aware Result: This study included 99 and 78 patients in the SAMe and non-
of the potential mechanism of QHF to alleviate NAFLD. SAMe groups. The median follow-up time was 12 months (range: 2 to 12
Method: To this end, we established a high-fat-diet-induced NAFLD months). There were differences in 7-day (99.0% vs. 89.7%, p = 0.015)
mouse model, which was treated with QHF for 12 weeks. The and 28-day (79.1% vs. 69.2%, p < 0.001) survival between the two
NAFLD phenotype was evaluated via histopathological analysis and groups, but not at 3 (27 vs. 27), 6 (30 vs. 31), or 12 (49 vs. 40) months
biochemical parameters, including serum levels of ALT, AST, TC, (all p > 0.05). Multivariate analysis showed SAMe therapy (HR=0.363,
TG, etc. A serum metabolomics study was conducted using ultra- 95%CI: 0.137-0.964, p = 0.042) was an independent prognostic factor
performance liquid chromatography coupled with tandem mass for 28-day survival in patients with AH. Additionally, age (HR=1.050,
spectrometry. 95%CI: 1.011-1.091, p = 0.012), albumin levels (HR=0.807, 95%CI:
Result: The results revealed that QHF mitigated NAFLD symptoms such 0.710-0.917, p = 0.001), and creatinine levels (HR=1.005, 95%CI:
as histopathological changes and liver cholesterol levels. Through the 1.001-1.009, p = 0.009) were independent prognostic factors for
serum metabolomics study, 396 differential metabolites were identified patients with AH at 28 days.
between the model and control groups, and 45 differential metabolites Conclusion: SAMe is associated with improved prognosis in patients
were identified between the QHF and model groups. Additionally, 36 with AH. The use of SAMe is an independent predictor of 28-day
differential metabolites were identified as candidate targets of QHF and survival in patients with AH.
subjected to pathway enrichment analysis. The results revealed that Table and Figure:Figure 1.Figure 1. Survival comparison of patients
these 36 differential metabolites were enriched in several metabolic with alcoholic hepatitis (AH) between the S-adenosyl-L-methionine
pathways such as tryptophan metabolism, glycerophospholipid (SAMe) group and non-SAMe group at different time points. (A) 28-
metabolism, insulin resistance, etc. day survival. (B) 3-month survival. (C) 6-month survival. (D) 12-month
Conclusion: Taken together, our results suggest that QHF might survival.
attenuate NAFLD partially by modulating 36 differential metabolites Figure 2.Figure 2. Survival of patients with alcoholic hepatitis and
and their correlated metabolic pathways, constituting information that different medication times. (A) 28-day survival. (B) 3-month survival.
might help us find novel therapies for NAFLD. (C) 6-month survival. (D) 12-month survival.

PP0553 PP0555
Paracetamol Toxicity treated with Hemoperfusion: A Case Report Composition of gut microbiota and alcohol-related liver disease: A
Sam Nogoy Fandood1 systematic review and meta-analysis
1
East Avenue Medical Center Quzeon City Xuanxuan Niu1, Huichun Xing1
BACKGROUND
1
Beijing Ditan Hospital, Capital Medical University, Beijing, China
Paracetamol (acetaminophen) is a widely used over-the-counter Background: Intestinal microbiome has been recognized as an
analgesic and antipyretic medication. While safe at therapeutic doses, important factor mediating the development of alcohol-related
excessive intake can lead to toxicity, causing severe liver damage and liver disease (ARLD). This article aims to provide a comprehensive
even acute liver failure (ALF). Paracetamol toxicity is one of the most description of gut microbiome changes in ARLD.
common causes of drug-induced liver injury worldwide, especially in Method: Pubmed, Embase, and web of science were searched from
developed countries. January 1, 2015 to September 1, 2024. There was no limit to language.
CASE SUMMARY According to the criteria, articles that provide gut microbiota analysis
We report the case of a 19/F woman who intentionally took 6.5 grams and report changes in diversity and abundance were selected after two
of Acetaminophen (Tylenol) as suicide attempt. She immediately screening sessions. Two reviewers extracted the data independently.
presented with abdominal pain and vomiting. Paracetamol assay taken Result: We compared the differences between ARLD patients and
10 hours post ingestion yielded 87 ug/ml. 48 hours after ingestion, healthy individuals, calculated the α-diversity index, and qualitatively
patient was seen at ER presenting with transaminitis (AST: 4027, summarized the β-diversity index and relative abundance of gut
ALT: 2211), jaundice (TB 7.78mg/dl) and coagulopathy (INR: 1.28). microbiota. The 17 studies included showed a decrease in α-diversity,
Acetylcysteine IV was started however favorable response was not including Shannon (SMD=-0.63, 95% CI= [-1.40, -0.14]), p<0.001),
see. Patient further presented with encephalopathy and coagulopathy Chao1 (SMD=-1.20, 95% CI= [-1.67, -0.74], p=0.022), OTUs (SMD=-
therefore, hemoperfusion was initiated, with treatment intervals of 48 h. 1.14, 95% CI= [-1.55, -0.73], p=0.010), while there was no significant
Her liver parameters improved gradually and were resolved after three difference in Simpson, ACE, inverse, Simpson, Pielou evenness. Out of
Hemoperfusion treatments. 21 studies on β-diversity, 16 reported significant differences between
CONCLUSION: ARLD and healthy control groups. Most studies have shown that ARLD
Hemoperfusion therapy is beneficial for abrogating toxic effect of patients experience a decrease in anti-inflammatory microorganisms
Paracetamol liver toxicity as it can adsorb toxins, including bilirubin (i.e., Bacteroidetes) and an enrichment of pro-inflammatory
and inflammatory mediators. microorganisms (i.e., Proteobacteria).
Conclusion: Intestinal microbiome changes in ARLD patients showed
PP0554 decreased diversity, decreased anti-inflammatory flora, and increased
pro-inflammatory bacteria in the study, which will be a promising target
Survival benefit of S-adenosyl-L-methionine in hospitalized for potential ARLD treatment.
patients with alcoholic hepatitis: a real-world cohort study
Fangfang Duan1, Yazhi Wang1, Yongping Zhang2, Song Yang1,3
PP0556
1
Capital Medical University Affiliated Beijing Ditan Hospital, 2People‘s
Hospital of Xinjiang Uygur, Autonomous Region, 3The Fourth People’s Hidden Danger: Hepatotoxicity Linked to Nutritional Supplements
Hospital of Qinghai Province Silvia Cvekova1,2
Background: S-adenosyl-L-methionine (SAMe) can improve the liver
1
II. Department of internal medicine gastroenterologic and geriatric,
function in patients with alcoholic hepatitis (AH), although its impact University Hospital Olomouc, 2Faculty of Medicine and Dentistry,
on prognosis remains unclear. This study examined the prognosis of Palacky University
patients with AH treated or not with SAMe. Background: Drug-induced liver injury (DILI) due to nutritional
Method: This retrospective study included hospitalized patients with supplements is increasingly prevalent. These cases can be challenging
AH. The patients were grouped based on whether they received to diagnose and often have a severe course.
SAMe. The characteristics and 7-day, 28-day, 3-month, 6-month, and Aims: To analyze cases of acute hepatitis potentially related to
12-month survival were compared. A Cox proportional hazard model nutritional supplements, emphasizing diagnostic and therapeutic
was used to identify independent predictors of 28 days survival in AH. approaches.
Methods: Retrospective analysis of two cases of acute hepatitis PP0558
meeting DILI criteria. Comparative Study of RUCAM and RECAM for Causality
Results: Assessment in a Chinese Multi-center Prospective Drug-induced
Case 1: A 41-year-old male presented with icterus, pruritus, liver injury Cohort
and acholic stools. Investigations revealed cholestatic hepatitis.
Yao Meng1, Mengmeng Zhang1, Tiantian Guo1, Zikun Ma1, Jinxin Gu1,
Anamnesis revealed selective androgen receptor modulator (SARM)
Cen Zhang1, Runjie Wei1, Meng He1, Mengyu Zhao1, Yu Wang1, Yan
use. Liver biopsy showed extrahepatocytic cholestasis. Treatment
Wang1, Xinyan Zhao1
included hepatoprotectives, ursodeoxycholic acid (UDCA), and
corticosteroids, with gradual improvement.
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
University
Case 2: A 51-year-old male presented with icterus and weight
loss. Investigations excluded other etiologies. Anamnesis revealed Background: The diagnosis of DILI depends on assessing the causal
testosterone undecanoate and Tribulus terrestris supplementation. relationship between suspected drugs and liver injury. Two widely
Hepatotoxic medications were discontinued, and treatment with used methods for this evaluation are RUCAM and RECAM. This study
hepatoprotectives and UDCA resulted in prompt improvement. aims to compare the diagnostic performance of RUCAM and RECAM
Conclusion: These cases highlight the diagnostic and therapeutic using data from a national multi-center prospective cohort.
challenges of DILI/herb-induced liver injury (HILI) caused by sports Method: Patients diagnosed with DILI or non-DILI liver diseases with
nutrition supplements. Cholestatic liver involvement was observed. drug exposure at Beijing Friendship Hospital between September 2022
Although treatment approaches varied, both cases demonstrated a and December 2024 were enrolled according to specific inclusion and
prolonged and potentially severe course of hepatopathy. exclusion criteria. The diagnostic performance of RUCAM and RECAM
was assessed by comparing the area under the ROC curve (AUC)
using the DeLong test. The consistency of RUCAM and RECAM with
PP0557
expert consensus was assessed using the Kappa test.
Rare Hepatic Subcapsular Hematoma Post-ERCP in an Adult Result: A total of 299 DILI patients and 43 non-DILI patients were
Healthy Female included in this study. The ages of the DILI group and the non-DILI
JESIAH JANELLE DELOS REYES1, CELINA ADRANEDA1 group are similar. Both DILI and non-DILI patients were predominantly
1
De Los Santos Medical Center female, with 188 (62.9%) female DILI patients and 34 (79.1%) female
Endoscopic retrograde cholangiopancreatography (ERCP) is a non-DILI patients, showing a statistically significant difference
procedure commonly used in gastroenterology, both serving as a (p=0.037). Laboratory test results, including ALT, AST, and TBIL levels,
diagnostic and therapeutic tool. Hepatic subcapsular hematoma were similar between the two groups. Both DILI and non-DILI patients
(HSH) is a rare complication of ERCP, with limited literature available primarily showed herbal medicines as suspected drugs, followed by
to date. This is a case of a 29-year-old female who presented with conventional medications. Notably, the RUCAM and RECAM scores for
6-day tolerable abdominal pain, jaundice associated with tea DILI were significantly higher in DILI patients than in non-DILI patients
colored urine, and acholic stools. The patient was managed as a (p<0.001).
case of obstructive jaundice secondary to proximal biliary stricture Most non-DILI patients had RUCAM and RECAM scores classified as
secondary to a peripancreatic lesion. The patient underwent ERCP “possible” or “unlikely/excluded”, while most DILI patients had scores
with stent insertion and endoscopic ultrasound (EUS) guided biopsy classified as “highly probable” or “probable”. For all patients, the AUC
of the peripancreatic lesion. The patient suddenly developed severe of RECAM was higher than that of RUCAM, though the difference was
right upper quadrant pain associated with decreased hemoglobin not statistically significant (p=0.134).
levels and hemodynamic instability 24-48 hours post operatively. Among 299 cases of DILI patients, 61 cases were reviewed by a panel
A CT aortogram of the abdominal aorta with contrast confirmed the of three clinical experts, who identified suspected drugs in sequential
presence of a large hepatic subcapsular hematoma (HSH). Initially, order based on LiverTox, the Chinese guidelines for drug-induced liver
percutaneous drainage of the subcapsular hematoma was considered, injury, Hepatox, drug package inserts, and rankings from case reports.
however, the continuous decrease in the amount of hematoma and the For these 61 DILI patients, the AUC for RUCAM was slightly higher than
hemodynamic stability of the patient was constantly improving. Hence, RECAM in DILI cases, but the difference was not statistically significant
the patient underwent serial monitoring of subcapsular hematoma (p=0.103). Among the 61 patients who were reviewed by three clinical
using whole abdominal ultrasound in a span of 6 months and was experts, 41 patients were identified that this liver injury was caused by
managed conservatively. This case highlights the rare complication a single medication. The consistency analysis was performed between
of ERCP and increasing awareness to aid in early diagnosis and the medication with the highest RUCAM and RECAM scores and the
managementEndoscopic retrograde cholangiopancreatography medication determined by expert consensus. The results showed that
(ERCP) is a procedure commonly used in gastroenterology, both the consistency of RUCAM with expert consensus was higher than that
serving as a diagnostic and therapeutic tool. Hepatic subcapsular of RECAM (0.963 vs 0.939, p<0.001).
hematoma (HSH) is a rare complication of ERCP, with limited literature Conclusion: RUCAM shows better diagnostic accuracy compared to
available to date. This is a case of a 29-year-old female who presented RECAM and aligns more closely with expert consensus. Both RUCAM
with 6-day tolerable abdominal pain, jaundice associated with tea and RECAM demonstrate excellent performance in diagnosing DILI
colored urine, and acholic stools. The patient was managed as a within a national multi-center prospective DILI cohort in China.
case of obstructive jaundice secondary to proximal biliary stricture Table and Figure:Figure 1.Table1. demographic and baseline
secondary to a peripancreatic lesion. The patient underwent ERCP laboratory data of the cases.
with stent insertion and endoscopic ultrasound (EUS) guided biopsy Figure 2.Figure 1. AUC of RUCAM and RECAM.
of the peripancreatic lesion. The patient suddenly developed severe
right upper quadrant pain associated with decreased hemoglobin PP0559
levels and hemodynamic instability 24-48 hours post operatively. Analysis of Clinicopathologic Feature and Diagnostic Difficulties
A CT aortogram of the abdominal aorta with contrast confirmed the of Drug-induced Autoimmune-like Hepatitis (DI-ALH) and Review
presence of a large hepatic subcapsular hematoma (HSH). Initially, of Literature
percutaneous drainage of the subcapsular hematoma was considered,
Ying Qun Xiao 1, Chong Xie1, Fu Wang Xu1
however, the continuous decrease in the amount of hematoma and the 1
The Ninth Hospital of Nanchang (Affiliated Infectious Disease
hemodynamic stability of the patient was constantly improving. Hence,
Hospital of Nanchang University),
the patient underwent serial monitoring of subcapsular hematoma
using whole abdominal ultrasound in a span of 6 months and was Background: Drug-induced liver injury(DILI) results in a wide variety
managed conservatively. This case highlights the rare complication of complex phenotypes that can mimic almost all liver diseases. One
of ERCP and increasing awareness to aid in early diagnosis and of phenotype is associated with autoimmune features and shows
management histological features that highly overlaps with “idiopathic”(classical)
AIH, often associated with elevated serum hepatic autoantibody and by regular oral methylprednisolone.
lgG levels, and is increasingly attributed to the drugs, referred to as Subsequent abdominal ultrasounds indicated liver cirrhosis and
drug-induced autoimmune-like hepatitis(DI-ALH) in the literature. It is ascites. An enhanced CT scan of the chest and abdomen revealed
clinically difficult to distinguish the DI-ALH from the AIH. Based on the diffuse liver disease, uneven enhancement, unclear hepatic veins,
clinical and histoscopic characteristics of DI-ALH and hepatic pathology, portal hypertension, splenomegaly, and significant pelvic and
this article explores the utility of new biomarkers in the diagnosis of abdominal effusion, leading to the diagnosis of HSOS. The patient’s
DI-ALH, and compares the differences in clinicopathological features, history of taking “Quba Babusi tablets” for vitiligo was considered in
prognosis and treatment between DI-ALH and AIH. the diagnosis of HSOS.
Method: 101 patients hospitalized in our hospital and diagnosed with Laboratory tests showed elevated white blood cell count, hemoglobin,
DILI by liver biopsy from January 1st, 2016 to December 31st ,2023 and platelets, suggesting a myeloproliferative disorder. Bone marrow
were continuously collected. All patients met the diagnostic criteria of morphology and genetic testing confirmed PV. The patient was treated
China Guidelines for the Diagnosis and Treatment of Drug-induced with a combination of methylprednisolone, telmisartan, rivaroxaban,
Liver Injury 2023, among which 14 patients were further diagnosed with furosemide, spironolactone, recombinant interferon, and aspirin. After
DI-ALH; 41 cases diagnosed with AIH were enrolled additionally as the one month of treatment, the patient’s weight and 24-hour urinary protein
control group. All the clinical data of the above patients were collected decreased, and pleural and abdominal effusions were significantly
and statistically analyzed to observe the differences between DI-ALH reduced. After three months, the effusions had mostly resolved without
and AIH(Supplemental Table 1). Hematoxylin-eosin staining, masson recurrence, although the liver morphology and portal hypertension
three-color staining, CD38, MUM-1 and other immunohistochemical showed no significant improvement on follow-up imaging. The patient
staining of the samples of the two groups of cases were performed, continued with anticoagulation and comprehensive treatment, with
and the images were read by two experienced pathologists and consideration of TIPS if necessary.
scored pathology. This case underscores the importance of thorough diagnostic work-
Result: 1. DI-ALH can present many AIH-like features, the important up and a multidisciplinary approach to treatment in complex medical
of which is liver-related serology. 2. The morphological patterns cases. It also serves as a reminder to clinicians to pay close attention
of DI-ALH and AIH were similar, and the common pathological to basic test results and to follow up on any anomalies to uncover the
manifestations included: inflammation in the portal areas, lymphocytic underlying causes.
and plasma cell infiltration and varying degrees of liver fibrosis. (The
clinicopathological differentiation between DI-ALH and AIH is shown in
PP0561
Supplemental Table 2). 3. DI-ALH accounted for 13.8% of 101 cases
of DILI. Depressed TFAM Promotes Acetaminophen-induced
Conclusion: 1.Observing the expression of CD38, MUM1, IgG, IgG4 Hepatotoxicity Regulated by DDX3X- PGC1α-NRF2 Signaling
and other markers and the distribution of plasma cell infiltration under Pathway
the microscope was helpful to distinguish DI-ALH from AIH. 2.Liver Yaling Cao1, Sisi Chen1, Zihao Fan1, Ling Xu1, Zhenzhen Pan1, Mei
biopsy is an important means to help identify and confirm the diagnosis. Liu2, Feng Ren1
3.Discontinuing related drugs, most patients with DI-ALH would not 1
Beijing Institute of Hepatology/Beijing Youan Hospital, Capital
recur and do not need immunosuppression or hormonal therapy. Medical University, 2Department of Liver Oncology, Beijing Youan
However, AIH relapses after discontinuation of immunosuppressants Hospital, Capital Medical University
and requires long-term immunosuppressive therapy. Background: Acetaminophen (APAP)-induced acute liver injury (AILI)
Table and Figure:Figure 1.supplemental table 1: clinical features of is the most prevalent cause of acute liver failure and mitochondrial
DILI, DI-ALH and AIH dysfunction plays a dominant role in the pathogenesis of AILI.
Figure 2.supplemental table 2: The identifications of pathological Mitochondrial transcription factor A (TFAM) is an important marker for
features between DI-ALH and AIH maintaining mitochondrial functional homeostasis, but its functions in
AILI is unclear. This study aimed to investigate the function of TFAM
PP0560 and its regulatory molecular mechanism in the progression of AILI.
Method: The role of TFAM and DEAD (Asp-Glu-Ala-Asp) box
Case Report of Myeloproliferative Neoplasm Complicated with
polypeptide 3 X-linked (DDX3X) in AILI was determined with TFAM
Hepatic Sinusoidal Obstruction Syndrome and Focal Segmental
overexpression or DDX3X knockdown, respectively.
Glomerulosclerosis
Result: TFAM expression was suppressed in AILI patients. TFAM
Yuxuan Song1, Yajing Zhen1, Hui Ma1, Bo Feng1, Yandi Xie1 overexpression alleviated liver necrosis and mitochondrial dysfunction.
1
北京大学人民医院 Treatment of the AILI mouse model with N-acetylcysteine (NAC),
Introduction: a drug used to treat APAP overdose, resulted in significant TFAM
This case report presents a rare and complex medical scenario involving activation. In vivo experiments confirmed that TFAM expression was
a 19-year-old male patient who was diagnosed with three concurrent negatively regulated by DDX3X. Mechanistic studies showed that
conditions: Polycythemia Vera (PV), Hepatic Sinusoidal Obstruction nuclear respiratory factor 2 (NRF-2), a key regulator of TFAM, was
Syndrome (HSOS), and Focal Segmental Glomerulosclerosis (FSGS). selectively activated after DDX3X knockdown via activated peroxisome
PV is a type of Myeloproliferative Neoplasm (MPN) characterized proliferator-activated receptor γ coactivator 1 (PGC-1α), in vivo and in
by thrombotic complications, while HSOS is a clinical syndrome vitro.
often caused by microthrombi in the liver’s blood vessels, leading to Conclusion: This study demonstrates that depressed hepatic TFAM
symptoms like abdominal bloating, liver pain, ascites, jaundice, and plays a key role in the pathogenesis of AILI, which is regulated by the
hepatomegaly. FSGS is a renal condition that presents with edema and DDX3X- PGC1α-NRF2 signaling pathway.
oliguria. The co-occurrence of these three diseases in the same patient Table and Figure:Figure 1.A pattern diagram depicting TFAM inhibition
has not been previously reported, highlighting the importance of early promoting acetaminophen induced hepatotoxicity via DDX3X-PGC1α
recognition and diagnosis of the underlying conditions and exploring -NRF2 signaling pathway
the correlations between them. Figure 2.This study demonstrates that depressed hepatic TFAM
Case Description: plays a key role in the pathogenesis of AILI, which is regulated by the
The patient initially presented with recurrent abdominal bloating, lower DDX3X- PGC1α-NRF2 signaling pathway.
limb, and scrotal swelling. Initial tests revealed a serum albumin of
17g/L, serum creatinine of 143umol/L, and a 24-hour urinary protein PP0562
of 4.2g/d. A CT scan showed bilateral pleural effusion, abdominal
effusion, portal hypertension, and splenomegaly, leading to a Sinusoidal Obstructive Syndrome Following Allogeneic Stem Cell
diagnosis of nephrotic syndrome. A renal biopsy confirmed FSGS. The Transplant: A Case Report of Recovery in a 65-Year-Old Male
patient was treated with methylprednisolone and rituximab, followed Weilun Gao1,2, Chuyi Liao3,2
1
Department of Gastroenterology, Royal Melbourne Hospital, further evaluated by administering Lactobacillus plantarum. After 28
Parkville, Victoria, Australia, 2Department of Medicine, University of days of intervention, plasma, feces, and liver samples were collected.
Melbourne, Parkville, Victoria, Australia , 3Department of General The characteristics of the intestinal microbiota and metabolites were
Medicine, Western Health, Sunshine, Victoria, Australia detected by 16S rDNA sequencing of feces and by LC-MS/MS of
Introduction: Sinusoidal Obstructive Syndrome (SOS), previously plasma.
known as veno-occlusive disease (VOD), is a potentially life-threatening Result: Lactobacillus plantarum could ameliorate alcohol-induced
complication of allogeneic stem cell transplantation (allo-SCT). It is liver injury. After the intervention of Lactobacillus plantarum, plasma
characterized by damage to the hepatic sinusoidal endothelial cells, AST decreased in mice, liver oil red indicated a decrease in the degree
leading to liver dysfunction and portal hypertension. Timely diagnosis of steatosis, and TG decreased in liver tissue. Relative abundance of
and intervention are critical for recovery. beneficial bacteria such as Lactiplantibacillus, Faecalibacterium and
Case Presentation: A 65-year-old male with KMT2a amp TP53 mutated Bifidobacterium increased while the relative abundance of harmful
acute myeloid leukemia underwent allogeneic stem cell transplantation bacteria such as Helicobacter and Klebsiella decreased. L-carnitine
(HLA matched unrelated donor) at Royal Melbourne Hospital following and theophylline increased in plasma and were positively correlated
reduced intensity conditioning with fludarabine, melphalan and with elevated genus.
thymoglobulin. The patient had no pre-existing liver disease and Conclusion: Lactobacillus plantarum ameliorate liver injury in mice
tolerated the conditioning regimen well initially. with ALD
Day +14 Post-Transplant: The patient developed right upper quadrant Table and Figure:Figure 1.The Effects of Lactobacillus plantarum on
abdominal pain, hepatomegaly, and weight gain (+11.5kg) due to the Blood Biochemistry and Liver Pathology in Mice with alcohol-
fluid retention meeting Baltimore criteria for SOS. Laboratory tests related liver injury
showed: Alanine Aminotransferase (ALT): 215 U/L (normal: 5-40 U/L), Figure 2.The Impact of Lactobacillus plantarum on the Intestinal
Aspartate Aminotransferase (AST): 290 U/L (normal: <35 U/L), Alkaline Microbiota and Plasma Metabolites of Mice with alcohol-related liver
Phosphatase (ALP): 320 U/L (normal: 30-110 U/L), Gamma Glutamyl injury
Transferase (GGT): 300 U/L (Normal <65 U/L), Total Bilirubin: 190
umol/L (normal: <21 umol/L ) PP0564
Doppler ultrasound revealed hepatomegaly, ascites, and reversal of
Propensity Score Matching Analysis for alcohol-related liver
portal venous flow, consistent with SOS.
disease
Management: The patient was admitted to ICU for hemodynamic
and ventilatory in the context of fluid overload, complicated by acute Fangfang Duan1, Shanshan Song1, Hang Zhai1, Yazhi Wang1, Jun
kidney injury and metabolic acidosis. He received fluid management Cheng1, Song Yang1
via filtration, and defibrotide was initiated at 25 mg/kg/day for 14 days.
1
Capital Medical University Affiliated Beijing Ditan Hospital
Over the next 14 days, liver function tests gradually improved, ascites Background: This study aims to investigate the impact of comorbidity
resolved, and the patient’s bilirubin normalized. with chronic hepatitis B (CHB) on the survival rates and incidence of
Day +35 Post-Transplant: The patient demonstrated significant clinical liver cancer in patients with alcohol-related liver disease (ARLD).
improvement: ALT: 42 U/L (normal: 5-40 U/L), AST: 26 U/L (normal: <35 Method: Patients with ARLD and those with ARLD co-morbid with
U/L), ALP: 104 U/L (normal: 30-110 U/L), GGT: 105 U/L (Normal <65 CHB were included in this study and designated as the ARLD group
U/L), Total Bilirubin: 34 umol/L (normal: <21 umol/L ). The patient was and the ARLD + HBV group, respectively. Propensity score matching
discharged with instructions for close follow-up. (PSM) was then employed to compare survival rates and liver cancer
Discussion: SOS is a known complication of allo-SCT, this can be development between these two groups.
associated with either myeloablative or reduced intensity conditioning Result: Among the 404 patients, 254 were in the ARLD group and 150
regimens containing busulfan and Melphalan. The pathophysiology in the ARLD + HBV group. After propensity score matching, each group
involves injury to sinusoidal endothelial cells, leading to obstruction comprised 67 patients. Initially, the ARLD + HBV group exhibited lower
and subsequent hepatic injury. Early recognition and prompt initiation 5-year survival rates compared to the ARLD group (51.3% vs. 70.1%,
of defibrotide are critical to improving outcomes. In this case, timely p < 0.001). However, PSM mitigated this difference, with survival rates
recognition and management of fluid overload led to full recovery now comparable (61.2% vs. 60.9%, p = 0.390). Notably, the ARLD
without long-term hepatic complications. + HBV group showed a higher incidence of liver-specific mortality
Conclusion: This case highlights the importance of early diagnosis and after matching (32.6% vs. 6.2%, p = 0.018). Furthermore, although a
management of SOS in post-transplant patients. Vigilance for signs of higher proportion of patients in the ARLD + HBV group developed liver
SOS, including hepatomegaly, fluid retention, and LFT derangements, cancer post-matching, the difference was not statistically significant
is essential for timely intervention and favourable outcomes. compared to the ARLD group (15.7% vs. 9.8%, p = 0.170).
Conclusion: Co-morbidity with chronic hepatitis B in ARLD patients
PP0563 elevates the risk of liver-related mortality.
Table and Figure:Figure 1.Figure 1. Evaluation of liver-specific mortality
Effects of Lactobacillus plantarum on intestinal microbiota and by different etiology of liver disease. (A) Comparison of liver-specific
plasma metabolism in mice with alcohol-related liver injury mortality between the ARLD group and the ARLD+HBV group before
Yifan Xu1, Yanxu Hao1, Song Yang1, Huichun Xing1 propensity score matching. (B) Comparison of liver-specific mortality
1
Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital between the ARLD group and the ARLD+HBV group after propensity
Medical University score matching.
Background: Previous studies have found changes in the genus Figure 2.Figure 2. Evaluation of development of liver cancer by
(species) of Lactobacillus in alcohol-related liver disease in both different etiology of liver disease. (A) Comparison of development of
clinical and mouse experiments. Different Lactobacilli play different liver cancer between the ARLD group and the ARLD+HBV before
functions in different disease states. Previous studies have found the matching. (B) Comparison of development of liver cancer between the
improvement effect of Lactobacillus on alcohol-induced liver injury in ARLD group and the ARLD+HBV after matching.
mice , and some studies have also shown the pathogenic effect of
Lactobacillus. Therefore, the functions of different strains need to be PP0565
further studied and evaluated.
Dysbiosis of the gut microbiota associated with death in alcoholic
Method: A mouse model of alcoholic liver injury (C57BL/6N male
liver cirrosis with sarcopenia
mice) was established using the modified Lieber-DeCarli control
and alcoholic liquid feed. Liver function and liver histopathological Min Quan1, Min Li, Yifan Xu, Song Yang
evaluation were conducted to establish the liver injury model. The
1
Department of Hepatology, Beijing Ditan Hospital, Capital Medical
effect of characteristic bacteria (lactobacillus) on liver injury was University, Beijing 100015, China
Background: Patients with alcoholic liver cirrhosis (ALC) frequently model treated with ethanol as a suitable cell model for ALD have not
experience sarcopenia and gut dysbiosis. Nevertheless, less is been reported.Alcohol-related liver disease (ALD) remains the leading
known about the relationship between microbial changes linked to cause of chronic liver disease worldwide, accounting for approximately
sarcopenia and the prognoses of ALC patients. This study aimed to 25% of deaths from cirrhosis. But clinical treatment options for ALD
identify sarcopenia-related microbial changes and the related risks are still limited. The development of new drugs requires effective
and outcomes of patients with ALC. preclinical research models, such as cell models. HepG2 cells treated
Method: Between May 2018 and May 2021, 94 patients with ALC and with ethanol are often used to explore the pathology and treatment
23 healthy volunteers were prospectively enrolled and followed-up for of ALD. However, the advantages and limitations of the HepG2 cell
39.1 months to evaluate their survival. The skeletal muscle index at the model treated with ethanol as a suitable cell model for ALD have not
level of the third lumbar vertebra (L3-SMI) and fecal microbiota were been reported.
analyzed. Cox proportional hazards regression models were used to Method: HepG2 cells were treated with 100mM ethanol for 48 hours
estimate survival. (referred to as the HepG2- Ethanol) to serve as a cell model of ALD.
Result: The body mass index, total cholesterol levels, and model The cell model was observed by oil red O staining. Transcriptome
for end-stage liver disease (MELD) scores of patients with ALC with sequencing of HepG2-Ethanol model was performed. Clinical data from
sarcopenia were significantly reduced compared with those of patients the GSE142530 dataset were used to analyze the pathophysiological
with ALC without sarcopenia (P < 0.001, P = 0.033, and P = 0.004, mechanisms of alcoholic hepatitis (N_AH) and alcoholic cirrhosis (N_
respectively). The diversity of the gut microbiome of patients with EC). The transcriptome data mentioned above were used to analyze
ALC was significantly reduced compared to that of healthy controls the similarity of HepG2-Ethanol group with N_AH group and N_EC
(P<0.001). In patients with ALC, the relative abundance of Escherichia group in alcohol metabolism and cell damage pathways.
coli, Klebsiella pneumoniae, Klebsiella, Streptococcus, Veillonella, and Result: Our findings indicate that the HepG2-Ethanol model exhibited
Proteobacteria were significantly increased (P < 0.001, P = 0.009, P comparable performance to clinical patient pathology in most
= 0.004, P < 0.001, P < 0.001, and P < 0.001, respectively), whereas alcohol-related “cell damage” pathways, particularly in individuals
the abundance of Prevotella was decreased (P < 0.001), indicating diagnosed with alcoholic cirrhosis (N_EC group).However, in the
that alterations of these bacteria are specific features of patients with classical pathways related to alcohol metabolism, the pathological
ALC. The relative abundance of Veillonella was significantly increased manifestations of HepG2-Ethanol model are significantly different
in patients with ALC with sarcopenia compared to that in those without from those of clinical patients. Some pathways exhibit a degree of
sarcopenia (P = 0.027). During the 2-year follow-up period, 26 patients similarity with the HepG2-Ethanol model and Clinical model such as
(27.7%) died. The mortality rate of patients with ALC with sarcopenia the calcium signaling pathway and the intestinal immune network for
was significantly higher than that of those without sarcopenia (50% vs IgA production pathway,suggesting significant research potential.Our
12.5%; P < 0.001). Multivariate logistic regression further confirmed results showed that the HepG2-ethanol model has significant potential
that the L3-SMI, MELD score, blood creatinine level, Veillonella for investigating liver cell damage caused by alcohol, although it may
abundance, and Proteobacteria abundance were independently not effectively represent alcohol metabolism. This finding provides
associated with the 2-year survival of patients with ALC (P = 0.012, P = a theoretical basis for the application of HepG2-ethanol in future
0.017, P = 0.004, P = 0.045, and P = 0.016, respectively). However, the regulation and also provides a feasible method to explore a better ALD
abundance of Faecalibacterium may protect against sarcopenia (odds model by using transcriptome.
ratio, 0.003; P = 0.032). Conclusion: The HepG2-ethanol model has significant potential for
Conclusion: Alterations in the gut microbial composition of patients investigating liver cell damage caused by alcohol, although it may not
with ALC are associated with sarcopenia and mortality. Individuals effectively represent alcohol metabolism.
with sarcopenia-related Veillonella experienced significantly worse Table and Figure:Figure 1.Figure1
clinical outcomes. Modifying the gut microbiota could be a therapeutic
strategy for improving the clinical outcomes of patients with ALC with PP0567
sarcopenia.
Table and Figure:Figure 1.Fig 1. The composition and diversity of gut Myosteatosis is closely associated with sarcopenia and worse
microbiota in ALC with (ALCS) or without (ALCNS) sarcopenia and short-term outcomes in male patients with ARLD in China
healthy controls (HC). (A) The observed species was significantly Yu Zhang1, Song Yang1
different between patients with ALC with sarcopenia and those without 1
Department of Hepatology, Beijing Ditan Hospital of Capital Medical
sarcopenia (P < 0.05). (B) Genus level in fecal samples of healthy University
controls, ALC with or without sarcopenia. (C and D) LDA scores Background: The burden of alcohol-related liver disease (ARLD)
computed for differentially abundant taxa in the fecal microbiome. The is increasing in China. Patients with ARLD are more likely to have
length of each bar in dicates the effect size associated with a taxon, comorbid muscle damage, such as myosteatosis and sarcopenia,
which is significantly different when comparing to other groups (by the which may impair their survival. This study aimed to evaluate the
Kruskal-Wallis and Wilcoxon tests). LDA, linear discriminant analysis; relationship between the prognoses of patients with ARLD and
Figure 2.Fig 2. Kaplan–Meier estimate of the ALC patients stratified. myosteatosis, identified using the mean muscle attenuation.
(A) Kaplan–Meier curves for total survival of patients with ALC. (B) Method: We conducted a prospective multicenter study involving
Kaplan–Meier curves for survival of patients with sarcopenia and 308 hospitalized patients with ARLD. Sarcopenia and myosteatosis
without sarcopenia. were evaluated using computed tomography scans. The 6-month
cumulative incidence of relevant events was assessed by competing
PP0566 risk analysis. We used Cox proportional hazards regression models to
evaluate the impact of sarcopenia and myosteatosis on mortality.
Evaluation of the HepG2-Ethanol Model for Transcriptomic
Result: At enrolment, 116 (37.66%) patients presented with isolated
Analysis in Preclinical Research of Alcohol-Related Liver Disease
myosteatosis, 21 (6.82%) with isolated sarcopenia, 99 (32.14%) with
Yang Wang1, Xiaoxue Yuan, caixia Zhao, Jiaxi Li, Ronghua Jin, Xi combined sarcopenia and myosteatosis and 72 (23.38%) patients
Wang, Song Yang showed no muscle changes. The 6-month cumulative incidence of
1
No.8 Jingshun East Street, Chaoyang District, Beijing, China. death in patients with either sarcopenia and myosteatosis (13.13%)
Background: Alcohol-related liver disease (ALD) remains the leading was over twice that of patients without muscle changes (4.16%), or with
cause of chronic liver disease worldwide, accounting for approximately isolated myosteatosis (5.17%), and was significantly higher than that
25% of deaths from cirrhosis. But clinical treatment options for ALD of patients with isolated sarcopenia (9.5%). Multiple Cox regression
are still limited. The development of new drugs requires effective analysis showed that visceral adipose tissue area, subcutaneous
preclinical research models, such as cell models. HepG2 cells treated adipose tissue area, VA-TI (visceral adipose tissue index), SA-TI
with ethanol are often used to explore the pathology and treatment (subcutaneous adipose tissue index) and TBiL (total bilirubin) were
of ALD. However, the advantages and limitations of the HepG2 cell independent prognostic factors of 6-month survival with hazard ratios
(95% confidence intervals) of 0.923 (0.876-0.972), 1.075 (1.015- age of 56.43 years. Among the participants included in the study,
1.139), 1.277 (1.101-1.481), 0.801 (0.684-0.937), and 1.016 (1.003– the prevalence of vitamin D deficiency was 35.7%. Serum 25(OH)D
1.029), respectively. levels in Vitamin D deficiency group and Non-vitamin D deficiency
Conclusion: Myosteatosis, whether alone or combined with group were 12.80 (8.43-15.40) and 35.52 (28.11-35.11), respectively.
sarcopenia, is highly prevalent in patients with ARLD and is associated Spearman’s correlation analysis showed that after adjusting for
with significantly worse short-term outcomes. Early diagnosis season, vitamin D deficiency was positively correlated with alcoholic
and intervention of myosteatosis, are important for optimizing the hepatitis (AH), cirrhosis, ascites, sarcopenia, total bilirubin (TBIL),
management of patients with ARLD. model for end-stage liver disease (MELD) and Maddrey discriminant
Table and Figure:Figure 1.Cumulative incidence of death function (MDF)≥32. Logistic regression analysis showed that vitamin
Figure 2.Cox regression analysis for identifying independent prognostic D deficiency is a significant and independent factor associated with
factors the severity of ALD both in the univariate analysis (OR=2.568; 95%CI:
1.169-5.639; P=0.019) and in the multivariate analysis (OR=3.747;
95%CI: 1.352-10.382; P=0.011). Based on the ROC curve, the cut-off
PP0568
value of the 25(OH)D levels for predicting sarcopenia was 22.74 ng/
Comparison of Baseline Characteristics and Survival Rates in ml with 58.3% sensitivity and 72.3% specificity, and the cut-off value
ALD Patients with and Without Metabolic Syndrome of the 25(OH)D levels for predicting SBP was 14.2 ng/ml with 48.1%
Yazhi Wang1, Fangfang Duan1, Song Yang1 sensitivity and 85.2% specificity in patients with ALD.
1
Beijing Ditan Hospital Conclusion: Vitamin D deficiency was associated with the severity
Background: Alcoholic liver disease (ALD) is increasingly recognized of ALD. Our results suggest that serum 25(OH)D levels might be a
as one of the most common liver diseases in China, often worsened valuable predictor of sarcopenia and SBP in patients with ALD.
by excessive alcohol intake and metabolic syndrome (MeS). The
interaction between alcohol consumption and metabolic dysfunction PP0570
is vital for understanding ALD’s progression and management,
Involvement of oxidative stress, lipid dysmetabolism and gut
emphasizing the need to address metabolic issues in these patients.
microbial dysbiosis in oxaliplatin-induced fatty liver disease:
A recent multi-society Delphi consensus statement introduced a new
evidence from a tree shrew model
nomenclature for fatty liver diseases, highlighting the link between ALD
and MeS. This framework indicates that ALD should be considered Youzhi Lin1, Yulei Lu1, Fei Yi2, Chunlong Gui3, Xinglong Tan3, Wende
alongside metabolic disorders, as they can significantly influence Chen3
disease outcomes. However, few studies have investigated the survival
1
guangxi medical university cancer hospital, 2People‘s Liberation
rates of patients with ALD and accompanying metabolic abnormalities. Army Hospital No. 923, 3Guangxi Medical University
Method: Consecutively hospitalized adult patients with ALD were Background: Oxaliplatin is commonly used to treat colorectal cancer,
collected from January 2015 to December 2018 in Beijing Ditan Hospital but it induces drug-induced fatty liver disease in a substantial proportion
of Capital Medical University. They were divided into two groups: those of patients. How it induces such liver injury is poorly understood and
with MeS and those without. A comparison of baseline characteristics whether the gut microbiome is involved remains unknown.
and survival rates between the two groups was conducted, with a Method: A model of oxaliplatin-induced fatty liver disease was
significance threshold set at p < 0.05. established in male tree shrews by injecting them intraperitoneally six
Result: The study included a total of 567 patients, with 517 in the times, once every two weeks, with oxaliplatin at 7 mg/kg. During the
ALD with MeS group and 50 in the PureALD group. Patients with ALD acute and chronic phases of liver injury, liver tissue was analyzed in
and MeS were older (54.32 years vs. 52.64 years, p=0.031), had a terms of histopathology, oxidative stress and transcriptional profiling,
higher rate of cirrhosis (83% vs. 70%, p=0.033), higher total bilirubin while feces were subjected to microbial profiling based on 16S rRNA
levels (95.95 µmol/L vs. 69.42 µmol/L, p=0.028), and lower alanine sequencing.
aminotransferase levels (80.86 U/L vs. 178.13 U/L, p<0.05). There Result: The tree shrew model showed severe hepatocyte steatosis
was no statistically significant difference in the 24-month survival rates and ballooning during the acute phase, mild hepatic steatosis and
between the two groups (p=0.381). sinusoidal dilatation during the chronic phase, and persistent hepatic
Conclusion: In conclusion, the short-term survival of patients with ALD oxidative stress during both phases. Transcriptional profiling of
and MeS is comparable to that of those without MeS. Additionally, no liver tissue identified 1503 genes differentially expressed between
significant differences in survival rates were observed in the subgroups oxaliplatin-treated and control animals, of which 601 genes differed
of liver cirrhosis and liver hepatitis. between treated animals in the acute or chronic phases of fatty liver
Table and Figure:Figure 1. disease. The genes differentially expressed in both phases of disease
were enriched in pathways related to oxidative stress and lipid
metabolism. Microbial profiling of gut feces showed that oxaliplatin
PP0569
increased the relative abundance of potentially harmful bacteria
Vitamin D deficiency is related to liver disease severity and predict such as Parabacteroides, Rikenella, Alistipes and Faecalitalea,
sarcopenia and spontaneous bacterial peritonitis in alcohol- while reducing the abundance of anti-oxidative bacteria such as
related liver disease: a cross-sectional study Lactococcus and Flavobacterium. Abundance of several microbial
Qiufeng He1, Fangfang Duan2, Song Yang2 genera in the gut correlated with liver expression of genes involved in
1
Public Health Clinical Center of Chengdu, 2Beijing Ditan Hospital, oxidative stress and lipid metabolism as well as with levels of oxidative
Capital Medical University stress markers, and/or fat deposition in the liver.
Background: Vitamin D deficiency is associated with poor outcomes Conclusion: Our results suggest that our tree shrew model can
in various chronic diseases. Recently, vitamin D has been attracting faithfully replicate key characteristics of oxaliplatin-induced fatty liver
attention due to its importance in alcohol-related liver disease (ALD). disease, and that such disease involves oxidative stress and lipid
Method: Hospitalized patients with ALD were retrospectively enrolled dysmetabolism in the liver as well as dysbiosis of microbiota in the gut.
between January 2021 and April 2024. Vitamin D deficiency was
defined as serum 25(OH)D levels<20 ng/mL. Spearman’s correlation PP0571
analysis was used to explore variables associated with vitamin D
APRI can be used as an effective predictor of liver injury in
deficiency. Logistic regression analysis was used to analyze the factors
patients with hepatocellular carcinoma treated with PD-1/PD-L1
affecting the severity of ALD. A receiver operating characteristic (ROC)
inhibitor combination therapy: A single-center retrospective study
curve was created to identify the cut-off point of the serum 25(OH)D
level for predicting SBP and sarcopenia in patients ALD. JingMing Zhang1, Zheng Ling1, Zheng Ling2, RongHui Xie1, YuRou
Result: The study included 108 males and 7 females with an average Jin1
1
Mengchao Hepatobiliary Hospital, 2Fuzhou First General Hospital
Background: To investigate the clinical characteristics of programmed proportions of patients who progressed to chronic drug hepatitis or
cell death-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitors in the treatment autoimmune hepatitis were not significantly different between the two
of liver cancer and the factors affecting liver injury, and to identify groups (both P>0.05).
appropriate predictors of liver injury. Conclusion: In the context of NAFL, DILI is more likely to be cholestatic,
Method: Data from patients with liver cancer, who were treated with has a greater degree of liver injury , have more pronounced expression
PD-1/PD-L1 inhibitors at our hospital between October 2018 and of immune factors.
January 2023, were retrospectively collected and analyzed. Baseline
data were collected before immunotherapy initiation. The primary PP0573
endpoints were the the degree of liver injury.
Result: Data from 253 patients were enrolled in this study, of whom Efficacy and safety of magnesium isoglycyrrhizinate in preventing
190 were Child–Pugh class A and 63 Child-Pugh class B at baseline. novel antitumor drug-induced liver injury in patients with malignant
There were 123 cases of liver injury during treatment and follow-up. hematological diseases: a multicenter, retrospective study
After univariate and multifactorial logistic regression analyses, positive Chen Liang1, Li Liu1, Rong Li Zhang1, Dong Lin Yang1, Yi He1, Ai Ming
AST to Platelet Ratio Index (APRI) and hepatis B surface antigen Pang1, Si Zhou Feng1, Ming Zhe Han1, Er Lie Jiang1
(HBsAg) were independent risk factors for liver injury in patients with 1
State Key Laboratory of Experimental Hematology, National Clinical
hepatocellular carcinoma treated with PD1/PD-L1-based combination Research Center for Blood Diseases, Institute of Hematology & Blood
therapy (odds ratio 1.060 [95% confidence interval (CI) 2.068–4.027; Diseases Hospital, CAMS& PUMC, Tianjin, China
OR 2.638 [95% CI 1.203–5.786], respectively). The APRI score Background: Background and Aims: Novel antitumor drugs (targeted
demonstrated good predictive ability for liver injury (area under the drugs and immune checkpoint inhibitors) are commonly used in
curve [AUC] 0.860), with a sensitivity and specificity of 85.4% and patients with malignant hematological diseases, and previous studies
73.1%, respectively. When APRI combined with HBsAg detection was have shown that novel antitumor drugs can easily inducing Drug-
used, not only was the prediction efficiency high (AUC 0.864), but the induced liver injury (DILI) (incidence of 17.4%-70.4%), which affects
specificity (82.1%) and sensitivity (76.9%) were also good. the clinical efficacy, the effective prevention of novel antitumor drug-
Conclusion: The APRI score alone or in combination with HBsAg test induced liver injury is of great significance in patients with malignant
results can serve as an effective predictor of liver injury in patients with hematological diseases. In this study, we observed the efficacy and
HCC undergoing PD-1/PD-L1 inhibitor-based combination therapy. safety of magnesium isoglycyrrhizinate (MgIG) in the prevention of
Table and Figure:Figure 1.ROC analysis of factors associated with novel antitumor drug-induced liver injury in patients with malignant
hepatotoxicity during PD-1/PD-L1 combination immunotherapy in hematological diseases, which will provide more evidence-based
patients with hepatocellular carcinoma. clinical application of MgIG in hematology for the prevention of liver
Figure 2.ROC analysis of the predictive efficacy of combination therapy injury.
targeting PD-1/PD-L1 in patients with hepatocellular carcinoma. Method: METHODS: This study was conducted at Institute of
Hematology & Blood Diseases Hospital, CAMS& PUMC as the main
PP0572 center, with the participation of 11 sub-centers across the country. The
study population included malignant hematological patients over 18
Clinical Features and Prognosis of Drug-Induced Liver Injury in
years of age who were using novel antitumor drugs and concomitantly
the Context of Non-Alcoholic Fatty Liver
using MgIG for preventive hepatoprotection, and whose total bilirubin
Zhao Ying1, Li Jian Zhou2, Liu Yong Gong3, Zhu Yu Jing1, Zhang Yan1, (TBiL), aspartate aminotransferase (AST), alanine aminotransferase
Zheng Wen Wen1, Ma Lin1, Wang Chun Yan4, Li Jia3 (ALT), and alkaline phosphatase (ALP) indexes were normal before
1
Tianjin Medical University, 2The Second People‘s Hospital of Xining antitumor therapy. The primary observation endpoint was the incidence
City, 3Clinical School of the Second People‘s Hospital, 4Clinical School and severity of liver injury after patients were treated with the novel
of the Second People‘s Hospital antitumor drugs (with reference to the National Cancer Institute Criteria
Background: Acute DILI events that are caused by chronic for the Evaluation of Adverse Events (CTCAE) version 5.0), and was
liver disease are not uncommon. Some researchers believe that analyzed for the incidence of liver injury in patients on the 21, 30, and
nonalcoholic fatty liver (NAFL) increases the overall risk of DILI. The 60 days after antitumor treatment, the secondary observation endpoint
clinical characteristics and prognosis of DILI in the context of NAFLD was the incidence of adverse reactions of MgIG during treatment.
are still unclear. Therefore, hospitalized patients with NAFLD combined Result: RESULTS: From October 2023 to May 2024, a total of 456
with DILI at the Tianjin Second People’s Hospital were included in this patients with malignant hematological diseases treated with novel
study. The clinical manifestations, classifications, severities, laboratory antitumor drugs and concomitant prophylactic hepatoprotection with
indicators, and clinical outcomes of the enrolled patients were MgIG were enrolled; the median dose of MgIG was 174.23 mg, and the
analyzed, and the clinical characteristics and prognosis of NAFL+DILI median duration of treatment was 8.6 days (Table 1&2). The incidence
patients were evaluated. of post-treatment DILI was 3.5%, while the degree of severity of
Method: Eighty-nine patients diagnosed with DILI and 110 patients hepatic injury was also low (grade 0: 53.2%;grade 1-2: 42.2%; grade 3
diagnosed with both DILI and NAFL at the Tianjin Second People’s and above: 4.7%) (Table 3); the incidence of DILI was 2.3%, 3%, and
Hospital were enrolled. Clinical data, including demographic 1.5% in patients on the 21, 30, and 60 days after treatment, which were
characteristics, clinical features, laboratory test results, pathology at a low level (Table 4). The incidence of adverse reactions of MgIG
findings, autoantibody titers, suspected drugs, and outcomes, were during treatment was 2%, 0.9%, and 2.6% on the 21, 30, and 60 days,
collected from the two groups of patients. All enrolled patients were respectively, with a high safety profile (Table 5).
followed up to determine the liver function recovery time. Conclusion: CONCLUSION: The results of this study indicate that
Result: Compared with the patients in the DILI group, those in the MgIG is effective and safe for the prevention of novel antitumor drug-
NAFL+DILI group had higher body mass indices (BMIs), Controlled induced liver injury in patients with malignant hematological diseases,
Attenuation Parameter (CAP) scores, and triglyceride, total cholesterol, which is worthy of further exploration and clinical promotion.
low-density lipoprotein, and insulin levels. The levels of the cytokine Table and Figure:Figure 1.Table1 Antitumor drug medication details ;
interleukin-4 and complement C3 were also greater in the NAFL+DILI Table2 Median dose of MgIG and median duration of treatment
group than in the DILI group. The proportions of patients with cholestatic- Figure 2.Table3 Incidence and severity of liver injury;Table4 Incidence
type DILI (16.4%vs 4.5%), cholestasis seen on pathoscopy was more of DILI in patients at 21, 30, and 60 days after treatment;Table5
likely to occur (40.9%vs 25.8%),grade 2 or above DILI(48.18% vs Incidence of adverse reactions of MgIG at 21, 30, and 60 days after
40.45%), a recovery time for liver function ranging from 90 to 180 day treatment
(30.6%vs 15.5%) ,were greater in the NAFL+DILI group than in the
DILI group. All the abovementioned differences between the groups PP0574
were statistically significant (P<0.05). The autoantibody positivity rates
did not significantly differ between the two groups (P>0.05), and the
Substance P promotes the interaction between liver sinusoidal PP0576
endothelial cell and macrophage through Gas6-MerTK to mediate Biomimetic Ceria Lipoprotein Nanoparticle Enable NAC-Enhanced
inflammation resolution and repair in APAP-induced liver injury Macropinocytosis-Dependent Liver-Targeting Delivery for the
Fan Li1, Yi Ming Wang2, Ming Ni1, Ling Lu3 Treatment of APAP-Induced Liver Injury
1
Nanjing Medical University, 2Department of Liver Surgery, Peking Yaoxing Chen1, Gan Jiang2, Yan Huang1, Shuying Song1, Haoshuang
Union Medical College Hospital, Chinese Academy of Medical Fu1, Bingying Du1, Xiaoling Gao2, Qing Xie1
Sciences and Peking Union Medical College, 3Nanjing Medical 1
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao
University,Chinese Academy of Medical Sciences
Tong University School of Medicine, Shanghai, China., 2Department
Background: Neuropeptides including Substance P have been of Pharmacology and Chemical Biology, State Key Laboratory of
reported to participate in tissue repair. Efferocytosis mediated by TAM Systems Medicine for Cancer, Shanghai Universities Collaborative
(Tyro3, AXL, and MerTK) family plays an essential role in the regulation Innovation Center for Translational Medicine, Shanghai Jiao Tong
of inflammation resolution and repair. Here, we investigate the precise University School of Medicine, Shanghai, China.
mechanism by which Substance P activates MerTK-mediated Background: Drug-induced liver injury (DILI) is a severe liver disease
macrophage efferocytosis in APAP-induced liver injury. mainly caused by the overdosed acetaminophen (APAP), resulting in
Method: Substance P global knockout mice, MerTK myeloid-specific excessive reactive oxygen species (ROS). N-acetylcysteine (NAC)
Cre mice and wild-type mice were subjected to a model of APAP- is the currently only approved drug in APAP-induced liver injury, but
induced hepatotoxicity. The inflammation and tissue repair indicators with limited application due to the short therapeutic time window and
were analyzed. concentration-related adverse effects. Therefore, novel strategies to
Result: MerTK myeloid-specific knockout inhibits macrophage improve the therapeutic effect for DILI need to be explored. Ceria
efferocytosis, hampering the inflammation resolution and repair in have the antioxidant effect with the potential for the treatment of DILI.
APAP-induced liver injury. Substance P global knockout impairs However, the bare forms tend to agglomerate and thus cause failure
MerTK-mediated macrophage efferocytosis, suppressing the of lesion targeting, reduced biological activity, and potential toxicity.
inflammation resolution and repair in APAP-induced liver injury. In In this study, we developed a cerium oxide encapsulated biomimetic
mechanism, Substance P enhances the secretion of Gas6 from liver reconstituted high-density lipoprotein nanoparticles (CeO2-rHDLs) to
sinusoidal endothelial cell, thus activating macrophage efferocytosis achieve efficient DILI lesion accumulation. The combination synergic
through MerTK. therapeutic effect of CeO2-rHDLs with NAC was also tested.
Conclusion: Our findings demonstrates that neuropeptide Substance Method: CeO2-rHDLs were constructed through the water-in-oil
P elevates Gas6 secretion from liver sinusoidal endothelial cell to reverse microemulsion and the film-rehydration method. The electron
promote MerTK-mediated macrophage efferocytosis, which mediates microscopy and dynamic light scattering detector were utilized for
inflammation resolution and repair in APAP-induced liver injury. the characterization. The liver-targeting capacity was evaluated via
Table and Figure:Figure 1.MerTK myeloid-specific knockout inhibits the in vivo imaging system and laser-scanning confocal microscope.
macrophage efferocytosis, hampering the inflammation resolution and Therapeutic efficacy was evaluated in vitro using ROS probes and
repair in APAP-induced liver injury. apoptosis detection kit. The ability to improve the DILI prognosis was
Figure 2.Substance P enhances the secretion of Gas6 from liver evaluated by survival analysis, serum liver function indicators and
sinusoidal endothelial cell, thus activating macrophage efferocytosis immunohistochemical staining.
through MerTK. Result: The average size of CeO2-rHDLs was 32.87±3.39 nm, which
presented a spherical morphology. The in vivo nanoparticle distribution
PP0575 showed that the enrichment of CeO2-rHDLs in the liver can augment
after APAP-induced liver injury, which could be further enhanced
Clinical and Subclinical Characteristics and Treatment Results of
by the NAC administration. After the pre-treatment of inhibitors of
Acute Liver Failure at Thai Nguyen National Hospital
various uptake pathways, the internalization of CeO2-rHDLs into
Le Thu Hien1, Le Quoc Tuan2, Dinh Cong Tiep2, Dinh Cong Dang2
hepatocytes was only inhibited via the macropinocytosis inhibitor
1
Thai Nguyen University of Medicine and Pharmacy, 2Camkhe 103 ethylisopropylamiloride (EIPA) by almost 70%. The in vivo accumulation
Clinic of CeO2-rHDLs at the liver could also be effectively reduced via EIPA
Background: Acute liver failure (ALF) is a rare and often heterogeneous by 40%. Additionally, CeO2-rHDLs have been shown to reduce ROS
presentation of severe liver dysfunction in a patient with otherwise no and improve mitochondria membrane potential. In the DILI mouse
pre-existing liver disease. Though it has high morbidity and mortality, model, CeO2-rHDLs can significantly improve liver function with the
its overall survival has improved through intensive care management. reduction of liver necrosis. This therapeutic efficiency can be further
Aim: To describe the clinical, subclinical characteristics and treatment improved by the combination with NAC with 100% survival rate for 72
results of acute liver failure at Thai Nguyen National Hospital. h.
Method: Descriptive, prospective, interventional study on patients Conclusion: This study has developed a CeO2-rHDLs platform for
with acute liver failure due to different causes at Thai Nguyen National the treatment of DILI. Double-enhanced macropinocytosis-dependent
Hospital, from January 2023 to September 2024. uptake mediated the efficient liver targeting. CeO2-rHDLs rescued
Result: The mean age of the study subjects was 49 ± 18.5. The the injured mitochondria by reducing cellular ROS, and significantly
youngest patient was 47, the oldest was 68, and there were more improved the prognosis of DILI-bearing mice, which can be enhanced
males than females. by the combination with NAC. Overall, this therapeutic nanoplatform
The main cause of acute liver failure is acute poisoning, accounting for provides a novel use for NAC and a novel strategy for the DILI
83.36%, of which mainly poisoning with traditional medicine. Jaundice treatment.
was a clinical symptom present in most patients (92.8%). Table and Figure:Figure 1.Biomimetic Ceria Lipoprotein Nanoparticle
The rate of death/return accounted for 47.56%. Hepatic brain level, Enable NAC-Enhanced Macropinocytosis-Dependent Liver-Targeting
SOFA, NH3 have a strong positive correlation with the risk of death of Delivery for the Treatment of APAP-Induced Liver Injury
patients with acute liver failure. Some factors have a role in the prognosis
of overall mortality in patients with acute liver failure including SOFA >
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8 points, mechanical ventilation, NH3 >70 U/l, lactate > 3 mmol/l, INR
> 2. There was clinical improvement and some liver function tests after Metabolomics and non-invasive clinical biomarkers for Polygonum
treatment. multiflorum-induced cholestasis hepatitis after histological
Conclusion: Research results have certain contributions in clinical confirmation
practice, contributing to the prognosis and treatment of patients with Jing Jing1, Jiabo Wang, Xinyan Zhao, Ruilin Wang
acute liver failure. 1
The Fifth Medical Center, PLA General Hospital
Background: Cholestatic hepatitis (CSH) that is the common
histological patterns of drug-induced liver injury (DILI) appeared hepatic sinusoidal obstruction syndrome (HSOS). In this study, the
frequently to suffer fatal outcomes. The underlying mechanism of aim of our study is to develop a novel prognostic model based on
CSH by a metabolic view is hardly understanding. This study aimed to sarcopenia, which helps to identify high-risk patients.
identify non-invasive biomarkers to characterize the histological finding Method: A total of 156 PAs-induced HSOS patients were enrolled
in CSH caused by drugs using a metabolomics approach. from January 2010 to October 2022. The relevant data of patients
Method: We retrospectively analyzed clinical and pathological data were collected. Univariate and multivariate Cox proportional hazards
from patients with Polygonum multiflorum-induced DILI (PM-DILI) analysis were used to determine prognostic factors. Then, a prognostic
hospitalized at a specialized liver disease center in Beijing from model based on sarcopenia was developed and assessed.
January 2008 to December 2022. For patients who had undergone liver Result: At a median follow-up interval of 45.9 months, 73.7% (115/156)
biopsy, these sections were reviewed centrally by one liver pathologist patients survived. Sarcopenia was observed in 42.3% (66/156) of
and one hepatologist. Afterwards, an untargeted serum metabolomic patients with PA-induced HSOS, 57.6% (38/66) of male patients
analysis identified candidate metabolites in PM-DILI patients with and 42.4% (28/66) of female patients. Further study demonstrated
different histological patterns, and the predictive performance of these aspartate aminotransferase (AST), urea nitrogen, thrombin time
potential biomarkers was tested. (TT) and sarcopenia (AUTS) were independent prognostic factors.
Result: Out of 1824 inpatients diagnosed with DILI, 533 patients Then, AUTS, a prognostic model, was developed and validated as a
had DILI caused by herbs and their products, 110 patients were good prognostic predictor with an area under the receiver operating
attributed to PM-related DILI. In 41 patients with PM-DILI undergone characteristic (ROC) curve of 0.782, and the cut-off value for poor
liver biopsy, acute hepatitis (AH) (n=26, 63.4%) and cholestasis outcome prediction was 0.16 (sensitivity 90.2%, specificity 50.4%).
hepatitis (CSH) (n=12, 29.3%) accounted for 92.7% of the cases Conclusion: A prognostic model (AST, urea nitrogen, TT and
with liver biopsies (Figure 1). Compared with DILI patients with AH, sarcopenia) based on sarcopenia was a good predictor for the
Model for End‐Stage Liver Disease (MELD) scores of those with CSH prognosis of patients with PAs-induced HSOS, which provided
had remarkedly higher (11.5[8.0,15.5] vs 16.0[13.3,17.8], p=0.033). accurate and early identification of high-risk patients.
In differentiating CSH from AH, 170 annotated metabolites related to Table and Figure:Figure 1.
glycerophospholipid, glycosphingolipid, sphingolipid and linoleate Figure 2.
metabolism were identified. From the metabolic fingerprint, we found
the metabolomic characteristics of CSH highlighting a relationship of
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the trade-off between different metabolites from two pairs of metabolite
cycles (Land’s cycle and sphingomyelin [SM] cycle) (Figure 2). Atractylodes macrocephala polysaccharides ameliorate
In Land’s cycle, phosphatidylcholine levels were upregulating as acetaminophen-induced acute liver injury through intestinal flora
lysophosphatidylcholine levels were downregulating. Analogously, in Jiali Wu1, Shuai Gong1, Biao Jia1, Yangpeng Li1, Jiao Guo1
SM cycle, SM/lysoSM levels were increased while lactosylceramide/ 1
Guangdong Pharmaceutical University
trihexosylceramide levels were decreased. Among these, we found Background: Drug-induced liver injury (DILI), especially
metabolite signatures (area under the receiver operating characteristic acetaminophen (APAP)-induced acute liver injury (AILI), is a major
curve [AUC] = 0.9667, 95% confidence interval [CI] = 0.9046-1), cause of acute liver failure globally, with rising cases due to overuse,
including two metabolites- SM (d18:0/22:2[13Z,16Z] [OH]) (AUC = 0.9, particularly during the COVID-19 pandemic. N-acetyl-L-cysteine
95% CI = 0.7599-1) and LysoSM (d18:0) (AUC = 0.8, 95% CI = 0.6104- (NAC) is the current treatment, but its limitations highlight the need
0.9896), demonstrated more robust capabilities than serum total for alternative therapies. Traditional Chinese medicine, BZ, has
bilirubin of peak, immunoglobulin G and MELD score for identifying or demonstrated protective effects on the liver and gut microbiota.
predicting CSH in patients with PM-DILI (p<0.05) (Figure 2). This study investigates the potential of Atractylodes macrocephala
Conclusion: The non-invasive metabolomic fingerprints show polysaccharides (AMPs) , a key component of Atractylodes, in
promise as biomarkers for the identification of CSH in patients with alleviating AILI and its underlying mechanisms.
DILI. They also suggest disturbances in phospholipid and sphingolipid Method: AILI was induced in Balb/c mice (6-8 weeks) with a 250mg/kg
homeostasis as a potential mechanism of CSH. dose of APAP. Histopathological, biochemical, and molecular analyses
Table and Figure:Figure 1.Figure 1 Examples of the three histological were performed. The therapeutic effect of AMPs was assessed through
patterns in patients PM-related DILI. (A) Acute hepatitis (AH) showing fecal microbiota transplantation (FMT) and 16S rDNA sequencing to
moderate lobular inflammatory necrosis with mixed inflammatory cell explore gut microbiota changes in AILI.
infiltration (H&E, ×400). (B) chronic hepatitis (CH) indicating moderate Result: AMPs treatment significantly reduced liver necrosis and
hepatitis both in portal and periportal areas (H&E, ×400). (C) and (D) serum ALT/AST levels. TUNEL staining showed decreased apoptosis,
cholestatic hepatitis (CSH) displaying notably higher bile duct injury while qPCR and Western blot analyses revealed downregulation of
and moderate hepatitis both in portal and periportal areas (H&E, ×400; pro-apoptotic genes (Bax) and upregulation of anti-apoptotic genes
Cytokeratin 7, ×400). (Bcl-XL, Bcl-2). Inflammatory response was reduced, as indicated by
Figure 2.Figure 2. Selection and features of metabolic fingerprint to lower expression of cytokines (Il-1β, Il-6, TNF-α, Nlrp3). FMT confirmed
unravel underlying pathophysiological changes of DILI patients with that AMPs improved liver injury, reduced apoptosis, and enhanced
CSH. (A) Hierarchical cluster analysis of the AUCs and p value in expression of anti-apoptotic genes. Additionally, 16S rDNA sequencing
significantly differentiating CSH from AH. (B) Summary of metabolic demonstrated that AMPs modulated gut microbiota, increasing
pathways associated with CSH in patients with DILI. The metabolic diversity and reversing dysbiosis, with key differential bacteria such
fingerprint of CSH focused on the credible information of the trade- as Roseburia and Mogibacteriaceae potentially influencing AILI
off between two pairs of metabolite cycles, Land’s cycle and progression.
sphingomyelin (SM) cycle. (C) Comparison of ROC curve analysis for Conclusion: AMPs mitigates liver apoptosis and inflammation in both
distinguishing CSH from AH. human liver cell and mouse AILI models. By restoring gut microbiota
balance, it presents a promising new therapeutic approach for AILI.
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A prognostic model for pyrrolizidine alkaloids-induced hepatic PP0580
sinusoidal obstruction syndrome based on sarcopenia D-mannose protects against acetaminophen-induced
Yangyang Zhou1, Yuhu Song1 hepatotoxicity in mice
1
wuhan union hospital Qin Haixia1, Tong Shiwen1, Yin Wenwei1
Background: Sarcopenia has been shown to be associated with the 1
the Second Affiliated Hospital of Chongqing Medical University
prognosis of patients with liver cirrhosis, hepatocellular carcinoma, Background: The liver is the principal metabolic organ in the human
liver failure. However, the impact of sarcopenia on survival has not body, responsible for synthesis, detoxification, and metabolism. Acute
been investigated in patients with pyrrolizidine alkaloids (PAs)-induced
liver injury (ALI) can be caused by factors such as drugs, alcohol, and isoniazid (INH) gradually.
ischemia-reperfusion, autoimmunity and viruses, with drug-induced Following the addition of INH, the patient developed jaundice. ATT
liver injury (DILI) being particularly common. Acetaminophen (APAP) was temporarily discontinued due to suspected drug-induced liver
is a widely used medication globally, and its excessive intake can lead injury, but her condition continued to worsen, with rising liver markers,
to severe liver injury or even acute liver failure. D-mannose, a bioactive leukocytosis, high procalcitonin, and high fever. Hepatitis markers were
monosaccharide, has shown potential in anti-inflammatory, blood negative. Abdominal sonography revealed a normal liver with signs of
glucose regulation, anti-tumor, and urinary tract infection prevention cholecystitis and mild ascites. Further imaging, including abdominal
activities, and it exhibits certain protective effects on liver diseases. MRI and Magnetic Resonance Cholangiopancreatography (MRCP),
However, the protective effect of d-mannose on APAP-induced acute showed hepatomegaly with periportal edema, gallbladder edema
liver injury has not been studied. This study aims to investigate the indicative of acute hepatitis, and splenomegaly.
protective effect of d-mannose on APAP-induced acute liver injury in Meropenem was administered due to the patient’s deteriorating
mice and its underlying mechanisms. condition and possible infection. Autoimmune etiology was excluded
Method: Mice were divided into two groups: APAP group and with a negative ANA test. Upon further evaluation, the patient’s
APAP+Man group. To evaluate the therapeutic effect of d-mannose clinical presentation aligned with DRESS syndrome, likely triggered
on APAP-induced acute liver injury, 20% (w/v) d-mannose were by meropenem. The diagnosis was confirmed using the RegiSCAR
supplemented in drinking water four week before APAP(300mg/ criteria, classifying it as a probable case due to the presence of fever,
kg) administration for Man group. Liver tissues and blood samples eosinophilia, liver and spleen involvement, and other characteristic
were collected at sacrifice (24 h after dosing with APAP) for clinical features. Bocquet’s and J-SCAR criteria were also used to confirm the
chemistry, histopathology and metabolomics analyses.Liver injury diagnosis. Both the Naranjo Adverse Drug Reaction Probability Scale
was assessed by measuring serum alanine aminotransferase (ALT) and the World Health Organization-UMC Causality Scale concluded a
,aminotransferase (AST) and H&E staining. Hepatic protein and mRNA possible adverse drug reaction.
levels of IFN-r, TNF-a, IL-6 and HMGB-1 were evaluated by ELISA and The patient’s condition improved following the discontinuation of the
real-time PCR. Flow cytometry was used to determine the expression suspected drugs and initiation of glucocorticoid therapy, and her liver
levels of CD45.2, CD11b, and GR-1 in intrahepatic lymphocytes (IHL). function is being closely monitored for recovery.
Result: Pretreatment with d-mannose significantly attenuated the
increase in ALT and AST activities. Histological assessment showed
PP0582
that d-mannose reduced hepatocyte necrosis and intrahepatic
hemorrhage induced by APAP. We found that d-mannose significantly Macrophage-specific TREM1 up-regulation exacerbates drug-
suppressed the expression of inflammatory cytokines (IL-1β, IL-6 and induced hepatic steatosis through macrophage inflammatory
MCP-1), serum IL-1β and IL-6 levels detected by ELISA exhibited polarization.
similar alterations. Flow cytometry revealed that mannose reduced the JING LIU1
recruitment of Ly6G+ neutrophil in the liver. 1
The First Affiliated Hospital, Zhejiang University School of Medicine,
Conclusion: This study reveals the potential preventative effect of Hangzhou 310003, China
d-mannose against on APAP-induced acute liver injury in mice, which Background: Drug-induced liver injury (DILI) caused by voriconazole
may be mediated by reducing the recruitment of neutrophils. Future features liver lipid accumulation and inflammation infiltration, yet the
investigations are warranted to further explore the impact of d-mannose underlying mechanisms are still poorly understood. Studies have
on the function of liver immune cells and other potential mechanisms. indicated a correlation between liver injury and TREM1 expression.
Table and Figure:Figure 1.d-mannose reduces APAP-induced liver However, the role of TREM1 in drug-induced hepatic steatosis remains
injury unclear. This study aims to deeply elucidate the key role of TREM1 and
its underlying mechanisms in drug-induced hepatic steatosis.
PP0581 Method: This study explored the relationship between drug-induced
hepatic steatosis and soluble TREM1 (sTREM1) with clinical samples.
Persistent Jaundice in A 20-Year-Old : A Rare Case of Drug
A comprehensive set of methodologies were employed, such as
Induced Liver Injury Associated with DRESS Syndrome Induced
conditional gene knockout and over-expression mouse models, an in
by Meropenem
vitro co-culture system, multi-omics analysis, and diverse molecular
Shahnaz Medina1,2, Maulana Suryamin1, Irwin Tedja1, Radita biology techniques, to elucidate the crucial role of TREM1 in drug-
Ikapratiwi1,2 induced hepatic steatosis.
1
Department of Internal Medicine, Persahabatan General Hospital, Result: Macrophage TREM1 was found substantially up-regulated
Jakarta, Indonesia, 2Department of Internal Medicine, Universitas in drug-induced hepatic steatosis. Then, using clinical samples, we
Indonesia/ Dr. Cipto Mangunkusumo National Central Public Hospital revealed a positive correlation between drug-induced hepatic steatosis
, Jakarta, Indonesia and sTREM1 sourced by monocyte-derived macrophages (MoMFs).
Introduction We found that targeted down-regulation of macrophage TREM1
Idiosyncratic drug-induced liver injury (DILI) can occasionally manifest alleviated voriconazole-induced inflammation infiltration and hepatic
alongside severe cutaneous adverse reactions (SCARs), one of steatosis. Further investigations showed that voriconazole significantly
which is Drug Reaction with Eosinophilia and Systemic Symptoms increased TREM1 expression and enhanced its interaction with TLR4.
(DRESS) syndrome, also known as Drug-Induced Hypersensitivity This synergistic interaction initiated the activation of the PI3K/AKT and
Syndrome (DIHS). DRESS is a severe and potentially life-threatening NF-κB inflammatory pathways, as well as NLRP3, driving macrophage
hypersensitivity reaction that may progress to acute liver failure, inflammatory polarization. Pharmacological inhibition of TREM1
significantly increasing the risk of mortality. Early diagnosis and attenuates the progression of drug-induced hepatic steatosis.
treatment are crucial for improving patient outcomes. Conclusion: Our research underscored the pivotal role of macrophage
Case Description TREM1 in the inflammation attributed to hepatic steatosis induced by
We present the case of a 20-year-old female admitted with jaundice for voriconazole, providing compelling evidence for the beneficial effects
one week, high fever for two days, shortness of breath, nausea, and of targeting macrophage TREM1 as a strategy to mitigate drug-
vomiting. The patient had a history of chronic cough and shortness of induced hepatic steatosis.
breath for more than a month, previously treated at various hospitals. Table and Figure:Figure 1.Graphical Abstract
In June 2024, she was diagnosed with pleural effusion and underwent
thoracocentesis, which improved her respiratory symptoms. She was
PP0583
later diagnosed with pulmonary tuberculosis (TB) and initiated first-
line anti-tuberculosis treatment (ATT) in August 2024. The patient’s
hepatic enzymes and bilirubin levels markedly increased by week two
of treatment. ATT was modified, continuing with ethambutol, rifampicin,
Oral Budesonide as an Effective Alternative Treatment of Immune- PD-1 antibody (AK104) therapy. Magnesium isoglycyrrhizinate and
Mediated Hepatobiliary Toxicities Associated with Immune ursodeoxycholic acid were ineffective, and artificial liver therapy was
Checkpoint Inhibitors: A Case Series required. After initial improvement, liver function deteriorated again.
Lan Sun Wang1, Antonio Pizourno Machado2, Kadon Nathaniel Sirolimus was introduced during the third artificial liver session.
Caskey2, Abdullah Shaikh1, Ethan Miller1, Yinghong Wang1, Haochi Result: The patient in Case 1 initially showed elevated laboratory
Zhang1 values, including alkaline phosphatase (ALP, 260 U/L), gamma-glutamyl
1
University of Texas MD Anderson Cancer Center, 2University of Texas transferase (GGT, 942 U/L), total bilirubin (TBIL, 180.7 µmol/L), and
Southwestern Medical Center direct bilirubin (DBIL, 118.3 µmol/L).Following one week of sirolimus
treatment, ALP (297 U/L), GGT (558 U/L), TBIL (59 µmol/L), and DBIL
Background: Immune checkpoint inhibitors (ICIs) are increasingly
(39.1 µmol/L) decreased, with sirolimus blood levels maintained at
used in cancer treatment. This has resulted in a corresponding rise in
4.33 ng/mL.During four months of follow-up, liver function remained
immune-related adverse events (irAEs), including immune-mediated
stable, symptoms improved, and no adverse events occurred.
hepatobiliary toxicity (IMH). Current guidelines recommend high
The initial laboratory tests of the patient in Case 2 showed elevated
dose systemic corticosteroids to manage IMH, which confers a risk
levels of ALP (481 U/L), GGT (594 U/L), TBIL (230.8 µmol/L), and DBIL
for significant side effects. Budesonide is an oral glucocorticoid with
(118.4 µmol/L).Sirolimus was introduced during the third artificial liver
minimal systemic bioavailability which offers an alternative therapeutic
session, leading to rapid improvement within three days (TBIL, 91.9
option for IMH while avoiding many of the side effects of systemic
µmol/L, DBIL, 58.9 µmol/L). Sirolimus levels were maintained at 6.50
corticosteroids. There is currently limited data on the use of budesonide
ng/mL. This therapy effectively controlled bilirubin and enzyme levels.
in the management of IMH.
Conclusion: ICI-induced ChILI poses significant challenges in
Method: This case series was compiled through retrospective review
treatment, with limited benefits from traditional therapies and artificial
of an electronic medical record from a prospectively collected cohort
liver support in refractory cases. Sirolimus showed significant efficacy
of patients with various cancers who were treated with ICIs and
in restoring liver function and alleviating symptoms in steroid-resistant
subsequently developed IMH. Patients received budesonide 9 mg/
patients. These findings suggest that sirolimus is a promising treatment
day either as their initial therapy or after conversion from systemic
for managing refractory irAEs.
corticosteroids. Liver biochemical tests were monitored until patients
Table and Figure:Figure 1.Changes in Bilirubin and Sirolimus Levels
achieved biochemical remission, defined as ALT <40 U/L. A small
During Treatment in the Two Cases. a. Changes in Direct Bilirubin,
number of patients with IMH were rechallenged with ICI therapy using
Indirect Bilirubin, and Sirolimus Blood Concentration Over Time in
budesonide as secondary prophylaxis.
Case 1. b. Changes in Direct Bilirubin, Indirect Bilirubin, and Sirolimus
Result: A total of 21 patients received budesonide as the initial
Blood Concentration Over Time in Case 2.
therapy for IMH treatment. Of this subset, 19 patients (91%) achieved
Figure 2.Basic Data and Clinical Characteristics of the Two Cases
biochemical remission within 60 days, 1 patient achieved remission
by day 94, and 1 patient had an inadequate response and required
escalation to alternative therapy. Of the 14 patients who were PP0585
converted from systemic steroids to budesonide, 13 (93%) achieved A retrospective study of clinical characteristics and steroid
biochemical remission within 60 days and 1 patient achieved remission therapy in immune checkpoint inhibitor-mediated hepatitis
in 98 days. A smaller group of 4 patients with IMH were rechallenged Feilan Yang1, Lei Fu1
with ICI therapy using budesonide as secondary prophylaxis, and 3 of 1
Xiangya Hospital, Central South University
these patients were able to continue therapy without IMH recurrence.
No patient in our case series experienced adverse effects attributable Background: With the widespread use of immune checkpoint inhibitors
to budesonide therapy. (ICIs), immune-mediated hepatitis (IMH) is becoming increasingly
Conclusion: Oral budesonide offers a well-tolerated and viable option common. Our study aims to analyze the clinical characteristics and
for the management of IMH, either as initial therapy or after conversion steroid treatment of IMH patients, providing more evidence to improve
from systemic corticosteroids. There may be a potential role for the safety of ICIs in clinical practice.
budesonide as secondary prophylaxis against IMH recurrence with Method: From January 2020 to December 2022, cancer patients
resumption of ICI therapy. received at least one dose of PD-1 or PD-L1 inhibitors therapy in a
Table and Figure:Figure 1.Table 1. Budesonide treatment outcomes hospital in southern China were recruited for this retrospective study. The
causality of hepatotoxicity was determined by evaluating the patient’s
overall condition, excluding other possible causes of liver damage,
PP0584 such as hepatitis viral infections (new infections or reactivations),
Sirolimus Efficacy in Treating Steroid-Resistant Immune-Mediated active alcoholic hepatitis, autoimmune liver disease, medications
Liver Injury: Two Clinically Successful Case Reports other than ICIs, and tumor progression. The rank-sum test was used
Shuying Huang1, Tao Zeng1, Jiao Gong1, Yutian Chong1, Xinhua Li1 for comparisons of continuous variables, and the chi-squared test
1
Third Affiliated Hospital of Sun Yat-sen University and multiple comparisons were used for comparisons of categorical
variables. Comprehensive analyses were conducted to explore the
Background: Immune checkpoint inhibitors (ICIs), a cornerstone of
factors influencing the occurrence, the clinical characteristics, and the
cancer immunotherapy, often cause immune-related adverse events
steroid efficacy of IMH.
(irAEs) such as liver injury (ChILI), for which no specific treatments
Result: A total of 744 patients were enrolled, of which 341 developed
are available. Corticosteroids frequently fail in steroid-resistant cases,
IMH. IMH was more prevalent in female (54.7% vs 41.5%, P=0.001),
particularly in immune-related cholangitis. Research suggests that
and younger patients (P<0.001). The type of PD-1 or PD-L1 inhibitors
sirolimus, an mTOR inhibitor, can promote bile excretion in zebrafish
did not influence the incidence of IMH. In contrast to patients with
models and modulate immune responses. This report presents
various other malignancies, those with hepatocellular carcinoma
two cases of refractory ICI-induced ChILI successfully treated with
experienced a higher rate of IMH(P<0.001). Conversely, patients
sirolimus, offering a potential solution to the treatment challenges of
with lung cancer showed a lower rate of IMH(P<0.001). In our
irAEs.
study, 79 patients received PD-1/PD-L1 inhibitors monotherapy and
Method: Case 1
only 29 patients (36.7%) experienced IMH, which had a lower risk
A 46-year-old male with pleomorphic sarcoma developed cholestasis-
of developing hepatitis compared to that with combined targeted
dominant ChILI after anti-PD-1 therapy (toripalimab and penpulimab).
therapy (P=0.009). But patients combined with chemotherapy did
Initial treatment with methylprednisolone and mycophenolate
not increase liver injury incidence (P=0.300). In addition, concomitant
mofetil failed, indicating steroid resistance. Sirolimus combined with
underlying liver diseases, including hepatitis B (non-reactivation)
corticosteroids was started.
(P<0.001), liver cirrhosis (P=0.005), and fatty liver disease (P=0.028),
Case 2
were all significantly associated with IMH. Furthermore, further
A 62-year-old female with cervical cancer developed ChILI after anti-
multivariate analysis showed that female, younger than 45 years
old, and hepatocellular carcinoma were independent risk factors for due to different drugs. We aim to describe the the clinicopathological
IMH. Corticosteroids administration had increased improvement rate features, outcomes, and HLA risk factors for recurrent drug-induced
(P=0.011). There was no difference between patients who received liver injury (NCT06547229).
sufficient or insufficient recommend dosage of corticosteroids. Method: Retrospective cohort data were collected from 11 patients
Conclusion: The female, younger than 45 years old, and with recurrent DILI out of 651 confirmed DILI cases between 2014 and
hepatocellular carcinoma were independent risk factors for IMH. 2024. Demographic, laboratory, and clinical data from both episodes of
Steroids administration is favor for IMH. Early identification, intervention DILI were collected and analyzed. Competing etiologies of liver injury,
of IMH, and individualized treatment may be beneficial. particularly autoimmune hepatitis (AIH), were thoroughly excluded.
Table and Figure:Figure 1.Table1 Clinical characteristics of patients A propensity score matching (1:1) approach was used to match
treated with immune checkpoint inhibitors recurrent DILI patients with age- and gender-matched DILI patients
Figure 2.Figure 1 (A) Improvement rates with or without corticosteroids who experienced only one episode despite repeated drug exposure.
administration in G2-G4 patients. (B) Improvement rates with sufficient HLA allele frequencies were compared between the recurrent DILI
or insufficient dosage of corticosteroids in G2-G4 patients. group and the general population.To validate the findings on genetic
susceptibility, a prospective cohort of DILI patients (NCT05060289)
with recurrent DILI was utilized for verification.
PP0586
Result: The incidence rate of recurrent DILI in our retrospective cohort
Interleukin-19 Is a Key Determinant of Selectively Limiting was 1.84%. Among the 11 patients with recurrent DILI, the majority
Proinflammatory Macrophage Infiltration and Protects Against were female (83.3%). The mean age at the initial episode was 59.36
Drug-induced Liver Injury years (SD = 6.78), whereas the mean age at the second episode was
Xiao Peng1,2, Gao Yan Hang1, He Yong2,3 62.72 years (SD = 7.71), showing a statistically significant difference
1
Department of Hepatology, First Hospital of Jilin University, Jilin (P < 0.001). The latency period and the pattern of liver injury were not
University, Changchun, Jilin, China, 2Shanghai Institute of Materia significantly different between the two episodes (P = 0.328 and P =
Medica (SIMM), Chinese Academy of Sciences, Shanghai, China, 0.687, respectively).Patients with recurrent DILI experienced a longer
3
University of Chinese Academy of Sciences, Beijing, China time to normalization of alanine aminotransferase (ALT) (P = 0.004) and
Background: Acetaminophen (APAP) overdose is a leading cause of total bilirubin (TB) (P < 0.001) compared to those with a single episode
acute liver failure worldwide. Interleukin-19 (IL-19) and IL-22 belong to of DILI in the retrospective cohort. However, there was no significant
the IL-10 family, which all activate the signal transducer and activator difference in the recovery time for ALT and TB between the first and
of transcription 3 (STAT3). IL-19 exerts its function via binding of IL-20 second episodes of liver injury in the recurrent group.Two patients
receptor 1 (IL-20R1) and IL-20R2. IL-22 is well-known for its epithelial with recurrent DILI progressed to chronic liver injury (no normalization
protection and anti-bacterial function, showing great therapeutic for more than a year) , but all patients with recurrence eventually
potential for hepatology damage; but the function of IL-19 remains recovered. Liver biopsies were performed in six individuals, three of
largely unknown. Here we examined the functional roles of IL-19 in whom showed cholestasis as the main histological feature, but no
APAP-induced liver injury. significant massive necrosis was observed.Even after excluding cases
Method: Il19 knockout (Il19KO) mice and wild-type (WT) littermates of liver injury caused by Polygonum multiflorum, the HLA-B 35:01 and
were generated and injected with APAP to induce acute liver injury. HLA-A 02:06 alleles were significantly more frequent in recurrent DILI
The effect of IL-19 on APAP-induced liver injury was tested by patients compared to population controls (HLA-B 35:01: OR = 13.68,
administration of recombinant IL-19 protein. Clodronate was used to 95% CI: 4.37–36.97, P-BH = 0.000775; HLA-A 02:06: OR = 6.23, 95%
deplete macrophages. CI: 1.99–16.80, P-BH = 0.0217).In the prospective validation cohort,
Result: After injection of APAP in mice, serum levels of IL-19 were HLA-B*35:01 remained significantly associated with recurrent DILI
highly elevated. APAP injection upregulated IL-20R1 and IL-20R2 (Table 1).
expression in liver monocyte-derived macrophages (MoMFs). Conclusion: Recurrent DILI is associated with prolonged normalization
Interestingly, compared with WT mice, Il19KO mice were more times for ALT and TB levels. Additionally, recurrence is significantly
susceptible to APAP-induced hepatocyte damage and inflammation. linked to the HLA-B*35:01 allele.
Furthermore, administration of recombinant IL-19 protein significantly Table and Figure:Figure 1.Table 1: Genetic susceptibility in the
suppressed liver MoMF infiltration, thus ameliorating APAP-induced experimental and validation cohorts versus healthy controls
liver injury. Bulk RNA-seq analyses suggested that Il19 deficient mice
had a distinct transcriptional landscape characterized by an increased PP0588
inflammatory status after APAP challenge. As expected, Il19KO mice
Risk Factors for Acute Hepatitis Induced by Anti-Tuberculosis
had greater degree of MoMF infiltration and oxidative stress than
medications in the Kashmiri population.
WT mice post APAP injection. More importantly, proinflammatory
macrophage depletion by CVC diminished the susceptibility of Il19KO Usman Ghani1, Abrar Umar2
mice to APAP-induced liver injury. Mechanistically, IL-19 could not
1
Div. Headquarter Teaching Hospital MIRPUR AJK in Kashmir, 2MIMC,
lead to STAT3 activation in macrophages but increased the post- Mirpur AJK
translational SUMOylation of CCAAT/enhancer-binding protein beta Background: uberculosis (TB) remains a major health issue in Kashmir,
(C/EBPβ), which plays a central role in inducing the transcription of with many patients requiring treatment with anti-TB medications.
genes encoding several proinflammatory chemokines such as MIP-1β. While these drugs are effective for treating TB, they can also lead
Conclusion: IL-19 plays an immunosuppressive role in APAP-induced to liver complications, including acute hepatitis. Acute hepatitis due
liver injury via limiting macrophage infiltration. Administration of IL-19 to anti-TB medicines is a well-recognized but often underreported
may be a novel strategy for the treatment of drug-induced liver injury. issue. This study aims to identify the risk factors that contribute to the
development of acute hepatitis in TB patients receiving treatment in
PP0587 Kashmir. Understanding these factors is crucial for improving patient
care and minimizing liver damage.
Clinicopathological Features and Genetic Susceptibility Screening Method: We conducted a retrospective cohort study at Divisional
of Recurrent Drug-induced Liver Injury (RDILI-GS) Headquarters Teaching Hospital, Mirpur in Kashmir from feb 2022-jun
Mengmeng Zhang1, Lan Wang2, Yao Meng1, Tiantian Guo1, Zikun 2023.
Ma1, Yu Wang1, Xinyan Zhao1 The study included patients diagnosed with TB who began the
1
Beijing Friendship Hospital, Capital Medical University, 2Department standard anti-TB regimen (rifampicin, isoniazid, pyrazinamide, and
of Gastroenterology, Beijing Chuiyangliu Hospital ethambutol). We reviewed patient records to identify those who
Background: Recurrent drug induced liver injury (DILI) is not explicitly developed acute hepatitis, characterized by a significant rise in
documented. Patients who suffered DILI may have another episode liver enzymes or noticeable jaundice during treatment. We gathered
data on potential risk factors, such as age, gender, pre-existing liver
conditions, other medications, nutritional status, and lifestyle factors Clinical features and prognosis of two pathological acute
(e.g., alcohol consumption). A statistical analysis was then performed cholestatic patterns
to identify which factors were most strongly linked to the development Jialuo Wang1, Yuxiang Gong1, Yuan Yang1, Shasha Li1, Yujia Lu1,
of acute hepatitis. Yongfeng Yang1
Result: A total of 200 TB patients undergoing anti-TB therapy were 1
Nanjing Second hospital
included in the study. Of these, 18% developed acute hepatitis during
Background: The pathological morphological features of acute
treatment. The risk of developing hepatitis was higher in patients
cholestasis are primarily characterized by two main patterns: bland
who were older (≥50 years), male, had existing liver problems, or
cholestasis and cholestatic hepatitis. The condition clinically presents
had a history of alcohol use. Specifically, 30% of patients aged 50
with an acute onset, a prolonged recovery, and a multifactorial
and older experienced acute hepatitis, compared to just 12% in
etiology. The study aims to investigate the features and identify factors
patients younger than 50 years (p=0.02). Those with a history of liver
associated with poor prognosis of acute cholestasis.
disease were at a significantly higher risk, with 40% developing acute
Method: A single-center, retrospective observational study was
hepatitis, compared to just 12% in those without prior liver conditions
conducted. Demographic, clinical, and prognostic data were
(p=0.01). Alcohol consumption also played a role: 25% of patients who
collected, and pathological slides were analyzed retrospectively.
consumed alcohol developed acute hepatitis, while only 14% of non-
Clinical outcomes including recovery, and liver-related death were
drinkers were affected (p=0.03). Multivariate analysis confirmed that
recorded. Cox regression analysis was used to identify the risk factors
being over 50 years old (OR=2.5, 95% CI: 1.4–4.5), having a history
associated with outcomes.
of liver disease (OR=3.1, 95% CI: 1.8–5.5), and alcohol use (OR=1.9,
Result: A total of 146 cases were included, with 87 male patients. The
95% CI: 1.1–3.2) were independently linked to an increased risk of
mean age was 49.7 ± 12.8 years. Based on liver pathology findings,
acute hepatitis.
patients were classified into the bland cholestasis group(75 cases)
Conclusion: Acute hepatitis is a significant concern for patients
and the cholestatic hepatitis group(71 cases). The bland cholestasis
undergoing anti-TB treatment in Kashmir, particularly among those who
group was further divided into three subgroups based on the severity
are older, have pre-existing liver conditions, or drink alcohol. These
of cholestasis (score:1, 2, and 3). The recovery time of the cholestatic
findings emphasize the need for careful monitoring of liver function in
hepatitis group was longer than that of the bland cholestasis group (P
high-risk patients. Early detection and intervention can help prevent
= 0.0025), and the 6-month survival probability was lower (P = 0.034).
serious liver damage and improve patient outcome.
Multivariate Cox regression analysis revealed that a cholestasis score
of 3, cholestatic hepatitis, and elevated DB/TB levels were independent
PP0589 risk factors for biochemical recovery in cholestatic liver disease (HR =
HYX1-derived exosomal let-7c-5p protects against acute liver 0.147, CI: 0.059~0.368; HR = 0.169, CI: 0.078~0.365; HR = 0.068,
failure by inhibiting SLC11A2-mediated ferroptosis CI: 0.009~0.531). Age ≥ 60 years, infection, and combination with
Qi Yang1, Huixin Tang1, Xiaoxuan Liu1, Li Bai1, Yu Chen1 immune-related diseases were independent risk factors for survival in
1
Beijing Youan Hospital, Capital Medical University cholestasis patients (HR = 5.3603, CI: 1.6015~17.9415; HR = 3.4165,
CI: 1.0727~10.8812; HR = 5.8151, CI: 1.1297~29.9335), while albumin
Background: Acute liver failure (ALF) represents fatal acute level was an independent protective factor for survival (HR = 0.7583,
decompensation of hepatic function. We previously have documented CI: 0.6336~0.9074).
that the transfer of hepatic stem cell HYX1 confers the hepatoprotection Conclusion: Among patients with acute cholestasis, drug-induced
against ALF. Herein, we aimed to demonstrate that miRNA carried liver injury (DILI) was the most common etiology. Bland cholestasis
by HYX1-derived exosomes (Exos) exerts a hepatoprotective effect patients had a better prognosis compared to those with cholestatic
against ALF and to dissect the underlying molecular mechanism. hepatitis. The severity of cholestasis was associated with a longer
Method: Normal mice were pre-treated with HYX1-Exos followed recovery time.
by acute insult, and hepatic damage was assessed. HYX1-Exos Table and Figure:Figure 1.
were subjected to miRNA sequencing. The ferroptosis levels were Figure 2.
evaluated in ALF mice with or without HYX1-Exos treatment. The
special ferroptosis-related miRNAs were screened and identified. Let-
7c-5p agomir was injected into normal mice followed by acute insult, PP0591
then hepatic damage and ferroptosis levels were evaluated. The Knockout of Zinc-α2-glycoprotein 1 (AZGP1) Disrupts Metabolic
targeted relationship between let-7c-5p and SLC11A2 was analyzed. Homeostasis and Enhances Inflammatory Responses,
The molecular basics underlying the hepatoprotection conferred by Exacerbating Liver Injury
let-7c-5p was dissected, and focused on SLC11A2. The levels of let- Pan Xu1, Wan Zhou2, Wei Cai3, Yuhang Zhou4, Yuerong Zhang2, Qiufu
7c-5p were detected and the extent of ferroptosis was assessed in Wang4, Fang Wei5
ALF patients with different prognosis. 1
Department of Clinical Laboratory, Medical Sciences Research
Result: HYX1-Exos alleviated ALF, as shown by improved hepatic Center, University-Town Hospital of ChongQing Medical University,
architecture and reduced pathology scores. miRNA sequencing 2
Department of Gastroenterology, University-Town Hospital of
analysis displayed that exosomal miRNAs could be enriched in Chongqing Medical University, 3Department of Clinical Laboratory,
ferroptosis pathway. Inhibiting ferroptosis led to significant mitigation Medical Sciences Research Center University-Town Hospital
in hepatic damage. The ferroptosis levels were remarkably decreased of Chongqing Medical University, 4Medical Sciences Research
after HYX1-Exos treatment. Let-7c-5p might be the major miRNA Center University-Town Hospital of Chongqing Medical University,
responsible for the hepatoprotection. Let-7c-5p agomir mitigated 5
Department of Hepatology, Three gorges hospital affiliated to
ALF by inhibiting ferroptosis signaling. Let-7c-5p targetedly inhibited chongqing medical university
SLC11A2. SLC11A2 over-expression aggravated ferroptosis, thereby Background: To elucidate the pathogenesis of liver failure and identify
breaking down the hepatoprotection conferred by let-7c-5p carried by precise biomarkers and therapeutic targets for the disease. AZGP1,
HYX1-Exos. Liver failure patients with good prognosis exhibited higher a secreted protein, is closely associated with lipid metabolism and
let-7c-5p expression and reduced ferroptosis extent. energy homeostasis, and serves as a biomarker for renal injury. It
Conclusion: Let-7c-5p carried by HYX1-Exos protects from ALF by also predicts the response to tolvaptan treatment in patients with liver
inhibiting SLC11A2-mediated ferroptosis. Our finding sheds novel cirrhosis and ascites. However, the role of AZGP1 in liver injury has not
insights into the pathogenesis and therapy of ALF. been previously reported.
Table and Figure:Figure 1.An illustration of molecular mechanism by Method: Significant changes in metabolism related genes of liver
which let-7c-5p carried by HYX1-Exos protects from ALF. tissue were identified through RNA-seq analysis in wild-type C57BL/6J
hepatotoxicity model. Construct models of APAP-induced liver injury at
PP0590 early (3 and 6 hours), middle (12 hours), and late (24 hours) stages, as
well as an LPS/D-GalN-induced liver injury model. Employ RT-PCR and lymphoplasmacytic infiltration, interface hepatitis, hepatocyte rosettes
Western blot analysis to assess changes in AZGP1 gene expression and emperipolesis in patients with DI-ALH were lower than those in
in mouse liver tissues. Perform multiple immunofluorescence and patients with AIH (P<0.05).
immunohistochemistry to examine the expression and localization Conclusion: The degree of inflammatory damage in DI-ALH
of AZGP1 in different cells of liver tissues. Assess the serum levels patients was more severe than that in DILI patients. The autoimmune
of AZGP1, IL-1, IL-6, and TNFα in AZGP1 knockout mice with acute phenomenon of DI-ALH patients is relatively milder, which may provide
liver failure using RayBiotech ELISA, while the BS-2800 automated clues for the differential diagnosis of DI-ALH and AIH.
biochemical analyzer is used to measure transaminase levels, Table and Figure:Figure 1.Table 1 Demographics, clinical
including ALT and AST. Morphological methods such as HE staining characteristics and outcome of cases with DILI and DI-ALH
and TUNEL staining were employed to assess the impact of AZGP1 Figure 2.Figure 1 Comparison of pathological characteristics between
knockout on liver injury. Transcriptome combined with metabolomics DI-ALH group and AIH group
analysis was used to analyze the differential genes and metabolites of
mice with liver injury in WT and KO mice.
PP0593
Result: Azgp1 was significantly downregulated in the metabolism
related genes of liver tissue in mice with liver failure, and a negative Modulatory Effects of the Clostridium Metabolites, p-cresyl
correlation was found with the degree of liver failure in both patient Sulfate and p-cresyl Glucuronide on Primary Biliary Cholangitis
serum and mouse liver tissue and serum. Comparison of protein levels Inflammations
in solid organ tissues showed that AZGP1 expression was higher in Haiyan Yu1, Haiyan Fu1, Yingmei Tang1
liver tissue, and single-cell sequencing showed that AZGP1 was most 1
Department of Gastroenterology, the Second Affiliated Hospital of
expressed in liver cells. After knocking out AZGP1, mice lost weight, Kunming Medical University
and their serum ALT, AST, and blood glucose levels slightly increased Background: Primary biliary cholangitis (PBC) is an autoimmune
compared to wild-type mice, with no significant changes in blood disease characterized by non-suppurative inflammation of the small
lipids. After inducing liver injury models with LPS/D-GalN and APAP, and medium bile ducts in the liver. The content of Tyr in bile is related
serum ALT and AST levels increased more significantly in knockout to the activity of hepatobiliary system inflammation. p-cresyl sulfate
mice, and pathological results showed more severe damage to liver (pCS) and p-cresyl glucuronide (pCG) are derived from Tyr by gut
structure. Transcriptomic analysis shows that it is mainly enriched bacterial decomposition involving the liver. However, the knowledge
in fatty acid metabolism, energy reserve metabolism, inflammatory of the role of pCS and pCG in intrahepatic inflammation and biliary
response, and cytokine secretion processes. Metabolomics analysis epithelial cells(BECs) is limited. The study aimed to explore the effects
shows that the differential metabolites are mainly fatty acids, Amino of the intestinal Clostridium-derived metabolites pCS and pCG on
acids, purines, and vitamins. intrahepatic inflammation and intrahepatic BECs.
Conclusion: AZGP1 knockout mice showed intolerance to LPS/D-GalN Method: Human intrahepatic biliary epithelial cells (HIBEpiCs) were
and APAP, dysregulation of fat energy metabolism and inflammatory cultured in vitro to observe the effects of different concentrations of
process, and were more likely to cause liver failure. Therefore, AZGP1 pCS and pCG in cell morphology. The stage cell cycle and apoptosis
is expected to be an effective measure of liver injury. were determined by flow cytometry. The 27 female SPF C57BL/6 mice
were divided into pCS, pCG, and control groups. The livers were
PP0592 harvested, and HE stained to observe inflammation. The expression
of Caspase-3, Bax, and Bcl-2 in the liver was detected by Western
Clinical characteristics of drug-induced autoimmune-like hepatitis
Blotting, and that of TGF-β and IFN-γ in the serum was detected using
Dantong Ma1,2, Shuang Yang1,2, Lili Gao1,2, Xuesong Gao1,2, Xuefei ELISA.
Duan1,2 Result: pCS and pCG blocked the S-phase of HIBEpiCs and promoted
1
International Medical Department, Beijing Ditan Hospital, Capital apoptosis.The lymphocytes infiltrated the portal area of the liver, and
Medical University, 2National Center for Infectious Diseases (Beijing) the severity of inflammation increased in the pCS and pCG groups.
Background: The patients with drug-induced autoimmune-like The expression of IFN-γ and TGF-β in the serum increased, and that
hepatitis (DI-ALH) and with those with autoimmune hepatitis (AIH) of Caspase-3 and Bax enhanced, while that of BCL-2 decreased
have very similar clinical, biochemical, immunological and histological gradually in the pCS and pCG groups.
features. The analysis of the clinical and pathological characteristics Conclusion: pCS or pCG can promote the occurrence and
and clinical follow-up of the patients with DI-ALH were beneficial to development of intrahepatic inflammation and is associated with the
distinguish DI-ALH from AIH. inflammation-related factors IFN-γ and TGF-β, and the intrahepatic
Method: A retrospective study was conducted on the clinical and BECs were injured by promoting apoptosis.
pathological data of drug-induced liver injury (DILI) patients admitted
to Beijing Ditan Hospital, Capital Medical University, between January
PP0594
2018 and January 2023.
Result: A total of 312 DILI patients were included and divided into Drug interaction with UGT1A1 polymorphism increases the
DI-ALH group (n=73) and DILI group (n=239). The proportion of occurrence of drug-induced liver injury
female patients with DI-ALH was higher than that in DILI group [80.8% Yujia Lu1, Keying Ou1, Yueyang Ma1, Chuansu Yuan1, QingFang
(59/73) vs 68.6% (164/239), P<0.05]; Chinese herbal medicine was Xiong1
the most commonly suspected drug causing DILI; The levels of TBA, 1
Department of infectious disease and liver Disease, the Second
TBIL, DBIL, GLO, and IgG in DI-ALH group were higher than those Hospital of Nanjing, Affiliated to Nanjing University of Chinese
in DILI group, while the levels of CHE, ALB, and PTA were lower Medicine
than those in DILI group. The differences were statistically significant Background: DILI is a common reason for approved drugs to be
(P<0.05). The positive rates of autoantibodies, ANA and Anti-SLA withdrawn from the market, while UGT1A1 is an enzyme involved in the
were higher in DI-ALH group (P<0.05); Hepatic ballooning, interface metabolism of approximately 10% of drugs. A systematic evaluation of
hepatitis, and lymphoplasmacytic infiltration were more pronounced in the relationship between UGT1A1 genetic polymorphism and DILI is of
patients with DI-ALH. Among the 73 patients with DI-ALH, 70 were significant importance.
treated with immunosuppressants. They were divided into biochemical Method: Blood routine tests, liver function assessments, and
remission group and relapse group based on whether there was abdominal imaging results of hospitalized patients diagnosed with DILI
recurrence after discontinuing six months of immunosuppressants. between June 2022 and June 2023 were collected, and the UGT1A1
Patients in remission group were considered to have a diagnosis of gene was analyzed using Sanger sequencing.
DI-ALH. Patients in relapse group were diagnosed with AIH. IgG level, Result: A total of 85 DILI patients were enrolled, including 53
autoantibody positivity rate, and ANA positivity rate in remission group males. The average age was 37.42±16.27(4~71)years.There was
were lower than those in relapse group (P<0.05). The incidence of
no significant differences between the DILI group and healthy University of Hong Kong, Hong Kong SAR, China, 4Humanity and
control group (P > 0.05). The proportion of UGT1A1 polymorphism Health Clinical Trial Center, Humanity and Health Medical Group,
site in DILI(52.94%) was higher than controls [22.1%, OR (95%CI) Hong Kong SAR, China, 5Zhongshan Hospital, Fudan University,
3.964(2.08-7.557), P<0.001]. Both of them predominantly exhibited Shanghai, China
the UGT1A1*6 and UGT1A1*28 polymorphisms, the proportion were Background: Chronic Drug-Induced Liver Injury (DILI) occurs in
80% (36/45) and 85.71% (18/21), respectively (χ2=0.314, P=0.575). A 8–20% of cases. This study validated the BNR-6 relapse prediction
search of relevant databases identified that 20 drugs (24.09%, 20/83) model and assessed biomarkers HMGB1 and CK18 in chronic DILI.
are UGT1A1 inhibitors in DILI patients. In DILI patients, there were no Method: A cohort of 112 chronic DILI patients admitted between
significant differences in age, gender, TBIL, IBIL, ALT, AST, ALP, GGT, March 2023 and March 2024 were prospectively followed for one year.
WBC, HB, PLT, the type of injury , or the grade of injury (P > 0.05) , The BNR-6 model was validated using Kaplan-Meier analysis and
whether comparing the polymorphism group with the wild-type group Log-rank tests. HMGB1, CK18-M30, and CK18-M65 were measured
or the UGT1A1 inhibitors group with the non-UGT1A1 inhibitors group. at baseline, 6, and 12 months. Biomarker dynamics were analyzed
Compared with the wild-type group (17.5%), the proportion of taking using Mixed-effects models.
UGT1A1 inhibitors in the polymorphism group was higher(53.33%, Result: The cumulative 12-month relapse rate was 27.9%. High-risk
χ2=11.73, P=0.001) . patients identified by BNR-6 had a higher relapse rate compared to
Conclusion: UGT1A1 polymorphisms and inhibitors of UGT1A1 low-risk patients (39.84% vs. 15.0%, P=0.002), with a sensitivity of 57%,
enzyme associated with DILI. specificity of 74%, and accuracy of 62%. Relapse was associated with
Table and Figure:Figure 1.Study Design Flowchart elevated baseline HMGB1 [8.3 vs. 5.5 ng/ml], CK18-M30 [473.0 vs.
180.6 U/L], CK18-M65 [1077.0 vs. 360.6 U/L], and a lower CK18-M30/
PP0595 M65 ratio [0.43 vs. 0.51] (all P<0.05). Mixed-effects models indicated
significant relapse effects for all biomarkers (P<0.05), with no
Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4)
significant interaction was observed between time and relapse effects
Mediates Ferroptosis in Hepatocytes During Acetaminophen-
(all P>0.05).
induced Liver Injury and Predicts Clinical Outcomes
Conclusion: The BNR-6 model effectively predicts chronic DILI
Yu Wang1,2, Pengchong Li1,2, Xue Wang1,2, Jiahao Yuan1,2, Yan relapse. Elevated baseline HMGB1, CK18-M30, CK18-M65, and lower
Wang1,2, Zikun Ma1,2, Mengmeng Zhang1,2, Yao Meng1,2, Tiantian CK18-M30/M65 ratio may serve as predictive biomarkers for relapse
Guo1,2, Jinxin Gu1,2, Cen Zhang1,2, Jidong Jia1,2, Xinyan Zhao1,2 risk.
1
Beijing Friendship Hospital, Capital Medical University, 2State Key Table and Figure:Figure 1.
Laboratory of Digestive Health and National Clinical Research Center
of Digestive Disease
PP0597
Background: Acetaminophen (APAP) is a major cause of acute
liver injury globally, yet the regulatory genes and underlying Immune checkpoint inhibitor-associated hepatitis with grade ≥ 4
pathophysiological process remain insufficiently explored. This study (severe) survival: analysis of clinical and prognostic factors
aims to identify key genes involved in APAP-induced liver injury (AILI). Song Song Yuan1
Method: Proteomics was applied to screened differential proteins in 1
Department of Infection, The First Affiliated Hospital of Nanchang
liver tissues from AILI patients (N=6) and healthy controls (N=6). Single- University
cell sequencing analysis was conducted to validated differential genes Background: To further delineate the clinical features of ICIs hepatitis
using the GSE223561 database. Key differential genes identified with grade ≥ 4 (severe) and develop an easily applicable nomogram,
through the two omics were further validated through in AILI-induced based on readily-discernable clinical data, to predict transplant-free
mice and cultured cell lines. Finally, serum samples from Drug-induced survival
liver injury (DILI) patients were collected (N=61), and ELISA was used Method: This is a retrospective study that collected clinical data from
to evaluate whether a candidate gene coding protein could serve as a the First Affiliated Hospital of Nanchang University from January 2021
biomarker for predicting outcomes. to December 2024 in patients diagnosed with grade ≥ 4 (severe) irH
Result: Differential expression analysis in Proteomics identified ACSL4, due to immune checkpoint inhibitors based on Roussel Uclaf Causation
a key gene associated with the ferroptosis-lipid peroxidation pathway, (RUCAM) scale, and independent risk factors associated with death/
as being highly expressed in the AILI group. Single-cell sequencing liver transplantation was identified using both uni- and multi-variate
results were consistent with the proteomic findings, showing a Cox regression analyses.
significant increase in ACSL4 expression, especially in hepatocytes Result: A total of 45 patients with grade ≥4 adverse reactions (35
populations. males and 15 females) were collected, with an average age of 58.91 ±
In both in vivo and in vitro experiments demonstrated hallmark 11.39 years. The main clinical symptoms were fatigue, poor appetite,
characteristics of ferroptosis, such as mitochondrial damage, jaundice and pruritus. Among them, 16 cases were improved,
increased lipid peroxidation products, and significantly elevated accounting for 35.5% (16/45), and 29 cases were poor prognosis or
mRNA and protein levels of ACSL4. death, accounting for 64.5% (29/45). In the poor prognosis group,
ELISA results showed ACSL4 levels was significantly higher in poor there were 14 cases of acute liver failure, accounting for 48.2%
prognosis patients (liver transplantation/death) compared with recovery (14/29). By univariate analysis, the risk factors for poor prognosis were
patients [2973.0±1019 vs. 715 (492.9, 796.2) pg/ml, p<0.001]. neutrophil, HBV-DNA positive, PLT, AST, ALB, total bilirubin, PT and
Conclusion: ACSL4-mediated ferroptosis is likely involved in the infection (P<0.05). Multivariate COX analysis showed that neutrophils,
pathogenesis of AILI. Elevated ACSL4 levels in peripheral blood ALB, PT, total bilirubin and infection were independent risk factors
suggest its potential as a biomarker for assessing the prognosis of for death. The factors included in the prediction map were neutrophil
DILI. (HR=1.148, 95%CI =1.048-1.257), prothrombin time (HR=1.048,
95%CI =1.017-1.080), ALB (HR=0.880, 95% CI=0.823-0.941), total
PP0596 bilirubin (HR=2.487, 95%CI =1.134-5.452), infection (HR=3.378,
95%CI =1.744-6.543). This nomogram has a strong prognostic ability
Validation of BNR-6 prognostic model and clinical application of
and the area under the curve is 0.876.
HMGB1 and CK18 in chronic Drug-Induced Liver Injury
Conclusion: Grade 4 liver injury caused by immune checkpoint
Yuting Xiong1,2, Chunyan Wang2, Jing Chen3, Yudong Wang4, George inhibitors is severe and has a poor prognosis. Once it progresses
Lau4,5, DONG JI2,1 to liver failure, the mortality rate is extremely high. The inclusion of
1
307 Clinical Medical College of PLA, Anhui Medical University, neutrophils, prothrombin time, ALB, total bilirubin and nomogram
Beijing 100071, China, 2Senior Department of Hepatology, Fifth obtained by infection has a strong ability to predict the prognosis of
Medical Center of Chinese PLA General Hospital, Beijing 100039, severe liver injury associated with immune checkpoint inhibitors. It may
China, 3JC School of Public Health and Primary Care, Chinese
provide a reliable predictive tool for liver transplantation preparation in patient with alcoholic cardiomyopathy and liver cirrhosis
advance
PP0600
PP0598 Prolonged Elevated Heart Rate and 90-Day Mortality in Acute Liver
Analysis of lesions of liver in postmortem cases in Indian Failure
population Chenglong Ge1
Amar Ranjan1, Harshita Dubey1, Jaideep Menda1, Sathya Veera 1
The Second Affiliated Hospital of Nanchang University
Merla1 Background: Prolonged elevated heart rate (peHR) is known to
1
All India Institute of Medical Sciences, New Delhi be a significant risk factor for poor outcomes in critically ill patients.
Background: Lesions of liver cause significant morbidity and mortality However, research examining the link between peHR and acute liver
even without causing significant sign & symptom. Liver biopsy may not failure is currently lacking.
give the exact picture. Autopsy study may be a better choice. Method: In this study, we utilized the Multiparameter Intelligent
Method: Retrospective analysis of histopathological findings of Monitoring in Intensive Care IV (MIMIC-IV) database to identify patients
autopsy cases was done during year 2017 -20. Only those cases were diagnosed with acute liver failure. We defined peHR as a heart rate
selected, which showed positive histopathological finding in heart, exceeding 100 beats per minute for at least 11 out of 12 consecutive
lung, liver, spleen, kidney and brain. Total 70 cases were taken. The hours. Cox regression analysis was conducted to evaluate the
age group was between 4 days to 77 years. Male and female were relationship between peHR and 90-day mortality.
52 and 18 respectively. Out of total 70 cases, 41 showed significant Result: Out of the total cohort, 345 patients (60.9%) experienced
lesions in liver, which were analyzed. episodes of peHR, and the overall 90-day mortality rate was 40%. Our
Result: Most common lesion was moderate to severe degree of Hepatic findings indicate that peHR is an independent risk factor for mortality
steatosis which showed foci of cirrhosis 14/70 (20%). Grossly most of at 90 days (HR, 3.02; 95% CI 2.53–3.56; P < 0.001). Kaplan-Meier
the cases were mixed type of cirrhosis; macronodular & micronodular. survival curves demonstrated a marked reduction in the survival rate at
Next prominent group of diseases were cirrhosis (9/70)12.8%. Other 90 days for patients with peHR episodes (P < 0.001, 87.4% vs. 54.5%).
common diseases were chronic hepatitis & granuloma 4/70 (5.7%) Conclusion: This study highlights a significant association between
each. Cardiac cirrhosis was seen in 2/70 cases. Nonalcoholic hepatic peHR and increased 90-day mortality among a large group of ICU
steatosis was seen a case of 11 months old male baby who presented patients with acute liver failure.
with umbilical granuloma on gross examination and lung also showed
pneumonic features. Other conditions were hydatid cyst, metastasis
PP0601
from primary cancer of unknown origin and Acute inflammatory cell
infiltration in chronic hepatitis were seen in 1/70 cases. NOX2 Ablation Is A Promising Strategy Against Acute Liver Injury
Conclusion: Histopathological examination of Post mortem specimens By Reversing Oxidative Stress, Mitochondrial Dysfunction And
is conducted at limited centers in our country. This diminishes cGAS-STING Pathway-Dictated Inflammatory Response
opportunity of medical professionals to learn about liver pathology. Ziyi Yang1, Gaoyue Guo1, Chao Sun1
Key words: Liver Biopsy, liver diseases, autopsy 1
Tianjin Medical University General Hospital
Table and Figure:Figure 1.Figure 1: Hepatic steatosis_H & E stain, 100x Background: It is crucial to further characterize acute liver injury
Figure 2.Figure 2: Hepatic steatosis_H & E stain, 400x (ALI) in hopes of identifying novel therapeutic target. Recently, NOX2
which belongs to the sole family as enzymatic source of ROS has been
PP0599 linked to versatile pathologies, while its implication and regulation in
ALI remains elusive.
Alcoholic cardiomyopathy in patients with alcoholic liver cirrhosis:
Method: We performed in vivo and in vitro experiments using carbon
a study across 10 years
tetrachloride (CCl4)-induced ALI on wild-type (WT) and NOX2 knock
Chunya Wang1, Jing Chen2, Yupeng Guo3 out (NOX2KO) mice as well as HepG2 hepatocytes. Transcriptomic
1
Beijing Anzhen Hospital, 25th Medical Center of Chinese PLA General analysis, immunoblotting, various assays related to mitochondrial
Hospital, 3Mudanjiang Medical University dysfunction, inflammatory response and autophagic process were
Background: Available data regarding cardiomyopathy in patients conducted.
with alcoholic liver cirrhosis (ALC) are very limited because it often Result: NOX2 was significantly increased in liver tissues of ALI-
requires multidisciplinary assessments. As a serious disease, alcoholic WT mice challenged by CCl4 and HepG2 cells exposed to CCl4.
cardiomyopathy in patients suffering from ALC requires extra attention. However, genetic ablation of NOX2 dramatically ameliorated ALI-
Method: Adult ALC patients without a previous diagnosis of associated hepatic dysfunction and pathology in mice. Oxidative
cardiovascular diseases between January 2010 and December stress indicative of Nrf2 alteration and relevant measures were
2019 were included in the study. The prevalence rate of alcoholic ameliorated in ALI-NOX2KO mice. Several DNA repair/damage
cardiomyopathy in patients with ALC was calculated together with response, mitochondria and inflammatory pathways were identified
a 95% conffdence interval (CI) using the Clopper–Pearson exact according to RNA-sequencing. Moreover, NOX2 ablation reversed
method. various aspects concerning mitochondrial dysfunction, that is,
Result: A total of 1022 ALC patients were included. Male patients ultrastructural appearance, ATP synthesis, mtDNA release alongside
predominated (90.5%). ECG abnormalities were observed in 353 mitophagy. On contrary, process in relation to mitochondrial dynamics
patients (34.5%). Prolonged QT interval was most common in ALC was not impacted upon NOX2 modulation. Mechanistically, deletion
patients with ECG abnormalities, which occurred in 109. Thirty-ffve to overexpressed NOX2 in the context of CCl4-induced ALI may
ALC patients underwent the cardiac MRI examination and only one suppress toxicant-triggered inflammation and damages attributable
patient was found with cardiomyopathy. The estimated prevalence rate to mitochondrial damage-dictated cGAS-STING pathway, NLRP3
of alcoholic cardiomyopathy in all the ALC patients was 0.0286 (95% activation as well as impaired mitophagy.
CI, 0.0007–0.1492). There was no statistical difference regarding the Conclusion: Collectively, genetic inhibition of NOX2 alleviates ALI
prevalence rate between the group of patients with ECG abnormalities by maintaining mitochondrial homeostasis and suppressing resultant
and the group without ECG abnormalities. mtDNA leakage-mediated inflammation and cell deaths.
Conclusion: Although ECG abnormalities, especially QT prolongation, Table and Figure:Figure 1.Genetic ablation of NOX2 dramatically
existed in a proportion of ALC patients, cardiomyopathy in the patient ameliorated ALI-associated hepatic dysfunction and pathology in mice
population was not common. Further larger-sample studies based on Figure 2.NOX2ko attenuates injury by blunting the cGAS-STING
cardiac MRI are needed to verify our results. pathway-mediated inflammatory response
Table and Figure:Figure 1.Cardiac magnetic resonance features in a
 PP0602 distributed in the blood. The accumulation of PFASs increased with
Macrophage HIF-1α inhibition alleviates inflammation-induced the rising exposure dose. And the accumulation of PFASs in all tissues
acute liver failure in mice increased significantly when exposed with MPS. But co-exposure
with MPs had little influence on the distribution behavior of PFASs
Zhifu Xie1, Xiangrong Kong1, Wei Liu1, Jingya Li1
in the liver and blood. Moreover, exposure to PFASs and MPs had
1
Shanghai Institute of Material Medica, Chinese Academy of Sciences no significant effect on body weight under subchronic exposure of
Background: The development of acute liver failure (ALF) is environmentally relevant concentrations. Nevertheless, in the single
dependent on its local inducer. Inflammation is a high-frequency and exposure group of PFASs, all the mice showed obvious hepatomegaly,
critical factor that accelerates hepatocyte death and liver failure. In and the increase of liver weight in male mice was greater than that in
response to injury stress, the expression of the transcription factor female mice. Meanwhile, co-expose with MPs had no such significant
hypoxia-inducible factor-1α (HIF-1α) in macrophages is promoted by influence. Histological features revealed the co-exposure with small-
both oxygen-dependent and oxygen-independent mechanisms, thus sized MPs significantly aggravated the liver inflammation caused by
promoting the expression and secretion of the cytokine interleukin-1β PFASs exposure in male mice. Analysis of LDH, ATP, T-CHO, TG, CAT,
(IL-1β). IL-1β further induces hepatocyte apoptosis or necrosis by GSH-Px, and SOD in liver tissue indicated co-exposure with MPs had
signaling through the receptor (IL-1R) on hepatocyte. HIF-1α knockout no significant effect on the oxidative stress induced by PFASs, but it
in macrophages or IL-1R knockout in hepatocytes protects against significantly exacerbated the energy and lipid metabolism disorders
liver failure. However, whether HIF-1α inhibition in macrophages has a caused by PFASs, especially in male mice.
protective role in ALF is unclear. Conclusion: Therefore, this study found that small-sized MPs
Method: Male mice at the age of 8–10 weeks were given with or without exacerbated the PFASs burden on the mouse liver, aggravated
the HIF-1α inhibitor PX-478 at the indicated dose and frequency and hepatotoxicity in a sex-dependent manner. Multi-omics data will be
then subjected to i.p. injection of 10 μg/kg body weight LPS with further excavated to clarify the relevant mechanisms.
400 mg/kg D-GalN. Six hours after injection of LPS and D-GalN, blood Table and Figure:Figure 1.Figure.1 a, Serum concentrations of PFOA,
was collected from eye sockets for plasma biochemistry, and then PFOS and PFBA in male mice. b, Serum concentrations of PFOA,
mice were killed via anesthesia. PFOS and PFBA in female mice. c, Confocal fluorescence imaging of
Result: In this study, we revealed that the small molecule HIF-1α fluorescent-labeled microplastics in mouse tissues. d, Concentrations
inhibitor PX-478 inhibits the expression and secretion of IL-1β, but not of PFOA, PFOS and PFBA in male mice tissues. e, Concentrations
tumor necrosis factor α (TNFα), in bone marrow-derived macrophages of PFOA, PFOS and PFBA in female mice tissues. f, Body weight
(BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN- fluctuation of male mice in each exposure group. g, Body weight
induced ALF mice by decreasing the hepatic inflammatory response. fluctuation of female mice in each exposure group h, Liver weight
In addition, preventive or therapeutic administration of PX-478 fluctuation of mice in each exposure group.
combined with TNFα neutralizing antibody markedly improved LPS/D- Figure 2.Figure.2 a.b.c, Concentrations of LPS, sIgA and TNF-αin mice
GalN-induced ALF. intestinal tissues. d.e, Serum concentrations of D-Lac and DAO in
Conclusion: Our data suggest that PX-478 administration leads to mice. f.g.h.i.j.k.l, Concentrations and enzyme activities of LDH, ATP,
HIF-1α inhibition and decreased IL-1β secretion in macrophages, T-CHO, TG, CAT, GSH-Px, and SOD in mice liver tissues.
which represents a promising therapeutic strategy for inflammation-
induced ALF.
PP0604
Table and Figure:Figure 1.PX-478 combined with TNFα neutralizing
antibody treatment improves ALF synergistically Programmed cell death factor 4 aggravates sepsis-induced liver
Figure 2.PX-478 protects againstinflammation-induced acute liver damage through disturbed mitochondrial quality control system
failure Jiachi Yu1, Ruibing Li1, Tian Xia1, Jia Huang1, Jiacheng Jin1, Mianyang
Li1
PP0603
1
Department of Clinical Laboratory Medicine, the First Medical
Centre, Chinese PLA General Hospital
Co-exposure to per- and polyfluoroalkyl substances and
Background: Sepsis is the most common cause of death in intensive
microplastics aggravated hepatotoxicity in a sex-dependent
care units, caused by deregulated immune response to infection.
manner
Sepsis-induced acute liver dysfunction occurs in the early stage of
Tingting Wu1, Xiu Wang1
sepsis and can aggravates the progression of sepsis. However, there
1
The State Key Laboratory for Diagnosis and Treatment of Infectious is a lack of specific diagnostic markers for sepsis-induced liver injury
Diseases (SLI). Therefore, our study would screen potential biomarkers and
Background: Per- and polyfluoroalkyl substances (PFASs) and elucidate their roles in pathogenesis of liver damge during sepsis,
microplastics (MPs) are ubiquitous emerging pollutants in our daily life. which is of great significance for clinical diagnosis and provides
The latter can not only serve as a carrier of PFASs, but also might alter therapeutic targets for disease management.
their own characteristics and biological toxicity. Since the liver is the Method: Lipopolysaccharide (LPS) was utilized to build the SLI mouse
main target organ of PFASs, it remains unclear how MPs affect the model and then pathological alterations in livers were observed by
PFASs-induced hepatotoxicity. H&E staining, liver function were analyzed by ELISA, and inflammatory
Method: Polyethylene microplastics with different diameter sizes and and pro-apoptotic proteins were assessed by Western Blot. Differential
three representative PFASs (PFOA, PFOS, PFBA) were selected as the proteins of SLI were screened using LC-MS/MS, and further validated
objects. And C57BL/6 mice were exposed to different exposure doses through Western Blot and RT-PCR. CCK8 assays and TUNEL assay
through gavage to explore the influence of the co-exposure to MPs on were used to evaluate cell proliferation and apoptosis. Mitochondrial
the accumulation characteristic of PFASs. oxidative stress and membrane potential were assessed by MitoSOX
Result: After 21 days of exposure treatment, scattered fluorescence and JC1 staining. Furthermore, mito-tracker and lyso-tracker analysis,
signals of MPs were detected in the kidney, liver, and colon. PFASs along with Western Blot, were deployed to detect alterations of
mainly accumulated in the liver, kidney, and lung. And the detection mitochondrial quality control.
rates of PFOA, PFOS, and PFBA in all tissues were 28.6%, 100%, and Result: Increased inflammatory and apoptotic responses were
44.3%, respectively. Additionally, PFOS accumulated thousands of observed in the SLI mouse models, with liver dysfunction. Through
times more in the liver than PFOA and PFBA. In the single exposure differential protein analysis, the key protein PDCD4 was screened and
group, the accumulation levels of PFASs in male mice were significantly identified to be significantly upregulated during sepsis-induced liver
higher than those in female mice. However, in the combined exposure damage (p < 0.05). LPS exposure increased PDCD4 in hepatocytes,
group, the accumulation levels of PFOA and PFOS in female mice while genetic ablation of PDCD4 reduced LPS-induced hepatic
were significantly higher than those in male mice. Besides, PFOA and dysfunction. Proteomic analysis showed that PDCD4 ablation mainly
PFOS were mainly accumulated in the liver, while PFBA was mainly affected mitochondrial function. Molecular investigations confirmed
that loss of PDCD4 protected liver against sepsis though inhibiting macrophages
mitochondrial oxidative stress and membrane potential dysregulation.
Furthermore, upon LPS stress PDCD4 disrupted mitochondrial quality
PP0606
control, induced pathological mitochondrial fission and mitophagy, and
inhibited mitochondrial fusion and biogenesis. Co-IP assays indicated SOX9 promotes hepatocyte proliferation via paracrine TGF-α
that the accumulation of PDCD4 regulated mitochondrial fusion during liver regeneration
through the combination with mitochondrial inner membrane protein Shuqing Liu1
YME1L1, contributing to the imbalance in mitochondrial quality control. 1
Department of Gastroenterology, Shanghai East Hospital, Tongji
Conclusion: Our data show that LPS-induced liver damage is University School of Medicine,
associated with PDCD4 upregulation, which is followed by disrupted Background: The liver is an organ possessing enormous regenerative
mitochondrial quality control through the combination with YME1L1, potential. Previous studies have revealed that SOX9/HNF4α double
causing hepatocyte inflammation and apoptosis. Based on this, new positive hepatocytes contribute to chronic liver injury repairing. Deletion
potential therapeutic strategies for reducing PDCD4 and enhancing of HNF4α results in sustained hepatocyte proliferation after partial
mitochondrial quality control could be expected to treat spesis- hepatectomy. This study aims to explore the regulation of HNF4α on
induced liver damage. SOX9 expression and the effect of SOX9 on liver regeneration.
Table and Figure:Figure 1. Method: Standard partial hepatectomy (sHx), extended partial
hepatectomy (eHx), or CCl4 intraperitoneal injection were established
PP0605 for acute liver injury models. The correlation of HNF4α and SOX9
was investigated in hepatocyte-specific Hnf4α knockout (Hnf4αHKO)
The Pitfall of Fasting: Glucose Deprivation and Reacquisition
and Sox9 knockout (Sox9HKO) mice. The effect of SOX9 on liver
Exacerbate Acute Liver Injury in Mice by Triggering a Pro-
regeneration was assessed in Sox9HKO and SOX9 overexpression
inflammatory Response in Macrophages and NK Cells
(Sox9HOE) mice.
Boyu Long1, Yijuan Qin1, Feng Xiang1, Hong Ren1, Wenwei Yin1 Result: The expression of SOX9 and HNF4α was negatively correlated
1
Institute for Viral Hepatitis, Department of Infectious Diseases, The during liver regeneration. HNF4α suppressed SOX9 expression through
Second Affiliated Hospital, Chongqing Medical University upregulating miR124/381. Deletion of SOX9 reduced the liver/body
Background: Fasting and caloric restriction (CR) have been widely weight ratio and hepatocyte proliferation in sHx or CCl4-treated mice.
recognized for their potential health benefits. However, research Overexpression of SOX9 increased the survival rate in eHx-treated
also points to potential adverse effects of long-term CR. Individuals mice. Liver snRNA-sequencing and hepatocyte RNA-sequencing in
adhering to a 16+8 fasting schedule face a 91% higher mortality risk Sox9HKO mice revealed that depletion of SOX9 reduced hepatocyte
from cardiovascular diseases compared to those with a 12-16-hour proliferation and SOX9 transcriptionally activated TGF-α expression.
feeding window. Prolonged fasting has been linked to altered immune Canertinib, an EGFR inhibitor, partially abrogated the enhanced
responses to bacterial infections, potentially impairing the body’s hepatocyte proliferation induced by SOX9.
ability to combat infections and heightening the risk of heart disease. Conclusion: Our findings emphasize that the interplay between SOX9
Recent studies suggest that post-fasting refeeding may enhance the and HNF4α affects liver regeneration, and unravel the effect of SOX9
stemness of intestinal stem cells, potentially fostering tumorigenesis. promoting hepatocyte proliferation via paracrine TGF-α.
Therefore, further investigation into the impact of fasting on the liver, Table and Figure:Figure 1.
particularly its effects on immune cells across various liver diseases,
is crucial.
PP0607
Method: Mice were randomly assigned to a control group and a short-
term fasting (STF) group, with the latter undergoing a 24-hour fast while Research on the Impact of ER Stress on Apoptosis in Acute and
the former had ad libitum access to food. To evaluate the effects of STF Chronic Liver Injury under the Intervention of TCM
on liver injury, we utilized Poly I:C/D-GalN as an inducer and collected Peipei Huang1, Haibo Zhang2, Ruijuan Yan1, Zhanjie Chang1, Junzhe
blood and liver samples from mice for subsequent biochemical Jiao1, Jingtao Li1
analyses and cytokine level assessments. Anti-Asialo GM1 (AsGM1) 1
Hepatology Hospital, Affiliated Hospital of Shaanxi University of
was used to deplete NK cells, and Clodronate Liposomes (Clo-Lip) Chinese Medicine, 2Basic medical college of Shaanxi university of
to deplete macrophages. The contribution of immune cells to STF- Chinese Medicine
induced liver damage was investigated using flow cytometry, ELISA, Background: Acute and chronic liver injuries are critical in
and assessments of ALT and AST levels, as well as HE staining. the progression of liver disease, and their susceptibility and
Additionally, the role of different nutrients was explored by administering pathophysiological mechanisms are poorly understood. The
the glucose metabolism inhibitor 2-Deoxy-D-glucose (2D-G) at various endoplasmic reticulum (ER) is an essential cellular structure
fasting intervals and intragastrically delivering different nutrients. responsible for protein synthesis, lipid metabolism, and substance
Result: STF resulted in the recruitment and activation of pro- transport, crucial for maintaining cellular homeostasis. Recent studies
inflammatory macrophages and influenced the aggregation and have shown that ER stress is a key factor in the development of liver
activation of NK cells, thereby exacerbating liver damage. Depletion disease, and that hepatic cell death induced by ER stress is critical for
of the respective cells with Clo-Lip and AsGM1 revealed that the liver injury. ER stress is primarily mediated by three sensors: IRE1α,
exacerbation of damage was primarily due to the increased aggregation PERK, and ATF6. This paper explores the relationship between ER
and secretion of pro-inflammatory cytokines by macrophages, while stress and acute or chronic liver injury in search of new therapeutic
the enhancement and activation of NK cells were attributed to STF’s targets.
effects on macrophages. The application of 2D-G at different fasting Method: This study presents a systematic review of the role of ER
intervals and intragastric administration of various nutrients indicated stress in drug/alcohol/hepatic ischemia-reperfusion induced liver
that glucose deficiency and repletion were the primary culprits in the injury. It discusses the mechanisms through which ER stress activation
exacerbation of damage. leads to cellular adaptation and apoptosis and summarizes traditional
Conclusion: This study uncovers the potential detrimental effects of Chinese medicine (TCM) and active components targeting ER stress
STF on liver health. STF aggravates liver damage by increasing pro- for the treatment of acute or chronic liver injuries.
inflammatory macrophage numbers and activating NK cells, a process Result: Acute and chronic liver injuries are closely related to the
intricately linked to glucose deficiency and repletion. These findings homeostasis of the hepatocyte ER. Short-term ER stress can activate
suggest that STF is not uniformly beneficial, and its potential adverse the UPR adaptation pathway to restore homeostasis, but long-term
effects on the liver must be considered in clinical settings. severe ER stress can over-activate the UPR and trigger apoptosis,
Table and Figure:Figure 1.Glucose deprivation and reintroduction activating apoptotic molecules such as caspase-12 and leading to
exacerbate acute liver injury in mice hepatocyte apoptosis. Additionally, ER stress can activate inflammatory
Figure 2.The aggravation of liver injury is primarily facilitated by
pathways, prompting the release of inflammatory factors (TNF-α, IL-6), effect by suppressing M1 macrophage polarization via the STAT1/NF-
exacerbating the inflammatory response. Normal functions of the ER κB signaling pathway, thereby reducing inflammation during acute liver
include protein synthesis and lipid metabolism, and when ER stress injury.
occurs, it interferes with these metabolic processes, exacerbating liver
damage. Therefore, regulation of ER stress is crucial for the treatment
PP0609
of acute and chronic liver injury. We found that TCM and its active
components (such as ginsenoside CK, triptolide, ginsenoside Rg1, Case report: Complete viral suppression after switching to
emodin, Rhein, and flavonoid compounds, etc.) can regulate ER Tenofovir Amibufenamide (TMF) in a chronic hepatitis B patient
protein levels, modulate the IRE1α, PERK, ATF6 signaling pathways, with renal function impairment
effectively inhibit hepatocyte apoptosis and necrosis, and promote JUN LI1, BAOXIN QIAN1, Qing Ye1
liver repair. 1
Tianjin The Third Central Hospital
Conclusion: ER stress, as a signal transduction pathway, plays a A 33-year-old young male patient with HBeAg negative chronic
key role in the occurrence and development of liver disease, and its hepatitis B, positive for HBV DNA and elevated ALT, was initially treated
regulation is essential for reducing hepatocyte apoptosis and necrosis with TDF. After 6 months, the HBV DNA turned negative. During this
to protect liver function. This review of the mechanisms of ER stress period, he experienced a decline in renal function, eGFR decreased
and UPR in acute and chronic liver injury provides theoretical support from 105 to 72ml /(min*1.73m2),which was found to be associated with
for the use of TCM components as therapeutic targets. It establishes a duodenal ulcer bleeding in the bulb and Helicobacter pylori(HP)
a theoretical foundation for the application of TCM in the treatment of infection, as well as microcytic hypochromic anemia. After receiving
acute and chronic liver injury and provides new strategies for multi- quadruple therapy, the HP testing turned to negative by urea breathing
pathway, multi-target therapeutic approaches. test(UBT), acompany anemia improved and renal function restored.
Table and Figure:Figure 1.ER Stress Mediates Toxic Mechanisms in Due to persistent weakly positive urinary occult blood, TDF treatment
Acute and Chronic Liver Injury. was switched to TMF after 12 months. After 12 and 24 months of TMF
treatment, high-sensitivity HBV DNA was undetectable, indicating
PP0608 complete viral suppression, along with a stable renal function.HBsAg
was 4642.64 IU/ml,4336.69 IU/ml,3095.59 IU/ml at baseline, 12mon
Protective Effects of Macrophage Iron Deposition on Liver
and 24 mon, respectively.
Inflammation via STAT1/NF-κB Pathway Inhibition in Experimental
Keywords: Chronic Hepatitis B, Tenofovir Amibufenamide (TMF),
Acute Liver Injury
Quantitative Hepatitis B Surface Antigen,Renal Function.
Xiaofan Wang1,2, Ziyu Rong1,2, Tianhui Liu1,2, Ping Wang1,2, Lin Liu1,2,
Xu Fan1,2, Xinyan Zhao1,2, Min Cong1,2, Jidong Jia1,2
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical PP0610
University, 2State Key Laboratory of Digestive Health and National Serum High Sensitivity C Reactive Protein (HS-CRP) as a Marker
Clinical Research Center of Digestive Disease of Steroid Responsiveness and Event-Free Survival (EFS) in
Background: Iron deposition is frequently observed in patients with Autoimmune Hepatitis, and its Correlation With Liver Fibrosis on
liver disease; however, its effects and underlying mechanisms remain Histology
poorly understood. This study aimed to investigate the role and Simi Tahiliani1, Manish Kumar1
mechanisms of iron deposition in different liver cell types during acute 1
ABVIMS and Dr RML Hospital
liver injury. Background: Liver biopsy is the gold standard for assessing
Method: Patients diagnosed with MASH (metabolic dysfunction- fibrosis and necro-inflammatory activity in autoimmune hepatitis, but
associated steatohepatitis) through liver biopsy were enrolled. Based advanced liver disease and patient reluctance create challenges.
on Prussian blue staining results, patients were categorized into Therefore, researchers are exploring non-invasive biomarkers as
groups with or without hepatic iron deposition. Serum ferritin levels and surrogates, notably leptin and human epididymis protein (HE4). Highly
the severity of liver fibrosis were compared between groups. In vivo, sensitive C-reactive protein (HS-CRP) is a non-specific inflammation
mice were treated with iron dextran for 4 days or fed a high-iron diet marker studied in chronic hepatitis B, C, and metabolic dysfunction-
for 1 week to induce hepatic iron deposition, followed by CCl4 injection associated steatotic liver disease (MASLD). Still, its role in autoimmune
to model acute liver injury. Histological staining assessed liver iron hepatitis is unexplored. This study aimed to assess the association
deposition, inflammation, and necrosis, while serum aminotransferase between serum HS-CRP and liver fibrosis on histology in autoimmune
levels and iron metabolism- and inflammation-related gene and hepatitis, and its correlation with event-free survival (EFS) and treatment
protein expression were measured. The RAW264.7 cell line was used response at 6 months.
to explore the mechanism of macrophage-mediated effects of iron Method: Patients over 18 years with deranged liver function tests (LFT)
deposition on inflammation in vitro. or undiagnosed chronic liver disease (CLD) were recruited. Exclusions
Result: In the patient cohort, iron deposition was primarily observed included MASLD, hepatitis B, C, Wilson’s disease, hemochromatosis,
in hepatocytes. Compared to MASH patients without iron deposition, drug-induced liver injury, and acute liver failure. A sample size of 35
those with hepatocellular iron deposition exhibited significantly higher was calculated with an 80% power and 95% confidence interval. We
serum ferritin levels and a higher prevalence of severe liver fibrosis selected 44 patients, calculated the simplified score for autoimmune
at equivalent inflammation scores, suggesting an association between hepatitis, and performed ultrasound-guided liver biopsy. Patients with
hepatocellular iron deposition and poor prognosis. In mice, high-iron scores ≥6 and compatible histology were designated as ‘histologically
diets induced significant hepatocellular iron deposition (confirmed via proven autoimmune hepatitis’ (Group A, n=22); those with scores
Prussian blue staining), accompanied by increased inflammatory cell <6 were classified as ‘alternate group’ (Group B, n=22). ISHAK and
infiltration. Iron deposition altered the expression of iron metabolism- METAVIR scores were calculated for Group A, with correlations to HS-
related genes, including increased Fth1, Fpn, and Hamp, and CRP and Child-Turcotte-Pugh (CTP) scores analyzed. Group A was
decreased Irp1. These changes were further influenced by CCl4 followed for 6 months to assess treatment response and EFS.
exposure. High-iron diets exacerbated CCl4-induced inflammation, M1 Result: The mean HS-CRP was 5.58 ± 4.17 in Group A and 5.58 ±
macrophage polarization, and elevated serum ALT and AST levels. 4.03 in Group B, with median values 4.99 and 4.80, respectively. No
In contrast, intraperitoneal iron dextran administration deposited association between HS-CRP and the groups was found (χ2= 0.535,
iron in macrophages, attenuated CCl4-induced serum transaminase p= 0.911). In Group A, there was no correlation between HS-CRP
elevation, and reduced liver inflammation. RNA sequencing of primary and METAVIR (Spearman ρ= -0.03612, p= 0.8732) or ISHAK scores
liver macrophages identified the STAT1/NF-κB signaling pathway as (ρ=0.3902, p= 0.0726). HS-CRP correlated positively with CTP score
a potential mediator. In vitro studies confirmed that macrophage iron (ρ= 0.511, p<0.001) and mortality at 1 year (ρ= 0.497, p<0.01).
deposition mitigated inflammation through this pathway. However, it was not an independent predictor of mortality (Hazard ratio
Conclusion: Mild iron deposition in macrophages exhibits a protective
=1.025, p= 0.794). At 6 months, higher HS-CRP correlated with poor Medical University, Luzhou City, China
response to immunosuppression (ρ= -0.518, p=0.013). The ROC curve Background: Preliminary research suggests that statins could have
indicated a cut-off for lack of response at 4.98 mg/dL (Youden index potential medical effectiveness in treating diseases like cirrhosis
= 0.636, AUROC = 0.793), and for predicting readmission/mortality at and cholestatic liver disease, although their effectiveness is yet to
5.895 mg/dL (Youden index 0.49, AUROC 0.761). be confirmed. This Mendelian randomization (MR) investigation is
Conclusion: While sophisticated non-invasive markers are being intended to scrutinize the link between lipid traits and conditions like
explored in autoimmune hepatitis, HS-CRP remains an accessible tool autoimmune liver disease, chronic viral hepatitis, and cirrhosis.It also
for gauging inflammation. Higher baseline HS-CRP levels indicated evaluates the possible influences of lipid reduction drug targets such as
more readmissions/mortality and poorer treatment responses, 3-hydroxy-3-methylglutaryl–CoA reductase (HMGCR) and proprotein
suggesting these patients could require stronger immunosuppression. convertase subtilis kexin 9 (PCSK9) on these liver conditions.
However, due to the small sample size, the findings must be validated Method: For the MR study, variations in genes connected to lipid traits
on a larger population. and those regulating the production of targets for lipid-lowering drugs
Table and Figure:Figure 1.Fig. 1 ROC Curve for HS-CRP and response were obtained,which from the Global Alliance for Lipid Genetics and
to treatment as per EASL Protocol at 6 months the UK Biobank Study. The derived outcomes were then subjected
Figure 2.Fig. 2 Kaplan Meier Survival Curves for HS-CRP classes to a comprehensive meta-analysis. Finally, mediation analysis was
conducted to explore potential mediators.
PP0611 Result: An observable protective impact on PSC (OR=0.4396; 95% CI:
0.2974-0.6497; P < 0.0001) was evident from genetically anticipated
Comparison of the Diagnostic Value of RPR, GPI, FIB-4 and
HMGCR inhibition, and it is also conjectured to safeguard against
APRI in Patients with Autoimmune Hepatitis and Primary Biliary
Chronic Hepatitis B(OR=0.5161; 95% CI: 0.2963-0.8990; P=0.0195).
Cholangitis Overlap Syndrome in Advanced Liver Fibrosis
Suggestive evidence points to PCSK9 inhibition, predicted genetically,
Cailian Cai1, Hongyu Liu1, Keshan Wang1, Chao Jin1, Fangpeng Ling1,
having a protective response against primary biliary cholangitis (PBC)
Bingling Fan1, Minghua Su1
(OR=0.4879; 95% CI: 0.2864-0.8311; P=0.0083) and chronic hepatitis
1
The First Affiliated Hospital of Guangxi Medical University B (OR=0.5183 ; 95% CI: 0.3383-0.7941; P=0.0025).
Background: To compare the diagnostic value of four non-invasive Conclusion: As potential targets for candidate drugs treating PSC,
serological models, namely, red cell distribution width (RDW)-platelet chronic hepatitis B, and PBC, HMGCR and PCSK9 appear promising.
ratio (RPR), globulin-platelet index (GPI), 4-factor based liver fibrosis However, they may also pose risk factors for autoimmune hepatitis,
index (FIB-4), and aspartate aminotransferase-platelet ratio index cirrhosis, and chronic hepatitis C.
(APRI), for advanced liver fibrosis in autoimmune hepatitis (AIH) Table and Figure:Figure 1.FIGURE 1
and autoimmune hepatitis-primary biliary cholangitis (PBC) overlap
syndrome (AIH-PBC OS).To explore the best noninvasive fibrosis
PP0613
model to reduce the need for liver biopsy.
Method: A total of 209 patients with AIH and AIH-PBC OS who were Neutrophil extracellular traps promote autoimmune hepatitis
diagnosed by liver biopsy in the First Affiliated Hospital of Guangxi through inhibiting the suicide of CD8+ T cells
Medical University from January 2014 to April 2024 were enrolled. The Han Wang1
degree of liver fibrosis was staged using the Scheuer scoring system 1
Tongji Hospital, Tongji Medical College, Huazhong University of
of liver biopsy: S≤2 was the non-advanced liver fibrosis group (n=115), Science and Technology
and S>2 was the advanced liver fibrosis group (n=94). RPR, GPI, FIB- Background: Autoimmune hepatitis (AIH) is a chronic, progressive,
4, and APRI were calculated according to the formula, and the receiver and immune-mediated liver injury. Its prevalence has been increasing
operating characteristic (ROC) curve was plotted. The area under the worldwide. The treatment of AIH is challenging and currently relies on
ROC curve (AUC), sensitivity, specificity, positive predictive value, corticosteroid therapy. Innate and adaptive immunity play critical roles
negative predictive value, and accuracy were used to evaluate the in AIH pathogenesis. In AIH, CD8+T cells actively invade hepatocytes,
value of each model in the diagnosis of advanced liver fibrosis in AIH enter endosomal/lysosomal compartments, and are degraded
and AIH-PBC OS. (the “suicidal emperipolesis”)1. Our most recent findings revealed
Result: The mean age of 209 patients was 52 [44, 60] years old, 150 neutrophil extracellular traps (NETs) link the crosstalk between innate
cases were AIH, and 59 cases were AIH-PBC OS. The AUCs of RPR, and adaptive immunity by directly interacting with hepatic regulatory T
GPI, and FIB-4 in diagnosing advanced liver fibrosis in 209 patients cells2. However, the role of NETs in the setting of AIH remains unknown.
were 0.75, 0.73, and 0.68 respectively (P values all P<0.001). The Here we aim to elucidate the mechanisms by which AIH-induced NETs
sensitivities were 83.48%, 70.43%, and 59.13% respectively. The promote the development of AIH by arresting hepatic CD8+T cells and
specificities were They were 58.51%, 64.89%, and 73.40% respectively. preventing their suicidal emperipolesis.
The optimal cut-off values were 0.10, 2.18, and 2.55 respectively. Method: A well-established AIH model was performed by
The positive predictive values were 74.32%, 64.21%, and 59.48% hydrodynamic transfecting with human CYP2D6 plasmid into C57Bl/6
respectively. The negative predictive values were 71.11%, 71.05%, and mouse liver. DNase to inhibit NETs or peptidyl arginine deiminase 4
73.12%. respectively, the accuracies were 72.25%, 67.94%, 69.33% knockout (PAD4 KO) mice (genetically unable to form NETs) were
respectively. APRI has no diagnostic value for advanced liver fibrosis. utilized in vivo experiments.
The diagnostic value of RPR for advanced fibrosis is better than that of Result: AIH was successfully established as autoantibodies and
FIB-4 (P<0.05), but there is no significant difference between RPR and characteristic pathological features of AIH were observed in the mice
GPI, GPI and FIB-4. livers at four weeks. Utilizing 10x Genomics RNA-sequencing (RNA-
Conclusion: RPR, GPI and FIB-4 have certain predictive value for seq), we uncovered the presence of a distinctive cluster of autoreactive
diagnosing liver fibrosis in advanced OS stage of AIH and AIH-PBC, CD8+T cells that exhibited aggregation within the liver of AIH mice.
and the diagnostic efficiency of RPR is better than that of FIB-4. Cith-H3 and MPO levels (the specific NETs markers) increased in the
Table and Figure:Figure 1.ROC curve of RPR, GPI, FIB-4 and APRI for livers and sera of AIH mice, respectively. We confirmed a positive
diagnosing advanced stage fibrosis in AIH and AIH-PBC OS groups correlation between hepatic NETs and CD8+T cells in AIH patients
and mice. Using confocal microscopy, we observed NETs arresting
PP0612 CD8+T cells. Inhibiting NETs protected liver injury in AIH mice, which
was predominantly linked to the reduced quantity and functional
Genetic association of lipids and lipid-lowering drug target
impairment of hepatic CD8+T cells. In vitro, the transwell experiment
genes with autoimmune liver disease, chronic viral hepatitis and
revealed NETs possess the ability to hinder the migration of CD8+T
cirrhosis
cells towards hepatocytes. Flow cytometry indicated that NETs
Tao Yang1, Lu Muhan1
promoted CD8+T cells function by augmenting their secretion of TNF-α
1
Department of Gastroenterology, The Affiliated Hospital of Southwest
and IFN-γ. Seahorse data suggested the oxidative phosphorylation of PP0615
CD8+T cells enhanced significantly after NETs treatment. Bulk RNA- Construction of hybrid biomimetic nanosystem of mesenchymal
seq confirmed that most differentially expressed genes of CD8+T cells stem cells and dendritic cells and its targeted therapy for CD4+ T
after NETs treatment enriched in the metabolic pathways. cells in autoimmune hepatitis
Conclusion: NETs capture hepatic CD8+T cells and prevent their
Mengyi Shen1, Leyu Zhou1, Jingping Liu1, Li Yang1
suicidal emperipolesis. NETs promote AIH progression through the
crosstalk between innate and adaptive immunity and maybe the
1
West China Hospital, Sichuan University
potential therapeutic targets. Background: The infiltration and activation of CD4+ T cells play an
1.Volker Benseler, et al. Hepatocyte entry leads to degradation of important role in the pathogenesis of autoimmune hepatitis (AIH).
autoreactive CD8 T cells. Proc Natl Acad Sci U S A (2011). Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) is
2.Han Wang, et al. Regulatory T-cell and neutrophil extracellular shown to metabolic reprogram T cell phenotype in the treatment of
trap interaction contributes to carcinogenesisi in non-alcoholic AIH. However, it still falls short in targeting CD4+ T cells. Here, we
steatohepatitis. Journal of Hepatology (2021). constructed a novel targeted delivery system, that is, a hybrid bionic
Table and Figure:Figure 1. nanosystem of mesenchymal stem cells and dendritic cells, for the
treatment of AIH.
Method: Hybrid vesicle (Hy-EV) of MSC-EV and dendritic cell
PP0614
membrane vesicle (DCMV) were constructed using membrane fusion
Fatty Acid β-oxidation Enhances the Immune Regulatory Function technology. The targeting ability of Hy-EV was quantitatively detected
of Double Negative T cells through pSTAT4-OX40 Signaling using an IVIS imaging system and a confocal microscopy. The liver
Pathway protective effect of Hy-EV was evaluated by transaminase levels,
Zeyu Wang1, Hua Jin1, Guangyong Sun1, Dong Zhang1 histopathology,and inflammation.
1
Beijing Chaoyang Hospital Result: Hy-EV treatment effectively rescued liver injury and regulated
Background: Double-negative T (DNT) cells are a CD3+CD4-CD8- the imbalance of the immune microenvironment in AIH mice.
NK1.1- T cell subpopulation. DNT cells possess immunoregulatory Mechanistically, Hy-EV displayed enhanced targeting potency for
functions, exerting protective effects in liver injury by suppressing hepatic CD4+ T cells due to the overexpession of the key molecules
excessive inflammatory responses and maintaining hepatic immune which mediated DC-T cell contact. Lastly, multiple long-term
homeostasis. However, mechanisms by which DNT cells maintain their administration of MDV was proved safe in general.
survival and immunoregulatory functions through energy metabolism Conclusion: Hy-EV exerts an enhanced ability to target CD4+ T
remain unclear. Therefore, this study aims to investigate the impact cells in the treatment of AIH, which could be exploited as a potential
and mechanism of energy metabolism on immunoregulatory function therapeutic strategy for this disease.
of DNT cells and further achieve better treatment on autoimmune
hepatitis. PP0616
Method: Primary DNT cells and conventional CD4+ T cells from mice Extracellular inosine induces anergy in B cells to alleviate
were collected for lipidomic analysis and fatty acid β-oxidation (FAO) autoimmune hepatitis
levels. Single cell RNA sequencing was employed to elucidate FAO-
Nana Cui1, Qiwei Qian1, Yujie Zhou1, Heng Zhang2, Xiong Ma1
related gene expression between the two cell types, validated by flow
cytometry and RT-qPCR. DNT cells were stimulated with free fatty
1
Renji Hospital, School of Medicine, Shanghai Jiaotong University,
Shanghai Institute of Digestive Disease, 2The State Key Laboratory
acids and FAO inhibitor Etomoxir (Eto) and assessed for apoptosis,
of Drug Research, Shanghai Institute of Materia Medica, Chinese
proliferation, and functional molecule expression. Transcriptome
Academy of Sciences, Shanghai 201203, China
sequencing and validation was performed to screen for key regulatory
molecules. Finally, DNT and DNT-Eto were separately transferred via Background: Dysregulation of naïve BCR signaling and the generation
tail vein injection into a CD4+ T cell-mediated autoimmune hepatitis of antibody-secreting B cells (ASCs) have been implicated in the
mouse model induced by Concanavalin A (ConA). Therapeutic effects development of autoimmune diseases. Anergic B cells (BNDs) are
were observed. naïve B cells with low-density of surface IgM-BCR, thus demonstrating
Result: Compared to CD4+ T cells, DNT cells exhibited significantly attenuated autoantigen responsiveness. However, potential regulatory
higher intracellular fatty acid content, FAO levels, and related gene mechanisms of B cell anergy and their roles in autoimmune hepatitis
expression. DNT subpopulations with enhanced survival and (AIH) remain unestablished.
function demonstrated higher FAO levels. Supplementation with fatty Method: In patients with AIH, we examined the frequency of circulating
acids increased proliferation, reduced apoptosis, and enhanced B cell subsets and correlated BNDs and IgG plasmablasts with
immunoregulatory function of DNT cells. Conversely, inhibiting disease activity. Phenotypic and functional analysis was compared
FAO decreased proliferation, increased apoptosis, and weakened between BNDs and CNBs by flow cytometry. Human CD19+ B cells
immunoregulatory function of DNT cells. Further transcriptome were treated with inosine in vitro to induce anergy. The effect of inosine
sequencing revealed OX40 as a key molecule simultaneously regulating was also evaluated in a ConA-induced autoimmune hepatitis mouse
survival and immunoregulatory function of DNT cells, validated by model.
significantly reduced proliferation and functional molecule expression Result: A increase of antibody-secreting B cells (ASCs) and a parallel
in OX40 knockout DNT cells. Upstream promoter prediction of OX40 decrease of BNDs were observed in the PBMC from patients with
indicated that transcription factor pSTAT4 regulated OX40 expression, AIH. Furthermore, BNDs highly expressed the rate-limiting enzyme
thereby influencing survival and function of DNT cells. Finally, adoptive (CD73) and the final product of adenosine metabolism (inosine).
transfer of ConA model mice demonstrated that compared to the DNT Interestingly, inosine effectively enhanced the expansion of BNDs
treatment group, the DNT-Eto treatment group exhibited markedly and inhibited the activation of B cells as well as the differentiation
aggravated liver injury and significantly elevated liver enzyme levels. of ASCs. Mechanically, extracellular inosine was shuttled into cell
DNT cells in mice showed significantly enhanced survival and function via equilibrative nucleoside transporter 1 (ENT1) and then inhibited
compared to DNT-Eto, and exhibited a significantly stronger inhibitory the PARP14-STAT6 signaling pathway. Consistently, ex-vivo inosine
effect on CD4+ T cells in vivo compared to DNT-Eto. treatment improved the dysregulation of B cells from patients with AIH.
Conclusion: DNT cells possess high levels of FAO, which regulates In-vivo study revealed that inosine supplementation could alleviate
their survival and immunoregulatory function through the pSTAT4- hepatitis in the concanavalin A (ConA) mouse model.
OX40 pathway, enhancing their protective effect against autoimmune Conclusion: Our findings revealed that inosine was a crucial
hepatitis. metabolite that induced immune tolerance of B cells, thus proposing a
Table and Figure:Figure 1.DNT cells exhibit protective effect against novel therapeutic strategy for AIH.
autoimmune hepatitis through fatty acid β-oxidation. Table and Figure:Figure 1.
Figure 2.Graphic abstract Figure 2.
 PP0617 may achieve hepatic recompensation under immunosuppressive
The Application of Budesonide in the Treatment of Autoimmune therapy. The survival of the recompensated patients has been
Hepatitis - A Systematic Review Based on the PubMed Database improved.
Table and Figure:Figure 1.
Shenan Huang1, Qibo Hu1
Figure 2.
1
The Second Affiliated Hospital of Nanchang University
Background: Autoimmune hepatitis (AIH) is a disease characterized
PP0619
by elevated serum transaminase levels, hyperimmunoglobulin G (IgG)-
emia, positive serum autoantibodies, and moderate to severe interface MSCs ameliorate primary sclerosing cholangitis by reprogramming
hepatitis on liver histology. If left untreated, it will progress rapidly to the intestinal microbiota and augmenting vitamin B6
cirrhosis. The current first-line treatment regimen for AIH is prednisone Hongcui Cao1,2, Yingduo Yu1,2, Deying Chen3, Qiaoling Pan1,2, Jiong
(prednisolone) combined with azathioprine, but this treatment Yu1,2, Lanjuan LI3,2
regimen has more severe systemic adverse effects associated with 1
State Key Laboratory for the Diagnosis and Treatment of Infectious
glucocorticoids. The Chinese Guidelines for Diagnosis and Treatment Diseases, Zhejiang University School of Medicine, 2National Clinical
of Autoimmune Hepatitis (2021 Edition) mention that budesonide Research Center for Infectious Diseases, National Medical Center for
can be used as the first-line treatment regimen for AIH, suitable Infectious Diseases, Collaborative Innovation Center for Diagnosis
for patients with AIH who need long-term use of glucocorticoids to and Treatment of Infectious Diseases, 3State Key Laboratory for the
maintain treatment to reduce side effects. A multicenter clinical study Diagnosis and Treatment of Infectious Diseases, National Clinical
published in Gastroenterology in 2010 indicated that budesonide was Research Center for Infectious Diseases, The First Affiliated Hospital,
more effective than prednisone in inducing remission, but a multicenter Zhejiang University School of Medicine
clinical study published in Hepatology in 2022 indicated that Background: Mesenchymal stem cell (MSC) therapy has emerged as
budesonide, as a first-line drug, was less effective than prednisone, a prospective new approach for treating primary sclerosing cholangitis
but with fewer side effects. (PSC) and can also modulate the composition of the intestinal
Method: This article systematically reviews the articles in PubMed microbiota. Nevertheless, the specific mechanisms by which the gut-
regarding the treatment of autoimmune hepatitis (AIH) with budesonide, liver axis is regulated remain unclear.
to further explore the specific application of budesonide in AIH. Method: Mdr2-/- mice with or without placenta-derived MSCs (hP-
Result: Upon conducting a thorough analysis, it is deduced that MSCs) as the therapy or PSC model, while Mdr2+/+ mice as the
budesonide holds clinical significance as a primary therapeutic option control. The overall therapeutic efficacy of hP-MSCs on the injured liver
in the management of autoimmune hepatitis (AIH); however, the was evaluated. The causality between MSC therapy and the intestinal
precise timing for its implementation in clinical practice necessitates flora was evaluated by Spectrum antibiotic cocktail (ABX). Fecal
further investigation. samples in each group were for non-targeted metabolomics and 16S
Conclusion: Budesonide emerges as a viable first-line treatment rRNA gene sequencing, and the roles and functions of key differential
option for autoimmune hepatitis (AIH), particularly beneficial for metabolites were explored.
patients necessitating prolonged glucocorticoid maintenance therapy Result: The outcomes of liver histology, serum liver enzyme levels
to minimize associated side effects. Nevertheless, the precise criteria and inflammatory factors collectively verified the therapeutic efficacy
for its applicability necessitate comprehensive further investigation. of hP-MSC treatment. There were no significant differences in terms
of liver/body weight ratio, HE staining, serum liver enzyme levels
PP0618 and inflammatory factors between the mice in the ABX+Mdr2-/- and
ABX+ Mdr2-/- +MSC groups, indicating that the protective effect of
Predictors of Recompensation in Immunosuppressive Therapy for hP-MSC on the liver is likely to be intestinal microbiota-dependent.
Autoimmune Hepatitis Patients with Decompensated Cirrhosis hP-MSCs increased the diversity of the intestinal microbiota, altered
Yujie Zhang1, Fan Yang1, Yunke Peng1, Xiaoyan Ao1, Xianglin Wang1, the composition and function of the intestinal microbiota, particularly
Li Yang1, Xiaoli Fan1 manifested as an increase in the relative abundance of g_Parvibacter,
1
Sichuan University West China Hospital: West China Hospital of g_UCG-009, a reduction in the relative abundance of g_Alistipes,
Sichuan University g_Faecalibacterium, and a decrease in the functional pathway of
Background: Since the formal proposal of the Baveno VII lipopolysaccharide synthesis. Based on metabolomic analysis, 72
recompensation criteria, there have been no studies investigating fecal differential metabolites associated with hP-MSCs treatment were
whether patients with autoimmune hepatitis (AIH) and decompensated preliminarily screened. Pathway enrichment analysis revealed that
cirrhosis can achieve recompensation through immunosuppressive these differential substances were mainly enriched in the synthesis
therapy. This study aims to analyze the characteristics and clinical of vitamin B6. The differential microbiota, differential metabolites,
outcomes of AIH patients with decompensated cirrhosis, identify and biochemical indicators such as liver enzymes (ALT, AST, ALP)
risk factors influencing prognosis, and validate the definition of were found to be correlated. Among them, the metabolite of vitamin
recompensation as proposed in Baveno VII. B6, 4-Pyridoxic acid, exhibited a high correlation with the differential
Method: 84 patients with biopsy-confirmed AIH-related microbiota and liver enzymes. Biochemical detection indicated that
decompensated cirrhosis were included. The study analyzed their the content of vitamin B6 in serum increased after hP-MSCs treatment,
baseline characteristics and clinical outcomes and explored the factors and the relative abundance of the key enzyme Pyridoxal 5’-phosphate
influencing prognosis. Recompensation was defined as (i) resolution synthase for the synthesis of vitamin B6 by the intestinal microbiota
of complications; discontinuation of diuretic/HE therapy, (ii) absence also rose.
of variceal bleeding and (iii) sustained liver function improvement. Conclusion: This study promotes the understanding of the protective
Uni- and multivariable logistic regression analyses were performed to effect of hP-MSCs on PSC, reveals that it can modulate the intestinal
explore the factors associated with AIH recompensation. dysbiosis induced by PSC and increase the production of more vitamin
Result: In total, 84 patients with AIH with decompensated cirrhosis B6 by the microbiota for liver protection. These provide new preclinical
received immunosuppressive therapy, and 59 (70.2%) of them achieved evidence for the application of mesenchymal stem cells.
recompensation. The Kaplan–Meier survival analysis demonstrated
that the non-recompensation group exhibited a higher all-cause PP0620
mortality rate compared to the recompensation group (p<0.0001).
Coexistence of autoimmune hepatitis with other extra-hepatic
The baseline BMI (OR=1.606, 95% CI: 1.167–2.212, p=0.004), AST
autoimmune diseases
level (OR=1.006, 95% CI: 1.000–1.012, p=0.044), and MELD score
(OR=0.791, 95% CI: 0.675–0.926, p=0.004) was associated with the Hajar Elibrahimi1, Maryeme Kadiri1, Fatimazahra Chabib1, Nawal
recompensation in AIH-related decompensated cirrhosis patients. Lagdali1, Mohamed Borahma1, Fatimaezzahrae Ajana1
Conclusion: Most of patients with AIH and decompensated cirrhosis
1
ibn sina university hospital, gastro enterology department C
Background: Autoimmune hepatitis (AIH) is a chronic, immune- used continuously. Broad-spectrum antibiotics and methylprednisol
mediated inflammatory liver disease. Its diagnosis is based on was given intravenously.His acute pharyngitis,mycoplasma pneumonia
elevated transaminase levels, hypergammaglobulinemia (IgG), and blood routine all recovered after 2 weeks. The maintain therapy
the presence of autoantibodies—primarily antinuclear antibodies was switched to methylprednisol alone.
(ANA) and anti-smooth muscle antibodies (SMA)—and histological Clinical outcome: AIH may be fluctuating or intermittent, and will relapse
findings suggestive of the condition. It is often associated with other after full recovery, which can progress to fibrosis/cirrhosis if not treated
autoimmune diseases (AID). promptly. AIH in older men response well to immunosuppressant
The aim of our study is to highlight the epidemiological and evolutionary therapy. Azathioprine requires close monitoring and measurement of
characteristics of these AID in the context of AIH TPMP levels if possible to prevent severe myelosuppression. , which
Method: This retrospective and descriptive study was carried out should be taken seriously.
over a five-year period (2018–2022). It included all patients followed Keywords: Autoimmune hepatitis; cholelithiasis; Bone marrow
for autoimmune hepatitis. Various parameters were assessed for each suppression
patient, and the diagnosis of associated autoimmune diseases was
established based on clinical evidence and specific test results. PP0622
Result: Among the 68 cases of autoimmune hepatitis (AIH), 39 patients
were associated with other autoimmune diseases, representing an Predictors of response to steroids in children and adolescents
overall prevalence of 57.35%. with treatment naïve Severe Autoimmune hepatitis
The mean age was 42.71 years (ranging from 20 to 81), with a female- SAMANNAY DAS1, Rajeev Khanna1, Vikrant Sood1, Bikrantbiharilal
to-male ratio of 38:1. Raghuvanshi1, Seema Alam1, Tamoghna Biswas1, Anmol Anmol1,
AIH was linked to one autoimmune disease in 58.97% of cases (n=23), Archana Rastogi1
two autoimmune diseases in 33.33% of cases (n=13), and three 1
Institute of liver and biliary sciences
autoimmune diseases in 7.69% of cases (n=3). Background: Steroids are indicated in severe autoimmune
Primary biliary cholangitis (PBC) was the most common association, hepatitis(AIH) to avert liver transplantation (LT). There is limited
observed in 58.97% of cases (n=23), followed by autoimmune paediatric data on prediction of response to steroids . The present
thyroiditis in 41% of cases (n=16). Sjögren’s syndrome was reported study was conducted to identify predictors of response to steroids in
in 10.65% of cases (n=4). Biermer’s disease was associated in 7.69% children and adolescents with severe AIH.
of cases (n=3). Psoriasis, celiac disease, or alopecia were described Method: In this retrospective analysis of prospectively maintained
in 5.12% of cases (n=2), in association with either PBC or autoimmune database, children and adolescents below 18 years from January
thyroiditis. Associations with primary sclerosing cholangitis (PSC) or 2011 to May 2024 with severe AIH who received steroids were
rheumatoid arthritis (RA) were described in only 2.56% of cases (n=1). enrolled. Outcome was studied in terms of response to steroids which
The presence of autoimmune diseases did not affect the progression was defined clinically in terms of survival with native liver (SNL) or not
of AIH. Treatment outcomes were favorable in 92.3% of cases (n=36), (LT or death) by Day 28.
with complete symptom resolution. Persistent symptoms were observed Result: Fifty children (31 females) with a median age of 11.9 (6.5, 15)
in 5.12% of cases (n=2), while the development of hepatocellular years were studied. There were 9 deaths and 3 LT, while 38 (76%)
carcinoma (HCC) occurred in only 2.56% of cases (n=1). had SNL. On Multivariate cox regression analysis, advance HE (HR
Conclusion: La recherche d’autres maladies du système dans 5.2, p=0.024) and SURFASA score (HR=1.2, p=0.029) predicted
les hépatites auto-immunes doit être systématique du fait de leur poor response. SURFASA (AUROC 0.872) and AAPS scores (AUROC
fréquence et de l’importance d’une prise en charge adéquate. 0.827) were found to be superior to CLIF-SOFA (AUROC 0.798) and
Dans notre étude, l’association à d’autres maladies auto-immunes a PELD (AUROC 0.773). A cut-off of SURFASA score of -2.3 differentiated
été notée dans 57.35 % des cas, dont les plus fréquentes par ordre patients with good or poor response.
décroissant sont : la CBP (58.97%), et la thyroïdite auto-immune (41%). Conclusion: Response to steroids is seen in three-fourths of children
Dans la majorité des cas, l’HAI était associée à une seule maladie and adolescents with severe AIH. Advance HE and SURFASA score
auto-immune (58.97%). predicted poor response. SURFASA score >/= -2.3 help in identifying
patients in urgent need for LT.
PP0621 Table and Figure:Figure 1.Predictors of severe AIH
Figure 2.Univariate and multivariate analysis of AIH
Case report: An elderly male autoimmune hepatitis with
cholelithiasis and azathioprine-related severe myelosuppression
was treated PP0623
JUN LI1, YANKAI YANG1, JIA LIAN1 Exploring the spectrum of autoimmune hepatitis: acute, acute-on-
1
Tianjin The Third Central Hospital chronic, and chronic forms
AIH may be fluctuating or intermittent, and will relapse after full Dan Zhou1, Yi Shen1, Jie Sun1, Li Yang1
recovery, and the liver histology is characterized by the interface 1
West China Hospital of Sichuan University
hepatitis and Inflammation of the portal canal area. Background: This article establishes comprehensive and stringent
History: A 77 years old male Patient has a history of coronary heart criteria to differentiate acute, acute-on-chronic, and chronic autoimmune
disease and cerebral infarction. He first hospitalized for febrile and hepatitis (AIH), and explores the clinical characteristics and treatment
jaundice.ALB 29.6 g/L, ALT365U/L, TBIL336.3 umo/L, ANA 1:1000, outcomes across these subtypes for potential differences.
IgG28.3 g/L, gallbladder neck stone was detected, so acute cholangitis Method: This study consecutively enrolled patients with a definitive
and AIH was diagnosed. Hepatoprotective agent and methylprednisol diagnosis of AIH from 2012 to 2024, all of whom underwent liver biopsy
were given IV and discontinued after liver function normalization. and received standardized immunosuppressive therapy. Patients were
He was rehospitalized 5 months later for elevated liver enzyme, rigorously stratified based on four dimensions: onset time (threshold of
ALT172U/L, TBIL 49.9umol/L, ANA 1:1000, IgG 35.4g/L, this time he 6 months), acute presentation (TB ≥ 5 mg/dL or ALT/AST ≥ 10×ULN),
was diagnosed with AIH and liver fibrosis. Liver enzyme was recover presence of imaging cirrhosis, and histological fibrosis staging (S = 1
after prednisone for 7 days. He uses oral prednisone combine with as the cutoff). We compared the clinical features and response profiles
AZA as maintenance therapy. among the three groups (A-AIH, AC-AIH and C-AIH).
6 months later, he got the third admission due to sore throat and high Result: In 235 patients (median age 54 years, 86.4% female), with
fever, ALB30.5g/L, ALT23U/L, TBIL23.9umol/L, WBC0.32×109/L, a median follow-up of 51.9 months (25th-75th percentile, 21.8-78.8),
NEU0.08×109/L, HGB96g/L,PLT28×109/L, RC0.23%. over half of the patients (54.5%) exhibited cirrhosis at the time of
Diagnostic and treatment : AZA-associated acute hematopoietic liver biopsy. The cumulative full biochemical remission (FBR) rates
arrest and acute pharyngitis were considered. AZA was discontinued. for patients with A-AIH, AC-AIH, and C-AIH were 92.0%, 75.7%, and
Granulocyte-Macrophage colony-stimulatingfactor (GM-CSF) were
59.5%, respectively, demonstrating significant comparability (p = Introduction:
0.002). The median FBR times for the three groups were 2.9 months, 5.5 Chronic hepatitis B (CHB) is a major public health concern, often
months and 14.5 months, respectively (p = 0.0016). At the conclusion managed with antiviral therapy to suppress viral replication. For
of follow-up, the liver-related mortality rates for the A-AIH, AC-AIH, and nucleos(t)ide analogue-experienced CHB patients who meet specific
C-AIH were 0%, 8.8%, and 16.2%, respectively. criteria, combination therapy with pegylated interferon can lead
Conclusion: Among patients presenting with acute manifestations to clinical cure in a subset of patients, but may occasionally lead
of AIH, only a minority were classified as having genuine acute AIH. to influenza-like syndrome, cytokine storm, and the induction of
There were discernible differences in the FBR rates among the three autoimmune diseases. This case report highlights the challenges and
groups, with the A-AIH group exhibiting the highest cumulative FBR successful management of such complications in a 49-year-old female
and the shortest median time to achieve FBR, while the C-AIH group patient, raising concerns about the potential for coexistence with
appeared to have the poorest response and the highest liver-related autoimmune hepatitis or interferon-induced autoimmune-like hepatitis.
mortality rate. Case Description:
A 49-year-old female with a 21-year history of HBsAg positivity was
diagnosed with abnormal liver function during a routine examination
PP0624
two years ago. Laboratory tests revealed HBV DNA low-level replication
PD-L1 Loading Dendritic Cell Significantly Attenuate Liver Injury and positive anti-HBe. Additionally, she tested positive for some
in AIH Mouse via Regulating Th1/Th2 Cytokines autoantibodies, including ANA and Ro-52. She received combination
Lisha Yang1, Siqi Sun1, Jun Liu1, Xuying Yin1, Heng Liu1, Huan Cai1, therapy with entecavir and pegylated interferon at a local hospital.
Shanyan Zhang1, Jueqing Gu1, Hongyu Jia2 During treatment, the patient experienced fatigue, fever, and
1
State Key Laboratory for Diagnosis and Treatment of Infectious headaches. Her alanine aminotransferase (ALT) levels fluctuated
Diseases, National Clinical Research Center for Infectious Diseases, between 60-100 U/L. Despite these symptoms, interferon injections
National Medical Center for Infectious Diseases, Collaborative continued for eight months. Subsequently, she developed anorexia,
Innovation Center for Diagnosis and Treatment of Infectious jaundice, abdominal distension, and lower limb edema. Laboratory
Diseases, The First Affiliated Hospital, Zhejiang University School of tests indicated a rapid deterioration in liver function, leading to a
Medicine, Research Units of Infectious disease and Microecology, diagnosis of hepatic failure. Standard internal medicine treatments
Chinese Academy of Medical Sciences, 2State Key Laboratory for were ineffective.
Diagnosis and Treatment of Infectious Diseases, National Clinical Upon referral to our hospital, after excluding contraindications,
Research Center for Infectious Diseases, National Medical Center for corticosteroids and azathioprine were added to her regimen.
Infectious Diseases, Collaborative Innovation Center for Diagnosis
Gradually, her liver and coagulation functions normalized. After one
and Treatment of Infectious Diseases, The First Affiliated Hospital,
year of corticosteroid and azathioprine therapy, her liver function
Zhejiang University School of Medicine, Research Units of Infectious
stabilized, and a liver biopsy showed no active HBV infection but mild-
disease and Microecology, Chinese Academy of Medical Sciences,
to-moderate interface hepatitis and advanced fibrosis. Considering
Branch of the First Affiliated Hospital of Zhejiang University
her medical history and imaging findings, autoimmune hepatitis or
Background: Autoimmune hepatitis (AIH) is a chronic autoimmune interferon-induced autoimmune-like hepatitis was suspected, requiring
liver disease, characterized by aminotransferase activity elevation, long-term follow-up for further confirmation.
hyper-gammaglobulinemia, high titers of circulating autoantibodies, This case underscores the importance of timely intervention with
and so on. Although most of AIH patients respond well to steroid corticosteroids when acute liver decompensation occurs. It also
therapy with or without azathioprine (AZA), progression and end-stage highlights the need to carefully select patients for interferon therapy in
liver disease occur in 10%–20% of patients. Therefore, developing CHB, perform screening for autoimmune diseases, provide thorough
much more effective and safe therapeutic approaches is still unmet risk information, and monitor both efficacy and adverse reactions
need. dynamically.
Method: In this study, we constructed adenovirus vectors Ad.PD-L1
and Ad.PD-L2, which express programmed death ligand-1 (PD-L1)
and PD-L2, respectively. In vitro experiments showed that Ad.PD-L1 PP0626
and Ad.PD-L2 transduction into DCs had no obvious effects on the Clinical observation on PBC-AIH overlap syndrome treated with
immune phenotypes of DCs, as well as the stimulation activities on methylprednisolone instead of prednisone acetate combined with
co-cultured T lymphocytes. Then, we successfully prepared gene Ursodeoxycholic Acid (UDCA)
modified mouse DCs vaccines, DCs/PD-L1 and DCs/PD-L2, by Zheng Huan Wei1, Meng Ping1, Li Yu Chan1
transfection with Ad.PD-L1 and Ad.PD-L2, respectively. C57BL6 1
Shijiazhuang hospital of Traditional Chinese Medicine
derived AIH mice were established by intraperitoneally immunized by
Objective: There are many difficulties in the treatment of autoimmune
hepatocyte antigens mixed with complete Freund’s Adjuvant on day 0
liver diseases, especially PBC-AIH overlap syndrome. The current
and 21. On day 28 and 35, DCs/PD-L1 and DCs/PD-L2 were injected
standard treatment is mainly immunomodulatory therapy such as
intravenously to treat mouse AIH model.
glucocorticoid and immunosuppressant combined with UDCA,
Result: We found that DCs/PD-L1 and DCs/PD-L2 immunization
but some patients have poor therapeutic responses. We observed
significantly reduced the levels of anti-LSP and GPT. Moreover, we
that three cases of poor responses treated with prednisone acetate
also explored that DCs/PD-L1 and DCs/PD-L2 immunization increased
combined with UDCA, and the ideal effects were obtained after
Th1 cytokines level, while down-regulated Th2 cytokines in peripheral
changed to methylprednisolone.
blood.
Methods: The ages of the three patients were 41, 59 and 76
Conclusion: DCs/PD-L1 and DCs/PD-L2 significantly attenuate liver
respectively, and all of them were women and were diagnosed as
injuries in mouse AIH model via down-regulating Th1 cytokines and
PBC-AIH overlap syndrome. Prednisone acetate combined with UDCA
increasing Th2 cytokines. Therefore, DCs/PD-L1 and DCs/PD-L2 had
was used as standard treatment. The initial dosages of prednisone
great promising to be developed to be effective approaches for AIH
acetate were all 40mg, and were reduced regulately to 15mg-20mg as
patients.
maintenance dosages. As a result, the biochemical responses of the
patients were poor or liver biochemical indexes rebounded. According
PP0625 to the formula that 4mg of methylprednisolone was equivalent to
Hepatic Failure in a Middle-aged Female with Chronic Hepatitis 5mg of prednisone acetate, the treatment of prednisone acetate
B: Possible Coexistence with Autoimmune Hepatitis or Interferon- were changed to methylprednisolone, and the treatment dosages of
induced Autoimmune-like Hepatitis methylprednisolone were 12-16mg.
Xinhua Ren1, Qi Wang1, Wen Xie1 Results: Liver biochemical indexes of the three patients who initiately
underwent prednisone acetate combined with UDCA treatment were
1
Beijing Ditan Hospital Capital Medical University
as follows: (ALT 115 U/L, AST 183 U/L, Alb 28.2 g/L, Glb 43.5 g/L,
ALP 149 U/L, GGT 60 U/L), (ALT 41.3 U/L, AST 37.6 U/L, Alb 42.3 been recognized for its potential role in regulating gut barrier function
g/L, Glb 38.1 g/L, ALP 58 U/L, GGT 31 U/L) and (ALT 43.3 U/L, AST and immune responses. This study aims to investigate the therapeutic
34.9 U/L, Alb 42.6 g/L, Glb 31.2 g/L, ALP 176 U/L, GGT 131 U/L). mechanisms of Akk in AIH, focusing on its interactions with T follicular
After changed to methylprednisolone, the liver biochemical indexes of helper (Tfh) cells, short-chain fatty acids (SCFAs) such as butyrate,
the three patients were improved obviously, and the results were as and the associated metabolic pathways.
follows: (ALT 45.4 U/L, AST 46.1 U/L, Alb 39.7 g/L, Glb 32.3 g/L, ALP Method: We conducted gut microbiota analysis using high-throughput
87.8 U/L, GGT 47.2 U/L), (ALT 15.5 U/L, AST 24.9 U/L, Alb 40 g/L, Glb sequencing in AIH patients and healthy controls to assess the
36.7 g/L, ALP 62 U/L, GGT 23 U/L) and (ALT 31.1 U/L, AST 23.9 U/L, abundance of Akk and its association with liver inflammation. In vitro
Alb 42.2 g/L, Glb 28.6 g/L, ALP 121 U/L, GGT 113 U/L). None of the and in vivo models were used to evaluate the effects of Akk on Tfh
three patients had any disease relapse, and no obvious side effects cell differentiation, gut permeability, and inflammatory responses.
were found. The role of butyrate, a key SCFA produced by Akk, in modulating Tfh
Conclusion: After changed to methylprednisolone, the patients of cell glycolysis via the G-protein coupled receptor 43 (GPR 43)/SIRT
PBC-AIH overlap syndrome with poor therapeutic responses who 3/mTOR pathway was further explored through molecular biology
underwent prednisone acetate combined with UDCA treatment can techniques and metabolic assays.
obviously improve the liver biochemical indexes, and the effects are Result: Our results demonstrated a significant reduction in Akk
remarkable. abundance in AIH patients, which correlated with increased gut
permeability and heightened liver inflammation. Supplementation with
Akk or butyrate led to the activation of the GPR 43/SIRT 3 signaling
PP0627
pathway, which in turn suppressed Tfh cell glycolysis. This metabolic
Consensus recommendations for histological criteria of shift reduced Tfh cell differentiation and inflammatory activity.
autoimmune hepatitis from the International AIH pathology Group: Further mechanistic analysis revealed that SIRT 3, a mitochondrial
Multicenter validation with Focus on Chronic Liver Diseases in deacetylase, mediated this effect by promoting a shift from glycolytic
China to oxidative phosphorylation pathways in Tfh cells, thereby dampening
Li Wang1,2, Yongfeng Yang1,2 their pro-inflammatory phenotype.
1
The Second Hospital of Nanjing, 2Nanjing University of Chinese Conclusion: Akkermansia muciniphila appears to play a protective
Medicine role in AIH by modulating the gut-liver axis. Through the production of
Background: The International AIH Pathology Group (IAIH-PG) put butyrate, Akk activates the GPR 43/SIRT 3 pathway, which suppresses
forward the new histological criteria of autoimmune hepatitis (AIH) in the abnormal differentiation of Tfh cells and reduces liver inflammation.
2022, which have not undergone adequate verification. In this study, This suggests that Akk or its metabolites could be targeted in future
we verified the applicability of the new histological criteria in the therapeutic strategies for AIH, offering novel insights into the treatment
population of Chinese patients with chronic liver disease, comparing of autoimmune liver diseases.
it with the simplified criteria.
Method: The gold standard for diagnosis in all patients was based PP0629
on histological findings, combined with clinical manifestations and
Therapeutic plasma exchange does not improve survival in
laboratory tests, and determined after a follow-up period of at least three
autoimmune hepatitis related Acute on Chronic liver failure- An
years. A total of 640 patients with various chronic liver diseases from
analysis from AARC database
multiple centers underwent scoring using the new histological criteria
and the simplified criteria, comparing their diagnostic performance. Sunil Taneja1, NIpun Verma1, Ajay Duseja1, Shiv Sarin2, Rakhi
Result: In this study, the new histological criteria showed a sensitivity of Maiwall2, Ashok Choudhury2, Vinod Arora2, Mohamed Rela3, Dinesh
73.6% and 100% for likely and possible AIH, with specificities of 100% Jothimani3, Mamun Al Mahtab4, Shahinul Alam5, Saeed Hamid6, Amna
and 69.0%, respectively. The coincidence rates of possible AIH for the Subhan Butt6, Wasim Jafri6, Akash Shukla7, Manoj Sahu8, Sombat
new histological criteria, simplified histological criteria, and simplified Treeprasertsuk9, Kessarin Thanapirom10, Hasmik Ghazinyan11, Abdul
score were 81.7%, 72.8%, and 69.7%, respectively. For likely AIH, the Kadir Dökmeci12, Zaigham Abbas13, P N Rao14, Anand Kulkarni14,
rates were 89.2%, 75.9%, and 65.6%, respectively. Based on the new Mithun Sharma14, Anil Arora15, Ashish Kumar15, Sudhir Maharishi16,
histological criteria, all patients with AIH were correctly diagnosed. Sargsyan Violeta17, Saurabh Mukewar18, Ruveena Bhavani19, Sunil
Specifically, 73.6% were diagnosed with likely AIH, and 26.4% were Dadhich20, Sanjeev Sachdeva21, Joy Vargese22, Gupse Adali23
possible AIH. Additionally, the simplified histological criteria achieved
1
Postgraduate Institute of Medical Education & Research,
a diagnosis rate of 98.6% for AIH, while the simplified score could only Chandigarh, India, 2Institute of Liver & Biliary Sciences, New Delhi,
diagnose 53.8% of AIH. India, 3Dr. Rela Institute, Chennai (India), 4Bangabandhu Sheikh Mujib
Conclusion: Compared with the simplified score and simplified Medical University , 5Crescent Gastro liver and General Hospital,
Dhaka, Bangladesh, 6Department of Medicine, Aga Khan University
histological criteria, the sensitivity and specificity of the new histological
Hospital, Karachi, Pakistan, 7Department of Gastroenterology,
criteria for AIH were significantly improved. The results indicate that
Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak
the new histological criteria exhibit high sensitivity and specificity for
Municipal Medical College, (LTMMC), Mumbai, India., 8Department
diagnosing AIH in China.
of Gastroenterology and Hepatology Sciences, IMS & SUM
Table and Figure:Figure 1.Figure 1.Details of the assessment of new Hospital, Bhubaneswar, Odisha, India, 9Department of Medicine,
histological criteria for the diagnosis of AIH. Chulalongkorn University, Bangkok, Thailand, 10Department of
Figure 2.Figure 2.ROC curves for the new histological criteria (AUC: Medicine, Chulalongkorn University, 11Department of Hepatology,
0.959), the simplified histological criteria (AUC: 0.858), and the Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia.,
simplified score (AUC: 0.784) in 518 patients. 1
2Department of Medicine, Ankara University School of Medicine,
Ankara, Turkey, 13Dr. Ziauddin University Hospital Clifton Karachi,
PP0628
1
4Asian Institute of Gastroenterology, Hyderabad, India, 15Department
of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New
Mechanisms of Akkermansia muciniphila in the Treatment of Delhi, India, 16SMS, Jaipur, India, 17Violeta Medical Centre, Armenia,
Autoimmune Hepatitis 1
8Midas Multispeciallity Hospital, Nagpur, India, 19University of
Chenchen Wang1, 刘杨 Malaya Medical Centre, Malaysia, 20SNMC, Jodhpur, India, 21GB Pant
1
山西中医药大学 Hospital, New Delhi, India, 22Gleneagles Global Health City, Chennai,
Background: Autoimmune hepatitis (AIH) is a chronic liver disease India, 23Istanbul Umraniye Training and Research Hospital, Istanbul
characterized by immune-mediated inflammation, and its pathogenesis Background: Therapeutic plasma exchange (TPE) is a well-
is closely linked to alterations in the gut microbiota. Akkermansia established treatment modality in management of acute-on-chronic
muciniphila (Akk), a prominent member of the gut microbiome, has liver failure (ACLF) patients, but its efficacy in treating autoimmune
hepatitis (AIH) related ACLF patients is yet to be established. UDCA are crucial for these patients to improve clinical outcomes and
Aim: To assess the efficacy of TPE in improving outcome in patients prevent disease progression.
with autoimmune hepatitis related ACLF
Method: Eighty nine autoimmune hepatitis related ACLF patients ( 35
PP0631
cases and 54 controls) were enrolled in the study. Cases underwent
standard volume TPE along with Standard Medical Therapy (SMT) AUTOIMMUNE HEPATITIS PRESENTING AS IRON OVERLOAD IN
while the controls were on SMT alone. The change in laboratory AN ADULT MALE: A DIAGNOSTIC CHALLENGE
parameters, clinical severity scores along with mortality rates were Ferdinand Maitim Anzo1, JoseGuillain E Cataluña1
noted and compared between the two groups. 1
Institute of Digestive and Liver Diseases, St. Luke’s Medical Center
Result: Results: The mean age of patients included in the study Quezon City, Philippines
was 40.2±14.1 years, predominantly females, 59 (66.3%). The acute BACKGROUND: Autoimmune hepatitis (AIH) is a rare, chronic liver
precipitant of ACLF was AIH flare in 43 (48.3%), HBV in 14 (15.7%), disease that affects individuals of all ages and ethnic groups, with
drug induced liver injury (DILI) in 14 (15.7%), HEV in 6 (6.7%), a higher prevalence in females. Seronegative AIH is even rarer,
combination of AIH and DILI in 5 (5.6%) and unknown in 7(7.8%). A total accounting for only 7% of cases. Diagnosing AIH can be difficult
of 34 patients underwent standard volume TPE . The MELD score was due to its overlap with other conditions, such hemochromatosis. Liver
significantly reduced at day 7 in the TPE group, (P < 0.05). However, biopsy is essential for histopathologic confirmation.
there was no statistically significant difference in AST, bilirubin, Child CASE PRESENTATION: A 58-year-old male with hypertension and
Pugh score, MELD Na and AARC score at day 7 in the two groups. diabetes presented with persistently elevated liver enzymes for
(Table 1) There was no significant difference in the survival between three months and developed jaundice and dark-colored urine but no
the TPE and SMT group (p>0.05). The mean survival in the TPE group abdominal pain or fever. Laboratory tests revealed elevated AST (172
was 19.7± 2.44 versus 18.1± 1.73 days (p=0.54) in SMT group. The U/L), ALT (248 U/L), alkaline phosphatase (232 U/L) and total bilirubin
most common cause of death was sepsis in 21(23.6%) patients. On (2.47 mg/dL), while albumin level (3.54 g/dL) is normal. Ultrasound
cox regression analysis strongest predictors of survival were baseline showed fatty liver without biliary obstruction. Abdominal MRI suggested
AARC, MELD score and gender of patient (p<0.001). the possibility of hemochromatosis. Iron studies showed elevated
Conclusion: TPE is not effective in improving outcome in patients with iron (200 µg/dL), TIBC (300 µg/dL), and ferritin (3,182 ng/mL), with a
autoimmune related ACLF, though there is improvement in the disease transferrin saturation of 60%. Other findings included elevated serum
severity score at day 7 IgG (312 IU/mL) and GGT (225 U/L). ANA, AMA, and ASMA were
Table and Figure:Figure 1.Changes in parameters at day 7 in PLEX negative, while the direct antiglobulin test was positive. Viral hepatitis
versus SMT group panel was negative. Liver elastography indicated cirrhosis (20.41 kPa,
F4). A liver biopsy revealed chronic hepatitis with interface activity,
PP0630 moderate lobular inflammation, mild steatosis, periportal fibrosis
with focal septa, and negative Perl’s stain in the hepatocytes. The
Autoimmune Hepatitis - Primary Biliary Cirrhosis (AIH-PBC)
HFE gene mutation test was normal. These laboratory and histologic
Overlap Syndrome Unmasked during Anti-Tuberculosis Therapy
findings confirmed the diagnosis of autoimmune hepatitis. The patient
Tristan Paulo Madrigal1, Katrina Austero2, Mara Teresa Panlilio1 was started on steroid therapy, achieving clinical and biochemical
1
Division of Gastroenterology, Department of Medicine, Philippine remission, including normalization of iron saturation levels. He is
General Hospital, 2Department of Laboratories, Philippine General currently maintained on mycophenolate mofetil for long-term remission.
Hospital CONCLUSION: AIH can present with a variety of clinical symptoms,
Background: Autoimmune hepatitis - primary biliary cirrhosis (AIH- including unexplained liver dysfunction and elevated iron levels,
PBC) overlap syndrome represents a significant yet underrecognized making it challenging to distinguish from iron overload syndrome or
variant of autoimmune liver disorders, accounting for less than 10% of hemochromatosis. Prompt diagnosis and treatment with steroids
cases. Patients present with a mixed hepatocellular and cholestatic achieves biochemical remission, including normalization of iron
pattern of liver injury. Due to its non-specific clinical and laboratory overload.
features, diagnosis is frequently delayed, particularly when drug- Key words: Autoimmune hepatitis; Iron overload syndrome;
induced liver injury (DILI) is being considered, as it exhibits a similar Hemochromatosis; Case report
pattern of liver test abnormalities.
Case Presentation: A 22-year-old female presented with jaundice and
PP0632
pruritus. Four months prior to this consultation, she was diagnosed
with pulmonary tuberculosis and was started on anti-tuberculosis Diagnostic potential of Ribosomal protein L30 in Primary Biliary
therapy (ATT). Three weeks into treatment, she developed jaundice Cholangitis
and generalized pruritus, prompting discontinuation of the ATT. She Zhiyu Zeng1,2,3, Dongliang Li3, Xiaoyong Zhang4
was initially given silymarin and phospholipids, but her symptoms 1
State Key Laboratory of Organ Failure Research, Guangdong
did not improve. She eventually consulted at our institution due to Provincial Key Laboratory of Viral Hepatitis Research, Department of
worsening symptoms and liver tests. Initial laboratory investigations Infectious Diseases, Nanfang Hospital, Southern Medical University,
revealed a mixed hepatocellular and cholestatic pattern of liver injury. Guangzhou 510515, China, 2Key Laboratory of Infectious Diseases
Due to the chronicity of symptoms even after withholding the offending Research in South China, Ministry of Education; Guangdong
drug, an underlying chronic liver disease was suspected. Further Provincial Clinical Research Center for Viral Hepatitis; Guangdong
investigations showed a normal liver and biliary tree on magnetic Institute of Hepatology, Guangzhou 510515, China, 3Department
resonance cholangiopancreatography (MRCP), a positive anti-nuclear of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support
antibody (ANA), while anti-mitochondrial antibody (AMA), anti-liver Force, Fuzhou 350025, China, 4Nanfang Hospital, Southern Medical
kidney microsomal type 1 (anti-LKM 1), and anti-smooth muscle University
antibody (anti-SMA) were all negative. Her liver biopsy revealed portal Background: Diagnosis of primary biliary cholangitis (PBC) remains
inflammation, ductular reaction, and interface hepatitis. She was then difficult, especially since autoantibody-negative cases of PBC may
treated with ursodeoxycholic acid (UDCA) and prednisone. Within be underreported, complicating detection and suggesting potentially
weeks of starting these medications, she showed clinical improvement, more severe clinical presentations. This underscores an urgent need
including resolution of jaundice and improvement in liver function tests. to identify additional plasma biomarkers for non-invasive diagnostic
Conclusion: AIH-PBC overlap syndrome poses a diagnostic methods.
challenge, particularly when it mimics DILI. It highlights the importance Method: We conducted an extensive cohort study and utilized
of excluding a chronic liver disease in cases of persistent liver injury, immunome protein array analysis to identify potential biomarkers for
even after discontinuation of a suspected offending drug. Early PBC diagnosis. Subsequently, we validated the predictive capability
recognition and timely initiation of immunosuppressive therapy and of the ribosomal protein L30 (RPL30) antibody, a novel candidate
biomarker, through an enzyme-linked immunosorbent assay (ELISA) emphasize family support, leading to higher social function scores
and examined its association with clinical features. compared to individualistic cultures, where independence is prioritized.
Result: In our study, we detected RPL30 exhibited the highest Conclusion: The PBC-40 scale is a useful tool for assessing HRQoL in
penetrance fold change difference among 25 self-antigens prevalent PBC patients, but its interpretation varies across medical, psychological,
in PBC utilizing the immunome protein array of Sengenics’ KREX™. and cultural contexts. Hepatologists emphasize the need for biomarker
The analysis of anti-RPL30 optical density (OD) values using a receiver integration to improve objectivity, while psychologists highlight the
operating characteristic curve resulted in an area under the curve of importance of mental health evaluation to enhance accuracy. Cultural
0.807, with an optimal cut-off value of 0.0711, demonstrating both differences significantly influence how patients respond to the scale,
specificity and sensitivity at 80%. Notably, 16/20 PBC individuals indicating a need for localized adaptations to ensure reliability and
tested positive for anti-RPL30, compared to 4/20 healthy controls relevance across diverse populations.
(P<0.001). Expanding to a larger PBC cohort, 49/63 (77.78%) tested Table and Figure:Figure 1.Comparison of PBC-40 Scale Evaluation
positive for RPL30 compared to 6/38 (15.79%) controls (P<0.0001). Across Disciplines and Cultures
The proportion of anti-RPL30 (0.0711<OD value <0.1332) in the PBC
group, was significantly higher than control groups. Additionally,
PP0634
significant differences were observed between anti-RPL30 positivity
rates in specific autoantibody-negative PBC subgroups and controls. A Worse subgroup of PBC: jaundice in patients with ductopenia
The increase of alkaline phosphatase/ gamma-glutamyl transpeptidase Tingting Lv1, Weijia Duan1, Xinyan Zhao1, Jidong JIA1
level along with either anti-RPL30 or other autoantibodies elevated 1
Department of Liver Research Center, Beijing Friendship Hospital,
the diagnosis rate of PBC from 61.29% to 79%. Anti-RPL30 show a Capital Medical University
high positive rate in AMA/AMA-2/anti-gp210/anti-Sp100 negative PBC Background: Objective: Hyperbilirubinemia is associated with poor
(96%,90.9%,91.5%,90.2%) .Correlation analysis of anti-RPL30 OD prognosis in primary biliary cholangitis (PBC), yet not all PBC patients
values with clinical data of PBC patients revealed a positive association with ductopenia (bile duct loss >50%) experience prolonged jaundice.
with the International Normalized Ratio and the Model for End-Stage This study aims to clarify the clinicopathological features, prognosis,
Liver Disease score (P<0.05). and underlying mechanisms of icteric PBC patients with ductopenia.
Conclusion: Our study highlights the potential of anti-RPL30 as a Method: Methods: This retrospective study included PBC patients
promising biomarker for diagnosing PBC, particularly in autoantibody- with ductopenia confirmed by liver biopsy. Demographic and
negative cases. clinicopathological data, treatment response, and long-term prognosis
were recorded. Immunohistochemical staining for bile salt export
PP0633 pump (BSEP) and multidrug resistance-associated protein 2 (MRP2)
was performed on ductopenic patients with and without jaundice.
Cross-Disciplinary and Cross-Cultural Evaluation of the PBC-40
Result: Results: A total of 265 patients underwent liver biopsy, of
Scale
which 77 had ductopenia (18 with jaundice and 59 without). Patients
Dingrong Dong1, Hongli Liu2 with ductopenia and jaundice exhibited higher levels of total bilirubin
1
The Third People‘s Hospital of Xining City, 2The Second Hospital of (TBIL), total bile acids (TBA), cholesterol (CHOL), and triglycerides
Nanjing, Southeast University (TG) compared to those without jaundice, while levels of ALT, AST, ALP,
Background: The PBC-40 scale is widely used to assess the health- and GGT were similar between the groups (all P < 0.05). Ductopenic
related quality of life (HRQoL) in patients with primary biliary cholangitis PBC patients with jaundice had significantly lower survival rates than
(PBC). However, its relevance may differ across medical specialties those without jaundice (P < 0.05). There was no significant difference in
and cultural backgrounds. This study presents an evaluation by a UDCA response between the two groups based on Paris II, Barcelona,
hepatologist and a psychologist, highlighting differences in their and Rotterdam criteria (P > 0.05). The expression of MRP2, rather than
perspectives on the scale and exploring how patients from different BSEP, was significantly lower in patients with jaundice compared to
cultural backgrounds interpret and respond to its items. those without (P < 0.05).
Method: A hepatologist with expertise in psychology and a psychologist Conclusion: Conclusion: Jaundice in PBC does not follow the same
with clinical experience independently reviewed the PBC-40 scale and progression as ductopenia. Ductopenic PBC patients with jaundice
compared their assessments. The scale’s suitability for evaluating exhibit a similarly poor treatment response but worse prognosis
fatigue, cognitive function, social function, and emotional well-being compared to those without jaundice. Reduced bile salt transporter
was analyzed from both medical and psychological perspectives. expression likely contributes to the pathogenesis.
Differences in how patients from different cultural backgrounds Table and Figure:Figure 1.Demographic data, treatment response and
interpret and score the PBC-40 were explored to assess its cultural clincal outcome among PBC patients.
adaptability. Figure 2.MRP2 Expression among groups
Result: 1. Hepatology Perspective
Fatigue assessment is clinically relevant but does not correlate well
PP0635
with objective biomarkers. Pruritus and general health items align with
physiological markers such as liver function and inflammation levels. Global Epidemiology of Primary Biliary Cholangitis: A Systematic
The scale does not differentiate between physical and psychological Review and Meta-Analysis
fatigue, limiting its precision. Jarell Tan1, Ambrose Chung2, Jing Hong Loo3, Ethan Quek1, Sagar
2. Psychological Perspective Sharma1, Corrine Lee Singh1, Jacqueline Yap2, Wei Xuan Tay3, Yu
Emotional and social function items are highly subjective, influenced Jun Wong3
by psychological resilience. 1
Yong Loo Lin School of Medicine, National University of Singapore,
Anxiety and depression may exaggerate fatigue scores, affecting the 2
Duke-NUS Medical School, 3Department of Gastroenterology &
scale’s reliability. Hepatology, Changi General Hospital
The scale lacks measures for coping strategies and social support, Background: Primary biliary cholangitis (PBC) is an uncommon
which are crucial for psychological well-being. autoimmune liver disease with significant geographic variability
3. Cross-Cultural Differences in prevalence. We aim to comprehensively examine the temporal,
1)Fatigue Reporting: Patients from individualistic cultures are more likely regional, and global trends in the incidence and prevalence of PBC
to openly express fatigue, whereas patients from collectivist cultures from 1979 to 2023.
may underreport it due to cultural norms emphasizing endurance.2) Method: We systematically searched three electronic databases
Emotional Expression: Patients from individualistic cultures verbalize from inception to 20th August 2024 to include all studies reporting
psychological distress more frequently, while those from collectivist the incidence or prevalence of PBC. The outcomes of interest were
cultures may express distress through physical symptoms such as the prevalence and incidence of PBC. Subgroup analysis was
headaches or digestive issues.3)Social Function: Collectivist cultures
performed by study type, study period, method of diagnosis, gender, Conclusion: In PBC, the disruption of intrahepatic immune status may
geographical region, latitude, and Human Development Index affect the glucose metabolism balance of liver cells through TXNIP,
(HDI). The temporal trend of PBC prevalence and incidence was thereby shaping a local high glucose microenvironment and further
analyzed using meta-regression. The study protocol was registered in exacerbating intrahepatic immune disorders and inflammation levels.
PROSPERO (CRD42024595102).
Result: A total of 79 eligible studies were included, involving more
PP0637
than 361 million participants and 140,259 patients with Primary Biliary
Cholangitis (PBC) across 29 countries and 5 continents. The global ANALYSIS OF EPIDEMIOLOGY, THERAPY OF PRIMARY BILIARY
pooled prevalence of PBC was 18.1 cases per 100,000 people (95% CHOLANGITIS AND OVERLAP SYNDROME
CI: 14.5-22.2, I²=97%, 57 studies) among studies with low risk of bias. Lahana Ravoori1, Elena Kuharewa1, Anastasiya Zhuravleva1, Olga
The incidence rate was 1.79 cases per 100,000 person-years (95% CI: Tarasova1
1.35-2.29). PBC prevalence was higher among patients of the female 1
Peoples‘ Friendship University of Russia named after Patrice
sex, older age, and first-degree relatives, but was not influenced by Lumumba
countries’ latitude, HDI or diagnostic method of PBC. While the pooled Background: Primary biliary cholangitis (PBC) is an autoimmune
incidence rate remained stable, temporal analysis showed that the cholestatic liver disease characterized by biliary destruction
pooled prevalence of PBC has increased over the years. and intrahepatic cholestasis. Overlap syndrome of autoimmune
Conclusion: The rising prevalence of PBC represents a growing hepatitis(AH) and PBC is typically defined as concomitant or serial
healthcare burden. Our findings call for a re-evaluation of resources presentation with clinical features of both of these 2 different diseases.
required for early diagnosis and treatment to prevent complications in Diagnosis requires biochemical alteration, immunological studies and
patients with PBC. biopsy and the exclusion of other causes such as viral, toxic, metabolic
Table and Figure:Figure 1.Global Prevalence of Primary Biliary and hereditary.
Cholangitis Method: 36 patients were selected randomly into the study at Liver
Figure 2.Global Incidence of Primary Biliary Cholangitis Research Centre, RUDN University to evaluate prevalence of diagnosis
of overlap syndrome with laboratory analysis of Antinuclear antibody
PP0636 (ANA), Aspartate transaminase (AST), Alanine transaminase (ALT),
Gamma Glutamine transferase (GGT), anti smooth muscle antibody
Clinical Significance and Potential Mechanisms of Impaired
(ASMA) and choice of treatment in overlap syndrome and PBC.
Glucose Tolerance in Primary Biliary Cholangitis
Patients were studied separately on the basis of the age of diagnosis
Yinan Hu1, Ying Han1, Yulong Shang1 and patients gender with their connection with PBC and overlap
1
Air Force Medical University syndrome.
Background: Primary biliary cholangitis (PBC) is a type of autoimmune Result: Out of 36 patients, 47.2% were diagnosed with isolated PBC
mediated cholestatic liver disease. The incidence rate of PBC is and 52.7% were diagnosed with overlap syndrome. All the patients
increasing, and it is becoming an important cause of the global burden with the diagnosis of isolated PBC were positive for anti mitochondrial
of chronic liver diseases. The liver is an important organ that regulates antibodies (AMA), for the diagnosis of overlap syndrome out 52.7%, all
the homeostasis of glucose metabolism. It is unclear whether the were positive for abnormal increase in ALT, AST and GGT, 5.2% were
persistent abnormal immune activation and inflammatory state in PBC positive for ASMA, 5.2% were positive for increase in IgG, 84.2% were
will affect the balance of liver glucose metabolism. This study aims to positive for ANA. Epidemiological statistics show all the patients out
analyze the incidence and clinical significance of glucose metabolism of 36 were diagnosed after 50 years of age/ postmenopausal, 97.2%
disorders in PBC, and explore potential regulatory mechanisms. patients were females. Apart from choledeocholic acid for PBC, 68.4%
Method: The clinical analysis was conducted based on a retrospective of overlap syndrome were treated with steroids, 21.04% with combined
case-control study. 2-OA-BSA was used to induce PBC-like liver treatment with steroids and azathioprine, 10.5% with azathioprine
alterations in mice. RT-PCR, western blotting, immunohistochemical alone.
staining and flow cytometry were used to detect the key molecules Conclusion: Laboratory results will show AMA positive in patients
associated with liver inflammation and glucose metabolism. with PBC. There is a 50% chance of diagnosing PBC with concurrent
Result: A total of 130 PBC patients were included, and 26% (34/130) AH(overlap syndrome)as an initial diagnosis or follow up diagnosis.
of PBC patients were found to present impaired glucose tolerance Patients with the diagnosing of PBC with abnormal ALT, AST should
(IGT). This proportion is significantly higher than the global adult IGT be further investigated for ANA, ASMA for the diagnosing of overlap
prevalence rate (10.6%). Further comparison showed that the insulin Syndrome. Females are consistent and have strong relation (P
resistance index (TyG index) was significantly higher in PBC patients significant < 0.05) for the development of PBC and overlap syndrome
who did not respond to UDCA. TyG was an independent risk factor for in comparison with males, primarily affecting at the age of fifth or
poor biochemical response to UDCA in PBC patients. sixth decade of life. Ursodeoxycholic acid remains to be an effective
Analysis of transcriptome data of PBC patients showed that drug for PBC, While for the treatment for overlap syndrome is steroids
thioredoxin-interacting protein (TXNIP) was up-regulated in liver followed by combination of steroids with azathioprine or azathioprine
tissues and peripheral blood of PBC patients, with higher expression alone.
levels in those with poor long-term prognosis. The expression levels
of TXNIP were higher in PBC liver tissues with IGT. It was showed that
PP0638
PBC mice manifested with abnormal glucose tolerance. In addition,
an increase in TXNIP was observed in the liver of PBC mice, while Efficacy and Safety of Seladelpar in Patients With Primary Biliary
the expression of membrane-located GLUT2, a protein mediated the Cholangitis and Compensated Cirrhosis in the Phase 3 Placebo-
transfer of glucose across the plasma membrane of hepatocytes, was Controlled RESPONSE Trial
decreased. Knockdown of TXNIP was found to result in the increased Alejandra Villamil1, Ziad Younes2, Christopher L Bowlus3, John M
GLUT2 but reduced expression of inflammation markers, including Vierling4, Adam Vasura5, Andrea Galli6, Mordechai Rabinovitz7,
NLRP3, NF-κ B, and PPAR-α, indicating the roles of TXNIP in liver Frederik Nevens8,9, Susheela Carroll10, Ke Yang10, Linda Wu10, Daria
glucose metabolism and inflammation. B Crittenden10, Charles A McWherter11, Eric J Lawitz12
The immunohistochemical results indicated the presence of a 1
The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires,
significant infiltration of macrophages in the liver of both PBC patients 2
Gastro One, 3University of California Davis School of Medicine,
and mice. Human derived macrophage lines (THP-1) and mouse
4
Baylor College of Medicine, 5Department of Gastroenterology,
macrophage lines (RAW264.3) were treated with media containing University Hospital Ostrava, 6Gastroenterologia Clinica, Azienda
5.5mM, 25mM, and 50mM glucose concentrations, and it was found Ospedaliero Universitaria Careggi, 7University of Pittsburgh,
that under high glucose conditions, macrophage activation related
8
Hepatology and Liver Transplantation, University Hospitals KU
markers were significantly elevated. Leuven, 9Center of European Reference Network (ERN) RARE-LIVER,
1
0Gilead Sciences, Inc., 11CymaBay Therapeutics, Inc., 12Texas Liver blood samples were collected and sent for metabonomic analysis.
Institute, University of Texas Health San Antonio Result: The biochemical response rate in the combined treatment
Background: Patients with primary biliary cholangitis (PBC) and group was significantly better than that in the UDCA treatment group
cirrhosis have a high unmet need for second-line therapies. In (81.4% vs 64.3%, P=0.048). After one-year follow-up, the level of ALP
the Phase 3 placebo-controlled RESPONSE trial (NCT04620733), in the combined treatment group was continuously lower than that in
seladelpar, a first-in-class delpar (selective peroxisome proliferator– the UDCA treatment group, and the normalization rate of ALP was also
activated receptor [PPAR] delta agonist), significantly improved significantly higher in the combined treatment group. During the entire
biomarkers of cholestasis in patients with PBC over 12 months treatment, the levels of transaminase and creatinine in the combined
compared with placebo. In a prespecified subgroup analysis, a higher treatment group were still within the normal range, and the incidence
percentage of patients with cirrhosis met the composite biochemical of liver related adverse events was not increased.
endpoint (alkaline phosphatase [ALP] <1.67 × upper limit of normal Metabonomic analysis of plasma samples showed that the change
[ULN], ALP decrease ≥15%, and total bilirubin ≤ULN) in the seladelpar of glycerophospholipid metabolic pathway in PBC patients was the
arm (38.9%) vs the placebo arm (22.2%). We now report data on most active compared with healthy people. Longitudinal comparison
additional biochemical results and safety in patients with or without of the characteristics of plasma metabolome showed that, the most
cirrhosis in RESPONSE. significant metabolic changes occurred after 1 month of treatment.
Method: Patients with PBC with an inadequate response or intolerance In particular, in patients receiving combined therapy, the metabolic
to ursodeoxycholic acid, ALP ≥1.67 × ULN, and total bilirubin ≤2 × ULN pathway of glycerophospholipid changed most significantly. In
received daily oral seladelpar 10 mg or placebo (2:1 randomization) addition, it was found that the most significant metabolic pathway was
for 12 months. Cirrhosis was defined by medical history, liver biopsy, still glycerophospholipid metabolism in patients with ALP normalization
transient elastography (>16.9 kPa), laboratory findings, and/or receiving combined treatment, while the longitudinal metabolic
radiological features. Changes in ALP, gamma glutamyl transferase characteristics of patients without ALP normalization had no such
(GGT), and alanine aminotransferase (ALT) were assessed in patients changes.
with and without cirrhosis, as was safety. Conclusion: The initial combination of fenofibrate can effectively
Result: Of 193 enrolled patients, 27 (14.0%) had Child-Pugh class improve the biochemical response rate and has good long-term safety.
A compensated cirrhosis at baseline: 18 received seladelpar and Glycerophospholipid metabolic pathway might be the key in the add-
9 received placebo. Patients with cirrhosis had higher mean liver on effects of fenofibrate.
stiffness (18.8 kPa), ALP (345.8 U/L), and total bilirubin (0.97 mg/dL) at
baseline vs those without cirrhosis (7.9 kPa, 309.2 U/L, and 0.72 mg/ PP0640
dL, respectively). At month 12, the mean change from baseline in ALP
Long-Term Efficacy and Safety of Open-Label Seladelpar
for patients with cirrhosis on seladelpar was −121.4 U/L vs 23.2 U/L
Treatment in Patients With Primary Biliary Cholangitis: Pooled
for placebo, and −134.8 U/L for seladelpar vs −18.0 U/L for placebo
Interim Results for up to 3 Years From the ASSURE Study
in patients without cirrhosis. Greater numerical decreases in GGT and
Eric J Lawitz1, Palak J Trivedi2, Kris V Kowdley3, Stuart C Gordon4,
ALT were observed with seladelpar vs placebo regardless of cirrhosis
Christopher L Bowlus5, Maria Carlota Londono6, Gideon M
status. The types and incidences of adverse events with seladelpar
Hirschfield7, Aliya Gulamhusein7, Linda Wu8, Daria B Crittenden8,
were generally similar to those with placebo in patients with and without
Shuqiong Zhuo9, Carrie Heusner9, Cynthia Levy10
cirrhosis. No patients with cirrhosis discontinued seladelpar due to
adverse events. Elevations in ALT or aspartate aminotransferase of >3
1
Texas Liver Institute, University of Texas Health San Antonio,
× ULN occurred in 1 patient (5.6%) with cirrhosis on seladelpar vs 2
2
National Institute for Health Research Birmingham Biomedical
patients (22.2%) on placebo. Research Centre, Centre for Liver and Gastrointestinal Research,
College of Medical and Dental Sciences, University of Birmingham,
Conclusion: Seladelpar reduced biomarkers of cholestasis and liver 3
Liver Institute Northwest, 4Division of Hepatology, Henry Ford
injury in patients with PBC with compensated cirrhosis and in patients
Hospital, Wayne State University School of Medicine, 5Division of
without cirrhosis. Seladelpar was overall safe and well tolerated in
Gastroenterology and Hepatology, University of California Davis
patients with and without cirrhosis.
School of Medicine, 6Liver Unit, Hospital Clínic Barcelona, Instituto
Table and Figure:Figure 1.Changes in ALP in Patients With PBC With de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro
or Without Cirrhosis at Baseline Treated With Seladelpar or Placebo in de Investigación Biomédica en Red de Enfermedades Hepáticas
the RESPONSE Trial y Digestivas (CIBEREHD), 7Division of Gastroenterology and
Hepatology, Toronto Centre for Liver Disease, University of Toronto,
PP0639
8
Gilead Sciences, Inc., 9CymaBay Therapeutics, Inc., 10Division of
Digestive Health and Liver Diseases, University of Miami School of
Effectiveness and Safety of Fenofibrate in Treatment-Naive
Medicine
Patients With Primary Biliary Cholangitis
Background: ASSURE (NCT03301506) is an ongoing, open-label,
Yansheng Liu1, Yulong Shang1, Ying HAN1
long-term, Phase 3 trial of seladelpar—a first-in-class delpar (selective
1
Air Force Medical University
PPARδ agonist)—in patients (pts) with primary biliary cholangitis rolling
Background: Primary biliary cholangitis (PBC) is an autoimmune over from the Phase 3, placebo-controlled, registrational RESPONSE
mediated cholestatic liver disease. Ursodeoxycholic acid (UDCA) is trial (NCT04620733) or with prior participation in legacy trials (Phase 3
the only approved first-line treatment for PBC, but there are still 30%- ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-
40% of patients with poor response to UDCA and poor long-term 31731 [NCT03301506], CB8025-21838 [NCT04950764]). The parent
prognosis. Fenofibrate, as a peroxisome proliferator activated receptor studies required an inadequate response or intolerance to first-line
(PPAR) agonist, can alleviate cholestasis through a variety of ways, ursodeoxycholic acid. Here, we report pooled interim efficacy and
but its therapeutic effect on PBC, especially the long-term therapeutic safety for all pts in ASSURE.
effect, is lack of clear evidence. Therefore, this study aims to study the Method: Using a data cutoff of January 31, 2024, pt exposure to
long-term efficacy and safety of fenofibrate in the treatment of PBC. seladelpar in ASSURE (including exposure in pts who were randomized
Method: A total of 117 newly diagnosed PBC patients from 2016 to to the active treatment arm in RESPONSE) was analyzed. Key efficacy
2021 were randomly assigned to the UDCA standard treatment group endpoints included composite biochemical response (CBR; alkaline
and the UDCA+fenofibrate (200mg/day) combined treatment group phosphatase [ALP] <1.67× upper limit of normal [ULN], ALP decrease
according to 1:1. The blood routine, liver and kidney function, liver ≥15%, and total bilirubin [TB] ≤ULN) and ALP normalization. Pruritus
hardness and other indicators were monitored at 1 month, 3 months, was recorded using a numeric rating scale (NRS; 0–10) collected
6 months, 9 months and 12 months after the start of treatment. After daily through month (M) 6; change from baseline (BL) was assessed
the end of the visit period, the patient continued to maintain the original through M6 in pts with moderate-to-severe pruritus (NRS ≥4) at BL.
treatment plan, and was followed up at an interval of 6-12 months. The Exposure-adjusted adverse events (AEs) were calculated for each
year on study as incidence per 100 pt-years. BL was based on first Attenuation, Near Resolution, and Prevention of Pruritus in
exposure to seladelpar in ASSURE or RESPONSE. Patients With Primary Biliary Cholangitis Treated With Seladelpar:
Result: 337 pts received 10-mg seladelpar daily. 34 pts reached 30M A Secondary Analysis of Patterns of Pruritus Change in the
on study; 90 pts had ≥24M of seladelpar exposure. At BL, the mean RESPONSE Trial
(SD) age was 58.1 (9.7) years, 318/337 (94%) pts were female, mean Andreas E Kremer1, Cynthia Levy2, Marlyn J Mayo3, Christopher L
(SD) ALP was 287.5 (128.4) U/L, mean (SD) TB was 0.75 (0.34) mg/ Bowlus4, Kris V Kowdley5, Gideon M Hirschfield6, Susheela Carroll7,
dL, and 55/337 (16%) had cirrhosis. At M12, M24, and M30, 204/280 Ke Yang7, Linda Wu7, Daria B Crittenden7, Charles A McWherter8,
evaluable pts (73%), 90/124 (73%), and 30/37 (81%) met the CBR David EJ Jones9
endpoint, respectively, and ALP normalized in 106/280 (38%), 47/124 1
Department of Gastroenterology and Hepatology, University Hospital
(38%), and 15/37 (41%) pts, respectively. In the pruritus NRS, mean Zürich, University of Zürich, 2Division of Digestive Health and Liver
(SE) change from BL at 6M was −3.3 (0.24) among 99 evaluable pts. Diseases, University of Miami School of Medicine, 3Division of
Outcomes are in Figure 1. Exposure-adjusted AEs were observed in 86, Digestive and Liver Diseases, University of Texas SW Medical Center,
70, and 63 pts per 100 pt-years at M12, M24, and M36, respectively. 4
Division of Gastroenterology and Hepatology, University of California
There were no treatment-related serious AEs. Davis School of Medicine, 5Liver Institute Northwest, 6Division of
Conclusion: By M30 of the long-term ASSURE study, seladelpar Gastroenterology and Hepatology, Toronto Centre for Liver Disease,
resulted in a durable and sustained biochemical response in 81% of University of Toronto, 7Gilead Sciences, Inc., 8CymaBay Therapeutics,
pts, with an ALP normalization rate of 41%, and robust improvement in Inc., 9Department of Medical Sciences, NIHR Newcastle Biomedical
pruritus. Seladelpar continues to appear safe and well tolerated, with Research Centre
no new safety signals or change in frequency of AEs with up to 3 years Background: Cholestatic pruritus in patients with primary biliary
of exposure. cholangitis (PBC) is frequently debilitating and lacks effective
Table and Figure:Figure 1.(A) Composite Biochemical Response Rate treatments. In the Phase 3 RESPONSE trial (NCT04620733), seladelpar,
Through Month 30, (B) ALP Normalization Through Month 30, (C) ALP a first-in-class delpar (selective peroxisome proliferator–activated
Percentage Change From BL Through Month 30, and (D) Pruritus NRS receptor [PPAR]-delta agonist), significantly decreased pruritus in
Change From BL Through Month 6 patients with PBC with moderate to severe pruritus (numerical rating
scale [NRS] ≥4 at baseline) vs placebo. Here, we further evaluated
PP0641 pruritus patterns in RESPONSE.
Method: Patients with PBC who received ursodeoxycholic acid (UDCA)
Phase I Studies of a Novel Pulsatile FXR Ligand for Treating
for ≥12 months or were UDCA intolerant and had alkaline phosphatase
Cholestatic Liver Diseases
≥1.67 × upper limit of normal (ULN) and total bilirubin ≤2 × ULN were
Guanguan Zhao1, Jingjing Shi1, Gaihong Wang1, Hualing Pan1, randomized 2:1 to receive daily oral seladelpar 10 mg or placebo for
Shengsheng Yang1, Rong Deng1, Zhenwei Zhang1, Jia Li2, Eric H 12 months. We assessed trends in mean NRS over time and change in
Xu1,2 pruritus using various thresholds of improvement (eg, ≥3- and ≥4-point
1
Cascade Pharmaceutic, 2Shanghai Institute of Materia Medica, reductions in NRS, near resolution of itch [NRS ≤1]) in patients with
Chinese Academy of Sciences NRS ≥4 or NRS ≥7 (severe itch) at baseline. Development of pruritus in
Background: Cholestatic liver diseases, including Metabolic patients without itch (NRS = 0) at baseline and safety by subgroup of
Dysfunction-Associated Steatohepatitis (MASH), Primary Sclerosing baseline NRS (≥4 or <4) were also evaluated.
Cholangitis (PSC), and Primary Biliary Cholangitis (PBC), represent Result: Overall, 72 of 193 enrolled patients had baseline NRS ≥4,
significant therapeutic challenges with limited treatment options. with 49 randomized to seladelpar and 23 to placebo; 16 seladelpar
Farnesoid X receptor (FXR) ligands have shown promise in treating and 12 placebo patients had NRS ≥7. Among patients with NRS ≥4 at
NASH by modulating bile acid synthesis and metabolism. This study baseline, seladelpar reduced the mean itch intensity from moderate to
aims to investigate the efficacy and safety of Linafexor (CS0159), a mild from month 3 through month 12, whereas the mean itch intensity
pulse FXR ligand with a short half-life, to align with the metabolic cycle for placebo remained moderate (Figure, left). For patients with baseline
of bile acids and optimize its therapeutic potential. Circadian rhythm NRS ≥4, 46.9% of patients on seladelpar had a ≥3-point NRS decrease
and metabolic up-and-down regulation are fundamental aspects of vs 21.7% on placebo at month 12; a ≥4-point NRS decrease was
animal physiology, and drug design should consider these factors for achieved by 30.6% of seladelpar patients vs 8.7% on placebo (Figure,
optimal effectiveness and safety. right). A higher proportion of patients with baseline NRS ≥4 (26.5%)
Method: In vitro assays were conducted to assess Linafexor’s FXR and NRS ≥7 (18.8%) on seladelpar experienced near resolution of itch
agonistic activity and selectivity. A 12-week, randomized, placebo- at month 12 vs 0% of patients on placebo. In patients without itch at
controlled study was performed in a murine NASH model, with baseline, 26.7% (4/15) of placebo patients reported pruritus at month
Linafexor treatment administered daily at three dosage levels (0.1, 0.3, 12 vs 0% (0/30) of seladelpar patients. Adverse events were reported
and 1.0 mg/kg). Liver histology, serum bile acid levels, and expression in 88.9% and 84.3% of patients with baseline NRS ≥4 and NRS <4,
of genes involved in bile acid synthesis and metabolism were analyzed. respectively, with similar proportions across treatment arms.
Result: Linafexor demonstrated potent and selective FXR activation in Conclusion: Seladelpar reduced pruritus severity in patients with PBC
vitro. In the murine NASH model, Linafexor treatment led to significant with a durable effect over time and even led to near resolution of itch
reductions in liver steatosis, inflammation, and fibrosis across all in some patients, an effect not observed with placebo. Seladelpar
dosages, with the 0.3-1.0 mg/kg dose showing the greatest efficacy. mitigated new onset of itch in patients without pruritus and was overall
Serum bile acid levels and expression of genes involved in bile acid safe and well tolerated regardless of baseline itch.
synthesis and metabolism were modulated in a circadian-dependent Table and Figure:Figure 1.Mean Pruritus NRS Over Time and Declines
manner, consistent with Linafexor’s short half-life and the inherent in NRS in Patients With PBC With Moderate to Severe Pruritus (NRS ≥4)
metabolic rhythms of animal physiology. in the RESPONSE Trial
Conclusion: Linafexor (CS0159), a pulse FXR ligand with a short
half-life, demonstrated significant efficacy in treating Cholestatic liver
PP0643
diseases, including MASH, by modulating the metabolic cycle of
bile acids in accordance with the fundamental principles of animal Direct bilirubin demonstrates superior predictive value for long-
physiology. The circadian-dependent effects on bile acid metabolism term outcomes compared to total bilirubin in patients with primary
may contribute to its enhanced efficacy and safety profile. biliary cholangitis
Sha Chen1, Buer Li1, Shuxiang Li1, Tingting Lv1, Weijia Duan1, Jidong
Jia1
PP0642 1
Liver Research Center, Beijing Friendship Hospital, Capital Medical
University; Beijing Key Laboratory of Translational Medicine on Liver
Cirrhosis; National Clinical Research Center for Digestive Diseases,
Beijing; State Key Laboratory of Digestive Health, Beijing, China Davis School of Medicine, 11Gilead Sciences, Inc., 12CymaBay
Background: Total bilirubin (TB) has traditionally been a key prognostic Therapeutics, Inc.
indicator for patients with primary biliary cholangitis (PBC), yet the role Background: Seladelpar, a first-in-class delpar (selective peroxisome
of direct bilirubin (DB) has been largely ignored. Our study aims to proliferator–activated receptor [PPAR]-delta agonist), is in development
investigate the prognostic significance of DB in PBC, with a special for the treatment of primary biliary cholangitis (PBC). The Phase 3,
focus on the population with elevated TB but normal DB after one year placebo-controlled RESPONSE study (NCT04620733) in patients with
of ursodeoxycholic acid (UDCA) treatment. PBC with an inadequate response or intolerance to ursodeoxycholic
Method: We retrospectively reviewed the medical records of PBC acid demonstrated significant improvements in cholestatic markers
patients and obtained their follow-up data through regular outpatient and pruritus with seladelpar over 1 year. Similar proportions of
visits and phone interviews. Transplant-free survival (TRS) was defined seladelpar- and placebo-treated patients experienced adverse events
as survival without liver-related death or liver transplantation (LT). (AEs) and serious AEs (SAEs). To assess long-term safety, data from
Hepatic events were defined as encephalopathy, ascites, variceal all patients with PBC exposed to seladelpar 10 mg in 6 studies with
bleeding, or hepatocellular carcinoma. similar entry criteria were pooled.
Result: A total of 553 PBC patients who met the inclusion and exclusion Method: AE data from 2 placebo-controlled and 4 open-label studies
criteria were enrolled in the study. Patients were divided into three were pooled for all patients treated with seladelpar 10 mg as of 31
groups based on TB12 and DB12 levels (TB and DB after 12 months Jan 2024, beginning with first exposure to seladelpar, including all
of UDCA treatment): Group 1 with elevated TB12 and DB12 (n=145), exposure periods and excluding treatment gaps. Placebo exposure
Group 2 with elevated TB12 and normal DB12 (n=88), and Group 3 with was pooled from the 2 placebo-controlled studies. Exposure-adjusted
normal TB12 and DB12 (n=308). Patients in Groups 2 and 3 showed incidence rates of AEs, SAEs, and AEs of interest (defined as liver-,
milder baseline disease severity, with lower levels of liver enzymes, TB, muscle-, renal-, and pancreatic-related AEs) were calculated.
DB, lower proportion of cirrhosis, and higher albumin levels compared Result: As of the data cutoff, a total of 486 patients received seladelpar
to Group 1. Interestingly, Group 2 had a higher proportion of males, but 10 mg: 355 were treated for ≥1 year, 170 for ≥2 years, 66 for ≥3 years,
similar liver enzyme and albumin levels to Group 3. 36 for ≥4 years, and 10 for ≥5 years. The exposure-adjusted incidence
After a median follow-up of 5.42 years, 63 patients (11.4%) reached an rates (per 100 patient-years) for seladelpar 10 mg were 48.3 for AEs,
endpoint (17 LT and 46 liver-related deaths). Groups 2 and 3 had higher 8.0 for SAEs, 9.8 for Grade ≥3 AEs, and 6.1 for liver-related AEs. There
TRS rates and lower hepatic events incidence than Group 1 (Fig.1A, were no treatment-related SAEs. Muscle, renal, and pancreatic AEs
both p<0.001). However, no significant differences were observed occurred in <7 patients per 100 patient-years. Placebo exposure
between Groups 2 and 3 in TRS rates or hepatic events incidence. included 152 patients: 117 were treated with placebo for ≥12 weeks,
Multivariate Cox analyses identified cirrhosis, age at diagnosis, 84 for ≥6 months, and 57 for 12 months in RESPONSE. The exposure-
baseline platelet count, aspartate aminotransferase (AST12), alkaline adjusted incidence rates (per 100 patient-years) for patients treated
phosphatase (ALP12), amma-glutamyl transpeptidase (GGT12), and with placebo were 132 for AEs (rate reflective of shorter exposure time
DB12 after 12 months of UDCA therapy as independent predictors of for placebo patients), 7.8 for SAEs, 12.2 for Grade ≥3 AEs, and 13.3
long-term outcomes (Table 1). Baseline TB and TB12 were associated for liver-related AEs (with other AEs of interest occurring at lower rates).
with prognosis in univariate analysis but did not remain significant in AEs leading to treatment discontinuation occurred in 2.9 patients per
the final model. Finally, patients with normal ALP12 and DB12 had 100 patient-years in seladelpar patients and 5.6 per 100 patient-years
better TRS rates than those with normal ALP12 and elevated DB12 in placebo patients.
(Fig.1B, p=0.011). Conclusion: Analysis of a large safety database for seladelpar in PBC
Conclusion: DB is a more reliable predictor of long-term outcomes patients with exposure through 5 years indicated that seladelpar was
than TB in PBC patients, with those having normal DB after 1 year of well tolerated with a safety profile similar to that of placebo.
UDCA treatment showing better survival. Table and Figure:Figure 1.
Table and Figure:Figure 1.Table 1 Univariate and multivariable Cox
regression analysis for transplant-free survival in PBC patients. PP0645
Figure 2.Fig 1. (A) Kaplan–Meier plots for transplant-free survival in
PBC patients stratified by TB12 and DB12 levels. (B) Kaplan–Meier Single-Cell RNA Sequencing for a Rare Case of Primary Biliary
plots for transplant-free survival in PBC patients stratified by ALP12 Cholangitis-Associated Hepatocellular Carcinoma Reveals a
and DB12 levels. Distinct Immune Landscape and Potential Therapeutic Targets
Zhenwei Qian1, Jie Han2,3, Aizier Ainiwaer2, Yinying Lu2
1
Peking University 302 Clinical Medical School, Beijing, 100039,
PP0644 China, 2Department of Hepatology, the Fifth Medical Center, Chinese
Long-Term Safety of Seladelpar 10 mg With Up to 5 Years of PLA General Hospital, Beijing, 100039, China, 3Medical School of PLA,
Treatment in Patients With Primary Biliary Cholangitis Beijing, 100853, China
Palak J Trivedi1,2, Stuart C Gordon3,2, Aliya Gulamhusein4, Alejandra Background: Primary biliary cholangitis (PBC) is a chronic,
Vilamil5, Eric J Lawitz6,2, John M Vierling7,2, Maria Carlota Lodoño8, autoimmune-mediated cholestatic liver disease. Although
Andreas E Kremer9,2, Christopher L Bowlus10,2, Sarah Proehl11, hepatocellular carcinoma (HCC) is a recognized complication of
Shuqiong Zhuo12, Linda Wu11, Daria B Crittenden11, Charles A cirrhotic PBC, it remains relatively rare and poorly characterized at
McWherter12 the single-cell level—particularly in patients with coexisting cirrhosis.
1
National Institute for Health Research Birmingham Biomedical Here, we report the first known single-cell transcriptomic profiling
Research Centre, Centre for Liver and Gastrointestinal Research, of peripheral blood, peritumoral tissue, and tumor tissue in a single
College of Medical and Dental Sciences, University of Birmingham, 60-year-old female diagnosed with PBC cirrhosis and HCC.
2
Liver Unit, University Hospitals Birmingham Queen Elizabeth, Method: Paired samples were obtained from the patient’s peripheral
3
Division of Hepatology, Henry Ford Hospital, Wayne State University blood (PB), peritumoral (P), and tumor (T) tissues during surgical
School of Medicine, 4Division of Gastroenterology and Hepatology, resection. Single-cell RNA sequencing (scRNA-seq) was performed to
Toronto Centre for Liver Disease, University of Toronto, 5The Liver construct a high-resolution cellular atlas of the tumor microenvironment.
Autoimmunity Unit, Hospital Italiano de Buenos Aires, 6Texas Liver
Cell type annotation and differential gene expression analyses were
Institute, University of Texas Health San Antonio, 7Baylor College
conducted to identify key immune populations and dysregulated
of Medicine, 8Liver Unit, Hospital Clínic Barcelona, Instituto de
pathways.
Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro
Result: Immune Cell Distribution: We observed robust infiltration of
de Investigación Biomédica en Red de Enfermedades Hepáticas
y Digestivas (CIBEREHD), 9Department of Gastroenterology and cytotoxic lymphocytes—including CD4+ T cells, CD8+ T cells, and
Hepatology, University Hospital Zürich, University of Zürich, 10Division NK cells—in the peripheral blood and peritumoral region, yet their
of Gastroenterology and Hepatology, University of California presence was markedly diminished in the tumor core. This points to a
potentially unique immunopathology in PBC-associated HCC, wherein 0.510, P = 6.172 × 10- 5) were positively associated with an increased
peripheral and peritumoral immune activation is high, but effective risk of PSC.
tumor infiltration is limited. Conclusion: Evidence on the causal relationship between 29
Plasma Cell Enrichment: Intriguingly, a significant enrichment genetically predicted modifiable risk factors and the risk of AIH,
of plasma cells was detected within the tumor compartment, suggesting PBC, and PSC is provided by this study. These findings provide fresh
possible humoral immune remodeling or an immunosuppressive niche perspectives on the management and prevention strategies for AILD.
that favors B-lineage differentiation. Table and Figure:Figure 1.Visualization of methods and designs in this
Tumor Cell Transcriptome: Tumor cells demonstrated study.
upregulated expression of several key oncogenic and metabolic Figure 2.Causal effects of the modifiable risk factors on PBC.
regulators, including EGFR, GHR, and PRKAG2 components. These
may represent promising therapeutic targets in PBC-related HCC,
PP0647
where traditional HCC treatments often lack robust efficacy.
Conclusion: Our single-cell atlas offers unprecedented insight into the Clinical performance of AMA-M2, anti-gp210 and anti-sp100
immune and tumor-cell heterogeneity in a rare case of PBC cirrhosis antibody levels in primary biliary cholangitis: When detected by
with HCC. The pronounced immune activation in the periphery, multiplex bead-based flow fluorescent immunoassay
contrasted by low tumor infiltration, underscores the need to overcome Mingjun Liu 1, Zhan Wang1, Yongxin Li1, Weize Gao1
local immunosuppression or exclusionary signals. Furthermore, 1
The Affiliated Hospital of Qingdao University
the discovery of upregulated EGFR, GHR, and AMPK pathways in Background: Primary biliary cholangitis (PBC) is a chronic
the tumor highlights novel opportunities for targeted therapy. These autoimmune cholangiopathy, characterized by the presence of some
findings open new avenues for understanding PBC progression to autoantibodies in the serum. This study aimed to evaluate the clinical
HCC and pave the way for tailored immunotherapies in this rare but significance of AMA-M2, anti-gp210 and anti-sp100 antibody levels
challenging clinical scenario. detected by multiplex bead-based flow fluorescent immunoassay
Table and Figure:Figure 1.Single-Cell Atlas of PBC-Associated HCC (MBFFI) in PBC.
Reveals Immune Cell Distribution and Tumor-Specific Gene Expression Method: This study cohort included 238 PBC patients, 81 autoimmune
Figure A: UMAP visualization of single-cell clusters from PBC-HCC hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE)
patient samples Figure B: Relative enrichment (Ro/e) of major cell patients, and 118 healthy controls. Serum AMA-M2, anti-gp210 and
types across PB, P, and T compartments Figure C: Expression density anti-sp100 antibody were detected by MBFFI and immunoblotting
of EGFR, GHR, and PRKAG2 in tumor cells assay (IBT). The relationship between three antibody levels and
cirrhosis, liver function, cholestasis markers and therapeutic effect to
PP0646 ursodesoxycholic acid (UDCA) was evaluated in PBC.
Result: MBFFI were presented good coincidence rate (87.39%-
Genetic association and causal relationship between multiple
95.38%) with IBT. The level of AMA-M2, anti-gp210 and anti-sp100
modifiable risk factors and autoimmune liver disease: a two-
antibodies in PBC patients were higher than other disease group and
sample mendelian randomization study
healthy controls (p < .01). When compared with the healthy controls
Mingjun Liu1, Weize Gao 1, Zhan Wang1, Yongxin Li1 group, the AUC of AMA-M2, anti-gp210 and anti-sp100 antibodies
1
The Affiliated Hospital of Qingdao University were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210
Background: The intricate etiology of autoimmune liver disease antibody levels have diagnostic value in patients with liver cirrhosis
(AILD) involves genetic, environmental, and other factors that yet to (AUC: 0.7567). We found that when combine detect these three
be completely elucidated. This study comprehensively assessed antibodies, the sensitivity was higher than individually detection.
the causal association between genetically predicted modifiable risk High level of serum anti-gp210 antibody could be related to worse
factors and AILD by employing Mendelian randomization. liver function and more severe cholestasis in PBC patients. Moreover,
Method: Genetic variants associated with 29 exposure factors were serum antibody levels may decrease or remained flat in patients who
obtained from genome-wide association studies (GWAS). Genetic responded well to UDCA.
association data with autoimmune hepatitis (AIH), primary biliary Conclusion: The detection of AMA-M2, anti-gp210 and anti-sp100
cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also antibody levels by MBFFI showed good performance in the diagnosis
obtained from publicly available GWAS. Univariate and multivariate of PBC. Serum anti-gp210 antibody level is related to cirrhosis, poor
Mendelian randomization analyses were performed to identify potential liver function and severe cholestasis in PBC.
risk factors for AILD. Table and Figure:Figure 1.Venn diagram shows the antibody pattern of
Result: Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, PBC patients detected by IBT and MBFFI.
95%CI 1.423-1.843, P = 2.506 × 10- 13) was significantly associated Figure 2.Diagnostic performances of AMA‐M2, anti‐gp210 and anti‐
with an increased risk of AIH. Genetically predicted smoking initiation sp100 antibodies in PBC and PBC cirrhosis.
(OR = 1.637, 95%CI 1.055-2.540, P = 0.028), lower coffee intake (OR
= 0.359, 95%CI 0.131-0.985, P = 0.047), cholelithiasis (OR = 1.134,
PP0648
95%CI 1.023-1.257, P = 0.017) and higher C-reactive protein (CRP)
(OR = 1.397, 95%CI 1.094-1.784, P = 0.007) were suggestively Exon 3 of the Numb gene is equivalent to full-length Numb in
associated with an increased risk of AIH. Genetically predicted alleviating cholestatic liver fibrosis through inhibition of the
inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127-1.303, ductular reaction
P = 2.015 × 10- 7) and RA (OR = 1.417, 95%CI 1.193-1.683, P = Yannan Xu1, Mengyao Zong1, Wen Xu1, Shihao Zhang1, Danyang
7.193 × 10- 5) were significantly associated with increased risk of Wang1, Xinrui Zheng1, Feifei Xing1, Junyi Zhan1, Jiamei Chen1,
PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI Gaofeng Chen1, Ping Liu1, Wei Liu1, Yongping Mu1
1.005-1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1
Shuguang Hospital affiliated to Shanghai University of Traditional
1.086, 95%CI 1.017-1.160, P = 0.014) and higher CRP (OR = 1.199, Chinese Medicine (TCM)
95%CI 1.019-1.410, P = 0.028) were suggestively associated with an Background: Numb, a determinant of stem cell fate, performs biological
increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560- functions after alternative splicing of exons 3 and 9 of the Numb gene.
0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699-0.995, P = Our previous research revealed that Numb expression was reduced in
0.044) levels were suggestive protective factors for PBC. Genetically cholestatic liver fibrosis (CLF) and that overexpressing the Numb gene
predicted smoking initiation (OR = 0.630, 95%CI 0.462-0.860, P = increased the anti-CLF effect of bone marrow mesenchymal stem
0.004) was suggestively associated with a decreased risk of PSC. cells (BM-MSCs). However, whether the Numb gene or its exon has
Genetically predicted IBD (OR = 1.252, 95%CI 1.164-1.346, P = 1.394 direct anti-CLF activity been unclear. The objective of this study was to
× 10- 9), RA (OR = 1.543, 95%CI 1.279-1.861, P = 5.728 × 10- 6) and first clarify the therapeutic effect of the Numb gene on CLF and then
lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141-
compare the anti-CLF effects of full-length Numb and exon 3 of Numb. Background: Cholestasis is a disease characterized by impaired bile
Method: In vivo, first, AAV.Numb was transplanted into the livers of rats secretion and excretion, leading to intrahepatic bile accumulation and
with CLF induced by bile duct ligation (BDL) to confirm its anti-CLF increased bile components in the blood. Currently, therapeutic options
effect through evaluation of the progression of CLF, Notch signaling for cholestasis are limited. Our previous study found that sulfasalazine
activation, the ductular reaction (DR), and hepatic progenitor cell (SASP), a drug used to treat ulcerative colitis, delayed CCl4-induced
(HPC) differentiation. Second, AAV.Numb or AAV.Numb-Exon3 was liver fibrosis in relation to its improvement of bile salt secretion pathway.
transplanted into the livers of the rats with CLF, and their anti-CLF Therefore, this study aims to investigate the protective effects of SASP
effects were compared. In vitro, AAV.Numb or AAV.Numb-Exon3 was on the liver in an ANIT (α-naphthylisothiocyanate)-induced cholestasis
transfected into WB-F344 cells, which were then treated with sodium model.
butyrate to observe cell differentiation. Method: Gavaging 80 mg/kg ANIT 4 times in SD rats induced
Result: AAV.Numb and AAV.Numb-Exon3 alleviated CLF and a subacute cholestatic model (Fig. 1A), 40 male and 40 female
suppressed the activation of Notch signaling and the differentiation rats weighing 80-110 g were randomly divided into control, ANIT,
of HPCs into biliary epithelial cells (BECs), and the anti-CLF effect of ANIT+SASP (150 mg/kg), and ANIT+UDCA (100 mg/kg) groups. The
Numb-Exon3 was similar to that of full-length Numb. In addition, we effects on liver function and liver pathology were observed.
confirmed that Numb-Exon3 inhibited the differentiation of WB-F344 Result: Serological indicators showed that, compared with the ANIT
cells into BECs while inducing their differentiation to a hepatocyte group, SASP treatment significantly decreased the hepatocyte injury
phenotype. markers ALT and AST in both male and female rats. The cholestatic
Conclusion: Exon 3 of Numb has effects equivalent to those of full- marker ALP was significantly decreased in male rats and showed a
length Numb on alleviating CLF by inhibiting the DR and promoting downward trend in female rats, while TBA was significantly decreased
liver regeneration. in both genders. Notably, TBil levels were significantly reduced after
SASP treatment, outperforming UDCA, which is a first-line treatment for
PP0649 cholestasis (Fig.1B). Liver HE staining and Masson staining revealed
that SASP significantly decreased inflammatory cell infiltration in the
Concurrent Nonalcoholic Fatty Liver Disease Decreased Liver portal area and the degree of liver fibrosis in the cholestatic model,
Fibrosis Severity in Patients with Primary Biliary Cholangitis with no significant difference compared to UDCA treatment, while the
Zilong Wang1, RUI HUANG2 therapeutic effects are more pronounced in males (Fig.2A). Further
1
Peking University People’s Hospital, Peking University Hepatology analysis showed that liver TBA levels decreased significantly after
Institute, 2北京大学人民医院 SASP treatment, from 4.066 μmol/g to 2.635 μmol/g in males and from
Background: Primary biliary cholangitis (PBC) is a chronic autoimmune 3.909 μmol/g to 2.978 μmol/g in females, respectively (Fig.2B).
liver disease. Nonalcoholic fatty liver disease (NAFLD) is a prevalent Conclusion: Our study confirms that SASP can improve ANIT-induced
chronic metabolic liver disease linked to insulin resistance, obesity, cholestasis, as evidenced by reductions in liver and serum bile acid
and genetic factors. The incidence of NAFLD is on the rise, leading to levels, with better therapeutic effects observed in males. Ongoing
an increased prevalence of concurrent PBC and NAFLD. Yet, there is research into the pharmacological mechanisms will lay the foundation
a paucity of clinical data on how NAFLD impacts the progression and for SASP repositioning in the treatment of cholestasis.
prognosis of PBC. Table and Figure:Figure 1.Fig.1. (A) Schematic of the experimental
Method: This retrospective study enrolled patients diagnosed with design and schedule for the ANIT model. (B) Biochemical analysis of
PBC. NAFLD patients were identified according to the 2023 American the serum of rats from different groups.
Association for the Study of Liver Diseases (AASLD) guidelines. The Figure 2.Fig.2. (A) Histological analysis of liver tissues, (B) TBA analysis
primary outcome measured the percentage of patients achieving a of rats liver from different groups.
complete biochemical response, while secondary outcomes included
non-invasive fibrosis scoring systems and a transplantation-free survival PP0651
risk model. Statistical analyses employed independent samples
Neutrophil extracellular traps-induced pyroptosis of liver
Student’s t-test or Mann-Whitney U test for continuous variables and
sinusoidal endothelial cells exacerbates intrahepatic coagulation
Pearson’s chi-square or Fisher’s exact test for categorical variables,
in cholestatic mice
with significance set at a two-tailed P-value of less than 0.05.
Result: Among 363 patients diagnosed with PBC, 87 (24.0%) were Muxin Yu1, Jinming Zhang2
also diagnosed with NAFLD. Biochemical response rates did not
1
Jiaxing university, 2The second affiliated hospital of Jiaxing University
differ significantly between patients with PBC alone and those with Background: Neutrophil extracellular traps (NETs) and NOD-like
concurrent PBC and NAFLD (P>0.05) (Table 1). However, after one receptor protein 3 (NLRP3) inflammation are key contributors to
year of ursodeoxycholic acid (UDCA) treatment, significant differences cholestatic liver disease (CLD). However, the relationship between
were observed in APRI and FIB-4 scores between PBC patients NETs release and inflammasome activation, as well as its contribution
with and without NAFLD (APRI: 0.35 vs 0.47, P=0.02; FIB 4 score: to intrahepatic coagulation in CLD, remains unexplored. This study
1.95 vs 2.53, P=0.01) (Figure 1,2). The GLOBE score revealed that explores NETs-induced liver sinusoidal endothelial cells (LSECs)
patients with both PBC and NAFLD had higher 5-, 10-, and 15-year pyroptosis on intrahepatic coagulation in CLD.
liver transplant-free survival rates compared to those with PBC alone Method: Wild-type (WT) and PAD4-/- mice underwent bile duct ligation
(81.9%, 58.3%, and 38.0% respectively, all P<0.05) (Table 2, Figure 2). (BDL) or sham surgery for 7 or 14 days. The liver analysis assessed
Conclusion: Patients with concurrent PBC and NAFLD do not intrahepatic coagulation, inflammation, fibrosis, NETs release, and
significantly impact the biochemical response to UDCA but may NLRP3 activation. Primary LSECs were exposed to NETs with or without
improve the degree of liver fibrosis and long-term prognosis. MCC950. Pyroptosis and LSECs procoagulant activity were quantified.
Table and Figure:Figure 1. Result: BDL mice exhibited significantly increased inflammation,
tissue factor (TF), and fibrin deposition compared with controls. NETs
PP0650 release in the liver was increased significantly in WT BDL mice and was
responsible for intrahepatic coagulation. PAD4 deficiency reduced TF
Sulfasalazine Improves ANIT-Induced Cholestasis and fibrin expression, improving hepatic sinusoid function. RNA-seq
Xuan Wang1, Jing Xu1, Yu Zhang1, Hnag You1, Jing Xiao1, Zongyi Liu1, revealed BDL-induced enrichment of coagulation, neutrophil activation,
Yong Sun1, Duo Li1, Mingli Peng1 and pyroptosis pathways. In vivo, NETs increased intrahepatic
1
Department of Infectious Diseases, Key Laboratory of Molecular NLRP3 and IL-1β expression in BDL mice. However, NLRP3 inhibition
Biology for Infectious Diseases (Ministry of Education), Institute of (MCC950) or activation (BMS-986299) did not alter NETs release.
Infectious Diseases and Hepatology, the Second Affiliated Hospital of Furthermore, NETs-induced NLRP3 activation increased intrahepatic
Chongqing Medical University, Chongqing, China. coagulation, inflammation, and fibrosis. Finally, we demonstrated
that NETs triggered LSECs dysfunction and pyroptosis, upregulating
TF and phosphatidylserine production and enhancing procoagulant indices but also delay histologic progression and improve survival
activity. without transplantation. However, a significant proportion of patients
Conclusion: NETs-induced LSECs pyroptosis exacerbates have an inadequate response to UDCA and require timely addition of
intrahepatic coagulation in cholestasis. Targeting NETs and LSECs second-line therapy or immunosuppressants. The aim of this study is
pyroptosis holds promise for treating chronic liver injury in CLD. to investigate the clinical and pathological characteristics of patients
Table and Figure:Figure 1. with PBC who had inadequate response to UDCA
Method: 154 patients diagnosed as PBC with UDCA monotherapy
for at least 1 year were involved in this study. All included patients
PP0652
were divided into two groups according to Paris-I and II Criteria: well
Biochemical Response and Clinical Outcome of Primary Biliary response group (n=100) and inadequate response group (n=54) to
Cholangitis Patients with Mild Interface Hepatitis UDCA. By retrospective analysis, the general conditions, clinical
Tingting Lv1, Weijia Duan1, Xinyan Zhao1, Jidong JIA1 manifestations, biochemical tests, immunological tests and liver
1
Department of Liver Research Center, Beijing Friendship Hospital, histology in patients of the two groups were analyzed. Univariate
Capital Medical University; logistic regression analysis and multivariate logistical regression were
Background: There is ongoing debate regarding whether used to analyse the pathological and clinical features of PBC patients
immunosuppressants are necessary for the management of mild who had inadequate response to UDCA
interface hepatitis. This study aimed to investigate the biochemical Result: The baseline of alkaline phosphatase (ALP), gamma-
response and clinical outcomes of primary biliary cholangitis (PBC) glutamyltransferase (GGT), aspartate aminotransferase (AST), total
patients with mild interface hepatitis (MIH) following treatment bilirubin (TBIL), globulin (GLB), total bile acid (TBA), triglyceride
with ursodeoxycholic acid (UDCA) alone or in combination with (TG), immunoglobulin G (IgG) in inadequate response group were
immunosuppressants (IS). The goal was to provide clinical evidence significantly higher than those in well response group(P<0.05). The
to guide the management of these patients. baseline albumin of patients in inadequate response group was lower
Method: This retrospective study included PBC patients diagnosed than that in well response group (P<0.05) while there were no significant
via liver biopsy at Beijing Friendship Hospital from January 2009 differences in the levels of immunoglobulin M (IgM), immunoglobulin
to January 2023. Demographic information, biochemical indices, A (IgA) and anti-mitochondrial antibody-M2 (AMA-M2) between two
and clinical outcomes were collected from medical records and groups. In inadequate response group, inflammation grade 3-4 and
follow-up through telephone or WeChat. Histological features were fibrosis stage 3-4 was more common than that in well response group.
independently evaluated by two clinicopathologists, and patients were Chi-square test showed that interface hepatitis, cholestasis and bile
categorized into groups with and without MIH. The MIH group was duct deletion were significantly different between the two groups (P
further divided based on treatment: UDCA alone or UDCA combined < 0.05), and these pathological changes are more likely to occur in
with IS. Biochemical responses to treatments were analyzed, and inadequate response group. Univariate logistic regression analysis
Kaplan-Meier survival curves were used to compare survival outcomes showed that baseline GLB, AST, ALP, GGT, TBIL, IgG, fibrosis stage
across groups. 3-4, cholestasis, interface hepatitis and bile duct deletion were all
Result: A total of 192 patients were included in the study, categorized independently associated with inadequate response to UDCA in PBC
as follows: PBC without MIH (n = 35), PBC with MIH treated with UDCA patients. Multivariate logistic regression analysis showed that baseline
(n = 127), and PBC with MIH treated with UDCA plus IS (n = 30). ALP, IgG, interface hepatitis and bile duct deletion are risk factors for
Patients with MIH showed a poorer biochemical response to UDCA inadequate response to UDCA in patients with PBC
monotherapy compared to those without MIH, as assessed by the Conclusion: Univariate and multivariate analyses confirmed baseline
Barcelona, Toronto, and POISE criteria (P < 0.05). Furthermore, MIH ALP, IgG, interface hepatitis and bile duct deletion as significant
patients had relatively lower liver transplant-free survival rates (HR: risk factors for inadequate response to UDCA in PBC patients. Early
2.93, 95% CI: 0.38–22.45, P = 0.300), and higher adverse liver-related identification of these features can guide timely second-line therapy or
events (HR: 2.24, 95% CI: 0.80–6.28, P = 0.125). In patients with MIH, immunosuppressant use
treatment with UDCA plus IS significantly reduced aminotransferase
levels and improved levels of immunoglobulin G (P = 0.003) and total PP0654
bilirubin (P = 0.010), compared to UDCA monotherapy. However,
Clinical Characteristics and Treatment situation of Primary Biliary
Kaplan-Meier survival analysis revealed no significant differences in
Cholangitis in Guangxi of China
survival outcomes between the two treatment groups (HR: 0.5013,
95% CI: 0.2029–1.238, P = 0.1345). JINFENG LI1, Diefei Hu2
Conclusion: MIH is commonly observed in patients with PBC. PBC
1
Department of Infectious Diseases, Wuming Hospital Affiliated to
patients with MIH exhibit poorer biochemical responses and a higher Guangxi Medical University, Nanning, Guangxi China, 2Department of
incidence of adverse outcomes compared to those without MIH. Infectious Diseases, The First Affiliated Hospital of Guangxi Medical
Although combining UDCA with IS partially improved biochemical University, Nanning, Guangxi China
responses in MIH patients, it did not significantly impact survival Background: Primary biliary cholangitis (PBC) is the most common
outcomes. A stratified treatment approach based on disease severity autoimmune liver disease. The prevalence of PBC in China is the
showed slight improvements in prognosis. second highest within the Asia-Pacific region and shows a increasing
Table and Figure:Figure 1.Flowchart of included patients trend year by year. However, as it often presents with atypical clinical
Figure 2.biochemical response among patients symptoms which can easily lead to misdiagnosis or missed diagnosis.
Comprehensive and contemporary data pertaining large populations
of patients with PBC in Guangxi are missing. This study aimed to
PP0653
identify the clinical characteristics and treatment situation of patients
Analysis of pathological and clinical features of primary biliary with PBC in Guangxi of China.
cholangitis with inadequate response to ursodeoxycholic acid Method: Clinical data of patients with PBC who were admitted to the 1st
Hongmei Wu1, Jialin Qu1, Xiaofeng Shi1, Yu Lei(Corresponding affiliated Hospital of Guangxi medical university from January 2013 to
author)1 December 2023 were retrospectively reviewed. Patients were divided
1
Department of Infectious Diseases, Institute for Viral Hepatitis, into two groups, cirrhosis group and non-cirrhosis group, assessed the
The Second Affiliated Hospital of Chongqing Medical University, different clinical characteristics and treatment situations between the
Chongqing 400072, China two groups. Most patients had received ursodeoxycholic acid (UDCA)
Background: Primary biliary cholangitis (PBC) is a common treatment and had the experience of being hospitalized.
progressive autoimmune liver disease. Ursodeoxycholic acid (UDCA) Result: A total of 78 patients with PBC were included. The average
is the first-line treatment for PBC which could improve biochemical age of patients was 52.29±11.98 years , while patients aged 40-59
years accounts for 61.54%( 48/78). The male-to-female ratio was
1:7.67. Cirrhosis was present in 48.72% (38/78) of patients. The onset non-PBC liver diseases. These results underscore the need for liver
of the disease appears to be sporadic and widespread throughout biopsy and comprehensive clinical evaluation in patients positive for
Guangxi, with the most cases registered from Nanning, Guangxi. The anti-sp100 to ensure accurate diagnosis.
most common clinical symptom was jaundice (32 cases, 41.03%), Table and Figure:Figure 1.Table 1 Diagnostic Categories of Patients
followed by fatigue and asymptomatic cases (both 30 cases, 38.46%). Positive for Anti-sp100 Alone Undergoing Liver Biopsie
Approximately 61.54% (48/78) of these patients accompanied by
autoimmune hepatitis (AIH) and 53.85% (42/78) were hyperlipidemia.
PP0656
GGT and ALP levels markedly elevated, with an average level of 341
U/L and 285 U/L respectively. The positive rates of ANA, AMA and Effectiveness of Statins as an Adjuvant Therapy for Primary
AMA-M2 were 100% , 75.6% and 69.2%, respectively. Before initiating Biliary Cholangitis: A Meta-Analysis Study
treatment, there was a significant difference in ALB levels between the Xuan Guoyun1, Ye Ming2, Song Zirui2, Liu Ning2, Shao Lichun1, Xuan
non-cirrhosis and cirrhosis groups (p-value < 0.05), with lower albumin Yunhao3, Xuan Lele4
(ALB) levels in the cirrhosis group. The detail data was show below 1
Department of Gastroenterology, The Air Force Hospital of Northern
figure. After two weeks of treatment with UDCA and glucocorticoids, Theater PLA, Shenyang 110042, China., 2College of Basic Medicine,
both GGT and ALP levels significantly decreased, particularly in the Air Force Medical University, Xi‘an 710000, China., 3Hangzhou dianzi
non-cirrhosis group. university, Hangzhou 310000, China., 4Department of Neurology,
Conclusion: The onset of Primary biliary cholangitis (PBC) is insidious. Donghai Country People‘s Hospital, Lianyungang 222300, China.
Besides jaundice and fatigue, a high proportion of patients are Background: Approximately 76% of PBC patients exhibit significant
asymptomatic. The incidence of accompanying cirrhosis newly treated alterations in their lipid profile, with markedly elevated cholesterol
patients is relatively high. We need to strengthen our capabilities in levels being the predominant feature. There is evidence suggesting
diagnosing and treating PBC. that the combined use of fibrates, which are drugs used to treat
Table and Figure:Figure 1.PBC Symptoms dyslipidemia, can improve biochemical parameters in PBC patients
Figure 2.Liver Function Indexes Changes Before and After One Week who have an inadequate response to UDCA, possibly through the
and Two Weeks of Treatment with UDCA and Glucocorticoids in PBC activation of peroxisome proliferator-activated receptor α (PPARα).
Consequently, clinical guidelines recommend the discretionary use
PP0655 of fibrates in combination therapy for PBC patients with a suboptimal
response to UDCA. However, there is currently no evidence-based
Diagnostic Distribution of Patients Positive Alone for Anti-sp100: medical support for the use of statins, which lower serum cholesterol
A Retrospective Study Based on Liver Biopsy by inhibiting HMG-CoA reductase, as an adjunctive therapy for PBC,
Hongli Liu1,2, Xing Liu3, Yifan Hu4, Shasha Li5, Xixuan Wang1,2, Yijun despite the characteristic hypercholesterolemia in these patients. This
Bao4, Yu Zhang1,2, Li Wang4, Zhixiang Du4, Miaoyang Chen4, Qingfang study aims to conduct a meta-analysis using the Cochrane systematic
Xiong4, Yandan Zhong4, Caiyun Zhang6, Duxian Liu7, Ping Huang4, review methodology on published randomized controlled trials to
Wenquan Zeng4, Min Ai4, Kai Zhang3, Yongfeng Yang2,1,4 investigate the efficacy of statins as an adjuvant therapy for PBC,
1
Clinical Specialty, Second Clinical College, Southeast University, thereby guiding clinical practice.
2
Department of infectious disease and liver disease, The Second Method: The included studies were identified in English databases,
Hospital of Nanjing, Teaching Hospital of Southeast University, including PubMed, Embase, and The Cochrane Library (updated
3
Department of Clinical Research Center, The Second Hospital to January 2022), by a manual search for relevant literature using
of Nanjing, Affiliated to Nanjing University of Chinese Medicine, the search terms “ursodeoxycholic acid”, “UDCA”, “statin”, “PBC”,
4
Department of Infectious Disease and Liver Disease. The Second “primary biliary cholangitis”, “primary biliary cirrhosis” and “randomized
Hospital of Nanjing, Affiliated to Nanjing University of Chinese controlled trial”. Further literature was searched to prevent omission.
Medicine, 5Department of Hepatology, The Second Hospital of
Result: A total of 262 articles met the initial search criteria. Following
Nanjing, Clinical Teaching Hospital of Medical School, Nanjing
the exclusion of conference papers and those lacking key data based
University, 6 Department of Clinical Research Center, The Second
on title and abstract screening, 5 articles were finally included in the
Hospital of Nanjing, Affiliated to Nanjing University of Chinese
analysis. Five studies reported the effects of statin therapy on PBC
Medicine, 7Department of Pathology, The Second Hospital of Nanjing,
Affiliated to Nanjing University of Chinese Medicine patients; however, the findings indicated that statins did not significantly
improve relevant biochemical indicators of liver function of PBC.
Background: Anti-sp100 antibodies are specific markers for primary Conclusion: PBC patients commonly exhibit dysregulated lipid
biliary cholangitis (PBC). Previous studies have focused on the metabolism, primarily characterized by elevated serum cholesterol.
diagnostic distribution of antimitochondrial antibodies (AMA) and their Fibrates, as first-line lipid-lowering agents, have been shown to have
subtypes in PBC-positive patients. However, clinical observations show potential value in combination therapy for PBC patients with inadequate
that some patients are positive for anti-sp100 but are not diagnosed response to UDCA. Therefore, the role of lipid-lowering as an effective
with PBC. This study examines the diagnostic distribution of patients treatment strategy for PBC remains a topic of interest. Whether statins,
who tested positive for anti-sp100 alone in a cohort undergoing liver which primarily regulate cholesterol, can also be used in conjunction
biopsy. with UDCA to improve biochemical markers in PBC patients with poor
Method: A retrospective analysis was conducted at the Second UDCA response is unclear, and no relevant clinical studies have been
Hospital of Nanjing from January 2017 to December 2023. Seventy- reported. Only a few clinical studies have examined the use of statins
two patients who underwent liver biopsy and tested positive for anti- alone in PBC. This meta-analysis suggests that statins alone do not
sp100 alone were included. The final diagnoses, including PBC and improve biochemical liver function indicators in PBC patients. Further
non-PBC cases, were analyzed. basic and clinical research is needed to explore whether statins play a
Result: Among the 72 patients who tested positive for anti-sp100 alone role in the treatment of PBC.
and underwent liver biopsy, 33 (45.8%) were diagnosed with primary Table and Figure:Figure 1.Baseline characteristics of the trials included
biliary cholangitis (PBC), while 39 (54.2%) were classified as non- in the meta-analysis.
PBC. Within the non-PBC group, the diagnoses were distributed as Figure 2.Meta-analysis of clinical events and biochemical parameter
follows: autoimmune hepatitis (8 cases, 11.1%), chronic hepatitis B (9 changes in the included studies.
cases, 12.5%), drug-induced liver injury (8 cases, 11.1%), metabolic-
associated fatty liver disease (5 cases, 6.9%), and smaller proportions
for alcohol-related liver disease (1 case, 1.4%), chronic hepatitis C PP0657
(1 case, 1.4%), and sinusoidal obstruction syndrome (1 case, 1.4%). Lipid peroxidation of intrahepatic biliary epithelial cells in Primary
Additionally, 6 patients (8.3%) had unknown liver diseases. Biliary Cholangitis
Conclusion: Anti-sp100 positivity is not exclusively associated with Ting Jiang1, Hui Jin Yang2
PBC. A significant proportion of patients (54.2%) were diagnosed with 1
The First People‘s Hospital of Yunnan Province, Kunming, China.,
The Second Affiliated Hospital of Kunming Medical University,
2
Result: Overall, 128 patients were randomized to seladelpar and 65 to
Kunming, China. placebo with mean baseline ALP 314.6 U/L and 313.8 U/L, respectively;
Background: Enhanced lipid peroxidation of small bile ducts in 53 (27.5%) patients had baseline ALP ≥350 U/L. Seladelpar reduced
Primary Biliary Cholangitis (PBC) has recently been reported, but its ALP at month 12 similarly across all subgroups, including patients
role for pathological initiation and progression has remained unclear. with cirrhosis, those aged <50 years at PBC diagnosis, and those of
Herein, we carried out a comparative analysis of the lipid peroxidation Hispanic/Latino ethnicity, vs placebo. For patients with baseline ALP
in various stages PBC and HBV controls. ≥350 U/L, seladelpar led to a greater decrease (−44.8%; −216.1 U/L)
Method: Liver biopsies of 33 treatment-naïve PBC patients with in ALP vs placebo (−11.6%; −56.4 U/L); similar percent decreases
positive anti-AMA2 immunoglobulin and abnormal obstruction were seen in patients with baseline ALP <350 U/L. Seladelpar reduced
enzymes were performed. 27 paraffin embedded livers of matched ALP similarly across baseline ALP quartiles. Among patients who did
HBV control patients were collected. Immunofluorescent staining of not meet the composite biochemical endpoint at month 12, ALP was
4-hydroxynonenal (HNE) protein adducts was performed, histological decreased by −129.9 U/L with seladelpar vs −6.4 U/L with placebo.
stages and hepatic function were evaluated. Seladelpar prevented worsening of ALP, with 7 (5.5%) seladelpar
Result: Immunofluorescent staining of liver biopsies showed that patients vs 19 (29.2%) placebo patients with increases in ALP from
HNE was significant increase in PBC than HBV (p<0.001). Notably, baseline at month 12. AEs were reported in 86.4% of patients with
correlation analysis showed that the HNE were closely associated with baseline ALP <350 U/L and 84.9% of patients with ALP ≥350 U/L, with
Ludwig stages (r2 = 0.5931, P<0.001). HNE in intrahepatic bile ducts similar proportions among seladelpar vs placebo patients.
can be used to discriminate between treatment-naïve PBC patients Conclusion: Seladelpar led to robust and consistent ALP decreases
from HBV controls (Area under curve=0.867). across all subgroups studied. Substantial ALP decreases were also
Conclusion: These results validate that enhanced lipid peroxidation of observed in patients who did not meet the composite endpoint criteria
small bile ducts in PBC. Moreover, we also found that lipid peroxidation at month 12. Seladelpar was overall safe and well tolerated, regardless
of small bile ducts may play a vital role in the pathological initiation and of baseline ALP level.
progression of liver, the detailed pathogenic molecular mechanism is Table and Figure:Figure 1.ALP Changes With Seladelpar vs Placebo
worth further study. by Baseline ALP Quartile (RESPONSE Trial)
Table and Figure:Figure 1.Figure 1. Immunofluorescent staining of
hepatic HNE protein adducts in patients with PBC and HBV. (A) PP0659
Immunofluorescent staining of hepatic HNE protein adducts in patients
Clinical analysis of 168 patients with primary biliary cholangitis
with various stages PBC and HBV. HNE, 4-hydroxynonenal protein
adducts; DAPI, 4’,6-diamidino-2-phenylindole. (B). Differentially Li Wang1
expression of HNE in each group were captured by a fluorescence
1
Yantai Qishan Hospital
microscope. P< 0.0001, HBV&PBC; P< 0.001, PBC I-II&PBC III-IV. (C) Background: To retrospectively analyze 168 patients with primary
Correlation between the HNE and the Ludwig stages. biliary cholangitis (PBC) diagnosed clinically and/or pathologically in our
Figure 2.Figure 2. Disease discrimination based on the HNE. hospital from 2015 to 2022, analyze their demographic characteristics,
biochemical, immune and positive rates of autoantibodies, and analyze
the risk factors for progression to cirrhosis.
PP0658
Method: According to the pathology, it was divided into grades I-Ⅳ and
Alkaline Phosphatase Changes With Seladelpar Across Subgroups the overlap syndrome group overlapping with autoimmune hepatitis
of Primary Biliary Cholangitis Patients in the RESPONSE Trial (AIH), and the clinically diagnosed cases with cirrhotic manifestations
Kris V Kowdley1, Kidist K Yimam2, Sonal Kumar3, Edward Mena4, were classified into grade IV. The differences between groups were
Alan Bonder5, K Gautham Reddy6, Christophe Corpechot7, Susheela analyzed by rank sum test or analysis of variance of multiple samples,
Carroll8, Ke Yang8, Linda Wu8, Daria B Crittenden8, Charles A chi-square test for enumeration data. Univariate and multivariate
McWherter9 Logistic regression analysis was used to obtain the risk factors for
1
Liver Institute Northwest, 2Sutter Pacific Medical Foundation, progression to cirrhosis.
California Pacific Medical Center, 3Clinical Hepatology, Weill Cornell Result: The average age was 56.3 ± 11.6 years, with 30 (17.9%)
Medical College, 4California Liver Research Institute, 5Beth Israel males and 138 (82.1%) females. Among the 168 patients, 34 (20.2%)
Deaconess Medical Center, 6University of Chicago Hospitals, were in stage I, 24 (14.3%) in stage II, 14 (8.3%) in stage III, 74
7
Reference Center for Inflammatory Biliary Diseases and Autoimmune (44.1%) in stage IV, and 22 (13.1%) in overlap syndrome. The age
Hepatitis, French Network for Rare Liver Disease in Children and of stage IV (59.7 ± 11.8) was significantly higher than that of other
Adults (FILFOIE), European Reference Network RARE-LIVER, Saint- groups (p=0.013). There were 120 patients (71.4%) with positive anti-
Antoine Hospital and Research Center, Assistance Publique-Hôpitaux mitochondrial antibody M2 (AMA-M2), 73 patients (43.5%) with positive
de Paris, Sorbonne University, 8Gilead Sciences, Inc., 9CymaBay antinuclear antibodies (ANA), 37 patients (22%) with positive Gp210,
Therapeutics, Inc.
and 11 patients (6.6%) with positive Sp-100. The AST level in the
Background: Alkaline phosphatase (ALP) is an important marker overlap syndrome group was comparable to that in stage III patients,
in primary biliary cholangitis (PBC) associated with risk for disease and was significantly higher than that in other groups (p=0.039).
progression. In the pivotal, Phase 3, placebo-controlled RESPONSE There was no significant difference in alkaline phosphatase (AKP) and
trial (NCT04620733), seladelpar, a first-in-class delpar (selective gamma-glutamyl transpeptidase (GGT) levels between groups. The
peroxisome proliferator–activated receptor [PPAR]-delta agonist), led total bilirubin (TB) [40.9 (18.2, 65.2)] and total bile acid (TBA) levels
to a significantly higher percentage of patients with PBC achieving the [46.6 (15.4, 120.7)] in stage IV (p<0.001) were significantly higher than
composite biochemical endpoint (ALP <1.67 × upper limit of normal those in other groups, and the positive rate of AMA-M2 in stage IV was
[ULN], ALP decrease ≥15%, and total bilirubin [TB] ≤ULN) compared 62 (83.8%), which was significantly higher than that in other groups
to placebo (61.7% vs 20.0%) and decreased mean ALP levels after 1 (p=0.009). There was no difference in age and gender distribution,
year (−42.4% vs −4.3%, respectively). Here, we report additional data AKP and GGT levels between the AMA-M2 positive and negative
on ALP changes in the RESPONSE trial. groups. The positive rate of ANA in the AMA-M2 positive group (59,
Method: Patients with PBC who received ursodeoxycholic acid 49.2%) was significantly higher than that in the AMA-M2 negative
(UDCA) for ≥12 months or were UDCA intolerant and had ALP ≥1.67 group (14, 29.%) (p=0.018). There was no significant difference in
× ULN and TB ≤2 × ULN were randomized 2:1 to daily seladelpar plasma IgA, IgM and IgG levels between the stages and between the
10 mg or placebo. We assessed ALP changes across demographic AMA-M2 positive and negative groups. Multivariate Logistic regression
subgroups, across baseline ALP quartiles, and in patients who did analysis showed that age [OR=1.05, 95%CI: 1.02 ~ 1.08, p=0.001]
not meet the composite biochemical endpoint. Worsening of ALP and AMA-M2 positive [OR=3.18, 95%CI: 1.47 ~ 6.87, p=0.003] were
(increase >0 U/L from baseline) and safety by baseline ALP subgroup independent risk factors for progression to cirrhosis.
were also evaluated. Conclusion: The incidence of PBC in women is significantly higher
than that in men. AKP and GGT cannot distinguish the severity of well as the components into blood and liver after oral administration
clinical and pathological conditions. Age and AMA-M2 positive are the in rats were analyzed by UHPLC-Q-Exactive Orbitrap HRMS.
baseline risk factors for progression to cirrhosis. Subsequently, luciferase reporter gene assays of TGR5 were performed
Table and Figure:Figure 1.Table 1. Comparison of demographics, to determine the active components in total astragalus saponins to
biochemistry, and autoantibodies in AMA-M2 positive and negative active TGR5. A PSC mice model induced by 3,5-diethoxycarbonyl-
PBC patients [Mean ± SD or M (Q₁, Q₃)] 1,4-dihydro-2,4,6-coridine (DDC) and the Tgr5-/- mice were used to
Figure 2.Figure 1. Forest plot of multivariate logistic regression investigate the therapeutic effect and mechanism of calycosin. In
addition, AutoDock Vina docking, drug affinity response target stability
(DARTS) and cellular thermal displacement analysis (CESTA) were
PP0660
performed to validate the interaction of calycosin with TGR5.
Relationship between pruritus, sleep disorders and anxiety and Result: Calycosin is a main ingredient in total astragalus saponins
UDCA dose in patients with primary biliary cholangitis: a cross- to activate TGR5 through UHPLC-Q-Exactive Orbitrap HRMS and
sectional study luciferase reporter gene experiments. Calycosin significantly reduced
Yunzhuan Zhao1,2, Jing Liang2 the level of serum ALT, AST and ALP, reduced the positive area of sirius
1
-Nankai University, 2Tianjin Third Central Hospital red staining in liver tissue and hepatic Hyp content, and significantly
Background: Primary biliary cholangitis (PBC) is one of autoimmune improved the DR, bile acid metabolism disorders, and inflammation
liver disease characterised by non-suppurative cholangitis, with a associated with cholestasis in DDC-induced mice. The affinity between
prevalence of 49.2 per 100,000. Pruritus, sleep disorders, and the calycosin and TGR5 was evaluated by AutoDock Vina docking to
occurrence of anxiety are common extra-hepatic manifestations of indicate that the binding affinity between calycosin and TGR5 was -7.4
PBC, which greatly affects the quality of life of patients. This study aims kcal/mol. DARTS and CETSA experiments showed that calycosin bind
to investigate the incidence of pruritus, sleep disorder and anxiety in to TGR5 protein to enhance the stability of TGR5 protein to protect
PBC patients through cross-sectional study, and also to observe the against degradation caused by pronase and high temperature.
relationship between the above symptoms and UDCA dose application. Furthermore, the therapeutic efficacy of calycosin on PSC in DDC-
Method: This study focused on a cross-sectional study of 78 induced mice was abrogated in Tgr5-/- mice, suggesting the anti-PSC
patients diagnosed with PBC in our outpatient clinic from September effect of TAS depends on enhancing TGR5 expression. These results
to November 2024, all of whom had diagnosed with primary biliary suggested that calycosin attenuated PSC in mice through binding to
cholangitis or primary biliary cholangitis cirrhosis, and all of whom TGR5 protein to activate and up-regulate TGR5.
received ursodeoxycholic acid as a first-line medication. The clinical Conclusion: Our results demonstrated that calycosin is the active
symptoms, baseline chemistry data, UDCA dose of PBC patients were ingredient in total astragalus saponins that binds to TGR5 and activates
collected. The Self-Assessment Scale for Anxiety (SAS) was applied TGR5, as well as provided experimental data support for the treatment
for the assessment of anxiety disorders. Multifactorial regression of PSC with calycosin, and helped to further explore the potential
analyses related to pruritus were performed. clinical application value of TGR5 in the treatment of PSC.
Result: Of the 78 patients diagnosed with PBC in our hospital, 58
(74.36%) had compensated cirrhosis at the time of initial diagnosis, PP0663
28 (35.9%) were treated with UDCA standard dosage achieved (13-
A rare etiology of hepatic steatosis
15 mg/kg), 35 (44.9%) had pruritus symptoms, 32 (41.0%) had sleep
disorders, and 20 (25.6%) had anxiety disorders. The prevalence of Shasha Li1, Xing Liu2, Yongfeng Yang3
pruritus, sleep disorders and anxiety in patients with cirrhosis were
1
School of Medicine, Nanjing University, Nanjing, China, 2Department
28.6%, 25.0%, 35.0% respectively, and were not significantly different of infectious disease and liver disease, The Second Hospital of
from that of patients without cirrhosis(P>0.05). The prevalence of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing,
China, 3Department of infectious disease and liver disease, The
pruritus, sleep disorders and anxiety in patients in the UDCA-standard
Second Hospital of Nanjing, Clinical Teaching Hospital of Medical
dosage achieved group was 34.3%, 34.4%, 45.0%, respectively, and
School, Nanjing University, Nanjing, China
was not significantly different from that in the standard dosage not
achieved group(P>0.05). Background: A novel pattern of hepatic injury, distinguished by
Conclusion: This cross-sectional investigation showed that only 35.9% steatosis, has been recently identified in adult patients harboring
of patients were prescribed the standard UDCA dose, the prevalence heterozygous mutations in the autosomal ETFDH gene. These
of pruritus, sleep disorder, and anxiety were high in patients with PBC, individuals frequently exhibit symptoms such as muscle weakness,
however there were no significant relationship with the severity of exercise intolerance, myalgia, and rhabdomyolysis. Additionally, some
the patient’s disease, whether UDCA was applied, and whether the patients may develop cardiomegaly, cardiomyopathy, hepatomegaly,
standard dose of UDCA was reached. liver injury, and fatty liver, indicative of multi-organ damage. Ultimately,
Table and Figure:Figure 1.Basic characteristics of the study population these clinical manifestations lead to a diagnosis of multiple acyl-CoA
Figure 2.Prevalence of pruritus, sleep disturbance and anxiety in the dehydrogenase deficiency (MADD).
study population Objective: To examine the clinical features and ETFDH gene mutations
in a female MADD patient with a 10-year history and notable liver
steatosis, aiming to offer insights into this complex disease.
PP0661 Methods: The diagnosis of late-onset multiple acyl-CoA dehydrogenase
Calycosin attenuates primary sclerosing cholangitis in mice by deficiency was determined through a comprehensive assessment
up-regulating TGR5 that included clinical evaluation, biochemical testing, tandem mass
Enqi Tang1, Xiaohan Yu1, Qun Zhou1, Zheng Zhang1, Yue Liang1, Wei spectrometry analysis, and imaging studies. Genetic analysis of
Liu1, Ping Liu1, Jiamei Chen1 the ETFDH gene mutation was conducted on three family members
1
Institute of Liver Diseases, Key Laboratory of Liver and Kidney utilizing Whole Exome Sequencing (WES) and Sanger sequencing
Diseases (Ministry of Education), Shuguang Hospital Affiliated to methodologies.
Shanghai University of Traditional Chinese Medicine Results: The patient initially exhibited symptoms at the age of 19,
Background: Our previous study has demonstrated that total presenting with a BMI of 18 kg/m², and experienced recurrent
astragalus saponins ameliorated ductular reaction (DR), inflammation episodes of hypoglycemia, myocarditis, myalgia, and fatigue,
and liver fibrosis in primary sclerosing cholangitis (PSC) mice by particularly during periods of heightened stress. Laboratory
rescuing TGR5 expression. However, the main compound in total investigations demonstrated abnormalities in hepatocellular liver
astragalus saponins exerts the anti-PSC effect by up-regulating TGR5 enzymes, alongside elevated cardiac and muscle enzymes and
is not well understood. increased lactate levels. Magnetic resonance imaging (MRI) of the
Method: In this study, the components in total astragalus saponins, as liver revealed severe steatosis. Tandem mass spectrometry of blood
samples identified elevated levels of multiple acylcarnitines (C6, C8,
C10, C12), whereas gas chromatography-mass spectrometry analysis hepatic ciliopathy with nephronophthisis, deafness, dyslexia and
of urine yielded unremarkable results. Histological examination of the central nervous system impairment.
liver confirmed the presence of fatty liver changes. Genetic analysis Method: The aim of our study was to present the phenotypic genotypic
revealed two heterozygous missense mutations in the ETFDH gene: observations in five Indian children with novel biallelic variants and
c.1327T>C (p.Trp443Arg), inherited from the father, and c.1669G>A single exon deletions in DCDC2 gene. Prospective data of children
(p.Glu557Lys), inherited from the mother. A diagnosis of late-onset diagnosed with NSC between March 2023 to February 2024 in a
MADD was confirmed. High-dose vitamin B2 therapy led to rapid tertiary care institute in India were analyzed.
clinical improvement, and there was no recurrence during six months Result: Median age at first presentation was 51 days (30 days- 60
of follow-up. days). Two children presented with seizures due to intracranial bleed at
Conclusion: MADD should be included in the differential diagnosis 2nd month of life, and other two with jaundice and hepatosplenomegaly.
of adult-onset hepatic steatosis, particularly when accompanied by Three children had variceal bleed within 3 years and endotherapy had
systemic manifestations and involvement of multiple organ systems. been done. None of them had extra-hepatic manifestations such as
Prompt and accurate diagnosis can avert superfluous diagnostic renal disease or deafness. Liver biopsy in two children showed portal
interventions and enhance prognostic outcomes, thereby enabling the fibrosis and cholestasis. Magnetic Resonance Imaging of one child
implementation of suitable therapeutic strategies. showed focal narrowing and dilatations of bile duct while others had
minimal intrahepatic biliary radical dilatation. On Next Generation
Sequencing, four different novel variants were identified. Novel
PP0664
variants with frame shift variant in exon7 and splice site variant in intron
Genetic and clinical landscape of progressive familial intrahepatic 6 and single exon deletions in exon 2 and exon 5 of DCDC2 gene were
cholestasis type 1: Novel ATB8B1 variants and genotype- identified associated with NSC.
phenotype correlation This is the first case series of Neonatal Sclerosing cholangitis from
Hui Lin1 India due to novel variants of DCDC2 mutation. Homozygous single
1
Jinan University exon deletions in DCDC2 in exon2 and exon5 were reported previously
Background: Progressive familial intrahepatic cholestasis type 1 in patients with reading disability, language impairment without NSC.
(PFIC1) was a rare genetic disease caused by ATP8B1 variants. This Child with splice site variant had motor developmental delay which
study aimed to landscape the clinical and genetic features, and to improved with age. As these two children were 3 years and 9 months
explore the genotype-phenotype association in PFIC1 patients. respectively at last follow up, reading and language impairment could
Method: The clinical manifestations and laboratory alterations in 15 not be definitely established.
new PFIC1 patients as well as 70 reported ones in the PubMed and Conclusion: Till date only thirty-eight cases have been reported all
CNKI databases were collected and analyzed. over the world. Novel homozygous splice site, frame shift variants and
Result: Totally ten novel pathogenic/likely-pathogenic ATP8B1 variants homozygous single exon deletions of DCDC2 reported here widens
were detected. Clinical presentations included cholestatic jaundice, the spectrum of DCDC2 in NSC. NSC should be considered as
pruritus, hepatomegaly, diarrhea, deafness, and pancreatitis, with differential diagnosis of High GGT cholestasis and early onset portal
increased serum levels of transaminases, total/direct bilirubin and total hypertension after ruling out obstructive causes apart from PFIC 3 and
bile acids while normal or low γ-glutamyl transpeptidase (GGT). The KIF 12 expanding the horizon of decoding cryptogenic cirrhosis.
majority (71.2%, 42/59) of the PFIC1 patients responded insufficiently Table and Figure:Figure 1.
to oral ursodeoxycholic acid(UDCA). Among the patients(28.2%,24/85)
undergoing liver transplantation(LT), severe post-operational liver PP0666
steatosis(93.3%, 14/15) and intractable diarrhea (86.6%, 13/15) were
Integration of hepatitis B virus DNA into hepatocyte genomes of
rather commonly observed. However, LT combined with surgical biliary
cirrhotic chronic hepatitis B children
diversion (SBD) significantly reduced the complications and improved
the survival rates of the graft and patients. On the last follow-up, the Pan Zhao1, Yin Chen2, Yi Dong1, Shizhang Wei3, Weijie Li4
clinical outcomes were not promising in 44 cases (64.7%, 44/68).
1
Fifth Medical Center of Chinese PLA General Hospital, 2962nd
Compared to non-biallelic null ATP8B1 variants, patients with biallelic Hospital of PLA Joint Logistic Support Force, 3Cancer Hospital,
null variants manifested earlier onset ages as well as lower UDCA Chinese Academy of Medical Sciences and Peking Union Medical
College, 4Beijing Ditan Hospital
response and LT-free survival rate.
Conclusion: This study reported 15 new PFIC1 patients bearing 10 Background: Hepatitis B virus (HBV) infection remains a global health
novel ATP8B1 variants. This condition involved multiple systems, with challenge. During the phase of chronic infection, HBV can integrate
normal-GGT cholestatic hepatitis being a hallmark. The UDCA effect the whole or part of its genome into the host’s hepatocyte genomic
was uncertain, LT itself caused severe complications, and the outcomes DNA. As of now, much less is known about HBV DNA integration in
of the patients were generally unfavorable. However, patients might get early childhood cirrhosis.
benefit from combined operation of LT and SBD. Biallelic null ATP8B1 Method: Biopsy liver specimens from cirrhotic and matched non-
variants were associated with earlier clinical initiation as well as more cirrhotic chronic hepatitis B children were collected. A high-throughput
unpromising therapeutic response and clinical outcomes. sequencing method was used to detect HBV DNA integration.
Result: Twenty cirrhotic and 20 non-cirrhotic children with chronic
hepatitis B were included in the study. The mean ages of the cirrhotic
PP0665
group and non-cirrhotic group were respectively 2.9 years and 3.4
Phenotype Genotype Observations of Novel Biallelic Variants years, and no statistical difference existed between the two groups
of DoubleCortin Domain‐Containing protein 2 (DCDC2) Related (P=0.736). There was no significant difference across the two groups
Neonatal Sclerosing Cholangitis - “Expanding Horizon”’ (P=0.529) regarding the median number of HBV integrants. Serum
Deepa Janakiraman1, Nirmala Dheivamani2, Sindhuja T A2, HBV DNA level was correlated with the number of HBV integrants
Senthilkumar R2, Winston Thomas S2 (R2=0.322) in the multivariate linear regression analysis. Six differential
1
Institute of Child Health and Hospital for Children, Madras Medical intragenic high-frequency viral integration sites in cirrhotic children
College , 2Institute of Child Health and Hospital for Children were revealed, which were involved in metabolic processes or cell
Background: Neonatal Sclerosing Cholangitis (NSC) is associated cycle regulation, such as CUB and Sushi multiple domains 1 (CSMD1),
with progressive biliary fibrosis that often requires liver transplantation cut-like homeobox 1 (CUX1), protein tyrosine phosphatase receptor
in childhood. Children present early in life with jaundice, type T (PTPRT) and so on.
hepatosplenomegaly, hyperbilirubinemia and high serum gamma Conclusion: As the first study that specifically focuses on HBV
glutamyl transferase activity (GGT) or intracranial bleed. DCDC2 integration in early childhood cirrhosis, some frequently integrated
pathogenic variants have been reported to be associated with renal- hepatocyte genes were disclosed. Detailed associations between
genetic alterations induced by HBV integration and early childhood
cirrhosis need further exploration. from the Transplant Board and Hospital Ethics Committee, liver
Table and Figure:Figure 1.Possible pathways related to liver cirrhosis in transplants (LT) were performed for each pair. We analysed family
which the six genes may be involved concerns, operative approach, perioperative challenges, clinical data
and graft survival related to DLT.
Result: Eighteen MSUD patients underwent living donor LT, and
PP0667
their explanted livers (domino allografts) were transplanted into 20
Clinical and Genetic Study of Adult Progressive Familial Intra- recipients (Figure 1). Two older children with MSUD underwent split
hepatic Cholestasis 3 in China LT, benefiting four recipients. Of these recipients, eight had metabolic
Zhu Ping1, Liu Ying, Tian Jia Jun, Xiang Hui Ling diseases, five had biliary atresia, two were retransplants, and the rest
1
Tianjin Third Central Hospital had other conditions. Half of the DLT recipients’ families initially feared
Background: Progressive Familial Intrahepatic Cholestasis Type 3 the potential for new genetic conditions but consented after thorough
(PFIC 3) is a genetic liver disease characterized by cholestasis that counselling. All three surgeries in the domino liver transplant were
leads to liver damage and associated symptoms. The disease is performed simultaneously with coordinated teamwork. The MSUD
primarily associated with mutations in the ABCB4 gene, which encodes child’s hepatectomy was straightforward, and all livers were extracted
a protein involved in the transport of bile salts and phospholipids simultaneously by three synchronized surgical teams. Baseline and
across the liver cell membrane.The correlation between genotype and operative characteristics, and outcomes of the MSUD children and
clinical phenotype still unclear. This study retrospectively analyzed their domino liver recipients are summarized in Table 1. The MSUD
the clinical and pathological characteristics of 9 patients with ABCB4 children followed a branched-chain amino acid-free diet pre-transplant
gene-related cholestatic liver diseases. and an unrestricted diet post-transplant, with normalized amino acid
Method: A literature review was conducted using both Chinese and levels and no symptoms. The post-LT ICU and hospital stay durations
English databases to collect and organize published cases of adult were 12 (8–16) days and 34 (22–51) days, respectively. Patient survival
PFIC 3 in China. A systematic analysis and summary were performed among DLT recipients was 65% at a mean follow-up of 25 (15–31)
on the types of genetic mutations, clinical manifestations, laboratory months. No long-term vascular, biliary, or graft-related complications
findings, pathology, and prognosis of the disease. or occurrence of MSUD were observed in the DLT recipients post-
Result: Among the 9 patients analyzed, there were 5 males and 4 transplant.
females, with an average age at diagnosis of 26.3±10.1 years. The Conclusion: Comprehensive family counselling is essential when
main initial clinical manifestations included: jaundice (77.8%), pruritus considering the MSUD liver allograft. Since it is physiologically
(44.4%), and fatigue (33.3%). All patients exhibited pathological normal, the allograft should be offered to individuals awaiting liver
features of portal fibrosis and ductular proliferation. All patients had transplantation without fear of new disease occurrence. A multi-
non-homozygous mutations in the same allele, with 6 cases being disciplinary approach ensures long-term success, and DLT should be
compound heterozygous mutations and 3 cases being heterozygous adopted to address organ shortages.
mutations, resulting in the identification of 20 different mutations in the Table and Figure:Figure 1.A visual summary of the cohort, featuring
ABCB4 gene.Patients with normal MRD3 showed a complete response children with Maple Syrup Urine Disease and Domino Liver Transplant
to ursodeoxycholic acid (UDCA), with liver function fully returning to recipients.
normal; however, patients with MRD3 deletion or reduction had a poor Figure 2.Clinical characteristics and outcomes of Domino Liver
response to UDCA and required liver transplantation. Transplant donors and recipients.
Conclusion: The clinical phenotype of adult PFIC 3 exhibits significant
heterogeneity. There is a certain correlation between the ABCB4 PP0669
genotype and phenotype, but it does not fully determine the clinical
Comparative Analysis of Serum Sphingolipid Profile and Blood
phenotype and severity of liver disease. Additionally, the prognosis of
Lipids in Individuals with Gilbert’s Syndrome and Healthy Control
PFIC 3 patients is closely related to the status of MRD3 deletion.
Haitian Yu1, Chen Liang1, Shan Tang1, Dacheng Sheng1, Jianxia
Dong1, Xinyue Chen1, Zhongjie Hu1, Zhongping Duan1, Wei Hou1,
PP0668 Sujun Zheng1
Perioperative Management, Ethical Concerns, and Outcomes 1
Department of Hepatology, Beijing YouAn Hospital
of Pediatric Domino Liver Transplants from Maple Syrup Urine Background: We aimed to investigate the differences in serum
Disease Donors sphingolipid profiles and their association with blood lipids between
Vipul Gautam1, Vikram Kumar1, Vijaykant Pandey2, Sumit Goyal2, individuals with Gilbert’s syndrome(GS) and healthy control(HC).
Vaibhav Nasa2, Vivek Yadav2, Shweta A Singh2, Dibya Jyoti Das3, Method: This cross-sectional study enrolled 224 participants including
Subhash Gupta4 112 individuals with GS and 112 age- and gender-matched HC. Clinical
1
Pediatric Hepatology, Max Centre for Liver and Biliary Sciences, data were collected to analyze the correlation between bilirubin and
2
Anaesthesia and Critical Care, Max Centre for Liver and Biliary blood lipids. In addition, liquid chromatography-mass spectrometry
Sciences, 3Critical Care Medicine, Max Centre for Liver and Biliary was employed to quantify 53 serum sphingolipid metabolites in
Sciences, 4Liver Transplant Surgery, Max Centre for Liver and Biliary a subset of 55 GS and 55 HC participants from the total cohort of
Sciences 224. OPLS-DA model was constructed using SIMCA 14.1 software
Background: Domino liver transplantation (DLT) addresses organ to identify distinct serum sphingolipid metabolites between the two
shortages by using enzyme-deficient but otherwise healthy livers groups.
from donors with metabolic disorders like Maple Syrup Urine Disease Result: The median age of 224 participants was 35 years, with males
(MSUD). This study highlights ethical challenges, family perspectives, comprising 29.5%. The GS group exhibited significantly higher levels
and decision-making dynamics while presenting our center’s of total bilirubin (TBIL) and high-density lipoprotein (HDL), along with
experience with pediatric DLT, including surgical approach and lower levels of triglycerides (TG) (all P<0.05). Moreover, pearson
outcomes. correlation analysis conducted on 224 participants and grouped by
Method: This retrospective study included all children who underwent gender, revealed distinct patterns. In males, TBIL levels were negatively
DLT between January 2019 and September 2024, expanding on our correlated with TG (r=-0.273, P<0.05), total cholesterol (TC) (r=-
earlier work (Kumar et al., 2023) with additional parameters, including 0.385, P<0.01) and low-density lipoprotein (LDL) (r=-0.405, P<0.01).
a larger cohort, and a detailed evaluation of long-term outcomes. In females, TBIL levels were positively correlated with HDL (r=0.196,
Each MSUD child was paired with a recipient having end-stage liver P<0.05). Analysis of serum sphingolipid in 55 GS and 55 HC participants
disease or a non-MSUD metabolic disorder. Guardians received revealed significant differences in 14 sphingolipids between the two
detailed counselling on the procedure, ethical concerns, and social groups. Compared to the HC group, the GS group had lower levels
implications before providing informed consent. Following approval of Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/25:0), Cer(d18:1/26:0),
Cer(d18:2/16:0), CerP(d18:1/22:0), HexCer(d18:1/22:0),
HexCer(d18:1/24:1), HexCer(d18:1/24:0), LacCer(d18:1/16:0), as well Result: The study included 422 patients with PALF of whom 195
as higher levels of CerP(d18:1/12:0), LacCer(d18:1/24:0), sphingosine- (46.21%) fulfilled the criteria of sepsis and 71 (16.8%) had culture-
1-phosphate, and dihydrosphingosine (all P<0.05). Correlation analysis positive sepsis. Bronchoalveolar fluid (45.7%) was the commonest
of 110 participants indicated that Cer(d18:1/26:0), Cer(d18:2/16:0), site of culture positivity followed by blood (35.8%). More than 80%
CerP(d18:1/22:0), HexCer(d18:1/22:0), HexCer(d18:1/24:0)were of cultures grew gram negative organisms with high prevalence of
positively correlated with TC. Additionally, dihydrosphingosine was carbapenem (77.1%) and multidrug (60%) resistance. Intensive
positively correlated with HDL (all P<0.05). care unit (ICU) stay, mechanical ventilation, grade 3-4 hepatic
Conclusion: The GS group exhibited a healthier lipid metabolism encephalopathy and use of extracorporeal liver support systems were
profile compared to the HC group. Notably, serum ceramide species associated with culture-positive sepsis. Patients with culture-negative
were significantly decreased, potentially contributing to the favorable sepsis had lower NLS and OS, while patients with culture-positive
blood lipids metabolism observed in GS individials. sepsis had outcomes comparable to patients without sepsis. However,
Table and Figure:Figure 1.Research flowchart. culture-positive severe sepsis patients had significantly lowered NLS
Figure 2.Fourteen differential sphingolipid metabolites between (33.3%) and OS (42.9%) at day 28.
Gilbert’s syndrome and healthy control. Conclusion: There is high prevalence of carbapenem and multidrug
resistant sepsis in PALF. ICU stay and use of extracorporeal support
PP0670 are factors independently associated with sepsis. While culture-
positive sepsis did not significantly affect survival, patients with severe
Ultrasonographic evaluation of gallbladder motor function in the sepsis had lower NLS and OS.
diagnosis and prognosis of intrahepatic cholestasis of pregnancy Table and Figure:Figure 1.Kaplan-Meier survival curve depicting and
Zhen Tian1, Fei WANG 1, Minghui Tai1 comparing native liver survival and overall survival in patients with and
1
The First Affiliated Hospital of Xi’an Jiaotong University without sepsis
Background: Intrahepatic cholestasis of pregnancy (ICP) is
characterized by skin pruritus and impaired liver function. Several PP0672
previous studies have revealed that the fasting and ejection volumes
Rotational Thromboelastometry Versus Conventional Haemostatic
of the gallbladder in cholestasis of pregnancy were greater than in
Tests in Children with Decompensated Cirrhosis undergoing
normal pregnancy. The goal of this study was to explore the specific
Invasive Procedures: A Randomized Controlled Trial
ultrasonic features of the gallbladder and evaluate the diagnostic and
prognostic values of ultrasound in ICP. Snigdha Verma1, Seema Alam1, Bikrant Bihari Lal1, Rajeev Khanna1,
Method: We induced a retrospective cohort of 60 ICP patients from Vikrant Sood1, Meenu Bajpai2, Amar Mukund3
January 2021 to December 2022, and compared their data with
1
Department of Pediatric Hepatology and Liver Transplantation,
those from healthy pregnant women (n=60). Gallbladder volume was
2
Department of Transfusion medicine, 3Department of Interventional
evaluated by real-time ultrasound examination after an overnight fast Radiology
and 30, 60, 120 and 180 min after a liquid test meal of 200 mL, and Background: This randomized controlled trial (RCT) was conducted
ejection fraction was calculated. Diagnostic and prognostic values of with the aim to evaluate the efficacy and safety of using ROTEM-
volume and ejection function of gallbladder were analyzed by receiver based transfusion strategy in decompensated cirrhotic children with
operating characteristic (ROC) curve. severe coagulopathy undergoing invasive procedures.
Result: Pregnant women in the ICP group had significantly higher Method: This was an open- label, RCT which included (i) children 6
gallbladder basal volume (43.49 ± 1.34 cm3 vs 26.66 ± 0.83 cm3, months -18 years of age with liver cirrhosis (ii) INR between 2.5 ≤ INR ≤
p<0.01) and higher ejection fraction compared with the healthy 3.5 for all invasive procedures and 2 to 2.5 for liver biopsy (iii) platelet
pregnant women. Ejection fraction (120 min) >54.55% might be used count between 20 × 109/L and 50 × 109/L for all invasive procedures
to predict ICP diagnosis, while Gallbladder volume (60 min) >12.52 (iv) listed for invasive procedures. An interactive web response system
cm3 might predict ICP severity. was used to randomize the patient. Patients randomized to the ROTEM
Conclusion: Our results indicate abnormal volume and ejection and conventional groups received blood component transfusion using
function of gallbladder in patients with ICP. Ejection fraction (120 min) predefined criteria.
can be used to predict ICP diagnosis, and Gallbladder volume (60 Result: A total of 326 invasive procedures were screened for
min) can be used to assess ICP severity. inclusion of which 68 were randomized, 2 patients were excluded, as
Table and Figure:Figure 1.Diagnostic and prognostic value of volume the procedure was cancelled for one and other one had withdrawn
and ejection fraction for ICP consent for the procedure. A total of 66 patients were included (33 in
each group with comparable baseline parameters). The volume of total
blood components, fresh frozen plasma (FFP) and platelets transfused
PP0671
was comparable between the two groups (OR: 1.68, p=0.378). There
Characterizing infections in pediatric acute liver failure: was no difference in procedure- related bleed and transfusion- related
Epidemiology, trends, risk factors and prognosis complications between the two groups. In our study the costs incurred
Tamoghna Biswas1, Bikrant Bihari Lal1, Vikrant Sood1, Pratibha Kale1, were higher in the ROTEM group.
Vikas Khillan1, Rajeev Khanna1, Seema Alam1 Conclusion: ROTEM is not cost effective in cirrhotics with severe
1
Institute of liver and biliary sciences coagulopathy. Higher thresholds for ROTEM are needed in
Background: Infections are common in pediatric acute liver decompensated sick patients to try and bring down the component
failure (PALF) patients. While studies in adults with ALF suggest an usage in the ROTEM arm.
association of sepsis with mortality, there is insufficient evidence from Table and Figure:Figure 1.CONSORT Diagram
the pediatric population. The present study aimed to explore the
prevalence, characteristics, predictors and outcomes of infections in PP0673
pediatric acute liver failure (PALF).
Modified Leipzig Versus Leipzig Score: An Agreement For
Method: This was a descriptive observational hospital-based study.
Diagnosis In Wilson Disease
Data was retrieved from a prospectively maintained database of PALF
Anmol Anmol1, Seema Alam2, Rajeev Khanna3, Vikrant Sood4, Bikrant
patients admitted between January 2012 and June 2024. ‘Sepsis’ was
Biharilal4
defined as presence of systemic inflammatory response syndrome
(SIRS) with suspected or proven infection. Patients with positive
1
senior resident, 2professor, 3Additional Professor, 4Associate Professor
bacterial and/or fungal cultures were labelled as ‘culture-positive Background: Leipzig score was developed at 8th international
sepsis’. Outcome measures included native liver survival (NLS) and meeting in Leipzig, Germany, in 2001 and is a scoring system
overall survival (OS) at day 28. validated in adults and children (sensitivity 94.3%, specificity 94.4%,
positive predictive value 90.9%, and negative predictive value 96.6%). respectively.
In 2019, “modified leipzig score” was derived, where additional points Conclusion: There is a significant difference in the prevalence
were allotted to positive family history, ceruloplasmin <5 mg/dl, and of UGT1A1 gene polymorphisms among patients with suspected
magnetic resonance imaging (MRI) changes whereas D‐penicillamine hyperbilirubinemia, with a higher proportion of slow metabolic types
challenge test was removed. The aim of this study was to determine in hepatology, gastroenterology, and hematology patients, and the
agreement between leipzig score and modified leipzig score for lowest proportion in neonatology patients. Testing for UGT1A1 gene
diagnosis in wilson disease. polymorphisms can help better understand the genetic background
Method: This was retrospective, single centre study (2017-2024), of hyperbilirubinemia and provide references for clinical diagnosis and
whereby 59 genetically proven patients with wilson disease previously treatment.
diagnosed using Leipzig score were reassessed with modified leipzig
score.
PP0675
Result: 59 genetically proven wilson disease patients (69.4% male)
were enrolled at median age of disease onset 9 years (7.2-10.2 Genetic Diagnosis Distribution in Hepatobiliary Ciliopathy
years). 61% children were compound heterozygous and remaining Patients: A Retrospective Study
were homozygous for ATP7B mutation. 86% of patients had Kayser- Hongli Liu1,2, Caiyun Zhang3, Xing Liu3, Yifan Hu4, Shasha Li5, Xixuan
Fleischer (KF) ring positive with median ceruloplasmin 6 (3-10), 24 Wang1,2, Yijun Bao4, Yu Zhang1,2,4, Li Wang4, Zhixiang Du4, Miaoyang
hour urinary copper 529 (242-1212). 72.8% of patients had direct Chen4, Qingfang Xiong4, Yandan Zhong4, Duxian Liu6, Ping Huang4,
coomb’s test (DCT) negative hemolysis with median reticulocyte Wenquan Zeng4, Min Ai4, Kai Zhang3, Yufeng Zheng4, Yuhang Weng4,
count of 3 (1.56-4.36) . Using JASP software for statistical analysis Zhiyuan Xu7, Yongfeng Yang1,2,4
comparison as well difference between calculated score i.e leipzig 1
Clinical Specialty, Second Clinical College, Southeast University,
score and modified leipzig score was performed. Results to determine 2
Department of infectious disease and liver disease, The Second
agreement between two score was done using Bland Altman analysis. Hospital of Nanjing, Teaching Hospital of Southeast University,
The mean difference between modified leipzig score and leipzig score
3
Department of Clinical Research Center, The Second Hospital
was 0.703 (95% CI 0.565 - 0.841). Pearson’s correlation was done, of Nanjing, Affiliated to Nanjing University of Chinese Medicine,
which showed significant correlation between the two scores (p <
4
Department of infectious disease and liver disease. The Second
0.001). Results were depicted using bland altman plot, rain cloud plot. Hospital of Nanjing, Affiliated to Nanjing University of Chinese
Conclusion: The agreement (mean difference of 0.703) and its effect Medicine, 5Department of Hepatology, The Second Hospital of
size showed this difference is not clinically meaningful. And the positive Nanjing, Clinical Teaching Hospital of Medical School, Nanjing
University, 6Department of Pathology, The Second Hospital of Nanjing,
correlation between the two scores is present. In resource limited areas
Affiliated to Nanjing University of Chinese Medicine, 7Department
the modified leipzig score can play an important role in the absence of
of Infectious Disease and Liver Disease. The Second Hospital of
genetic mutational analysis.
Nanjing, Teaching Hospital of Nanjing Medical University
Table and Figure:Figure 1.Bland altman plot
Figure 2.Pearson corelation Background: Hepatobiliary ciliopathies are a group of genetic
disorders caused by dysfunctions in primary cilia, often leading to bile
duct abnormalities, bile duct dilation, and polycystic liver disease. This
PP0674 study analyzed the genetic diagnosis distribution among patients with
The prevalence of UGT1A1 gene polymorphisms in patients with hepatobiliary ciliopathies at Nanjing Second Hospital to identify major
suspected hyperbilirubinemia genetic categories.
Xiangsha Kong1, Bo Feng1, Zixiang Huang2, Xu Cong1, Yijun Shi1, Method: We retrospectively analyzed genetic and clinical data of 16
Xiaofang Liu3, Nan Wu1 patients diagnosed with hepatobiliary ciliopathies from 2017 to 2021at
1
Peking University People‘s Hospital, Peking University Hepatology the Second Hospital of Nanjing. Genetic diagnoses were classified
Institute, Infectious Disease and Hepatology Center of Peking into five categories: ADPKD (Autosomal Dominant Polycystic Kidney
University People‘s Hospital, Beijing Key Laboratory of Hepatitis Disease), ARPKD (Autosomal Recessive Polycystic Kidney Disease),
C and Immunotherapy for Liver Diseases, Beijing International CHF (Congenital Hepatic Fibrosis), Caroli Disease, and other rare
Cooperation Base for Science and Technology on NAFLD Diagnosis, genetic types.
2
School of Basic Medical Sciences, Peking University Health Science Result: Among the 16 patients diagnosed with hepatobiliary ciliopathies
Center, 3Shanghai Koyee Biotechnology LTD at Nanjing Second Hospital, the most common genetic diagnoses
Background: This study aims to investigate the prevalence of UGT1A1 were ADPKD (Autosomal Dominant Polycystic Kidney Disease) and
gene polymorphisms in patients with suspected hyperbilirubinemia CHF (Congenital Hepatic Fibrosis), each accounting for 25% (4 cases)
and analyze the distribution of various UGT1A1 metabolic types of the cohort. ADPKD cases were primarily associated with polycystic
among different patient populations. liver and kidney disease, while CHF was characterized by bile duct
Method: A total of 652 patients with suspected hyperbilirubinemia, plate malformations. ARPKD (Autosomal Recessive Polycystic Kidney
including those from hepatology, gastroenterology, hematology, Disease) accounted for 18.75% (3 cases) and was strongly associated
and pediatric departments, as well as control cancer patients, were with bile duct dilation and portal hypertension. Caroli Disease, seen in
collected for UGT1A1 gene polymorphisms and related clinical data. 2 cases (12.5%), was marked by bile duct hamartomas and dilation.
The UGT1A1 metabolic types were classified according to international Additionally, 3 cases (18.75%) fell under the “Other Types” category,
nomenclature, and the prevalence rates of different haplotypes, which included 1 case of mixed ADPKD+CHF diagnosis presenting
homozygous mutations, and heterozygous mutations of UGT1A1 in with polycystic liver and bile duct abnormalities, 1 case involving a rare
different patient populations were calculated. PKHD1 mutation with polycystic liver and atypical bile duct dilation,
Result: The proportions of normal UGT1A1 metabolic type (1/1) in and 1 case with an unclassified PKD1 mutation associated with liver
patients from different departments were as follows: hepatology 11.2%, and bile duct abnormalities. These findings demonstrate the diversity
gastroenterology 14.5%, hematology 16.7%, neonatology 48%, and of genetic diagnoses in hepatobiliary ciliopathy patients, with ADPKD
control cancer patients 47.2%. The proportions of intermediate UGT1A1 and CHF being the most frequently observed.
metabolic types (1/6, 1/28) in patients from different departments were Conclusion: This study provides an overview of the genetic diversity in
as follows: hepatology 29.5%, gastroenterology 25%, hematology hepatobiliary ciliopathies diagnosed at the Second Hospital of Nanjing.
28.3%, neonatology 32%, and control cancer patients 43%. The Further research into rare ciliopathy-related mutations will contribute to
proportions of slow UGT1A1 metabolic types (6/6, 28/28, 6/28) in improved classification and management of these disorders.
patients from different departments were as follows: hepatology Table and Figure:Figure 1.Table 1 Genetic Diagnosis Distribution in
59.2%, gastroenterology 60.5%, hematology 55%, neonatology 20%, Hepatobiliary Ciliopathy Patients
and control cancer patients 9.9%. Additionally, the prevalence rates of
UGT1A1 *7, *27, *63, and *60 loci were 3.3%, 4.5%, 6.8%, and 51.2%, PP0676
Clinical characteristics, treatment effects and predictive factors of PP0678
liver cirrhosis in patients with Wilson’s disease hepatic type A Case of Cholestasis in an Adult Male: The Mystery of a Long-
Yujia Lu1, Chuansu Yuan1, Yueyang Ma1, Keying Ou1, QingFang Unresolved Condition
Xiong1 Ying Liu1, Ping Zhu1, Ling Hui Xiang1
1
Department of infectious disease and liver Disease, the Second 1
Department of Gastroenterology and Hepatology, Tianjin Third
Hospital of Nanjing, Affiliated to Nanjing University of Chinese Central Hospital
Medicine
A 41-year-old male presented with jaundice, having undergone
Background: Wilson disease (WD) is a rare autosomal recessive partial hepatectomy and cholecystectomy for intrahepatic bile duct
genetic disease that can be treated with drugs. The lack of a single, stones ten years prior. Despite treatment with ursodeoxycholic acid
specific diagnostic indicator leads to diagnostic difficulties, leading to and magnesium isoglycyrrhizinate, his gamma-glutamyl transferase
disease progression to cirrhosis and even liver cancer. (γ-GGT) levels remained elevated. One month before admission, he
Method: The clinical characteristics, imaging, pathological developed severe jaundice after taking an antitussive medication.
manifestations, and genetic testing results of 48 WD patients who have Laboratory tests indicated severe liver dysfunction, with significantly
a Leipzig score ≥4 were collected retrospectively. elevated γ-GGT (1023 U/L), alkaline phosphatase (381 U/L), and total
Result: All of the 48 patients diagnosed WD had liver damage, bilirubin (243.2 μmol/L). Tests for viral hepatitis and autoimmune liver
Males accounted for 54.17%. The median age at diagnosis was 28 disease were negative.
(10.25~40.5)years, 39.58% patients had cirrhosis. The most prevalent Imaging showed irregular liver morphology, splenomegaly, ascites,
mutation was c.2333G>T (p.Arg778Leu) in 41.30%(19/46). Imaging portal vein dilation, and partial dilation of intrahepatic bile ducts. A liver
showed fatty liver in 31.25%(15/48), and “honeycomb-like” cirrhosis biopsy revealed fibrous septa, nodular transformation, and cholestasis
nodules in 73.68%(14/19). Compared with non-cirrhosis group, with bile thrombi, indicating chronic cholestatic liver disease. Genetic
Cirrhosis group had a higher positive rate for the K-F ring , an older age analysis identified compound heterozygous mutations in the ABCB4
at diagnosis and a higher level of IgG, had lower levels of ALT, AST, ALP, gene, consistent with progressive familial intrahepatic cholestasis type
WBC and PLT (P<0.05); Age at diagnosis (OR=1.072, 95%CI=1.007- 3 (PFIC-3). Immunohistochemical staining showed decreased MDR3
1.142, P=0.03) and K-F ring (OR=18.657, 95%CI=1.451-239.924, protein expression in liver tissue.
P=0.025) were independent predictors of WD cirrhosis. The best AUC PFIC is an autosomal recessive disorder leading to intrahepatic
values for age at diagnosis add K-F ring in predicting WD cirrhosis cholestasis due to impaired bile secretion. PFIC-3, specifically caused
was 0.909,. The average follow-up time of 33 patients was 48.6 (12~72 by ABCB4 mutations, results in reduced phospholipid secretion into
) months. The biochemical recovery rate was more than 60% after bile, leading to damage to bile duct cells and cholestasis, which can
12~72 months of treatment with Zinc gluconate and/or penicillamine . progress to cirrhosis and portal hypertension. Clinical manifestations
Conclusion: Age at diagnosis combined with K-F ring is a simple and often include cholestasis and complications from cirrhosis. Diagnosis
effective predictor of WD cirrhosis. Zinc gluconate and penicillamine relies on genetic testing, as biopsy findings are non-specific.
are safe and effective treatments. Immunohistochemical staining that shows reduced or absent MDR3
Table and Figure:Figure 1.Graphical Abstract expression on the hepatocyte bile canalicular membrane can aid in
Figure 2.Liver Histological Manifestations of WD Patients and Imaging diagnosing PFIC-3. However, normal MDR3 expression does not
findings of the patient before and after treatment sufficiently exclude the diagnosis of PFIC-3, as mutations may lead
to MDR3 dysfunction while still allowing for normal synthesis and
PP0677 localization.
ERCP combined with Jianpi Qingdan decoction was used in the The patient’s genetic testing confirmed PFIC-3. He received treatment
treatment of anastomotic stricture complicated with suppurative with UDCA and other hepatoprotective agents, leading to temporary
cholangitis with Biloma in children with PH1 after liver improvement in liver function. However, he later experienced worsening
transplantation jaundice and was diagnosed with decompensated cirrhosis. Currently,
he is on the liver transplant waiting list and continues UDCA treatment.
Shi Xin1,2
Research indicates that liver transplantation offers very high survival
1
上海中医药大学附属曙光医院, 2上海中医药大学
rates for PFIC-3 patients and can significantly improve cholestatic
ERCP combined with Jianpi Qingdan decoction was used in the symptoms.
treatment of anastomotic stricture complicated with suppurative
cholangitis with Biloma in children with PH1 after liver transplantation
Abstract: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder
PP0679
caused by systemic oxalate deposition due to liver enzyme deficiency, PKHD1-deficient cholangiocytes promote HSC activation through
and combined liver-kidney transplantation is currently recommended STAT3-initiated transcriptional activation of SPP1
as first-line treatment. After liver transplantation, biliary complications Mengfan Jiao1, Chuanlong Zhu1
such as anastomotic stenosis (AS) and purulent cholangitis (SC) are 1
Department of Infectious Disease, The First Affiliated Hospital of
often complicated, which significantly affects the quality of life of Nanjing Medical University
patients. Endoscopic retrograde cholangiopancreatography (ERCP) Background: Autosomal recessive polycystic kidney and hepatic
is the “gold standard” for the diagnosis of BC, and it is effective in disease (ARPKD) is a rare hereditary liver disorder, with polycystic
relieving biliary obstruction and guiding the use of antibiotics based kidney and hepatic disease 1 gene (PKHD1) being the most frequently
on bile susceptibility results.Traditional Chinese medicine gallbladder mutated gene. The hallmark features of ARPKD encompass abnormal
is one of the six intestines, “the intestines are used for the general dilation of cholangiocytes, progressive hepatic fibrosis, and polycystic
purpose”,Jianpi Qingdan decoction can soothe the liver and liver and kidneys as commonly observed clinical manifestations.
strengthen the spleen, dampness and yellowing, clear heat and clear Method: Whole-exome sequencing (WES) was employed to identify
the intestines, help to reduce cholestasis, restore normal excretion, and the presence of PKHD1 mutations in patients with congenital hepatic
improve biliary inflammation. In order to improve the understanding of fibrosis (CHF). Single-cell RNA sequencing (scRNA-seq) of liver tissue
clinicians about this disease, ERCP combined with Jianspleen Qingbile was performed, followed by DNA pull-down assay coupled with mass
decoction was reported in the treatment of a child with AS complicated spectrometry (MS) to screen for upstream transcription factors (TFs) of
with SC with biloma after PH1 liver-kidney transplantation. differentially expressed genes. CRISPR-Cas9 technology was utilized
Author’s name:SHI Xin1,2 to generate a PKHD1 gene knockout mouse model by excising exons
Author’s affiliation:1.Shuguang Hospital, Shanghai University of 3-4 of the murine PKHD1 gene.
Traditional Chinese Medicine, Shanghai 201203; 2.Shanghai University Result: WES revealed the presence of compound heterozygous
of Traditional Chinese Medicine, Shanghai 201203 mutations in the patient. Single-cell RNA sequencing results confirmed
a significant increase in cholangiocytes in patients with congenital
hepatic fibrosis (CHF). Among the secreted protein-mediated metabolism (56.8%, 95% CI: 52.3–61.4%) and TCA cycle dysregulation
interactions between cholangiocytes and hepatic stellate cells (HSCs) (43.2%, 95% CI: 39.0–47.5%) in immune-metabolic hotspots. The
in CHF patients, the most pronounced were SPP1 and integrin α8/β1, AI model achieved 89.2% predictive accuracy (AUC=0.89, 95% CI:
with SPP1 exhibiting markedly enhanced expression in the mutated 0.86–0.92) in identifying high-risk niches. Prioritized targets included
cholangiocytes. copper-induced upregulation of SLC40A1 (Ferroportin) and PDK1,
Our team successfully established PKHD1 gene knockout mice which functional testing confirmed as modulators of fibrosis severity.
and observed significant periductal fibrosis in the mice at 6 months. Conclusion: This study provides a comprehensive mapping of
Further investigation revealed that the RNA and protein levels of immune-metabolic interplay in WD using AI-driven single-cell spatial
SPP1 in liver tissues of CHF mice increased significantly with age. To multi-omics, identifying distinct immune niches and copper-induced
further elucidate the cause of elevated SPP1 expression in PKHD1- metabolic disruptions. The findings emphasize potential therapeutic
deficient cholangiocytes, DNA pull-down and MS were used to identify targets and establish a framework for precision therapies, advancing
transcription factor binding to SPP1. The intersection of these pulled- the understanding of WD pathophysiology.
down proteins with a transcription factor library and JASPAR-predicted
SPP1 transcription factors revealed seven potential SPP1 transcription
PP0681
factors. Interestingly, scRNA-seq analysis of the co-expression of these
potential transcription factors with the SPP1 gene showed showed A case of Wilson’s disease easily diagnosed as autoimmune
that, in CHF, the proportion of cholangiocytes co-expressing STAT3 hepatitis
and SPP1 was significantly higher compared to the control group. Lingling Yang1,2, Hui Zhu1, Lifang Chen1, Jingyu Zhang1, Liangtao
Conclusion: Cholangiocytes deficient in PKHD1 upregulate SPP1 Zeng3, Zhili Wen3
expression through the transcription factor STAT3. By binding to 1
Department of Gastroenterology, The Second Affiliated Hospital of
integrin receptors on the surface of HSCs SPP1 induces HSC Nanchang University, 2Department of Molecular Biosciences, The
activation, providing a feasible therapeutic target for the treatment of University of Kansas, Lawrence, USA, 3Department of Pathology, The
liver fibrosis associated with PKHD1 mutations. Second Affiliated Hospital of Nanchang University
Table and Figure:Figure 1. Aims: We aimed to report a case of Wilson’s disease which is easily
misdiagnosed as autoimmune hepatitis (AIH) so as to provide clinical
PP0680 significance for diagnosis and treatment of Wilson’s disease.
Case description: The patient was a 14-year old girl, hospitalized for
AI-Driven Single-Cell Spatial Multi-Omics Mapping of Hepatic
“whole body itching, accompanied by petechiae and ecchymoses
Immune Niches in Wilson’s Disease: Exploring Copper-Induced
on the limbs for 2 months”. She has a history of long-term use of
Immunometabolic Dysregulation for Targeted Therapy
Chinese herbal medicine. Admission examinations were: ALT 28.4
Sahnaz Vivinda Putri1, Prihantini Prihantini2, Rifaldy Fajar3, Rini u/l, AST 63 u/L , TBIL 44.6 umol/L, DBIL 27.3 umol/l, ALB 25.4 g/L,
Winarti4, Claudya Ananta Suryatomo5, Andi Nursanti Ureng6 ALP 123.7 u/l; ceruloplasmin 0.049 g/L; IgG 34.30 g/L, ESR 95 mm/L;
1
Health Management Laboratory, International University Semen ANA 1:100, anti-AMA++. CT showed multiple regenerative nodules
Indonesia, 2Machine Learning for BioMedicine Laboratory, Bandung in liver; liver stiffness: 12.7 kPa. Serum copper: 0.391 mg/L , 24-hour
Institute of Technology, 3Computational Biology and Medicine urine copper: 788 ug (normal 15 ~30 ug/24h) .Head MRI showed
Laboratory, Yogyakarta State University, 4Genomics and Molecular degeneration in basal ganglia under T1W1 and T2W1 signaling; the
Biology Research Laboratory, Yogyakarta State University, Fundus examination showed “K-F” ring; and genetic testing showed
5
Hepatology Research Unit, Bantaeng General Hospital, 6Department the mutation was located at exon 8 of the ATP7B gene.
of Pharmacy, Andini Persada College of Health Sciences
Methods: Based on the above data, the case was diagnosed as
Background: Wilson’s disease (WD) is a rare autosomal recessive “Wilson’s disease” clearly, however, the following questions arise:
disorder caused by ATP7B gene mutations, leading to toxic copper positive autoimmune markers (ANA, AMA, IgG) , elevated ESR, and
accumulation, hepatocyte damage, and systemic dysfunction, long-term use of Chinese herbal medicines. These factors suggest that
including liver fibrosis and failure. While genetic diagnostics have there could be an overlap with “AIH” or “drug-induced autoimmune liver
improved early detection, the role of immune-metabolic interactions injury”. Then liver biopsy was given and it showed moderate interface
in WD progression remains poorly understood. Copper-induced inflammation, lymphocytes and plasma cells infiltrating, lymphocytes
immunometabolic dysregulation is implicated in fibrosis and immune penetrating into hepatocytes, and hepatocytes regenerating in a
dysfunction. This study aimed to map spatial immune niches and “rosette-like” pattern, which are highly suggestive of AIH.
their interplay with hepatic metabolic pathways in WD using single- Results : Based on the above data, the diagnosis was “ Wilson’s
cell spatial multi-omics and AI-driven analysis to identify therapeutic disease combined with AIH”. Nevertheless, considering the monism
targets. of disease etiology, we find that the pathological features of Wilson’s
Method: Liver biopsy samples were obtained from 100 WD patients disease can be diverse including fatty degeneration, inflammatory
(50 early-stage, 50 late-stage) and 50 healthy controls via the necrosis, fibrosis and cirrhosis. Wilson’s disease can indeed simulate
International Wilson Disease Registry (IWDR) and BioBank Japan. AIH such as elevated transaminases, ANA positive, IgG increased,
Spatial transcriptomics and proteomics analyses were performed even histological features (e.g., severe interface inflammation,
using 10x Genomics Visium and NanoString GeoMx platforms, with lymphocyte and plasma cell infiltration, rosette), making it easily to be
single-cell RNA sequencing (scRNA-seq) providing cell-type-specific misdiagnosed as AIH. Then we give penicillamine, zinc and vitamin
resolution. Data integration used Harmony for batch effect correction B6 for the treatment of Wilson’s disease but without hormone. An
and graph convolutional networks (GCNs) to map immune-metabolic improvement in liver function, a decrease in IgG level and 24-hour
interactions. Bayesian structural equation modeling (SEM) inferred urinary copper were observed over the course of 6 months (Fig. 2 ).
causal relationships between copper metabolism and immune Therefore, the final diagnosis is Wilson’s disease, without the presence
dysfunction, while Shapley additive explanations (SHAP) prioritized of AIH based on the patient’s response to copper removal treatment.
therapeutic targets. Findings were validated using GEO and ENCODE Conclusion: Wilson’s disease can indeed simulate AIH, especially
datasets, with functional testing in Atp7b-knockout mouse models. in the early stages of liver involvement when the clinical signs and
Pathway enrichment and cell-cell communication analyses revealed laboratory finds can overlap. It is critically important to consider
immune-metabolic cross-talk. Wilson’s disease as part of the differential diagnosis in patients with
Result: The study identified 67 spatial immune niches in WD livers, suspected AIH, paticularly if the patient does not respond to standard
with copper-enriched zones showing a threefold increase in activated immunosuppressive therapy.
macrophages (p<0.001). Advanced WD stages revealed enriched
CD163+ macrophages and CXCL10+ T cells (OR: 4.12, 95% CI: 3.27–
PP0682
5.18), strongly linked to fibrosis progression (HR: 3.45, 95% CI: 2.86–
4.17, p<0.0001). Metabolomic profiling revealed disrupted glutathione
Liver transplantation for the treatment of arginase-1 deficiency (18.6%, 8/43) patients, including six having undertaken or awaiting
Dan Liu1, Bin Wu, Yandong Sun, Dahong Teng, Jinzhen Cai1 liver transplant, and three died due to liver failure or post-transplant
1
The Affiliated Hospital of Qingdao University complications; However, the cholestatic jaundice was alleviated in 11
and even resolved in other 11(25.6%, 11/43), while hepatomegaly was
Background: Argininemia is rare inborn error of metabolism which,
ameliorated in ten(33.3%, 10/30) and recovered in five patients(16.7%,
when untreated, presents in late infancy with growth delay and
5/30), respectively; The rest 13 patients (30.2%,13/43) were in stable
developmental regression. In developed countries, argininemia is
condition.
diagnosed early by newborn screening and is treated immediately with
Conclusion: ALGS1 was a genetic condition involving multiple systems
a protein-restricted diet. Liver transplantation for argininemia has rarely
with cholestatic hepatitis as the foremost clinical feature. Although
been reported.
hepatobiliary injury was rather refractory and unfavorable outcomes
Method: Our center admitted a 4 years old child with arginase-1
were observed in some patients, the cholestasis was attenuated and
deficiency in January 2021 and performed split liver transplantation
even resolved with the growing ages in nearly half of the patients.
with left lateral liver from donor. Record the trends of postoperative liver
The 12 novel JAG1 variants expanded the genetic spectrum of the
function and blood concentration of arginine for two years.
disease and provided genetic evidences for the definite diagnosis of
Result: Patient‘s liver function returned to normal range on fifth
the patients as well as the genetic counseling of the affected families.
postoperative day. The blood concentration of arginine decrease to
40.2μmol/L at 7 days after surgery. The pronunciation and the ability
of language expression was better than preoperative situation. Double PP0684
calf muscles hypertennia was relieve at 90 days after surgery. The ASSERT-EXT: Final Data From an Open-Label, Phase 3 Study of
typical symptoms such as spastic paraplegia, growth retardation Odevixibat in Patients With Alagille Syndrome
and pyramidal tract signs were obviously relieved at 3 months after Nadia Ovchinsky1, Madeleine Aumar2, Alastair Baker3, Philip Bufler4,
surgery. After two years of postoperative follow-up, the blood arginine Mara Cananzi5, Piotr Czubkowski6, Ozlem Durmaz7, Ryan Fischer8,
concentrations were in the normal range. After rehabilitation training, Giuseppe Indolfi9, Wikrom W Karnsakul10, Florence Lacaille11, Way S
the patient’s sports ability was significantly better compared with his Lee12, Giuseppe Maggiore13, Mathias Ruiz14, Etienne Sokal15, Wendy
preoperative performance L Van der Woerd16, Ekkehard Sturm17, Andrew Wehrman18, Fatine
Conclusion: This case demonstrates when conservative treatment is Elaraki19, Judy Zhu20, Alejandra Ramirez-Santiago20, Qingqing Li21,
ineffective for the Arg-1 deficiency, liver transplantation treatment can Henkjan J Verkade22
be used and the blood concentration of arginine recover to normal 1
Pediatric Gastroenterology and Hepatology, Hassenfeld
level. Children’s Hospital, NYU Langone, 2Univ Lille, CHU Lille, Pediatric
Gastroenterology, Hepatology, and Nutrition, Inserm U1286 Infinite,
PP0683 CHU Lille Pôle Enfant, 3Paediatric Liver Centre, King‘s College
Hospital, 4Department of Pediatric Gastroenterology, Nephrology,
Cholestasis amelioration with growing ages despite intractable
and Metabolic Diseases, Charité Universitätsmedizin Berlin,
hepatobiliary injury: JAG1 genotyping-based clinical 5
Paediatric Gastroenterology, Digestive Endoscopy, Hepatology,
characterization on 43 pediatric patients with Alagille syndrome
and Care of the Child With Liver Transplantation, Department of
type I Children’s and Women’s Health, University Hospital of Padova,
Li Guo1, Tao Jiang2, Jianwu Qiu3, Mei Deng1, Weixia Lin1, Xiaoling 6
Department of Gastroenterology, Hepatology, Nutritional Disorders,
Long4, Xiangran Cai1, Qing Zhou1, Shuangjie Li2, Yuanzong Song1 and Pediatrics, The Children’s Memorial Health Institute, 7Istanbul
1
The First Affiliated Hospital, Jinan University, 2The Children’s Hospital University, Istanbul Faculty of Medicine, 8Division of Pediatric
of Hunan Province, 3Yuebei People’s Hospital, 4Shenzhen Baoan Gastroenterology, Hepatology, and Nutrition, Children‘s Mercy
women‘s and Children‘s Hospital Hospital, 9Meyer Children‘s Hospital IRCCS, 10Division of Pediatric
Background: Alagille syndrome type 1 (ALGS1; OMIM:118450) was Gastroenterology, Hepatology, and Nutrition, Department of
an autosomal dominant condition presenting with cholestatic liver Pediatrics, Johns Hopkins University School of Medicine, Baltimore,
disease, facial malformations, heart defects, vertebral anomalies and
1
1Pediatric Gastroenterology-Hepatology-Nutrition Unit, Hôpital
Universitaire Necker-Enfants Malades, 12Department of Paediatrics,
ophthalmology abnormalities, with JAG1 being the causative gene. As
Faculty of Medicine, University of Malaya, 13Hepatology and Liver
a rare disease in general, the phenotype and genotypic characteristics
Transplantation Unit, Bambino Gesù Children‘s Hospital IRCCS,
of ALGS1 remained yet open for investigation thus far. This study aimed 1
4Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Hépatologie
to explore the clinical, biochemistry and genetic features of a patient
Gastro-entérologie et Nutrition Pédiatriques, 15Université Catholique
cohort with this disease. de Louvain, Cliniques St Luc, Service de gastroentérologie et
Method: The research subjects in this study included 43 new pediatric hépatologie pédiatrique, 16Department of Pediatric Gastroenterology,
ALGS1 patients. Next-generation sequencing and chromosomal Wilhelmina Children’s Hospital, University Medical Center
microarray analysis were performed, and the pathogenicity of the Utrecht, Utrecht, the Netherlands, 17Pediatric Gastroenterology
novel JAG1 variants was judged by the American College of Medical and Hepatology, University Children’s Hospital Tübingen,
Genetics (ACMG) standards and guidelines. The clinical and 1
8Division of Gastroenterology, Hepatology, and Nutrition, Boston
biochemistry data were analyzed qualitatively and quantitatively, and Children’s Hospital, 19Ipsen Pharma, 20Ipsen, 21Ipsen (Shanghai)
compared among different age groups or between JAG1 genotypes. Pharmaceutical Co., Ltd, 22Pediatric Gastroenterology/Hepatology,
Result: Among the 43 patients, 36 heterozygous JAG1 variants Department of Pediatrics, University of Groningen, Beatrix Children’s
were detected, including 12 novel ones being pathogenic or likely Hospital/University Medical Center Groningen
pathogenic. The clinical presentations included dysmorphic facies, Background: In the 24-week ASSERT study (NCT04674761), the
jaundice, heart malformations, growth failure, hepatomegaly, skeletal first and only phase 3 randomized study in patients with Alagille
malformations, ophthalmology abnormalities, renal manifestations, syndrome (ALGS), odevixibat significantly lowered pruritus and serum
and pruritus. Besides, direct hyperbilirubinemia, elevated serum bile acids (sBAs) vs placebo, and most treatment-emergent adverse
levels of alanine/aspartate aminotransferases(ALT/AST), γ-glutamyl events (TEAEs) were mild or moderate. The 72-week ASSERT-EXT
transpeptidase(GGT), alkaline phosphatase(ALP), and total bile study (NCT05035030) evaluated the long-term efficacy and safety of
acids(TBA), Dyslipidemia, as well as deficiency of vitamin D and odevixibat in patients with ALGS; here, we report final study data from
zinc were all more commonly observed in the patients. In line with ASSERT-EXT.
the growing ages, although the enzymatic activities above remained Method: Patients who completed ASSERT were eligible to enter
intractably elevated, direct hyperbilirubinemia, hypercholanemia, ASSERT-EXT; all patients in ASSERT-EXT received odevixibat 120 μg/
hypercholesterolemia and hypertriglyceridemia were ameliorated kg/day. The primary efficacy outcome was change in pruritus score
at varying degrees gradually. On the latest follow-up at their ages from baseline (BL) to weeks 69−72. Other outcomes included change
of 28(2,165) months, unpromising outcomes were observed in eight from BL in sBAs, proportion of patients with clinically meaningful
decrease in pruritus score (ie, ≥1-point reduction from BL), and TEAE Figure 2.Overlay and density visualization map of the keywords, and
incidence. Results were evaluated in patients who received odevixibat keywords with the strongest citation bursts (A, B, C). Visualization map
in both ASSERT and ASSERT-EXT (ODX/ODX) and those who received of literature co-citation clustering (D, E).
placebo in ASSERT and switched to odevixibat in ASSERT-EXT (PBO/
ODX); BL was pre‑odevixibat (ie, ASSERT BL for ODX/ODX and
PP0686
ASSERT-EXT BL for PBO/ODX).
Result: Of 52 patients who completed ASSERT, 50 patients (median Efficacy and Safety Of Odevixibat In A Subgroup Of Adult Patients
[range] age, 5.5 [1.0−15.9] years) continued into ASSERT‑EXT (ODX/ With Progressive Familial Intrahepatic Cholestasis In The PEDFIC
ODX, n=33; PBO/ODX, n=17). Mean (SD) pruritus scores at BL and 2 Study
weeks 69−72 of ASSERT-EXT were 2.8 (0.5) and 0.6 (0.7) for ODX/ Henkjan J Verkade1, Janis M Stoll2, Qingqing Li3, Tao Gu4, Fatine
ODX, respectively, and 2.2 (1.0) and 0.8 (0.8) for PBO/ODX; mean Elaraki4, Alejandra Ramirez-Santiago5
(SD) changes from BL to weeks 69−72 of ASSERT-EXT were −2.2 1
Department of Pediatrics, University Medical Center Groningen,
(0.9) points (ODX/ODX; P<0.0001 vs BL) and −1.7 (0.8) points (PBO/ 2
Department of Pediatrics, Washington University School of Medicine,
ODX; P<0.0001 vs BL; Figure A). Mean (SD) sBAs at BL and week 72
3
Ipsen (Shanghai) Pharmaceutical Co., Ltd, 4Ipsen Pharma, 5Ipsen
of ASSERT-EXT were 244 (115) and 119 (100) µmol/L for ODX/ODX, Background: While progressive familial intrahepatic cholestasis
respectively, and 265 (160) and 106 (84) µmol/L PBO/ODX; mean (SD) (PFIC) typically presents in infancy, symptoms may not occur until
changes in sBAs from BL to week 72 of ASSERT-EXT were −124 (136) adulthood in some patients. The phase 3 PEDFIC 1 and PEDFIC 2
µmol/L (ODX/ODX) and −139 (101) µmol/L (PBO/ODX; Figure B). The studies (NCT03566238; NCT03659916) evaluated the effects of
proportion of patients who achieved a ≥1‑point pruritus reduction from odevixibat, an ileal bile acid transporter inhibitor, in patients with PFIC.
BL at weeks 69−72 of ASSERT‑EXT was 93% (28/30) for ODX/ODX and To investigate treatment effects of odevixibat in adults with PFIC, we
77% (10/13) for PBO/ODX. During ASSERT-EXT, drug-related TEAEs examined its efficacy and safety in an adult subgroup from PEDFIC 2.
were reported in 18% (6/33; ODX/ODX) and 41% (7/17; PBO/ODX) of Method: PEDFIC 2, a 72-week, open-label extension study that was
patients; none were serious. The most common drug-related TEAE, ongoing at the time of the analysis, evaluated odevixibat 120 µg/kg/day
diarrhea, occurred in 6% (2/33; ODX/ODX) and 18% (3/17; PBO/ODX) in patients of any age with any type of PFIC. This analysis, in patients
of patients. A single patient, in PBO/ODX, discontinued the study to >=18 years of age, spanned from patients’ first dose of odevixibat to a
undergo liver transplantation. data cutoff of July 31, 2022. Serum bile acids (sBAs), patient-reported
Conclusion: Patients with ALGS in ODX/ODX entered ASSERT-EXT pruritus scores (range, 0–4; higher scores indicate worse symptoms),
with reduced pruritus and sBAs compared with BL; these results were hepatic paramters (total bilirubin and alanine aminotransferase [ALT]),
sustained with longer odevixibat treatment. Patients in PBO/ODX had and treatment-emergent adverse events (TEAEs) were evaluated.
mean reductions in pruritus and sBAs with odevixibat in ASSERT-EXT. Result: Five adult patients with PFIC (PFIC1, n=3; PFIC2, n=2)
The safety profile of odevixibat during longer follow up in ASSERT- enrolled in PEDFIC 2 (40% female; mean [range] odevixibat exposure,
EXT was consistent with that from ASSERT. These robust long-term 56.5 [24.0–90.4] weeks). At the data cutoff, 4 patients were ongoing in
data demonstrate sustained and durable efficacy and tolerability of the study and 1 had discontinued due to withdrawal of consent. sBAs
odevixibat for treatment of cholestatic pruritus in ALGS. ranged from 213–433 µmol/L at baseline (BL) and 11–446 µmol/L at last
Table and Figure:Figure 1.Figure: Mean pruritus scores (A) and serum assessment; 4 of 5 patients had reductions in sBAs at last assessment.
bile acid levels (B) over time during ASSERT and ASSERT-EXT in Four patients had reductions in pruritus at last assessment; reductions
patients with ALGS fom BL ranged from 0.2–2.5 points. Four patients with elevated total
bilirubin at BL (range, 26–1004 µmol/L) had a decrease or minimal
PP0685 change by last assessment (range,14–568 µmol/L). BL ALT levels were
elevated in 4 patients (range, 64–136 U/L); 4 patients had a reduction
Research trends and hotspots of adult Alagille syndrome: A
or minimal change by last assessment (range, 28–69 U/L). TEAEs
bibliometric analysis
were reported in 4 of 5 patients (80%); most were mild to moderate in
Qing Liu1, Chao Sun1 severity. Two patients had serious TEAEs: streptococcal septic arthritis
1
Tianjin Medical University General Hospital (n=1) and acute pancreatitis (n=1; patient had history of pancreatitis).
Background: Alagille syndrome (ALGS) is a complex and rare There were no drug-related TEAEs, and no patient discontinued due
autosomal dominant disorder that affects multiple systemic organs, to TEAEs.
including the liver, heart, kidneys, blood vessels, and eyes. However, Conclusion: In this analysis of adult patients with PFIC from PEDFIC 2,
as a rare disease, adult ALGS is still underrecognized clinically. The most appeared to experience clinical benefit with odevixibat, including
aim of this article is to review the research status and trends of adult reductions in sBAs and pruritus. Overall, the tolerability profile of
Alagille syndrome worldwide in the existing literature. odevixibat in these patients was consistent with previous reports.
Method: The authors utilized the Web of Science Core Collection Additional clinical investigation in this population is warranted.
database to identify articles on adult ALGS published from the database
inception to December 31, 2023. The authors used bibliometric PP0687
methods to analyze authors, institutions, countries, journals, and
references of 156 included articles through CiteSpace and VOSviewer. Cuproptosis-associated hub gene identification and immune cell
Result: The number of publications in this field has shown a volatile infiltration patterns in Wilson disease
growth trend this year. The United States published the most articles Shan Tang1, Wei Hou1, Haitian Yu1, Sujun Zheng1
and University of Pennsylvania is the leading institution in this area.
1
First Department of Hepatology, Beijing YouAn Hospital, Beijing,
The research on adult ALGS mainly focuses on molecular biology, China
genetics, health, nursing and clinical medicine. The keywords were Background: Wilson Disease (WD) is an autosomal recessive genetic
“human jagged1”,” mutations” and “children”. The keyword with the disorder caused by mutations in the ATP7B gene, which encodes
strongest citation burst is “children”. a copper-transporting ATPase predominantly expressed in liver
Conclusion: Our study systematically summarizes the results of cells. This enzyme plays a critical role in copper excretion, and its
adult ALGS researches, describes and predicts research hotspots dysfunction due to genetic mutations leads to copper accumulation
and trends on a global scale, which may be helpful for doctors and in various organs and tissues, particularly the liver and brain. This
researchers to improve their clinical understanding of this disease, and accumulation results in a wide range of symptoms, primarily involving
provide a valuable reference for future intensive investigation. hepatic, neurological, and psychiatric disturbances. Recent studies
Table and Figure:Figure 1. Geographic distribution of global articles suggest a potential link between Wilson Disease and cuproptosis, a
and cases on adult Alagille syndrome (A). Cooperation status of form of copper-induced cell death. This study aimed to investigate the
countries published research literature on adult Alagille syndrome (B). role of cuproptosis-related genes (CRGs) in the pathogenesis of WD
The dual-map overlay of journals related to adult ALGS (C).
and to elucidate the underlying molecular mechanisms. long-term effectiveness in patients with ALGS. Results from cohort
Method: First, we demonstrated the pivotal role of cuproptosis in 2 of ASSERT-EXT will help to determine the safety and tolerability of
the pathogenesis of WD using a mouse model. We then analyzed odevixibat treatment in patients aged <12 months with ALGS.
genes associated with both WD and cuproptosis, identifying key
genes through the application of two machine learning techniques.
PP0689
Additionally, we explored the correlation between these key genes and
immune cell populations, and identified the key pathways involved. Polymorphisms of Plasminogen Activator Inhibitor-1 (rs1799889)
Result: First, we found that cuproptosis was involved in liver injury in Gene as a Risk Factor of Childhood-Onset of Cavernous
ATP7B-/- mouse model. We then validated the expression of key genes Transformation of the Portal Vein
associated with cuproptosis in both the WD and healthy control mice. A Evelina Trashkun1, Diana Daduns1, Kseniya Gulyaeva1, Maxim
total of 14 differentially expressed copper-related genes (CRGs) linked Privalov1, Maria Nadinskaia1
to silicosis were identified. Further analysis revealed 6 key CRGs: Afp, 1
Sechenov First Moscow State Medical University (Sechenov
Alb, Lox, Gls, App, and Gpc1. Compared to healthy controls, WD University), Moscow, Russia
mice exhibited increased immune cell infiltration in dendritic cells, Background: Cavernous transformation of the portal vein (CTPV)
granulocytes, NK cells, germinal center B cells, and DC cells. is the leading cause of portal hypertension and the associated with
Conclusion: These findings highlight the strong association between variceal bleeding in children. The most of the paediatric patients with
WD and cuproptosis. Among the CRGs, Afp, Alb, Lox, Gls, App, and CTPV have local prothrombotic risk factors and the role of inherited
Gpc1 emerge as key players in WD by regulating DC cells, NK cells, thrombophilia is not well understood. Aim: To evaluate the association
and CD8 T cells. of childhood-onset CTPV with coagulation, platelet-related and
Table and Figure:Figure 1.Cuproptosis contributes to Wilson disease folate cycle gene polymorphisms, as well as polymorphisms of the
Figure 2.Distinct immune cell types in WD compared with healthy plasminogen activator inhibitor-1 (PAI-1) gene and selectin P ligand
controls (SELPLG) gene.
Method: A retrospective study of 31 patients with childhood-onset
PP0688 CTPV was carried out. In all patients, CTPV was confirmed by contrast-
enhanced abdominal computed tomography at the time of the study.
Open-Label Study of Odevixibat Safety and Tolerability in Infants
The group included 13 men and 18 women, with a median age of 5
Aged <12 Months With Alagille Syndrome: Clinical Study Design
[3; 12] years at first presentation of CTPV and a median age of 27
Nadia Ovchinsky1, Quanhong Ni2, Roshawn Watson2, Qingqing Li3, [23.5; 30] years at the time of the study. Healthy controls were 65
Alejandra Ramirez-Santiago2 volunteers: 27 men and 38 women, median age 28 [24; 36] years. All
1
Pediatric Gastroenterology and Hepatology, Hassenfeld Children’s were tested for polymorphisms of genes of coagulation factors (F): F2
Hospital at NYU Langone, 2Ipsen, 3Ipsen (Shanghai) Pharmaceutical (rs1799963), F5 (rs6025), F7 (rs6046), F12 (rs1801020), F13 (rs5985),
Co., Ltd fibrinogen (rs1800790); platelet-related glycoprotein Ib (rs41439349,
Background: In Alagille syndrome (ALGS), cholestatic liver disease rs6065) and integrin subunit alpha 2 (rs1126643), beta 3 (rs5918);
is commonly observed and often presents in the first 3 months of folate cycle: methylenetetrahydrofolate reductase (rs1801133),
life, resulting in increased serum bile acid levels and severe pruritus. methionine synthase (rs1805087), methionine synthase reductase
Odevixibat is approved in the United States for the treatment of (rs1801394); PAI-1 gene (rs1799889) and selectin P ligand (SELPLG)
cholestatic pruritus in patients aged 12 months and older with gene (rs2228315). Real-time polymerase chain reaction was used to
ALGS. In the phase 3, placebo-controlled, 24-week ASSERT study detect polymorphisms. Hardy-Weinberg equilibrium was estimated
(NCT04674761), odevixibat was efficacious in improving pruritus and for the distribution of genotype frequencies for all polymorphisms.
reducing serum bile acids in children aged >12 months with ALGS. Groups were compared using the model of common and multiplicative
ASSERT-EXT (NCT05035030) is an ongoing, phase 3, open-label study inheritance.
in patients with ALGS that includes 2 cohorts: cohort 1 is a 72-week Result: The distribution of the genotype and allele frequencies for the
extension study evaluating long-term safety and efficacy of odevixibat studied polymorphisms was in accordance with the Hardy-Weinberg
in patients who completed the ASSERT study, and cohort 2 will equilibrium in both groups. None of the patients had a mutation in
evaluate the safety, pharmacokinetics (PK), and pharmacodynamics the prothrombin gene and the Leiden mutation. There were also no
of 12 weeks of odevixibat treatment in infants aged <12 months with differences in allele and genotype frequencies between the groups for
ALGS. Here, we describe the study design of cohort 2 of ASSERT-EXT. the following polymorphisms: rs6046, rs1801020, rs5985, rs1800790,
Method: Cohort 2 is expected to enroll approximately 10 infants. rs41439349, rs6065, rs1126643, rs5918, rs1801133, rs1805087,
Eligible patients are aged ≤11 months with clinically confirmed ALGS, rs2228315. Only the rs1799889 substitution of the PAI-1 gene differed
body weight ≥2 kg, and gestational age ≥36 weeks. Key exclusion between groups: the frequency of the 4G allele was 1.4 times greater
criteria are presence or medical history of other types of liver disease, in the CTPV group (p=0.006), the frequency of the 4G/4G genotype
inflammatory bowel disease, chronic diarrhea requiring intervention, or was twice greater in the CTPV group (p=0.02) compared to the control.
chronic kidney disease; serum alanine aminotransferase (ALT) levels The common and multiplicative inheritance models are shown in the
>10-fold above the upper limit of normal (ULN) or total bilirubin levels table.
>15-fold above the ULN at screening; or biliary diversion surgery in the Conclusion: Carrying the 4G allele rs1799889 of the PAI-1 gene, as
6 months prior to study start or liver transplantation planned within 6 well as the 4G/4G genotype, is associated with childhood-onset CTPV.
months of study start. Eligible patients will receive odevixibat 120 µg/ Table and Figure:Figure 1.The common and multiplicative models of
kg once daily for 12 weeks. For administration in infants, odevixibat plasminogen activator inhibitor-1 (rs1799889) gene inheritance.
capsules can be opened and the contents sprinkled onto soft food
or mixed into infant formula or breast milk. The primary objective of
PP0690
cohort 2 is to evaluate odevixibat safety and tolerability, which will
be assessed by analyzing treatment-emergent adverse events and Recurrent liver dysfunction resulting in the diagnosis of XMEN
changes in physical examination, concomitant medications, vital signs, disease in a 20-year-old male
laboratory tests, and fat-soluble vitamin levels. Secondary objectives Rongqiang Liu1, Chun Liu1, Xuheng Teng1, Ling Gong2
are to evaluate odevixibat PK at day 1 and weeks 4, 8, and 12 and 1
Hangzhou Normal University, 2Department of Infectious Disease
changes in serum bile acid levels from baseline to week 12. After study (Liver Diseases), The Affiliated Hospital of Hangzhou Normal
completion, patients will complete a 2-week safety follow-up or may University
enroll in an optional extension. X-linked immunodeficiency with magnesium deficiency, Epstein-
Result: Not applicable. Barr virus (EBV) infection, and neoplasia (XMEN) is a rare genetic
Conclusion: Odevixibat has a well-established efficacy and tolerability disorder caused by loss-of-function mutations in the MAGT1 gene.
profile in patients aged >12 months with ALGS and has potential for
This disease presents with a wide range of clinical and immunological well as schistosomiasis, were negative. These findings confirmed
manifestations. The initially described patients typically exhibit idiopathic portal hypertension (Banti’s Syndrome). The patient
CD4 T-cell lymphopenia, immunodeficiency, EBV viremia, and EBV- declined splenectomy and devascularization. He was readmitted
associated lymphoproliferative disorders. for recurrent melena and underwent Balloon-Occluded Retrograde
We report the case of a 20-year-old Chinese male with a history of Transvenous Obliteration (BRTO) with splenic artery embolization. No
recurrent respiratory infections and elevated liver enzymes. Two weeks gastrorenal shunt was identified, so only splenic artery embolization
prior to admission, the patient developed fever, abdominal pain, was performed. Postoperative monitoring revealed no signs of splenic
and diarrhea. Laboratory tests at a local hospital revealed elevated abscess. The patient was discharged with resolution of pancytopenia,
C-reactive protein (13.83 mg/L), altered liver function tests (alanine maintained on beta-blockers. Two months later, follow-up CBC showed
aminotransferase [ALT] 510 U/L, aspartate aminotransferase [AST] 231 normal blood counts, and repeat endoscopy revealed persistent
U/L, and glutamyl transpeptidase [GGT] 225 U/L), and normal stool grade III esophageal varices, but significant resolution of gastric
analysis. The patient was initially diagnosed with acute gastroenteritis and complete resolution of duodenal varices. The patient has had no
and treated with liver protection and anti-infective medications, which further gastrointestinal bleeding since the procedure.
led to symptom improvement. Conclusion
Upon referral to our hospital, further immunological tests showed This case highlights the complexity of Banti’s Syndrome, a rare
decreased CD3 (23.1%), CD4 (5.7%), and a reduced CD4/CD8 ratio but significant cause of gastrointestinal hemorrhage and portal
(0.4). No significant abnormalities were observed in the humoral immune hypertension in young patients. The absence of hepatic fibrosis
response. Additionally, peripheral blood EBV DNA was detected at and exclusion of secondary causes were essential in establishing
1150 copies/mL. Abdominal contrast-enhanced CT scans revealed the diagnosis. Multidisciplinary management is crucial for optimal
splenomegaly, mild retroperitoneal and mesenteric lymphadenopathy, outcomes. Further research is needed to better understand the
and multiple lymph nodes adjacent to the bilateral iliac vessels. Four pathophysiology and refine treatment strategies for Banti’s Syndrome.
days after admission, the patient developed diarrhea and fever once
again. Fecal culture confirmed a Salmonella infection, and humoral
PP0693
immune testing showed decreased IgG (7.26 g/L) and IgM (0.95 g/L).
After 10 days of intravenous levofloxacin (200 mg daily), the patient’s Triple Rare Thrombosis Including Portal Vein Thrombosis
condition improved, and subsequent fecal cultures were negative for Associated with Vaccine-Induced Immune Thrombotic
Salmonella. Thrombocytopenia after Gam-COVID Vac Vaccination
Given the patient’s history of recurrent infections, elevated Maxim Privalov1, Kseniya Gulyaeva1, Alina Volkova2, Diana Daduns1,
transaminases, and chronic EBV infection, we considered the Evelina Trashkun1, Maria Nadinskaia1
possibility of a congenital genetic disorder. Whole exome sequencing 1
Sechenov First Moscow State Medical University (Sechenov
subsequently identified a hemizygous MAGT1 mutation (c.712C>T, University), Moscow, Russia, 2The Central Clinical Hospital of the
p. Arg238Ter), which was confirmed by family genetic analysis. Administrative directorate of the President of the Russian Federation,
Functional prediction using MutationTaster indicated that this mutation Moscow, Russia
is pathogenic, resulting in premature translation termination and Introduction: The incidence of vaccine-induced immune thrombotic
potential functional disruption of the protein. Based on these findings, thrombocytopenia (VITT) ranged from 3.2 to 16.1 cases per million
the patient was diagnosed with XMEN syndrome, a condition that, after the viral vector vaccines ChAdOx1-S (AstraZeneca, UK) and was
to our knowledge, has rarely been reported in Asia. Currently, there 4 times lower after Ad26.COV2.S (Johnson & Johnson, США). Single
is no specific treatment for this disease, but regular follow-up and cases of one localization (the cerebral sinus) thrombosis have been
infection prevention are crucial. This case highlights the importance of described after vector vaccine Gam-COVID-Vac. We describe the first
considering XMEN disease in the differential diagnosis of unexplained case of a successful resolution of a triple rare venous thrombosis after
liver injury and recurrent infections. administration of the Gam-COVID-Vac vaccine.
Case description: A 36-year-old woman developed fever above
PP0691 39.5°C, severe headache, generalized seizure, shortness of breath
and abdominal pain 10 days after her first dose of Gam-COVID-Vac
A Rare Case of Banti’s Syndrome Cured by Autosplenectomy
(consisting of two recombinant adenovirus vector components, type
Clarisse Bayani Porras1, IRSON LECIAS DORIA1, Alex Alcasid1 26 (rAD26) and type 5 (rAd5), both encoding the S glycoprotein of
1
SOUTHERN PHILIPPINES MEDICAL CENTER the SARS-CoV-2 virus (rAD26-S and rAD5-S). Work up revealed 92%
Introduction saturation, severe thrombocytopenia (platelet count 40,000 per mL),
Idiopathic portal hypertension (Banti’s Syndrome or Non-cirrhotic Portal mild anemia (hemoglobin concentration 104 g/L), ALT 76 U/L, AST
Fibrosis) is marked by elevated portal pressure without liver histologic 68 U/L and a 55-fold increase in D-dimer (13800 ng/ml). A triple rare
changes or extrahepatic portal vein obstruction. Its cause remains venous thrombosis: upper sagittal sinus, right main pulmonary artery,
unclear, though factors like arsenic exposure and hypervitaminosis portal vein thrombosis (PVT) was reached according to the computed
A are implicated. This case highlights diagnostic and management tomography angiography (Fig.). All screening tests for thrombotic
challenges in a young patient with severe gastrointestinal bleeding. microangiopathy, thrombotic thrombocytopenic purpura, immune
Case Report thrombocytopenia, antiphospholipid syndrome, paroxysmal nocturnal
A 23-year-old male with no significant medical history presented with hemoglobinuria and disseminated intravascular coagulation were
melena. He had a 7-year history of non-radiating, burning epigastric negative in the differential diagnosis. There was no history of heparin
pain, initially treated as nonpeptic ulcer disease with antacids use. A diagnosis of VITT was made and therapy was initiated, including
and PPIs, which provided minimal relief. Recently, the symptoms a direct oral anticoagulant, an anticonvulsant and therapy for infarct
worsened now associated with hematochezia, prompting a referral to pneumonia. After 3 weeks of therapy, the patient’s clinical condition
a gastroenterologist. Physical examination revealed a large palpable improved significantly, with normalization of saturation, platelets,
mass in the left upper quadrant, with no jaundice, ascites, or signs of hemoglobin and D-dimer; the clots in the upper sagittal sinus and right
chronic liver disease. Endoscopy showed grade 3 esophageal and main pulmonary artery were completely resolved. PVT persisted, so
gastric varices, treated with rubber band ligation and cyanoacrylate monitoring was done for possible development of portal hypertension:
injection. Lab results indicated preserved liver function, and no esophageal varices, no splenomegaly, platelet count was 299,000
splenomegaly raised suspicion for non-cirrhotic portal hypertension. per mL. Anticoagulation therapy with rivaroxaban was continued for 6
Investigations revealed pancytopenia, splenomegaly, a normal liver on months until complete resolution of PVT. Refusal of vector vaccination
ultrasound and fibroscan, and no portal vein thrombosis on Doppler. was recommended.
CT showed a normal liver, extrahepatic portosystemic shunt, gastric Conclusion: VITT is a very rare but life-threatening condition
varices, and minimal ascites. Liver biopsy was normal, and tests for characterized by the development of thrombosis, including rare
autoimmune, hypercoagulable, and myeloproliferative disorders, as localizations in the setting of thrombocytopenia. In the present case,
early diagnosis and early anticoagulant therapy resulted in rapid during a health checkup 12 years ago. Two years ago, he revealed
resolution of sagittal sinus and pulmonary artery thrombosis, whereas anemia, thrombocytopenia, elevated alkaline phosphatase, and
PVT required six months of anticoagulation treatment with complete hepatosplenomegaly. Further testing showed reduced ceruloplasmin
resolution. level of 0.14 g/L and elevated 24-hour urinary copper excretion of
135.08 ug. Sanger sequencing of the ATP7B gene for him and his
family revealed that he had compound heterozygous mutations
PP0694
p.I390V (c.1168A > G) in exon 2 and p.V1106I (c.3316G > A) in exon
A Rare Cause of Abdominal Pain and Recurrent Epistaxis 15. The Leipzig score is 7, confirming the diagnosis of WD. However,
Mingyu Zhu1, Yiqi Du2, Li Chen1 the splenomegaly with the volume of 18 cm × 9 cm × 26 cm could
1
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao not be explained by WD alone. The liver biopsy showed steatosis of
Tong University, School of Medicine, Shanghai, China, 2Department hepatocytes without evidence of fibrosis but significant extramedullary
of Gastroenterology, Changhai Hospital, Naval Medical University, hematopoiesis. Extramedullary hematopoiesis accompanied by
Shanghai, China hepatosplenomegaly, suggests the possibility of a myeloproliferative
A 30-year-old woman was admitted to a local hospital due to abdominal disease. Therefore, a bone marrow biopsy was performed indicating
pain. Abdominal computed tomography (CT) scan indicated cirrhosis marrow fibrosis. Further genetic testing of JAK2, MPL, and CALR
and thickened wall of left small bowels, which were suspected a mass. for myeloproliferative neoplasm revealed that he carried a deletion
Afterwards, the patient was referred to our hospital for further treatment. mutation p.L367Tfs*46 (c.1092_1143del) in the CALR gene, confirming
The patient denied any prior occurrence of parasitic infection or alcohol the diagnosis of PMF. He was treated with Ruxolitinib for PMF and zinc
consumption; however, she did report a 7-year history of recurrent sulfate 150 mg per day for WD.
epistaxis. The patient’s hemoglobin level reached a minimum of Discussion: WD is a rare genetic liver disease, and PMF is a rare
41g/L, prompting the initiation of long-term oral iron supplementation. hematologic disorder. To our knowledge, this is the first report of
Physical examination on presentation showed an anemic appearance, these two rare diseases occurring in an adult patient worldwide.
splenomegaly and black pigmentations on her lips without any other Hepatosplenomegaly is the main manifestation in this patient. Chronic
notable findings. Further complete blood count indicated mild anemia liver disease is the common cause of hepatosplenomegaly, and
with a hemoglobin of 92g/L and normal platelet counts of 208×10^9/L. splenomegaly is secondary to portal hypertension. Hematologic
Biochemical analyses indicated slight decreases in albumin of 33g/L. disorder should be considered in the presence of splenomegaly without
Hepatitis B and C virus serology and autoantibodies were negative. The portal hypertension accompanied by extramedullary hematopoiesis.
levels of ceruloplasmin and tumor markers were within the normal range. Bone marrow biopsy and genetic analysis are useful for differential
Chest CT showed vascular malformations in the upper and lower lobes diagnosis. As for the treatment, Penicillamine is the first line of therapy
of the right lung. Abdominal contrast-enhanced CT scan revealed liver for WD, but pancytopenia is one of the relative contraindications of
cirrhosis, portal hypertension, cavernous transformation of portal vein Penicillamine. Thus, oral zinc is preferred.
and splenomegaly. Small bowels in the left abdomen were thickened Conclusion: We reported the first case of coexistence of two rare
and intussusception was considered. Vibration-controlled transient diseases- Wilson’s disease and primary myelofibrosis in an adult
elastography showed a moderate liver stiffness measurement value of patient globally. Hematologic disorder should be considered as a
13.1kPa, with a normal controlled attenuation parameter value of 192 differential diagnosis in the presence of splenomegaly without portal
dB/m. The patient received bidirectional double-balloon enteroscopy hypertension, even if the patient had been diagnosed as chronic liver
procedure and three polyps (20mm, 40mm,50mm) were found. Then, disease.
en bloc resection was achieved through polypectomy. Meanwhile,
the patient received an ultrasound-guided percutaneous liver biopsy. PP0696
The Hematoxylin & Eosin staining demonstrated liver cirrhosis with
Ubiquitin-specific protease 22 deubiquitinates SMAD2 and
significant dilation of arteriae interlobulares hepatis, widening of some
promotes hepatic stellate cells activation in hepatic fibrosis
portal vein branches. The presence of unknown cirrhosis, significant
dilation of arteriae interlobulares hepatis in liver biopsy, pulmonary Jing Chen1,2, Cuihua Lu2
vascular malformations observed in the chest CT scan, coupled with
1
Medical School of Nantong University, 2Affiliated Hospital of Nantong
a history of epistaxis lasting up to 7 years, initially raised suspicion University
of hereditary hemorrhagic telangiectasia (HHT). Whole exome Background: Liver fibrosis is a progressive fatal disease characterized
sequencing was therefore conducted and identified heterozygous by aberrant activation of hepatic stellate cells (HSCs). Transforming
genetic variants in SMAD4 gene (GenBank: NM_005359.6), thereby growth factor-β1 (TGF-β1) acts as a potent inducer of myofibroblast
resulting in the diagnosis of Juvenile Polyposis with HHT syndrome. differentiation. Ubiquitin/de-ubiquitination system plays a regulatory
The missense mutation (c.1081C>T, p. Arg 361 Cys) identified in role in TGF-β1 signaling proteins via controlling their stability and
this patient is a novel finding. The symptoms of abdominal pain were activity. SMAD transcription factors, core intracellular transducers
improved after the polypectomy. Bevacizumab, an anti-VEGF antibody, of TGF-β1 cytokines, are precisely regulated for to ensure HSCs
was administered to the patient (5mg/kg, every 2 weeks). To date, the differentiation. Ubiquitin-specific protease 22 (USP22) has been
patient has not experienced gastrointestinal hemorrhage or severe reported to be implicated in oncogenesis in a wide range of tumors.
epistaxis, with a stable hemoglobin level. However, the role of USP22 in hepatic fibrogenesis and whether
USP22 regulate the turnover of SMADs has not been determined. Our
PP0695 study aimed to elucidate the effect and precise regulatory mechanism
of USP22 in the pathogenesis of liver fibrosis.
Coexistence of two rare diseases - Wilson’s disease and primary Method: Western blot, Immunohistochemistry (IHC), real-time
myelofibrosis - in an adult patient polymerase chain reaction, immunofluorescence and bioinformatics
Xiaowei Ai1, Zhen Wu1, Lijuan Feng1, Xinyan Zhao1, Xiaojuan Ou1, analysis were utilized to examine USP22 expression in HSCs and
Wei Zhang1, Hong You1 fibrotic liver tissues. The function of USP22 on HSCs activation was
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical determined by USP22 gene overexpression or knockout and TGF-β1/
University, Beijing, China SMAD signaling inhibitors administration. Nuclear fractionation,
Background: Wilson’s disease (WD) is an autosomal recessive immunofluorescence, cycloheximide and MG132 treatment were
disorder caused by mutations in the ATP7B gene, which disturbs employed to study the role of USP22 on SMADs translocation, stability,
copper metabolism. Primary myelofibrosis (PMF) is a myeloproliferative and degradation. The binding of USP22 to SMADs and the removal of
disorder linked to mutations in the genes including JAK2, CALR, and ubiquitin chains on SMADs were analyzed by co-immunoprecipitation,
MPL. Both are rare genetic conditions. in vivo and in vitro deubiquitination assays.
Case Presentation: A 44-year-old man was found with splenomegaly Result: We demonstrated that USP22 was significantly upregulated in
fibrotic livers. TGF-β1 induced USP22 expression and myofibroblast
differentiation in a TGF-β1/SMAD dependent manner and USP22 was St. Luke‘s Medical Center - Global City, 2St. Luke‘s Medical Center -
1

required for TGF-β1-stimulated HSCs activation in myofibroblasts. Global City

USP22 promoted the nuclear translocation of SMAD2/3/4. Besides, Background: Background: Chronic liver disease involves
USP22 binds to the MH2 domain on SMAD2 and acts as a progressive liver function deterioration, and late-stage liver cirrhosis
deubiquitinating enzyme that stabilized SMAD2 protein levels from is characterized by fibrosis and architectural distortion, often
proteasomal degradation. Further deubiquitination assays showed that necessitating liver transplantation. While some early-stage reversibility
USP22 relys on its enzymatic active site to reinforce the cleavage of has been documented, most advanced cases are irreversible. Liver
Lys48-linked poly-ubiquitin chains on SMAD2 and ultimately sustaining elastography, a noninvasive imaging test, is a valuable tool for diagnosis,
hepatic fibrogenesis. but its limited availability in resource-limited areas underscores the
Conclusion: USP22 may represent an attractive target for the need for alternative fibrosis scoring systems to diagnose chronic
treatment of liver fibrosis. liver disease. The objective of this study is to determine the accuracy
Table and Figure:Figure 1. of Aspartate Aminotransferase to Platelet Index Ratio (APRI) and
Fibrosis-4 Index (FIB4) in the diagnosis of chronic liver disease among
PP0697 adults who have suspected or confirmed diagnosis of chronic liver
disease.
The Real-World Study of Morphological Liver Re-compensation in
Method: Method: This study is an observational, analytical cross-
HBV-Related Decompensated Cirrhosis with Antiviral Therapy
sectional study. The participants included adult patients ≥18 years
Qijuan Zang1, Yinglii He1
of age who have suspected or confirmed diagnosis of chronic liver
1
Department of Infectious Diseases, First Affiliated Hospital of Xi‘an disease, who underwent liver elastography at the St. Luke’s Medical
Jiaotong University, Xi‘an, Shaanxi, China Center, Quezon City from January 2015 to November 2022.
Background: In patients with decompensated HBV-related cirrhosis, Result: Results: Two-hundred-eight samples were included and
antiviral therapy can improve liver function, potentially achieving analyzed in this study. Receiver Operating Characteristic (ROC) curve
recompensation. However, functional criteria like Baveno VII have of the actual APRI and FIB-4 score shows an area the curve (AUC) of
limitations in assessing long-term stability. While Baveno VII defines 0.76, denoting that FIB-4 score has significantly better discriminatory
recompensation as resolution of ascites, hepatic encephalopathy, ability in predicting F4 fibrosis than APRI score. The best cut-off score of
and absence of variceal bleeding for 12 months, 57.5% of patients APRI in predicting F4- fibrosis is >0.5835 (accuracy 71.64%, sensitivity
still experience recurrent decompensation during follow-up. This study 77.78%, specificity 66.06%), while the best cut-off score of FIB-4 is
introduces “morphological recompensation” based on liver volume >3.117 (accuracy 75.48%, sensitivity 67.78%, specificity 82.57%).
changes, offering a more reliable long-term standard. Liver volume Meanwhile, the best cut-off score of APRI in predicting F0 to rule out
reflects hepatocyte quantity, perfusion, and metabolism, providing a chronic liver disease is <0.5835 (accuracy 81%, sensitivity 77.78%,
functional status assessment via imaging. specificity 72.06%). The best cut-off score of FIB-4 in predicting F0
Method: A retrospective cohort study analyzed 169 patients with is <1.3969 (accuracy 85%, sensitivity 79.17%, specificity 80.88%).
decompensated HBV-related cirrhosis from 2012 to 2021. Eligible Lastly, APRI and FIB-4 scores are significantly positively correlated
patients had at least two CT scans taken one year apart. Long-term with the liver elastography METAVIR stages, implying that higher APRI
follow-up assessed liver volume changes and clinical indicators. and FIB-4 scores will result in higher or worse METAVIR stages on liver
Morphological criteria, including liver volume ratio (LV/ELV%) and elastography.
volume change rate (ΔLV), were compared with functional criteria Conclusion: Conclusion: In conclusion, while APRI and FIB-4 have
(Baveno VII). limitations in accurately predicting F4 fibrosis and ruling out chronic
Result: Patient Grouping: Of 169 patients, 37.3% achieved liver disease, they exhibit a direct association with liver elastography
recompensation with increased liver volume, while 62.7% did not and METAVIR stages. This correlation offers clinicians accessible and
showed volume reduction, highlighting distinct differences. convenient measurable parameters to identify individuals at potential
Liver Volume and Function: LV/ELV% correlated positively risk of advanced liver fibrosis or cirrhosis, aiding in the prioritization of
with serum albumin and negatively with INR, Child-Pugh, MELD, and subsequent evaluations and interventions.
ALBI scores. Patients with MELD >18 had transient volume increases
due to inflammation, without statistical significance compared to those
PP0699
with MELD 15-18.
Volume Changes and Recompensation: Recompensated Partial Splenic Embolization in a Cirrhotic Patient with Refractory
patients showed significant liver volume increases and partial Variceal Bleeding and Portal Venous Thrombosis
structural reversal. Non-recompensated patients had volume Rafael Mendoza1, David Nagtalon2, Ryan Uy2, Federico Peralta2,
reduction, indicating insufficient therapeutic response. Morphological Jasmin Gondayao2, Suzette Kho-Herman2, Ramon Santos-Ocampo2
recompensation showed greater stability than functional criteria. 1
St. Luke‘s Medical Center - Global City, 2St. Luke‘s Medical Center -
Criteria Development: Baseline LV/ELV% >80% and ΔLV Global City
> -20 cm³/year were identified as significant predictors of stable Background: Gastric varices are a less common but more
recompensation, enhancing predictive value beyond Baveno VII. complicated complication of portal hypertension, especially in relation
Long-Term Outcomes: Patients meeting morphological to its management. Compared to its esophageal counterpart, gastric
criteria had significantly lower rates of recurrent decompensation varices may need to be controlled endoscopically with tissue adhesives
compared to those meeting functional criteria alone. such as cyanoacrylate. In refractory variceal hemorrhage, more
Conclusion: First-line antiviral therapy is effective for decompensated invasive measures are considered such as transjugular intrahepatic
HBV-related cirrhosis. Morphological recompensation criteria, portosystemic shunt (TIPS), balloon retrograde transvenous obliteration
incorporating LV/ELV% >80% and ΔLV > -20 cm³/year, provide a (BRTO), or even splenectomy. This case report highlights the use of
more stable long-term prognostic tool. Integrating morphological and splenic artery embolization as an alternative option in a cirrhotic patient
functional standards is recommended for optimizing treatment and with portal vein thrombus (PVT).
management. Case Presentation: A 68-year-old male with cirrhosis from chronic
Table and Figure:Figure 1. hepatitis B, complicated by hepatocellular carcinoma (HCC), was
admitted due to hematemesis with anemia. Medical management
PP0698 with antibiotics and Octreotide drip, as well as supportive blood
transfusions done. Gastroscopy showed gastroesophageal varices
Aspartate Aminotransferase to Platelet Ratio Index (APRI) and
type 1 (GOV-1) for which beta blockers were initiated, with eventual
Fibrosis-4 Index (FIB-4) in Chronic Liver Disease: An Analytical
plan to do rubber band ligation once the gastric varices are lesser in
Cross-sectional Study
size. Subsequent dynamic CT scan of the liver showed multiple tumor
Federico Peralta1, Marc Yumena2, Sarah Bellido2
thrombi in the proximal main portal vein, immediately after the splenic Conclusion: Our results suggest that macrophages play a role in the
and superior mesenteric vein. The patient was doing well until he development and progression of cholestatic liver disease. Additionally,
again had hematemesis on the 4th hospital day. Repeat gastroscopy CB2 receptor agonists significantly alleviate the inflammatory response
showed GOV-1, where histoacryl glue was injected. The patient and to cholestatic liver fibrosis and ameliorate hepatic fibrosis through the
family were appraised for partial splenic embolization (PSE) on the HIPPO/YAP signaling pathway.
same day but were undecided. They later consented on the 7th day of Table and Figure:Figure 1.Effect of AM1241 on Yap, TAZ, CTGF, Arg1,
admission. The patient underwent splenic angiogram and PSE using Inos, CD11b ,F4/80, TGF-β and α-SMAin hepatic tissue homogenate of
polyvinyl alcohol particles and 500-700 micron microspheres, showing BDL-induced fibrosis rats’ model. N=5.
complete devascularization of approximately 70% of the spleen. Post- Figure 2.Effect of AM1241 on Arg1, iNOS, TNF-α, TGF-β, IL-6, IL-10,
procedure, patient able to tolerate gradual diet progression but on CD68, CD163, CB2, α-SMA, MCP1, MIP1 and MIP2 in hepatic tissue
the 9th day of admission, had recurrence of hematemesis, for which homogenate of BDL-induced fibrosis rats’ model. N=5
the patient eventually decided for palliative care. By the 10th day of
admission, the patient unfortunately expired.
PP0701
Discussion: Gastric variceal bleeding, while already tricky to treat, is
made more complicated with the presence of a PVT. Because of the mechanism of dact2 gene inhibiting the occurrence and
PVT, there is high resistance and limitation of venous outflow on top development of liver fibrosis
of the already high splenic blood flow associated with splenomegaly. Shenan Huang1, Zhili Wen1
While our patient’s variceal bleeding was initially temporized with 1
The Second Affiliated Hospital of Nanchang University
histoacryl glue injection, BRTO and TIPS may not be feasible Background: There are few reports about the relationship between
anatomically and that BRTO can actually exacerbate esophageal dact2 and liver fibrosis. The inhibitory mechanism
varices. Hence, a PSE was done to reduce splenic venous inflow into of dact2 in liver fibrosis is not clear, we need to further explore.
the portal vein, thereby reducing its contribution to the portal venous Method: in this experiment, we used lentivirus as a vector to construct
pressure. If done early, PSE might have significantly reduced portal lentivirus vector carrying dact2 gene, and packaged dact2 recombinant
pressure, as demonstrated in other case reports. However, given our lentivirus and its control vector.
patient’s overall poor prognosis, PSE was used as a salvage measure HSC-T6 infected cells were observed. The effect of dact2 gene
to control his refractory variceal bleeding. expression was activated by Wnt3a
HSC-T6 cells. Immunoblot was used to detect α - SMA expression,
PP0700 TGF - β 1, Smad3, Smad7, β -
Catenin and CyclinD1. The expression of MMP-2 and TIMP-1 was
Cannabinoid receptors improve cholestatic liver fibrosis by
detected by real-time PCR. At the
altering macrophage phenotype and HIPPO/YAP signaling
same time, dact2 recombinant lentivirus was injected into tail vein.
pathway
Carbon tetrachloride was used to
Jing LI1, Suxian ZHAO1, Yuemin NAN1
establish the liver fibrosis model. After 7 weeks of modeling, he staining
1
Hebei Medical University Third Hospital was used to observe the
Background: Cirrhosis is the progression of various chronic liver pathological changes of liver tissue, hydroxyproline was used to
diseases to a pathological stage characterized by diffuse fibrosis of analyze the changes of collagen
the liver, pseudo follicular formation, and proliferation of intra- and content in liver tissue, the expression of protein was observed by
extrahepatic blood vessels. Cirrhosis of the liver has a variety of immunohistochemistry, and the
causes, of which cholestasis is an important one. Herein, we explored expression of fibrosis related genes was detected by real-time PCR.
the therapeutic potential of targeting the cannabinoid-2 receptor Result: dact2 gene expression
(CB2-R) utilizing a commonly used mouse model of liver fibrosis, could inhibit the activation of HSC-T6 cells and reduce the expression
induced by bile duct ligation (BDL) of TGF - β 1. The percentage of
Method: Liver perforated paraffin tissues were collected from 50 Smad3, β - Catenin and cyclinD1 protein was 50.02%, 46.73%, 47.58%
patients with primary biliary cholangitis hospitalized in the Department and 37.50% respectively (P <
of Traditional and Western Medical Hepatology of the Hebei Medical 0.05).
University Third Hospital from 2021 to 2024, and the patients were Conclusion: in this study, dact2 gene
classified into early and late stages based on histological diagnostic can inhibit liver fibrosis.
criteria, and immunohistochemical staining for CD68 and CD163 was
performed on the patients with early and late stages, respectively.
PP0702
12-16 week-old C57BL/6J male mice were used and BDL was
performed as described earlier. Following surgery, the animals were Association Between Helicobacter pylori CagA Seropositivity and
randomly assigned to one of six groups: Sham, Sham (AM-1241- Liver Fibrosis and Cirrhosis: A Mendelian Randomization Study
treated), Sham (vehicle-treated), BDL, BDL(AM-1241-treated), and Jiao Li1, Mingming Zhang1, Hong Li1
BDL, (vehicle-treated). On postoperative day 1, all animals received a 1
Center of Infectious Diseases, West China Hospital, Sichuan
daily intraperitoneal injection of treatment or vehicle only, consisting of University
10 mg/kg of the CB2-R agonist AM-1241. Animals were sacrificed on Background: Chronic Helicobacter pylori (H. pylori) infection has been
postoperative day 14, and respective tissues were harvested following implicated in various extra-gastric diseases, including liver disorders.
exsanguination and perfusion with sterile, cold phosphate-buffered However, the causal relationship between H. pylori infection and liver
saline. The protein levels of YAP, TAZ, CTGF, α-SMA, ARG1, INOS, fibrosis or cirrhosis remains unclear.
CD11b, F4/80 and TGF-βwere detected by Western blotting, while the Method: We performed a two-sample Mendelian randomization (MR)
mRNA levels of IL-6, IL-10, TNF-α, TGF-β, INOS, ARG1, MCP1, MIP1α, analysis to investigate the potential genetic causal effect of H. pylori
MIP2, CD68, CD163, CB2 and α-SMA were examined by real-time infection, assessed by seropositivity to seven anti-H. pylori antibodies
polymerase chain reaction (RT-PCR). (IgG, CagA, Catalase, GroEL, OMP, UreA, VacA), on liver fibrosis and
Result: In advanced PBC patients, the expression of CD68 and cirrhosis. The genetic variants for H. pylori and fibrosis and cirrhosis
CD163 is significantly higher compared to that in early-stage patients. of liver were extracted from genome-wide association studies (GWAS)
The CB2-R agonist AM1241 is capable of modulating macrophage summary data. Single nucleotide polymorphisms (SNPs) with a
phenotypes, significantly reducing the expression of pro-inflammatory threshold of P < 5 × 10⁻6, R² > 0.001, and an aggregation window
cytokines in the liver and alleviating the inflammatory response in the of 10,000 kb were selected for analyses based on published data.
liver. Furthermore, AM1241 notably decreases the protein expression We primarily employed random-effects inverse variance weighted
levels of YAP, TAZ, CTGF, and α-SMA. Histologically, AM1241 restricts (IVW) method for causal estimation, supplemented by MR Egger,
the extension of fibroplasia and breaks the course of bridging fibrosis.
weighted median, and weighted mode. Sensitivity analyses, including Method: A total of 269 patients with HBV infection in the Department of
heterogeneity, pleiotropy, and leave-one-out analyses, were conducted Infectious Diseases of the First Affiliated Hospital of Guangxi Medical
to confirm the robustness of the results. University from November 2017 to October 2023 were enrolled in
Result: MR analysis using the IVW method revealed that genetically the long-term follow-up cohort. The transient elastography system
predicted seropositivity to H. pylori CagA antibody was significantly FibroScan was used to detect liver stiffness value . According to the
associated with an increased risk of fibrosis and cirrhosis of liver (OR LSM value, they were divided into non-hepatic fibrosis group (n = 69
= 1.16, 95% CI: 1.02–1.31, P = 0.026). No causal relationship was cases), mild liver fibrosis group (n = 107 cases), advanced liver fibrosis
observed between other H. pylori antibodies and fibrosis and cirrhosis group (n = 43 cases) and cirrhosis group (n = 50 cases). The level of
of liver. Sensitivity analyses found no heterogeneity or pleiotropy, ORC1 in serum was detected by enzyme-linked immunosorbent assay.
affirming the reliability our results. The differences of serum ORC1 levels in four groups were analyzed
Conclusion: Our MR study provides evidence supporting a potential and compared by Kruskal-Wallis test. Analyze the factors affecting
causal relationship between H. pylori CagA seropositivity and the level of serum ORC1 by multiple linear regression in patients with
increased risk of liver fibrosis and cirrhosis. These findings suggest that chronic HBV infection. Ordered Multi-classification Logistic regression
H. pylori infection, particularly CagA-positive strains, may contribute was applied to analysis the factors of affecting the degree of liver
to liver disease progression. Further research is warranted to explore Fibrosis .The receiver operating characteristic curve was used to
underlying mechanisms and potential therapeutic implications. analyze the predictive value of serum ORC1 in liver cirrhosis.
Table and Figure:Figure 1.Figure 1 MR-estimated genetic causal Result: The serum ORC1 level in advanced liver fibrosis group was
relationship between H. pylori infection (IgG, CagA, Catalase, GroEL, higher than that in non-liver fibrosis group (P<0.05).The level of serum
OMP, UreA, VacA) and fibrosis and cirrhosis of liver. ORC1 in liver cirrhosis group was higher than that in non-liver fibrosis
Figure 2.Figure 2 The causal effect of H. pylori CagA antibody on group and mild liver fibrosis group (P<0.05). There was no significant
fibrosis and cirrhosis of liver in different MR methods. difference between the other two groups (P>0.05). The results of
multiple linear regression analysis showed that the level of serum
PP0703 ORC1 was not affected by age and ALT ect (P>0.05). It was positively
correlated with LSM(P<0.05). The result of logistic regression analysis
Gut Akkermansia muciniphila mitigates hepatic fibrosis by showed that the older the age, the higher the levels of AST and serum
modulating riboflavin metabolism through the gut-liver axis ORC1 increase the risk of progression of hepatic fibrosis. (B > 0, OR >
Lu Zhang1, Lu Cui-HUA1 1, P < 0 05).The area under the curve of serum ORC1 in the diagnosis
1
Department Gastroenterology, Affiliated Hospital of Nantong of liver cirrhosis was 0.644(P<0.05).The sensitivity, specificity and
University, Medical School of Nantong University, Nantong 226001 consistency rate were 56.0%, 76.3% and 72.5%, respectively.
China Conclusion: The level of serum ORC1 in patients with chronic HBV
Background: Akkermansia muciniphila (AKK), a gut bacterium, is infection is related to the progression of hepatic fibrosis, which elevated
gaining recognition for its potential in treating metabolic disorders, level increases the risk of progression of hepatic fibrosis. It is expected
including its ability to combat liver fibrosis. to become one of the potential serological markers for monitoring
Method: In this study, we employed a CCl4-induced hepatic fibrosis dynamically and diagnosing helpfully of HBV-related hepatic fibrosis
mice to explore the mechanisms of AKK in intervening hepatic fibrosis. and liver cirrhosis.
Mice treated with AKK showed effective reversal of hepatic fibrosis,
including collagen deposition, inflammation, and hepatic injury, which PP0705
was attenuated in hepatic fibrosis mice treated with antibiotics.
Zinc-LNPs reverse liver fibrosis through regulating macrophage
Result: The therapy enhanced oxidative stress and vitamin
polarization
metabolism along the gut-liver axis. This led to the deactivation of
hepatic stellate cells and a modification in gut microbiota composition, Chengxia Xie1, Chen Li2
alongside an increase in riboflavin transport from the gut to the liver.
1
Department of Laboratory Medicine, West China Hospital, Sichuan
These metabolic improvements occurred with an increase in riboflavin University, Chengdu 610041, China, 2Centre for Translational
levels transported from the gut to the liver. Riboflavin displayed similar Research in Cancer, Sichuan Cancer Hospital & Institute, Chengdu
beneficial metabolic effects in vitro and in mice, effectively ameliorating 610000, China
hepatic fibrosis. Riboflavin itself showed promising effects, mirroring Background: Liver fibrosis is a pathological repair process triggered
AKK’s benefits by alleviating hepatic fibrosis. by ongoing liver injury and represents a critical intermediate stage in
Conclusion: These findings highlight AKK’s role in hindering hepatic the progression from liver injury to cirrhosis and even hepatocellular
stellate cell activation through oxidative stress management and carcinoma. However, no approved pharmacological treatment is
riboflavin metabolism modulation, suggesting its therapeutic viability currently available for the reversal of liver fibrosis, and thus effectively
for liver fibrosis intervention. block the disease process. Given the persistent deficiency of hepatic
Table and Figure:Figure 1. zinc (Zn) in the patients with chronic liver disease and cirrhosis, and
zinc’s demonstrated role in the regulation of macrophage polarization
and matrix metalloproteinase activity. This study aims to develop a
PP0704
targeted therapeutic strategy for liver fibrosis by leveraging zinc-
The diagnostic value of serum ORC1 in the progression of HBV- loaded lipid nanoparticles (Zn-LNPs), a novel nanotechnology-based
related liver fibrosis approach, to enhance therapeutic efficacy while minimizing toxicity.
Hongqian Liang1, Long Huang1, Aoli Ren1, Minghua Su1, Bobin Hu1, And further explore the molecular mechanism of targeted delivery of
Qingmei Li1, Tumei Su1, Qianbing Yin1, Aining Li1, Jianning Jiang1 zinc by Zn-LNPs to reverse liver fibrosis.
1
Department of Infectious Diseases, the First Affiliated Hospital of Method: Functionalized Zn-LNPs were engineered to specifically
Guangxi Medical University target macrophages in fibrotic liver tissue, with the goal of improving
Background: Our team’s previous study found that there was a zinc bioavailability directly within the damaged liver. The effectiveness
high frequency of HBVS-ORC1 integration gene formed near the of Zn-LNPs in reversing fibrosis was assessed, and their mechanisms
ORC1 promoter. In order to further explore the relationship between of action, particularly regarding ECM remodeling and macrophage
the overexpression of ORC1 and the occurrence of HBV-related liver behavior, were elucidated.
fibrosis, the liver stiffness measurernents (LSM) values measured by Result: The Zn-LNPs demonstrated a significant anti-fibrotic effect,
FibroScan were used as the reference criteria for the diagnosis of liver with enhanced ECM degradation and regulated M1 macrophage
fibrosis to explore whether serum ORC1 can reflect the degree of HBV- polarization, supporting a reduction in fibrotic burden. Targeted
related liver fibrosis and its potential function in the diagnosis of liver delivery significantly mitigated the toxicity commonly associated with
cirrhosis. non-specific zinc supplementation.
Conclusion: This study presents Zn-LNPs as a promising therapeutic
avenue for liver fibrosis, offering a safer, targeted approach to zinc autophagosome formation by regulating actin depolymerization
delivery. Future work will further explore the mechanisms underlying and has been demonstrated to interact with MYSM1 via CoIP mass
Zn-LNP-mediated reversal of fibrosis, providing new insights into the spectrometry. This study investigates whether MYSM1 could promote
treatment of chronic liver diseases and advancing therapeutic options the progression of liver fibrosis by regulating GSN to affect autophagy.
for liver fibrosis management. Method: Normal and fibrotic human liver samples were collected,
and primary hepatocytes from mice were isolated. The study aimed
to elucidate the interplay between MYSM1, GSN, hepatocyte
PP0706
autophagy, and liver fibrosis. A comprehensive set of techniques was
Helicobacter pylori-derived outer membrane vesicles induce liver employed, including immunohistochemistry, qRT-PCR, flow cytometry,
fibrosis progression through activating NLRP3 inflammasome immunofluorescence staining, transmission electron microscopy,
JIAO LI1, Xiaona Song1, Yalin Shen1, Hong Tang1, Hong Li1 and WB. To investigate the role of MYSM1 in liver fibrosis, the study
1
Center of Infectious Diseases, West China Hospital, Sichuan utilized hepatocyte-specific MYSM1 knockout mice. Furthermore,
University mouse models with hepatocyte-specific overexpression of MYSM1
Background: Clinical studies have identified Helicobacter pylori and knockdown of GSN were generated through the administration
infection not only as a major cause of gastric diseases but also as a of AAV8-TBG-MYSM1 and AAV8-TBG-sh-GSN viruses, respectively.
contributor to various extra-gastric conditions, including liver diseases. Models of liver fibrosis induced by carbon tetrachloride and
However, the mechanisms linking H. pylori infection to these extra- nonalcoholic steatohepatitis induced by methionine-choline deficiency
gastric manifestations remain poorly understood. Outer membrane were established. HEK293T cells were transfected with MYSM1 and
vesicles (OMVs) derived from H. pylori, with their nanometric structure ubiquitin mutant plasmids to assess the impact of MYSM1 on GSN
and capacity to deliver concentrated bacterial virulence factors over deubiquitination.
long distances, have been proposed as a key mediator connecting H. Result: During liver fibrosis, the expression of MYSM1 in hepatocytes
pylori infection to liver pathologies. significantly increased, correlating with both the severity of fibrosis and
Method: OMVs were isolated from the H. pylori strain G27 the degree of autophagy impairment. In vivo studies demonstrated
and characterized using scanning electron microscopy (SEM) that the deletion of MYSM1 reduced the accumulation of extracellular
and nanoparticle tracking analysis (NTA). Their protein and matrix and enhanced autophagy. Moreover, MYSM1 deletion resulted
lipopolysaccharide (LPS) content was confirmed through Coomassie in decreased GSN expression. In contrast, overexpression of GSN
Brilliant Blue staining, proteomics, AND silver staining. Fluorescent ameliorated these effects. Co-IP mass spectrometry confirmed
dye PKH26-labeled OMVs were incubated with LX-2 cells, a human an interaction between MYSM1 and GSN, indicating that MYSM1
hepatic stellate cell (HSC) line crucial in liver fibrosis progression. stabilizes GSN by inhibiting its ubiquitination. Overexpression of
Immunofluorescence microscopy with phalloidin and DAPI staining MYSM1 notably decreased the levels of K29-linked ubiquitination on
was performed to track OMV internalization into LX-2 cells. Liver fibrotic GSN. Additionally, GSN was found to hinder autophagy progression
markers (αSMA, Collogen1, Fibronectin, Timp1) were evaluated by by blocking autophagosome formation and disrupting the autophagic
qPCR and Western blot, while qPCR analysis was used to examine flux in hepatocytes.
the expression of NLRP3 inflammasome-related genes (NLRP3, Conclusion: MYSM1 promotes liver fibrosis by inhibiting the
Caspase-1, IL-1β, IL-18). ubiquitination of GSN and the associated autophagy in hepatocytes.
Result: SEM and NTA confirmed the successful isolation of OMVs, This study elucidates the mechanism and function of MYSM1 in the
characterized by a diameter of 100–200 nm. Proteomics and staining progression of liver fibrosis, providing a theoretical basis for the
analysis revealed the presence of abundant bacterial virulence proteins development of potential early interventions.
and LPS in OMVs. Immunofluorescence microscopy demonstrated Table and Figure:Figure 1.MYSM1 promotes liver fibrosis by inhibiting
that LX2 cells internalized PKH26-labeled OMVs within 24 hours, the ubiquitination of GSN and the associated autophagy in hepatocytes
leading to their activation. qPCR and Western blot analysis showed
a significant upregulation of αSMA, a key marker of liver fibrosis. PP0708
Furthermore, the expression of NLRP3 inflammasome-related genes
METTL3 suppresses liver fibrosis via m6A methylation-dependent
(NLRP3, Caspase-1, IL-1β, IL-18) was markedly elevated in OMV-
miR-30d-5p maturation
treated LX2 cells.
Conclusion: H. pylori-derived OMVs can be internalized by hepatic Zhijing Wang1, Xiya Lu2, Jing Li1, Meiyi Song1, Changqing Yang1
stellate cells, inducing their activation and upregulating liver fibrotic
1
Department of Gastroenterology and Hepatology, Tongji Hospital,
markers and NLRP3 inflammasome-related genes. These findings School of Medicine, Tongji University, Shanghai 200092, China,
suggest a potential mechanistic link between H. pylori infection and
2
Cancer Hospital of Dalian University of Technology, Shenyang
liver fibrosis via OMV-mediated activation of HSCs, offering new 110042, Liaoning Province, China
insights into the pathogenesis of H. pylori-associated liver diseases. Background: Liver fibrosis remains a global health problem without
Table and Figure:Figure 1.Figure 1. Isolation and Characterization of effective treatments. Activation of hepatic stellate cell (HSC) is a
H. pylori OMVs critical event during liver fibrogenesis. Epigenetic modification has
Figure 2.Figure 2. H. pylori OMVs induce hepatic stellate cell activation a significant effect on liver fibrosis, but as the most common RNA
and activating NLRP3 inflammasome modification in eukaryotes, the role of N6-methyladenosine (m6A)
modification in liver fibrosis still unclear.
Method: The content of m6A in total RNAs was detected by RNA
PP0707
m6A methylation quantification kit and RNA m6A Dot blot. Quantitative
The Deubiquitinase MYSM1 Stabilizes GSN to Exacerbate Liver real-time PCR and western blot were used to detect the expression
Fibrosis by Inhibiting Hepatocyte Autophagy of METTL3 in CCl4-induced liver fibrosis and activated HSC. Rat
Han Ding1,2, Le Wang1,2, Songbo Zhao1,2, Wanhua Ren1,2, Qiang hepatic stellate cell (HSC-T6) stimulated by TGF-β1 was transfected
Zhu1,2 with METTL3-overexpression plasmid and siRNA in vitro. Based on the
1
Shandong Provincial Hospital Affiliated to Shandong First Medical mouse model of CCl4–induced liver fibrosis, METTL3-overexpression
University, 2National medical center for infectious diseases AAV8 was used to explore the effect of METTL3 on liver fibrosis in
Background: Hepatocyte autophagy provides resistance to liver vivo. Then, a variety of molecular approaches and the functional
fibrosis. Deubiquitinases contribute to autophagy through modulation rescue experiments were carried out to clarify the mechanism of which
of the ubiquitination status of autophagy-related proteins. Myb-like METTL3 improved liver fibrosis by regulating the maturation of miR-
SWIRM and MPN domains 1 (MYSM1), a histone H2A deubiquitinase, 30d-5p.
is upregulated in hepatocellular carcinoma (HCC); however, its Result: We found a decrease of m6A modifications in CCl4-
impact on liver fibrosis remains unclear. Gelsolin (GSN) inhibits induced liver fibrosis mice and activated HSC. And METTL3, an
important component of the m6A methyltransferase complex,
was downregulated. In vitro, METTL3-overexpression reduced the Hippo Pathway, and ECM.
activation of HSC by inhibition the proliferation and expression of FOXM1 and FUBP3 are highly expressed in LF tissues, and
α-SMA and COL1A1. On the contrary, knockdown of METTL3 could FOXM1 is a protein binding gene of FUBP3.
aggravate HSC activation in vitro. And METTL3 overexpression also Adenovirus-mediated interference of FOXM1 and FUBP3
alleviated CCl4-induced liver fibrosis in vivo. Bioinformatics analysis expression can alleviate the process of LF induced by CCl4 in mice.
suggested that the maturation process of miR-30d-5p during hepatic Table and Figure:Figure 1.In vivo experiments
fibrosis was regulated by m6A modification. Meanwhile, METTL3 Figure 2.In vitro experiments
overexpression sufficiently decreased the expression of pri-miR-30d-
5p and increased the expression of mature miR-30d-5p in vivo and in
PP0710
vitro. While METTL3 inhibition had the opposite effect in vitro. We found
METTL3 could interact with the microRNA microprocessor complex The mechanism of puerarin ameliorates liver fibrosis in mice
protein DGCR8 and regulate the pri-miR-30d-5p process in an m6A- based on the regulation of TGF-β/Smad/SOX4 pathway
dependent manner in HSC-T6. The functional reverse experiments in Liu Yu Hui1, Liu Yi2, You Yu2
vitro showed that miR-30d-5p inhibitor was able to reverse the effect of 1
Department of Pharmacology, School of Pharmacy, Jiangxi University
overexpression METTL3 on HSC-T6 activation. And miR-30d-5p mimic of Traditional Chinese Medicine, 2Department of Gastroenterology,
blunted the promotion of si-METTL3 on HSC-T6 activation. The First Affiliated Hospital of Nanchang University
Conclusion: Our findings explicate the mechanism that METTL3 Background: To explore the mechanism study of Puerarin anti-hepatic
ameliorates liver fibrosis by regulating miR-30d-5p maturation in an fibrosis by regulating TGF-β/Smad3/SOX4 pathway
m6A-dependent manner and provide a new theoretical basis for the Method: C57BL/6J mice were randomly divided into four groups:
treatment of liver fibrosis. control group, hepatic fibrosis model group, low-dose puerarin
Table and Figure:Figure 1.METTL3 affected the liver fibrosis and treatment group and high-dose puerarin treatment group, body weights
activation of HSC. and liver weights were recorded, and liver tissues and serum were
Figure 2.METTL3 regulated the maturation of miR-30d-5p by DGCR8 collected from mice . Fibrotic changes in mouse liver were detected by
in HSC-T6. pathological and immunohistochemical staining; COL1A1, α-SMA and
cytokine mRNA expression in liver tissues were detected by qPCR;
PP0709 COL1A1, α-SMA, and TGF-β, p-Smad3, Smad3 and SOX4 proteins
were detected by WB. CCK8 was used to detect the effects of different
FOXM1 and FUBP3 Cooperatively Regulate Hepatic Stellate Cells
concentrations of Puerarin on the survival rate of human hepatic stellate
for the Amelioration of Liver Fibrosis
cells LX2, which were co-cultured with or without Pue stimulation by
Chaoxu Fu1,2, Hongxin Piao1,2 TGF-β1. qPCR was used to detect the mRNA expression of COL1A1,
1
Affiliated Hospital of Yanbian University, 2Yanbian University α-SMA and cytokines in hepatocytes, and WB was used to detect the
Background: Liver fibrosis (LF) results from the disruption of the liver’s protein expression of COL1A1, α-SMA and TGF-β, p-Smad3, Smad3
self - repair process with excessive extracellular matrix accumulation. and SOX4. Smad3 inhibitor was administered to observe the effect of
Activated hepatic stellate cells are vital for extracellular matrix synthesis Puerarin on TGF-β1-induced activation of hepatic stellate cells. SOX4
and deposition. FOXM1, a key transcription factor in cell proliferation, overexpression plasmid was given to observe the effect of Puerarin on
is linked to liver inflammation and fibrosis, but its LF role is unclear. TGF-β/Smad3/SOX4 pathway.
FUBP3, a single - stranded DNA - binding protein, influences fibrosis Result: : Puerarin significantly reduced liver weight and liver-weight-
- and inflammation - related genes via expression changes, is closely to-body-weight ratio in CCl4-induced hepatic fibrosis mice, and
related to FOXM1 and participates in RNA polymerase II transcription significantly improved the impaired liver function of ALT, AST, and
regulation. Their complex relationship requires further study. TBIL; Puerarin significantly attenuated the structural damage and
Method: Liver disease cohorts from the GEO database were analyzed collagen deposition of liver in CCl4-induced hepatic fibrosis mice;
for FOXM1 and FUBP3 expressions. A lentivirus was used to build a Puerarin attenuated COL1A1, α-SMA and cytokine mRNA expression
stable LX - 2 cell line, and an adeno - associated virus to interfere with in CCl4-induced hepatic fibrosis mice and TGF-β1-stimulated LX2
CCl4 - induced LF in mice. Transcriptome sequencing was done to cell activation; Puerarin reduced COL1A1, α-SMA and TGF-β1,
identify changes in hepatic stellate cells and mouse liver tissue. RIP - p-Smad3, Smad3, and SOX4 protein expression in CCl4-induced
seq was performed to determine the FOXM1 - FUBP3 interaction in LX hepatic fibrosis mice and TGF-β1-stimulated LX2 cell activation. There
- 2 cells. The silencing effect was examined by qRT - PCR and Western was no significant difference in activation of hepatic stellate cells by
blotting. The proliferation and migration of silenced LX - 2 cells were gerberellin after administration of Smad3 inhibitor. Administration of
detected by CCK - 8, cell scratch, and Transwell migration assays. The SOX4 overexpression plasmid promoted SOX4 protein expression, and
LF degree was evaluated by hematoxylin - eosin, Masson, and Sirius there was no difference in TGF-β1 and p-Smad3 protein expression.
red staining. The expressions of FOXM1, FUBP3, Collagen I, alpha - Conclusion: Puerarin inhibits TGF-β1-induced hepatic stellate cell
SMA, and related proteins in hepatic stellate cells and liver tissue were activation, and puerarin attenuates CCl4-induced hepatic fibrosis
detected by WB, cell immunofluorescence, immunohistochemistry, in mice, Puerarin may suppress hepatic stellate cell activation
and tissue immunofluorescence. by modulating the TGF-β/Smad/SOX4 signaling pathway thereby
Result: FOXM1 and FUBP3 in liver disease cohort data were attenuating hepatic fibrosis.
differentially expressed and highly expressed in CCl4 induced LF Table and Figure:Figure 1.
mouse liver tissues and LX-2 cells. Transcriptomic analysis showed Figure 2.
they were differential genes. Signaling pathways related to LF like
Hippo, TGF - β, MAPK, calcium, and focal adhesion had similar trends PP0711
in two groups with high enrichment. RIP - seq analysis indicated an
interaction between FUBP3 and FOXM1 in LX - 2 cells. In - vitro and Human Umbilical Cord-Derived Mesenchymal Stem Cells
in - vivo experiments showed silencing FUBP3 and FOXM1 down - Attenuate Liver Fibrosis by Inhibiting Hepatocyte Ferroptosis
regulated Collagen I and alpha - SMA in LX - 2 cells, inhibiting cell Through Mitochondrial Transfer
proliferation and migration. When adeno - associated virus interfered Zhiyu Xiong1, Yingan Jiang1
with FOXM1 and FUBP3, Collagen I and alpha - SMA were down -
1
Department of Infectious Diseases, Renmin Hospital of Wuhan
regulated, tissue inflammation, cell infiltration and collagen deposition University, Wuhan 430060, China
improved, and liver fibrosis in CCl4 - induced LF model mice alleviated. Background: Liver fibrosis is a reversible dynamic pathological
In both experiments, proteins related to TGF - β/Smad3/CTGF, Hippo process driven by chronic liver injury. Without effective interventions,
Pathway and ECM signaling pathways changed. liver fibrosis may progress into liver cirrhosis, liver failure, or even
Conclusion: FOXM1 and FUBP3 regulate the activation, proliferation, hepatocellular carcinoma, which pose a huge burden to the global
and migration of hepatic stellate cells via the TGF - β/Smad3/CTGF,
healthcare. Therefore, developing effective therapeutic treatments LSECs were detected by western blotting, immunofluorescence, and
for hepatic fibrosis are urgently needed. Although mesenchymal RT-PCR. Furthermore, primary LSECs isolated from normal SD rats were
stem cells transplantation has shown benefits in treating liver injury pretreated with GLS2 siRNA, GLS2 adenoviral vectors, and ESRRB
and improving live function, the mechanism involved remains siRNA, following stimulation with H2O2. The expression of GLS2, OGT,
unelucidated. Hepatocyte ferroptosis contributes to the pathogenesis eNOS, CD31, ESRRB, and O-GlcNAc glycosylation of ESRRB were
and advancement of chronic liver injury, and targeting ferroptosis has detected using western blotting and co-immunoprecipitation (co-IP).
been proposed as a promising strategy for treating liver fibrosis. Result: Compared to the WT-CCl4 group, the collagen deposition were
Method: In this study, a TAA-induced mouse model of liver fibrosis was remarkably increased in the Gls2LSEC-KO-CCl4 group; moreover, the
established to evaluate the therapeutic effects of hUC-MSCs infusion protein expression of vWF, COL1A1, and α-SMA also were upregulated
on ferroptosis, liver function, and hepatic fibrosis. In vitro, AML-12 with decreased ALB and GLS2 in liver tissue of the Gls2LSEC-KO-CCl4
hepatocytes were co-cultured with hUC-MSCs under oxidative stress group. For primary LSECs, the Gls2LSEC-KO-CCl4 group showed
conditions to investigate the effects on ferroptosis-related mitochondrial loss of GLS2 and prominently downregulation of eNOS expression
damage and lipid peroxidation. Scanning electron microscopy (SEM) in LSECs. Futhermore, the Gls2LSEC-KO-CCl4 group also showed a
and double immunofluorescence staining were used to visualize tunnel higher degree of LSEC capillarization, as evidenced by the level of
nanotubes (TNTs) and the transfer of healthy mitochondria from hUC- CD31. Our scRNA-seq data showed that compared to the WT-CTR
MSCs to hepatocytes. Furthermore, Cytochalasin D (CytoD), a TNT group, ESRRB expression was downregulated in capillarized LSECs
inhibitor, was applied to confirm the role of TNT-mediated mitochondrial of the WT-CCl4 group; whereas in the Gls2LSEC-KO-CCl4 group,
transfer in the inhibitory effects of hUC-MSCs on hepatocyte ferroptosis. this effect was aggravated. And ESRRB function was modulated by
Result: Here, we observed that human umbilical cord mesenchymal GLS2-mediated glutaminolysis. In vitro, the protein levels of GLS2,
stem cells (hUC-MSCs) infusion can alleviate TAA-induced mice liver eNOS, OGT, and ESRRB were reduced by H2O2 treatment in primary
ferroptosis and restore impaired liver function, as well as attenuate rat LSECs, whereas these effects were reversed by overexpressing
hepatic fibrosis. Consistent with the in vivo experiments, hUC-MSCs co- GLS2 with adenoviral vectors. Additionally, co-IP displayed that the
culture obviously inhibited ferroptosis-related mitochondria structure O-GlcNAc glycosylation of ESRRB was decreased by H2O2 treatment,
damages and lipid peroxidation in AML-12 cells. Mechanistically, which was recovered by overexpression of GLS2 with adenoviral
scanning electron microscopy (SEM) and double immunofluorescence vectors. Furthermore, knockdown of ESRRB aggravated H2O2-
staining revealed that hUC-MSCs reduced ferroptosis by transferring induced increase of CD31 expression.
healthy mitochondria to the damaged hepatocytes through tunnel Conclusion: Loss of GLS2 reduces ESRRB to accelerate LSEC
nanotubes (TNTs) under oxidative stress conditions. Conversely, capillarization and hepatic fibrosis by suppressing O-GlcNAc
Cytochalasin D (CytoD), a mitochondrial inhibitor, significantly glycosylation of ESRRB.
abrogated the inhibitory effect of hUC-MSCs on hepatocytes Table and Figure:Figure 1.Fig 1
ferroptosis. Figure 2.Fig 2
Conclusion: Our study shows the presence of TNTs and their
mediated mitochondrial transfer between hUC-MSCs and ferroptosis
PP0713
hepatocytes and highlights the therapeutic potential of hUC-MSCs to
treat liver fibrosis. Construction and Effectiveness Analysis of Prediction Model for
Table and Figure:Figure 1.Graphic abstract Cirrhotic Cardiomyopathy
Shuping Ma1
1
[email protected]
PP0712
Background: Cirrhotic Cardiomyopathy (CCM) is a severe
GLS2 Modulates LSEC Capillarization during Hepatic Fibrosis via
complication of cirrhosis, featuring impaired myocardial contraction/
O-GlcNAc Glycosylation of ESRRB
diastolic function and electrophysiological abnormalities. Most
Xingyuan Yang1, Yanfang Lu2, Xianxi Li1, Rui Wang1, Xiaoli Ma1, cirrhotic patients have CCM to varying degrees. CCM is difficult to
Bingxin Lu1, Yanqin Yue1, Wang Guo1, Jian Hou3, Xiaoying Luo*1 identify without stress stimulation, but early identification is crucial
1
People’s Hospital of Zhengzhou University, Department of for preventing heart failure. This study aims to analyze the clinical
Gastroenterology, Henan Provincial People’s Hospital, Microbiome characteristics of CCM in cirrhotic patients, construct a predictive
Laboratory, Henan Provincial People’s Hospital, Zhengzhou model, and evaluate its efficacy for early identification and intervention.
450003, China, 2Department of Nephrology, Henan Provincial Key
Method: We retrospectively selected 249 cirrhotic patients from The
Laboratory of Kidney Disease and Immunology, Henan International
Second Hospital of Hebei Medical University (2021-2023) and divided
Joint Laboratory of Kidney Disease and Microenvironment, Henan
them into cirrhosis cardiomyopathy and non-cardiomyopathy groups
Provincial Clinical Research Center for Kidney Disease, Henan
based on CCM diagnostic criteria. Clinical data collection included
Provincial People‘s Hospital and People‘s Hospital of Zhengzhou
University, Henan 450053, China, 3Department of Epidemiology general information (gender, age, etiology, Child-Pugh classification,
and Biostatistics, College of Public Health, Zhengzhou University, complications), laboratory data (WBC, RBC, HB, PLT, RDWSD,
Zhengzhou 450003, China RDWCV, CK, etc.), and imaging data (abdominal CT/ultrasound,
echocardiography). We constructed a CCM prediction model
Background: Liver sinusoidal endothelial cells (LSECs) defenestration using LASSO regression, optimal subset regression, and stepwise
and capillarization play a crucial role in activation of hepatic stellate regression, and selected the most concise and representative model
cells and the early stages of liver fibrosis. Our previous study has based on the area under the ROC curve (AUC). The efficacy of the
showed that glutaminase 2 (GLS2) is a potential target for modulating model was analyzed using ROC curves, calibration curves, clinical
LSEC phenotype and function. Herein, we aimed to elucidate the decision curves, and Bootstrap internal validation.
mechanisms underlying GLS2 in LSEC capillarization and hepatic Result: 1 .The variables included in this model are left atrial diameter,
fibrosis. age, red blood cell distribution width CV, Child-Pugh classification, and
Method: We generated the LSEC-specific conditional Gls2 knockout total bile acid. Through the analysis of the correlation matrix, the above
mice (Gls2LSEC-KO) using Cdh5-icre driver mice crossed to Gls2 five key variables are independent of each other and can be included
floxed mice, and administrated with carbon tetrachloride (CCl4) to in the prediction model.
construct a liver fibrosis mouse model. The thirty-six mice were divided 2 .Analysis of the efficacy of the CCM prediction model: The AUC of the
into the wild type control (WT-CTR), WT-CCl4, Gls2LSEC-KO-CTR, constructed prediction model is 0.813, the calibrated C-index is 0.79,
Gls2LSEC-KO-CCl4 groups (n=9 per group). Primary LSECs were and the Brier score is 0.124, which is less than 0.250. The calibration
isolated from the above mice groups. Hematoxylin and Eosin (H&E) and curve of the prediction model shows good alignment with the ideal
Masson staining were used for evaluating the intensity of liver fibrosis. curve, indicating good discrimination and calibration. Through the
The expression of GLS2, vWF, CD31, COL1A1, α-SMA, albumin (ALB), analysis of the clinical decision curve, when the probability threshold is
and endothelial nitric oxide synthase (eNOS) in liver tissue and primary within the range of 4% to 94%.
Conclusion: This study successfully constructed a prediction model Background: Cirrhosis is a major global health burden and a leading
for CCM, which is expressed as Logit(P) = -13.203 + 0.071 x age cause of morbidity and mortality worldwide. The power of immune
(years) + 0.674 x Child-Pugh grade B (yes = 1, no = 0) + 1.767 x Child- mechanisms is prominent during cirrhotic disease progression,
Pugh grade C (yes = 1, no = 0) + 0.142 x RDWCV + 0.005 x TBA + with the involvement of CD8+ T cells being particularly important.
0.105 x LA, and presented in the form of a nomogram (see Figure 10). Bystander CD38+HLA-DR+CD8+ T cells can be activated by the
After evaluating the modefs performance, its application and impact, cytokine IL-15 bystander in the absence of TCR stimulation. However,
as well as undergoing internal validation, the model exhibited good there is no evidence of a clear relationship between such cells and
efficacy in predicting CCM. , the development of liver fibrosis. Thus, the study aimed to explore the
connection between bystander-activated CD38+HLA-DR+CD8+ T
cells and cirrhosis and their intrinsic function mechanism.
PP0714
Method: Peripheral blood mononuclear cells (PBMC) were extracted
Simvastatin exerts anti-hepatic fibrosis effects and mechanisms from fresh blood of 30 cirrhotic patients and 10 healthy donors, and the
through modulation of M1 macrophage function fraction of CD38+HLA-DR+CD8+ T cells was evaluated in both groups
Wanping Yan1, Wei YE1 via flow cytometry. Subsequently, our study evaluated the correlation
1
The Second Hospital of Nanjing, Nanjing University of Chinese between CD38+HLA-DR+CD8+ T cells and the clinical indicators
Medicine. AST, ALP, TBil, INR, NLR, ALB, CHE, γ-GT, and ALT. Furthermore, to
Background: Liver fibrosis is a chronic liver disease characterized by examine the impact of cytokine IL-15 on CD38+HLA-DR+CD8+ T
excessive extracellular matrix deposition in the liver. Macrophages play cells, we utilized CD8+ T cells from healthy donors and assessed the
an important role in various physiological and pathological processes. functional modifications post-IL-15 stimulation using flow cytometry
Simvastatin in anti-hepatic fibrosis and its mechanism have not been and evaluated the cytotoxic capabilities via in vitro cytotoxicity assays.
fully elucidated. The aim of this study was to investigate whether Finally, the effects of engaging the IL-15 pathway on CD38+HLA-
simvastatin inhibits the development of hepatic fibrosis by regulating DR+CD8+ T cells function were analyzed in vitro by treating CD8+
macrophage function and its related mechanisms. T cells from healthy donors with IL-15 pathway inhibitors, such as the
Method: Firstly, mice model were divided into oil control, CCL4 JAK/STAT5 and PI3K/mTOR pathways.
model and simvastatin treatment group (Fig1) . Changes in liver Result: Here, we showed that the fraction of CD38+HLA-DR+CD8+ T
function and hepatic immune microenvironment were evaluated by cells appeared considerably greater in the cirrhotic group in both data
histopathology, blood biochemistry, western blot, RT-qPCR and flow sets of cirrhotic patients and healthy individuals. This study identified a
cytometry. Subsequently, in vitro experiments were performed using substantial link between these cells and the severity of cirrhotic illness,
human PBMC and THP-1 cell lines were induced as macrophage liver damage, and inflammatory markers.IL-15-stimulated CD38+HLA-
models in the in vitro experiments to explore the effects of simvastatin DR+CD8+ T cells from healthy donors exhibited proliferation, as
on macrophage phenotype and function as well as the mechanism evidenced by elevated ki-67 expression and up-regulated levels of
of the relevant signaling pathways. Finally, the effects of simvastatin cytotoxic molecules such as NKG2D, FasL, perforin, and Granzyme B.
on hepatic stellate cells via macrophages were investigated by Furthermore, these cells exhibit NKG2D- and FasL-dependent innate
co-culturing with LX-2 cells in simvastatin-untreated/treated M1 cytotoxicity independent of TCR participation. IL-15 was likewise found
macrophage conditioned medium (Fig2). to have no effect on mitochondrial mass and levels of mitochondrial
Result: The results of the in vivo experiments showed that simvastatin reactive oxygen species in these cells. Ultimately, we determined that
treatment reduced smooth muscle actin (α-SMA) expression in the the JAK/STAT5 and PI3K/mTOR pathways are essential for this IL-15-
liver and reduced the serum levels of alanine aminotransferase (ALT) induced category of innate cytotoxicity.
and glutamine aminotransferase (AST). The results of HE staining Conclusion: The JAK/STAT5 and PI3K/mTOR pathways are crucial
and Masson staining further indicated that the degree of fibrosis was for IL-15 activation of CD38+HLA-DR+CD8+ T cells, which rely on
reduced. Flow cytometry results showed that the expression of CD86, NKG2D and FasL to exhibit non-TCR-dependent innate cytotoxic-like
an M1 marker, was reduced in macrophages in the livers of simvastatin- activity, resulting in liver injury in cirrhotic individuals.
treated mice compared with CCL4 model , while the expression of
CD206, an M2 marker, was not significantly changed. Simvastatin PP0716
was shown to reduce the levels of pro-inflammatory cytokines IL-6,
Study on the Improvement of Liver Fibrosis by Shuxuening:
TNF-α, and IL-1β in the liver of mice. In the in vitro experiments, as
Multilayer Mechanistic Evidence Based on Network Pharmacology
detected by flow cytometry that simvastatin inhibited the polarization
and Molecular Docking
of PBMC-derived and THP-1-derived M1-type macrophages and
inflammatory factor secretion, but had no significant effect on M2- Tingyu Zhang1,2, Xin Sun1,2, Shihao Zheng1,2, Wenying Qi1,2, Xiaoke
type macrophages. Further studies showed that simvastatin inhibited Li1,2, Xiaobin Zao1,2,3
the expression of proinflammatory factors through PI3K/AKT/mTOR
1
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing
signaling pathway inhibited the polarization of M1-type macrophages, 100700, China;, 2Institute of Liver Diseases, Dongzhimen Hospital,
decreased the secretion of inflammatory factors, and enhanced the Beijing University of Chinese Medicine, Beijing 100700, China;, 3Key
expression of autophagy-related proteins. Finally, RT-qPCR and Laboratory of Chinese Internal Medicine of Ministry of Education and
Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine,
Western Blot experiments confirmed that simvastatin-treated M1
Beijing 100700, China
macrophage conditioned medium could significantly reduce the
expression of α-SMA in LX-2 cells. Background: Liver Fibrosis (LF) is a reversible over-repair response to
Conclusion: Simvastatin could inhibit the polarization and pro- hepatic tissue damage in the course of chronic liver disease. Traditional
inflammatory activity of M1 macrophages through the PI3K/AKT/ Chinese Medicine (TCM) has demonstrated significant therapeutic
mTOR pathway. It provides a new theoretical basis for the study of the effects in the treatment of LF. Shuxuening injection (SXN) is a widely
mechanism of simvastatin in the treatment of liver fibrosis. used and commercially available TCM known for its ability to dilate
Table and Figure:Figure 1.Schematic diagram of mouse model blood vessels and improve microcirculation. However, the therapeutic
Figure 2.Schematic diagram of the co-culture system effects and underlying mechanisms of SXN in the treatment of LF
remain unclear.
Method: We first obtained the target genes of SXN and LF from the
PP0715 TCMSP, BATMAN-TCM, and GeneCards databases. Subsequently,
IL-15-Activated CD38+HLA-DR+CD8+ T Cells Induce Liver Injury in we constructed an SXN-active component-LF network and performed
Cirrhosis via JAK/STAT5 and PI3K/mTOR Pathways enrichment analyses of the key targets and hub genes. Protein
Ke Liu1, Wei Ye1 and small molecule ligands were processed using AutoDockTools
1
The Second Hospital of Nanjing, Nanjing University of Chinese software, and molecular docking was conducted with AutoDock Vina
Medicine. to calculate binding energies.
Result: We first identified 27 bioactive components and predicted HC that are critical in regulating immune response, metabolism and
2,929 potential targets of SXN. Subsequently, 7,397 LF-related targets cell signaling. Notably, proteins P04004, P02765, and P02647 showed
were retrieved from the GeneCards database, and 924 disease targets significant differences in PoPH. In addition, 35 genes were identified
were filtered through analysis. By intersecting the SXN component as potential markers to distinguish PoPH from HC and PHTN. However,
targets and LF-related targets using the Venny tool, we identified 416 further experimental studies are required to validate these findings and
key targets. The GO enrichment analysis revealed these key targets to elucidate the underlying biological mechanisms.
were critical for regulating cellular responses in hypoxic environments. Table and Figure:Figure 1.Figure 1. Identification of DEPs. (A) Volcano
The KEGG enrichment analysis results showed that these key targets plot of DEPs between POPH and HC. (B) InterPro analysis (POPH vs.
were correlated to the JAK-STAT and HIF-1 signaling pathways. HC). (C) KEGG analysis (POPH vs. HC). (D) GO analysis (POPH vs.
These key targets were further used to construct a protein-protein HC). (E) Volcano plot of DEPs between POPH and PHTN. (F) InterPro
interaction network and ultimately identified a key module comprising analysis (POPH vs. PHTN). (G) KEGG analysis (POPH vs. PHTN). (H)
24 hub targets. Molecular docking analysis results indicated that there GO analysis (POPH vs. PHTN).
exhibited strong binding affinities between the bioactive components Figure 2.Figure 2. Identification of candidate markers. (A) Venn diagram
of SXN and hub targets, especially STAT3-Flavoxan, HIF1A-Flavoxan, showing common DEPs. (B) PPI network of the common DEPs. The
and EGFR-Flavoxan. darker the color, the larger the MCC value.
Conclusion: SXN might exert anti-LF effects by modulating the JAK-
STAT and HIF-1 signaling pathways. STAT3, HIF1A, and EGFR might PP0718
be the important targets for SXN in treating LF.
Table and Figure:Figure 1.Figure 1 Network Pharmacology and Akkermansia muciniphila: A Potential Modulator in Mitigating
Molecular Docking of Shuxuening Liver Fibrosis
Lei Ma1, Huichun Xing1
1
Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital
PP0717
Medical University
Plasma Proteomics Identify Biomarkers and Pathogenesis of
Background: Liver fibrosis is a major global public health issue
Portopulmonary Hypertension
with limited therapeutic options. The condition can progress to liver
JiaLin Du1, Diandian Hao1, Hui Wang1, YuZe Song1, YuLin Ren1, cirrhosis, liver failure or hepatocellular carcinoma, significantly
Xiaoyu Wen2 worsening patient outcomes. Studies have shown that gut microbiota
1
Center for Infectious Diseases and Pathogenic Biology / Department are closely associated with the occurrence and severity of liver fibrosis.
of Hepatology, The First Hospital of Jilin University, Changchun Akkermansia muciniphila, as a member of gut commensal bacterium,
130021, China., 2Center for Infectious Diseases and Pathogenic has been proposed as a next-generation probiotic. This study aims to
Biology / Department of Hepatology, The First Hospital of Jilin explore the potential impact of A. muciniphila on liver fibrosis.
University, Changchun 130021, China Method: Liver fibrosis was induced in 10-week-old C57 mice by
Background: Portopulmonary Hypertension (PoPH) is a significant carbon tetrachloride (CCl4) treatment for 8 weeks. At the same time,
complication in patients with portal hypertension (PHTN), defined one group of mice was treated with an A. muciniphila suspension via
as an elevation of pulmonary artery pressure on the basis of portal oral gavage.
hypertension. The pathogenesis of PoPH remains incompletely Result: Mice injected with CCl4 alone displayed significantly
understood. This study employs proteomics technology to identify elevated serum biochemical markers and inflammatory cytokines,
differentially expressed proteins (DEPs) and genes in PoPH and histopathological damage to the liver. However, mice treated with A.
compares them with those in PHTN and healthy controls (HC). The muciniphila via oral gavage exhibited a decrease in serum biochemical
resluts will deepen the understanding of the pathogenesis of PoPH markers and inflammatory cytokines, ameliorated histopathological
and support the identification of potential biomarkers. damage to the liver compared with the CCl4 group.
Method: This study enrolled patients with cirrhotic portal Conclusion: This study preliminarily suggests that supplementation
hypertension admitted from January 2023 to May 2024. Based on with A. muciniphila can alleviate CCl4-induced liver fibrosis.
echocardiographic results, patients were categorized into PoPH group Table and Figure:Figure 1.Differences in serum ALT, AST and IL-1β
and non-PoPH group, the latter defined as the PHTN group. From the levels among three groups of mice.
cohort, 12 PoPH and 12 PHTN patients and 6 HC. Serum samples Figure 2.Representative H&E, Masson, and Sirius Red staining of liver
were analyzed using Data-Independent Acquisition (DIA) quantitative tissues from three groups of mice.
proteomics. The DEPs identified in the PoPH vs. PHTN and PoPH vs.
HC comparisons underwent enrichment analysis via using GO, KEGG,
PP0719
InterPro databases and PPI. Network topology and node centrality
analyses were performed to identify hub proteins with Maximum Clique Aging Accelerates the Progression of Liver Fibrosis via
Centrality (MCC) rankings. Hyperacetylation of HnRNP U at K28 Site
Result: In the POPH vs. HC comparison, 374 upregulated proteins Xiaoli Ma1, Jian Hou2, Jinying Liu1, Wang Guo1, Xingyuan Yang1,
and 115 downregulated proteins were identified, whereas in the Yanqin Yue1, Bingxin Lu1, Rui Wang1, Xianxi Li1, Yu Guo1, Bingyong
PoPH vs. PHTN comparison, 18 upregulated and 38 downregulated Zhang*1, Xiaoying Luo*1
proteins were identified (Figure 1A, 1E). InterPro analysis revealed that 1
People’s Hospital of Zhengzhou University, Department of
DEPs in POPH vs. HC were enriched in enzymatic activity, immune Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou
response, protein inhibition, and cell signaling pathways, whereas 450003, China, 2Department of Epidemiology and Biostatistics,
those in POPH vs. PHTN were associated with metabolism, protein College of Public Health, Zhengzhou University, Zhengzhou 450003,
folding, and hormone synthesis (Figure 1B,1F). KEGG analysis China
indicated involvement in immune response, metabolism, and cell Background: Both aging and ribonucleoproteins (hnRNPs) play a vital
signaling for DEPs in both comparisons (Figure 1C, 1G). Similarly, GO role in the pathogenic process of aging-related diseases. Moreover,
analysis revealed roles in metabolic regulation and immune response our previous protein modification omics analysis have showed that
for PoPH vs. HC DEPs, and in cell signaling, ion transport, and cell aging promotes the progression of liver fibrosis in relation to increased
growth regulation for PoPH vs. PHTN DEPs (Figure 1D, 1H). By acetylation of hnRNP U. However, the mechanisms underlying hnRNP
taking the intersection of the two comparisons, we obtained 35 genes U and its acetylation sites in hepatocyte inflammation and liver fibrosis
distinguishing PoPH from HC and PHTN (Figure 2A). The PPI network with the elderly remain unclear. Herein, we investigate the role of
of these proteins are shown in Figure 2B. According to the MCC hnRNP U acetylation in liver fibrosis with aged animals, which may
ranking, the top three proteins were P04004, P02765, and P02647. provide a promising novel therapeutic approach against liver fibrosis
Conclusion: Through proteomic analysis, this study identified key with the elderly.
differentially expressed proteins (DEPs) and genes in PoPH, PHTN and Method: We constructed the CCl4-induced liver fibrosis with young
and aged rats, of which liver tissue was measured liver inflammation enhance the activation and cytotoxicity of NK92 cells in co-cultured
and fibrosis scores, as well as further performed acetylomic analysis system. Meanwhile, IL-10-induced senescent LX2 cells increased its
to identify the vital acetylated substrates and their sites. Replicative ligand expression of NK activating receptor such as ULBP2, MICA/B
senescent rat hepatocytes were treated with hnRNP U siRNA, CREBBP and PVR to further promote the activation of NK92 cells. Lastly, the
siRNA, SIRT1 siRNA, and transfected with hnRNP U wild type and enhanced immune function of NK92 cells by senescent LX2 induced
hnRNP U K28 acetylation site mutants, respectively. Western blotting by IL-10 were significantly blocked when NK92 cells were pretreated
and co-immunoprecipitation (Co-IP) were used to detect the levels by NKG2D antibody. In vivo, IL-10 gene treatment induced senescence
of CREBBP, SIRT1, hnRNP U, hnRNP U acetylation, and the crucial of HSCs in fibrotic mice to promote the ligand expression of NK cells
signalling pathway about cellular senescence. activation to decrease the production of collagen.
Result: In vivo, the degree of liver fibrosis, the elevated expression of Conclusion: Interleukin10 induces senescence of HSCs to promote
α-SMA and COL1A1 in liver tissue of aged rats with fibrosis was more the immune function of NK cells to attenuate liver fibrosis.
server than that in young rats with fibrosis. The acetylomic measurement Table and Figure:Figure 1.IL-10 induced senescence of LX2 to
of liver tissue showed acetylation of HnRNP U and its sites at K28 as enhance the activation of NK92 cells
a potential target for liver fibrosis with aged rats. In vitro, knockdown Figure 2.The senescent LX2 cells induced by IL-10 enhance the
of CREBBP or overexpression of SIRT1 inhibited H2O2-induced cytotoxicity of NK92 cells in the NKG2D dependent way
hyperacetylation of hnRNP U in senescent hepatocytes; whereas
knockdown of SIRT1 aggravated H2O2-induced hyperacetylation
PP0721
of hnRNP U by activation of the p53/p21 pathway. Furthermore, the
acetylation of hnRNP U at K28 site was significantly increased in Targeted Delivery of ITSN1 siRNA to Restore VEGF-Regulated
H2O2-treated senescent hepatocytes. Differentiation of LSEC for the Treatment of Liver Fibrosis
Conclusion: Aging accelerates hyperacetylation of hnRNP U at K28 Lanting Zhang1, Yunyu Zhao1, Yi Liu1, Xiao Yuan1, Weiming You1,
site to activating the p53/p21 pathway, thereby liver senescence and Yichen Yang1, Zixuan Xing1, Ning Gao1, Fengping Wu1, Wangxiao
liver fibrosis, indicating that targeting acetylation of hnRNP U at K28 He2, Fanpu Ji1
site may be a novel therapeutic approach for treatment of liver fibrosis, 1
The Second Affiliated Hospital of Xi ‘an Jiaotong University, 2The First
especially among aging population. Affiliated Hospital of Xi ‘an Jiaotong University
Table and Figure:Figure 1.figure 1 Background: During liver injury, capillarized liver sinusoidal endothelial
Figure 2.figure 2 cells (LSECs) restrict the exchange of substances between blood
and Disse space, accelerating the activation of hepatic stellate cells
PP0720 (HSCs) and the progression of liver fibrosis. The suppression of the
vascular endothelial growth factor (VEGF) signaling pathway in LSECs
Interleukin10 induces senescence of hepatic stellate cells to
is a crucial factor in LSECs dedifferentiation and dysfunction. Our prior
promote the immune function of natural killer cells to attenuate
research identified Intersectin 1 (ITSN1) as a key VEGF regulator. Here,
liver fibrosis
we designed a defensin-delivered ITSN1 siRNA nanoformulations to
Yuehong Huang1,2, Yizhen Chen, Xiaozhong Wang inhibit ITSN1 in LSECs in vivo and assess its anti-fibrotic effect.
1
Department of Gastroenterology and Fujian Institute of Digestive Method: At the cellular level, we inhibited ITSN1 mRNA in LSECs using
Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, lipofectamine transfection to observe effects on LSECs differentiation
3
50001, China. , 2Fujian Clinical Research Center for Digestive System and HSCs activation in co-culture. We then constructed a defensin
Tumors and Upper Gastrointestinal Diseases, Fuzhou, Fujian, 350001, delivery system combined with ITSN1 siRNA (RC100@siITSN1),
China.
assessed its safety in vivo, and evaluated targeted delivery to
Background: Fibrosis is a common pathological change of chronic LSECs using imaging in vivo and confocal microscopy. The RC100
liver diseases leading to cirrhosis and hepatocellular carcinoma. incorporated an Arg-Gly-X (RGX) structure, which mimics RGD
However, a specific therapy for liver fibrosis still absent. Natural killer peptides, to enhance adhesion to integrin-expressing cells (such as
(NK) cells play an important role in the progression and retrogression LSECs). Therapeutic effects of RC100@siITSN1 were assessed in a
of liver fibrosis. Our previous study shows that interleukin10(IL-10) CCl4-induced liver fibrosis mouse model through histological staining,
attenuated liver fibrosis by enhancing immune function of NK cells in qPCR analysis of HSCs activation markers, and serum ALT, AST levels.
mice, but the precise mechanism still unclear. Present study aims are Result: The study found that knocking down the expression of
to explore the directly or indirectly regulatory effect of IL-10 on immune ITSN1 mRNA in LSECs led to an increased porosity (Figure 1A) and
function of NK cells in vitro and in vivo and further clarify the underlying enhanced expression of differentiation markers (Figure 1B). When
mechanism of antifibrotic effect of IL-10. LSECs with reduced ITSN1 mRNA expression were co-cultured with
Method: In vitro, NK92 cells firstly were directly treated with IL-10 activated HSCs (Figure 1C), there was a notable inhibition of HSC
and flow cytometry and western blot assay were used to detect the activation (Figure 1D) and a reduction in collagen secretion (Figure
expression of activating receptor and production of cytotoxic granules 1E,F). Subsequently, we constructed and characterized RC100@
of NK 92 cells. Then, NK92 cells were cocultured with senescent LX2 siITSN1 peptide nanoformulations (Figure 2A,B) and verified its
induced by IL-10 or proliferating LX2 cells and detected the effect of IL- plasma stability. Compared with other major organs, RC100 exhibited
10 on immune function of NK92 cells through lactate dehydrogenase higher distribution and metabolic efficiency in the livers at 6 hours or
assay, immunofluorescence staining, flow cytometry and western blot 2 days post-injection in CCl4-induced liver fibrosis mice after injecting
assay. Lastly, NKG2D antibody was used to block the its receptors Cy5-labeled RC100 via the tail vein (Figure 2C). Immunofluorescence
and immune function of NK92 cells were evaluated once again. In analysis of liver tissue sections showed that RC100 was mainly
vivo, primary hepatic stellate cells (HSCs) from fibrotic mice with or distributed in LSECs within the liver (Figure 2D). Furthermore,
without IL-10 gene treatment were performed to measure the marker compared with the CCl4-induced liver fibrosis model group (control
of senescence and activation of HSCs, production of collagen, and the group), the RC100@siITSN1 treatment group showed reduced HSCs
ligands of NK cells activation by real-time polymerase chain reaction activation, decreased extracellular collagen deposition (Figure 2E),
(RT-PCR). and improved liver function (Figure 2F,G).
Result: Flow cytometry and WB results showed that IL-10 treatment Conclusion: This study highlights ITSN1 as a crucial molecule
had no direct effect on the expression of activating receptor and influencing the differentiation phenotype of LSECs. The strategy of
production of cytotoxic granules of NK92 cells. However, senescent targeting LSECs with defensin-delivered ITSN1siRNA to restore LSECs
LX2 cells induced by IL-10 markedly enhanced the activation and fenestrae represents a promising treatment for liver fibrosis.
cytotoxicity of NK92 cells compared to proliferating LX2 cells. Table and Figure:Figure 1.Figure 1. Effects of ITSN1 mRNA knockdown
Mechanically, senescent LX2 cells induced by IL-10 promoted the on the differentiation phenotype of LSECs and its impact on HSCs
expression of activating receptor NKG2D, NKp46 and CD226 and activation in co-culture. (A) SEM images of LSECs treated with lipo@
the release of cytotoxic granules both perforin and granzyme B to siNC (left) or treated with lipo@siITSN1 (right). (B) qPCR analysis of the
expression of differentiation markers (left) and capillarization markers metabolism and interferon-α response pathways. In QL1005-treated
(right) in the LSECs. (C) Diagrammatic representation of the co-culture mice, macrophage counts were significantly reduced, accompanied
experiments design. The untreated HSCs or treated with TGFβ 12h by downregulation of TGF-β and p53-related pathways.
were co-cultured with the ITSN1-silenced of LSECs by transwell for Conclusion: GLP-1/GDF15 dual-agonist showed a synergistic
24h. (D) qPCR analysis of the expression of marker genes for HSCs effect in reducing hepatic inflammation and fibrosis was observed in
activation. (E) The expression of α-SMA and COL1α1 in HSCs was chemical-induced fibrosis and MASH models, highlighting its potential
determined by confocal microscopy. (F) Western blot analysis of as a therapeutic candidate for treating liver fibrosis.
α-SMA and COL1α1 levels in the indicated treatment groups. *p<0.05,
**p<0.01, #p<0.001.
PP0723
Figure 2.Figure 2. Fabrication and characterization of RC100@siITSN1,
in vivo targeting detection, and evaluation of therapeutic efficacy Portal hypertension contributes to ascites formation via piezo1-
in CCl4-induced liver fibrosis in C57BL/6 mice. (A) TEM images of nuclear factor kappa B-aquaporin1 pathway in liver cirrhosis
the RC100@siITSN1. (B) Hydrodynamic diameter (left) and ZETA Ning Wei1,2, Li Du1, Long Zhuang Xiao1, Lei Zhang1, Yang Yang Zhou1,
potential (right) of RC100 or RC100@siITSN1. (C) Representative Hao Nan Gao1, Hui Ming Liu3, Bo Cheng Wang3, Hua Xiao Hou3, Yan
ex vivo fluorescence images showing the biodistribution of free Cy5 Li4, Hu Yu Song5
or Cy5+RC100 after 6 hours or 2 days i.v. injection in CCl4-induced 1
Department of Gastroenterology, Union Hospital, Tongji Medical
liver fibrotic mice (6 weeks). (D) Confocal microscopy images of College, Huazhong University of Science and Technology, 2The
liver sections from the liver fibrotic mice 2 days after i.v. injection Central Hospital of Wuhan, 3Division of Gastroenterology, Union
with Cy5+RC100. Immunofluorescence showing the colocalization of Hospital, Tongji Medical College, Huazhong University of Science,
RC100 (red) with LYVE1 staining (green) or CD34 staining (green).
4
Department of Gastroenterology, the First People‘s Hospital of
(E) Liver sections from normal/fibrotic mice stained with HE, Masson, Yunnan Province, Affiliated Hospital of Kunming University of Science
Sirius red, or immunochemistry (α-SMA, COL1α1). Groups: Normal and Technology, 5Department of Gastroenterology, Union Hospital,
(G0), CCl4+PBS (G1), CCl4+free siITSN1 (G2), CCl4+RC100 (G3), Tongji Medical College, Huazhong University of Science and
CCl4+RC100@siITSN1 (G4). Serum ALT (U/L) (F), and AST (U/L) (G) Technology, Wuhan
levels. Background: Portal hypertension is believed critical to the
development of cirrhotic ascites. However, a suitable murine model
has not been available until now, which confines the research on
PP0722
the mechanism underlying the contribution of portal hypertension to
A novel GLP-1/GDF15 dual-agonist reduces hepatic inflammation ascites formation.
and fibrosis in murine models of chemical-induced liver fibrosis Method: The role of portal hypertension in cirrhotic ascites was
and Metabolic Associated Steatohepatitis (MASH) determined through meta-analysis of portal pressure in cirrhotic
Yuanping Shi1, Yuanyuan Zhang2, Linong Ji1, Xiantong Zou1 patients and animal model. The mechanism underlying the involvement
1
Peking University People‘s Hospital, 2Beijing QL Biopharmaceutical of portal hypertension in ascites formation was explored.
Co., Ltd. Result: Meta-analysis showed hepatic venous pressure gradient
Background: QL1005, a glucagon-like-protein-1/growth differentiation (HVPG) in cirrhotic patients with ascites was significantly higher
factor 15 (GLP-1/GDF15) dual-agonist, shows significant effects in than those without ascites. In carbon tetrachloride (CCl4)-treated
reducing body weight and metabolic disorders in human and animal rats, portal pressure of cirrhotic rats with ascites was significantly
models with low-toxicity. This study aimed to explore the effects of higher than those without ascites. In a novel murine model created
QL1005 against hepatic fibrosis . by thioacetamide (TAA)/CCl4 administration plus partial portal vein
Method: The chemical-induced liver fibrosis model was established ligation (PPVL), a significant increase in portal pressure and ascites
in male mice by intraperitoneal injections of 10% CCl4 for 7 weeks. amount was observed in the TAA/CCl4+PPVL groups compared with
The MASH model was created by feeding mice a Western diet the TAA/CCl4 group. Then, in the mice treated with TAA/CCl4 plus
supplemented with fructose (WDF) for 26 weeks. During the last 3 or 6 PPVL, ascites amount decreased significantly in mice with endothelial
weeks, mice received daily subcutaneous injections of QL1005, GLP-1 cell-specific deletion of Piezo1(Piezo1ΔEC) compared with Piezo1flox/
(QL1005 with inactive GDF15), GDF15 (QL1005 with inactive GLP-1), flox mice.
or Vehicle at a dose of 30 nmol/kg. At the end of the experiments, Conclusion: We found that Piezo1 promoted the development
plasma and liver samples were collected for analysis. Single cell RNA of portal hypertensive ascites via nuclear factor kappa-B (NF-ĸB)-
sequencing were used to explore the cell-specific mechanisms of the aquaporin1(AQP1) pathway.
treatments in the WDF experiment. Table and Figure:Figure 1.Figure.1 the critical role of endothelial Piezo1
Result: During both hepatic injury and resolution phases (24 and 72 in the development of portal hypertensive ascites using Piezo1ΔEC
hours after last injection, respectively), QL1005 and GLP-1 significantly mice and Piezo1fl/fl mice;
reduced ALT and AST levels compared to Vehicle, while GDF15 Figure 2.Figure.2 Portal hypertension induced AQP1 expression in
showed no effect. QL1005 uniquely lowered TNF-α and MCP-1 levels peritoneal endothelium through Piezo1.
in both phases. No significant anti-fibrotic effects were observed during
the injury phase for QL1005 or the mono-agonists. In the resolution PP0724
phase, QL1005 reduced tissue injury and fibrosis, as shown by Sirius
HK2-Mediated Metabolic Reprogramming in Liver Fibrosis: A
Red staining, with a 38.2% decrease in α-SMA-positive regions and
Multi-Omics Approach
downregulation of α-SMA, type 1, and type 3 collagen mRNA levels.
Lu Han1, Fan Lu1, Shao Jie Chen1, Qing Xiu Zhang1, Hua Yue Wu1,
RNAseq analysis revealed decreased expression of genes related to
Tao Huang1, Xue Ke Zhao1
fibrosis, inflammation, apoptosis, and oxidative stress.
In the MASH model, treatment with all three agonists significantly
1
Affiliated Hospital of Guizhou Medical University
reduced weight gain and liver size. Liver enzymes, fasting blood Background: Liver fibrosis occurs as a result of ongoing liver damage
glucose, triglycerides, and cholesterol levels were also notably from conditions like hepatitis B/C and non-alcoholic fatty liver disease.
improved, with QL1005 showing the greatest effect. QL1005 The activation of hepatic stellate cells (HSCs) is central to this process,
significantly reduced the hepatic expression of a-SMA and COL1a1 with aerobic glycolysis being a critical contributor. Although hexokinase
as confirmed by immunohistochemistry and pro-inflammatory 2 (HK2) is a pivotal enzyme in glycolysis, its involvement in liver fibrosis
cytokines including IL-6, TNFα and IL-1, as confirmed by qPCR. In the is not yet fully understood.
scRNA-seq analysis of WDF mice, UMAP clustering identified 12 cell Method: Multi-omics analyses were conducted, which included RNA
clusters, which were assigned to distinct cell types based on known sequencing of 30 fibrosis/cirrhosis patients and 8 controls, in order
cell-type markers. In HSC, KEGG enrichment analysis revealed that to pinpoint differentially expressed genes (DEGs).Weighted gene
QL1005 may influence apoptosis, oxidative phosphorylation, fatty acid co-expression network analysis (WGCNA) identified gene modules
associated with fibrosis. By using single-cell RNA sequencing (scRNA- IL1β-upregulated SFXN1 promotes HSC activation and liver
seq), we analyzed HK2 expression in hepatic cells, and its presence fibrosis through inducing mitochondrial dysfunction and NLRP3
was validated by Western blotting and immunohistochemistry. HK2 inflammasome activation
knockdown and knockout (KO) in HSCs were assessed for effects Zhipeng Du1, Xu Han2, Caijun Rao3
on migration, wound healing, and transcriptomic changes. Machine 1
Department of Gastroenterology, Institute of Liver and
learning models were used to predict fibrosis based on glycolysis- Gastrointestinal Diseases, Tongji Hospital, Tongji Medical College,
related genes and validated on an external dataset. Clinical relevance Huazhong University of Science and Technology, 2Institute of Liver
was evaluated by correlating key gene expression with liver damage and Gastrointestinal Diseases, Tongji Hospital,Tongji Medical College,
markers. Huazhong University of Science and Technology, 3Department
Result: HK2 was significantly associated with liver fibrosis, with of Geriatrics, Tongji Hospital,Tongji Medical College, Huazhong
elevated expression in HSCs. HK2 knockdown impaired HSC migration University of Science and Technology
and wound healing. Machine learning models, especially random Background: Liver fibrosis is wound-healing response characterized
forest, predicted fibrosis with high accuracy (AUC 0.889). There was by excessive extracellular matrix (ECM) deposition. Hepatic stellate
a correlation between HK2 expression and clinical markers such as cells (HSC) activation is the central event of liver fibrogenesis.
ALT and AST. Sideroflexin 1 (SFXN1) is recently identified as a mitochondrial
Conclusion: To summarize, HK2 is involved in driving HSC activation transporter for iron, and is involved in mitochondrial dysfunction,
and migration, which in turn plays a part in the progression of liver however, its roles and mechanisms in the regulation of HSC activation
fibrosis. It serves as a potential therapeutic target as well as a and liver fibrosis remains unknown.
predictive biomarker for fibrosis. Method: SFXN1 expression was measured in human, mice and rat
Table and Figure:Figure 1. fibrotic livers and in rat primary HSC. The roles and mechanisms of
SFXN1 in the pathogenesis of liver fibrosis were explored using gain-
PP0725 and loss-of-function methods. Furthermore, NLRP3 specific inhibitor
Cardiac failure following transjugular intrahepatic portosystemic OLT1177 was adminstrated to measure its role in liver fibrogenesis.
shunt patients with cirrhosis Result: SFXN1 expression was upregulated in rat and mouse fibrotic
liver tissues and during rat primary HSC activation. Lentivirus-
Shu Me Du1
mediated knockdown of SFXN1 decreased HSC activation, while
1
West China Hospital of Sichuan University SFXN1 overexpression exerted the opposite effect. By mitoSOX
Background: Transjugular intrahepatic portosystemic shunt (TIPS) is staining, JC1 staining, transmission electron microscope observation,
effective in alleviating the complications of portal hypertension. Post- and DFOM (a Fe2+ chelator) incubation, we found that SFXN1
TIPS cardiac failure has become one of the main concerns recently. It promoted mitochondrial dysfunction by mediating mitochondrial
is as high as 20% after TIPS insertion in the Western population. This iron transport. Furthermore, SFXN1 promotes NLRP3 inflammasome
study was designed to evaluate the incidence of post-TIPS cardiac activation through inducing mitochondrial dysfunction, and finally
failure and predisposing factors in patients with cirrhosis. promotes HSC activation. By treatment with various pro-fibrotic
Method: Between September 2022 and April 2024, consecutive cytokines, we found that IL1β was the most powerful inducer of
cirrhotic patients who underwent elective TIPS were prospectively SFXN1 in LX-2. By explore JASPAR database, we found c-MYC might
screened for inclusion. Patients were excluded if they had (1) a history be the transcription factor responsible for SFXN1 transcription, and
of previous TIPS or surgical shunt; (2) medium to severe pulmonary knockdown of c-MYC by siRNA decreased the level of SFXN1 induced
hypertension; (3) heart failure; (4) End-stage renal disease requiring by IL1β. The in vivo study revealed that AAV6-mediated HSC-specific
hemodialysis; (5) respiratory failure; (6) malignancies with a life SFXN1 knockdown ameliorated the CCl4-induced mice liver fibrosis.
expectancy of less than 6 months. A systematic cardiac assessment OLT1177 administration alleviated CCl4-induced mice liver fibrosis in
was conducted in each patient, including biological parameters dose dependent manner, and the anti-fibrotic effect of larger amount
and transthoracic echocardiography. The primary endpoint was the of OLT1177 was greater than that of MCC950. Clinically, SFXN1
incidence of cardiac failure. was upregulated in liver from patients with liver fibrosis, and SFXN1
Result: 238 patients underwent TIPS during the study period, 210 met expression was positively correlated with NLRP3 and c-MYC.
inclusion criteria [aged 54.0 (47.0-61.0) years, 68.0% man]. Etiologies Conclusion: Our study revealed that SFXN1 is upregulated in HSC
of cirrhosis were hepatitis B viral infection in 120 (57.1%) patients, activation and liver fibrosis. IL1β upregulated SFXN1 expression
and the indication for TIPS was secondary prophylaxis in 166 (79.0%) through c-MYC, and SFXN1 promoted mitochondrial Fe2+ transport,
patients. Baseline echocardiography showed the ejection fraction mitochondrial dysfunction and NLRP3 activation, and thus promoting
was 68.0% (63.0%-72.0%), E/A was 1.0 (0.8-1.3), and Pro-BNP was HSCs activation and liver fibrosis. HSC-specific knockdown of SFXN1
103.0 (48.0-194.3) respectively. After a median follow-up of 12.0 (8.0- and treatment with OLT1177 ameliorated CCl4-induced liver fibrosis
17.0) months, only one patient (0.47%) experienced post-TIPS cardiac in mice. Our study suggests that targeting SFXN1/NLRP3 axis might
failure. 104 (49.6%) patients had post-TIPS echocardiography, end- provide novel strategy for the treatment of liver fibrosis.
systolic diameter (ESD), left ventricle (LV) diameter, and stroke volume
(SV) were slightly increased after TIPS (ESD, 30.0 vs 31.0, p=0.001; LV
PP0727
diameter, 48.0 vs 50.0, p=0.000; SV, 72.0 vs 82.0, p=0.000). Diastolic
function parameters, including left atrial volume index (LAVI), left MOLECULAR MECHANISMS OF TRANSCRIPTION FACTOR ZEB2
ventricular mass index (LVMI), and Mean E/e’ also showed a slight IN HEPATIC STELLATE CELL ACTIVATION AND LIVER FIBROSIS
increase after TIPS (LAVI, 36.7 vs. 41.1, p=0,000; LVMI, 91.4 vs. 98.5, REGULATION
Mean E/ e’, 8.9 vs. 9.5, p=0.014). However, 155 (73.8%) patients had Qianwen Zhao1, Fajuan Rui1, Jie Li1
edema, and 13(6.2%) patients needed liver transplantation or died. 1
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School,
Conclusion: Post-TIPS cardiac failure is rare in the current Chinese Nanjing University
cohort. The following echocardiography revealed that despite diastolic Background: The pathogenesis of liver fibrosis is highly complex,
function being impaired, patients with cirrhosis can increase cardiac with the persistent activation of hepatic stellate cells (HSCs) being a
contractility to compensate for the increased volume load shunted to critical driver of its initiation and progression. The transcription factor
the heart after TIPS. E-box binding zinc finger protein 2 (ZEB2) has been shown to regulate
fibrosis in organs such as the kidney and lung. However, its specific
PP0726 regulatory mechanisms in liver fibrosis remain poorly understood.
This study aims to elucidate the role of ZEB2 in HSC activation and its
mechanisms in liver fibrosis.
Method: Human HSC line LX-2 cells were stimulated with transforming
growth factor β (TGF-β), and ZEB2 protein expression was suppressed MSC‑derived exosomes modified with SAP enhances its
using Zeb2 siRNA to assess its regulatory effect on liver fibrosis. A therapeutic effect on liver fibrosis via CXCL6/ERK/MEK pathway
mouse liver fibrosis model was established via bile duct ligation (BDL) Qian Ding1, Guangchuan Wang1
and a choline-deficient amino acid (CDAA) diet. One week prior to 1
Shandong Provincial Hospital Affiliated to Shandong First Medical
fibrosis induction, mice were tail-vein injected with AAV6-shZeb2 University
driven by the Postn promoter to achieve HSC-specific knockdown of
Background: Liver fibrosis is a chronic liver disease with the presence
Zeb2. The impact of Zeb2 knockdown on liver fibrosis progression was
of progressive wound healing response caused by liver injury.
evaluated. RNA-seq and ATAC-seq analyses were employed to identify
Currently, there is no approved therapies for liver fibrosis. Exosomes
ZEB2 target genes and further elucidate its molecular mechanisms.
derived from mesenchymal stem cells (MSCs-Exo) have displayed a
Result: In vitro, TGF-β stimulation significantly upregulated both mRNA
prominent therapeutic effect on liver diseases including liver fibrosis
and protein levels of Zeb2 in LX-2 cells. Zeb2 knockdown markedly
and cirrhosis. Recent studies show that bioengineering techniques can
suppressed the expression of pro-fibrotic genes such as α-SMA,
modify exosomes to enhance their drug-loading efficiency, targeting
Postn, and Col1a1. In vivo, compared with control mice injected
ability, and resistance to clearance by the body. The aim of the present
with AAV6-shControl (shc-BDL and shc-CDAA), HSC-specific Zeb2
study was to find a new way to improve the therapeutic efficacy of
knockdown in BDL (shZeb2-BDL) and CDAA (shZeb2-CDAA) mice
natural MSCs-Exo in treating liver fibrosis.
resulted in significantly lower expression of pro-fibrotic genes and
Method: We used quantitative mass spectrometry to screen
reduced serum levels of liver injury markers ALT and AST. Masson’s
differentially expressed peptides in serum-derived exosomes from
trichrome and Sirius red staining confirmed decreased extracellular
cirrhotic patients and controls. Human hepatic stellate cell LX-2 cells
collagen deposition in shZeb2-BDL and shZeb2-CDAA mice. RNA-seq
were stimulated with TGFβ to mimic an in vitro microenvironment of liver
and ATAC-seq analyses revealed that ZEB2 enhances HSC activation
fibrosis. SAP was fused with exosomal enriched membrane protein
by suppressing TGF-β receptor 3 (TGFBR3), thereby amplifying the
(CD63) through genetic engineering technology to generate SAP
responsiveness of TGFBR1 and TGFBR2 to TGF-β signaling.
modified MSC derived exosomes (SAP-EXO). SAP-EXO was infused
Conclusion: Targeting ZEB2 in HSCs effectively prevents the onset
into a juvenile mouse model of fibrosis established after administration
and progression of liver fibrosis and alleviates liver injury in mice. Thus,
of CCl4.
ZEB2 may serve as a potential therapeutic target for liver fibrosis.
Result: The identified peptide, SAP, exhibited a lower expression level
Table and Figure:Figure 1.Figure 1. Zeb2 expression in LX-2 cells after
in serum-derived exosomes from cirrhotic patients compared with
TGF-β stimulation and changes in liver fibrosis after Zeb2 knockdown.
controls. It was found that SAP expressed lower in TGFβ stimulated
Figure 2.Figure 2/3. Knockdown of Zeb2 blocks liver fibrosis
LX-2 cells. Adding SAP protein relieved HSC activation. SAP-EXO
progression in the BDL and CDAA mouse model.
outperformed natural MSC derived exosomes (NC-EXO) in enhancing
the ability of exosomes to alleviate LX-2 activation. In vivo results
PP0728 also showed SAP-EXO may enhance the therapeutic effect on liver
Empagliflozin reduces CC4-induced liver fibrosis in mice fibrosis. To further screen for downstream target genes of SAP, RNA-
Fushuang Ha1, Junqing Yan1, Junjun Cai1, Yin Gu2, Tao Han3 seq analysis was performed on both control and SAP overexpressing
HSCs, and the CXCL2 downregulation accompanied by SAP
1
The Third Central Hospital of Tianjin, 2Tianjin NaiKai Hospital, 3Tianjin
Union Medical Center, Naikai University Affiliated Hospital overexpression was finally validated, as well as the reduction of ERK
and MEK phosphorylation.
Background: Liver fibrosis is a potentially reversible response to Conclusion: These results suggest that SAP-modified MSC derived
hepatic injury and inflammation. At present, however, there are no exosomes showed enhanced therapeutic effect compared to natural
approved pharmaceutical or biological medications for the treatment of MSC derived exosomes on liver fibrosis, the underlying mechanism
liver fibrosis. This study aimed to determine the effects of the sodium- may be mediated by CXCL6/ERK/MEK pathway. We provide a novel
glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin when used strategy for clinical liver fibrosis therapy.
as monotherapy for the treatment of liver fibrosis in a mouse model Table and Figure:Figure 1.Serum-derived exosomes from cirrhotic
induced by carbon tetrachloride (CCl4). patients expressed lower level of SAP and SAP showed anti-fibrotic
Method: The experimental mice were divided into three groups – effect in in vitro models. A. The morphology and B. diameter of serum-
normal control, liver fibrosis, and treatment – to evaluate liver function, derived exosomes; C. Expression of exosome surface markers CD81,
conduct an intraperitoneal insulin tolerance test, and investigate CD9, and TSG101 determined by Western blot analysis; D. volcano
histological changes in liver tissues. plot and E. heat map of the differentially expressed peptides in the
Result: There was no statistically significant difference observed in the proteomic data; F.SAP expression level of LX-2 with and without TGFβ
levels of alanine aminotransferase (ALT), aspartate aminotransferase stimulation; G. overexpression efficiency of SAP in LX-2 cells detected
(AST), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-2, by RT-qPCR; the effect of SAP overexpression on the H. FN protein
-6, and -1β between the treatment and liver fibrosis groups. In the expression, I. Cell proliferation and migration level of LX-2; the effect of
treatment group, no reduction in plasma glucose levels was observed SAP modified MSC-EXO on K. cell proliferation, L. cell migration, M. FN
during the insulin tolerance test. Empagliflozin treatment reduced and COL1A1 expression of LX-2. (n=3; *p<0.05; **p<0.01).
inflammation, necrosis, and fibrosis in liver tissue compared to that Figure 2.SAP modified MSC-EXO showed anti-fibrotic effect in in vivo
in untreated mice. The levels of the antioxidant enzymes superoxide models and the underlying mechanism may be mediated by CXCL2/
dismutase, malondialdehyde, glutathione peroxidase, and catalase in ERK/MEK pathway. A.H&E staining and Masson staining of mice
the treatment group were closer to those in the normal control than liver; B. The protein expression level of FN and COL1A1 of mice liver
the liver fibrosis group. The treatment group showed an increased tissue and C. Quantification; D. Volcano plot of the differential analysis
reduction in the number of Keap1-positive cells than the liver fibrosis of the transcriptomic RNA-seq data of LX-2 with and without SAP
group. overexpression; E. Candidate genes were validated using RT-qPCR; F.
Conclusion: Empagliflozin did not increase ALT or AST levels or Downstream signaling pathway screening using Western Blot and G.
induce hypoglycemia. Its mechanism of action in mitigating liver cell Quantification; H. proposed model of SAP modified MSC-EXO on liver
necrosis and fibrosis may involve the modulation of the Keap1-nuclear fibrosis therapy. (n=3; *p<0.05; **p<0.01).
factor-erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby
reducing oxidative stress in hepatic tissues.
Table and Figure:Figure 1. PP0730
Figure 2.Figure 2. Hematoxylin and eosin (H&E) staining of liver tissue Hepatic Stellate Cell-derived Microfibrillar-associated Protein 2
(×100) Prevents Liver Fibrosis by Regulating Extracellular Matrix and
Inflammation
PP0729 Wen Zhang1, Wenyue Wu1, Ning Zhang1, Hong Li1, Yameng Sun1,
Xiaodong Ge2, Hui Han2, Shuyan Chen1, Anjian Xu1, Sai SantoshBabu using LASSO regression and validated with high diagnostic accuracy
Komakula2, Chao Wang2, Nithyananthan Subramaniyam2, Qi Han1, (AUCs: 0.857–1.000). GSVA linked these genes to pathways involving
Aiting Yang1, Xuzhen Yan1, Natalia Nieto2, Hong YOU1, Wei Chen1 IFN-α/IFN-γ, TNF-α signaling, IL6-JAK-STAT3 signaling, hypoxia, and
1
Beijing Friendship Hospital, Capital Medical University, 2University of apoptosis. Immune cell infiltration analysis indicated increased M1
Illinois Chicago macrophages and CD8+ T cells, along with reduced resting NK cells
Background: Microfibrillar-associated protein 2 (MFAP-2) is a crucial in LC patients. Correlation analysis revealed associations between key
component of the extracellular matrix (ECM) microfibrils, yet its role in PRGs and specific immune cells.
liver fibrosis remains elusive. Conclusion: This study identifies novel PRGs, including ZBP1,
Method: Human tissue microarrays and dynamic liver fibrosis mouse TNFRSF25, and IL18, and highlights their roles in immune regulation
models were utilized to investigate MFAP-2 expression patterns. and signaling pathways such as PI3K-Akt in LC. These findings
MFAP-2 (Mfap2) deficiency (Mfap2-/-) or overexpression mice were advance our understanding of PANoptosis in LC pathogenesis and
subjected to carbon tetrachloride (CCl4) injection or bile duct ligation provide insights into potential diagnostic and therapeutic targets.
(BDL) to induce liver fibrosis. Histological, biochemical, bulk or single Table and Figure:Figure 1.Key Genes Identification and Model
cell RNA-sequencing (scRNA-seq), matrisomal proteomic, and in vitro Validation
analyses were conducted to elucidate the roles and mechanisms of Figure 2. Immune Cell Infiltration and Regulatory Networks of Key
MFAP2 in liver fibrogenesis and fibrolysis. Genes
Result: MFAP-2 was predominantly enriched in activated hepatic stellate
cells (HSCs) and upregulated in advanced liver fibrosis. Knocking it PP0732
out had minimal impact on the histology of liver fibrosis under CCl4 Host Fstl1 Defines the Impact of Stem Cell Therapy on Liver
stimulation but significantly exacerbated intrahepatic inflammatory Fibrosis by Potentiating the Early Recruitment of Inflammatory
infiltration in lobular areas, accelerated ECM remodeling characterized Macrophages
by an upregulation of insoluble matrisome members within the ECM,
Xiaohong Zheng1, Siyuan Tian1, Ting Li1, Jingbo Wang1,2, Wen Ning3,
and activated focal adhesion (FAK) signal in HSCs, hindering liver
Ying Han1
fibrosis regression after CCl4 cessation. Mechanically, inhibiting HSC- 1
State Key Laboratory of Holistic Integrative Management of
derived Mfap2 enhanced HSC interactions and increased matrisome
Gastrointestinal Cancers, Xijing Hospital of Digestive Diseases, Fourth
protein production, while reducing the interaction between HSCs and
Military Medical University, 2Science and Technology Innovation
liver-resident macrophages by decreasing macrophage migration
Research Institute, Tangdu Hospital, Fourth Military Medical
inhibitory factor (MIF) secretion from HSCs. Additionally, we validated
University, 3Key Laboratory of Medicinal Chemical Biology, College of
the role of Mfap2 deletion in BDL mouse model, demonstrating a Life Sciences, Nankai University
more pronounced effect on fibrosis progression. Adeno-associated
virus vector (serotype 6)-mediated Mfap2 overexpression in HSCs Background: Adult stem cell therapy holds great promise for
conferred protection against liver fibrosis in both models. treating decompensated liver cirrhosis on the basis of animal studies,
Conclusion: HSCs-derived MFAP-2 counteracts ECM remodeling despite uncertainty about its clinical therapeutic efficacy and unclear
and intrahepatic inflammation aggravation by inhibiting matrisome underlying mechanisms. Cirrhosis-associated inflammation may result
production and accelerating MIF secretion during liver fibrogenesis, in the observed heterogeneity in the therapeutic effect. Fstl1 is a
thereby favoring liver fibrosis regression post-etiology removal. profibrotic matricellular protein that participates in inflammation and
Table and Figure:Figure 1.Hepatic Stellate Cell-derived Microfibrillar- fibrogenesis.
associated Protein 2 Prevents Liver Fibrosis by Regulating Extracellular Method: Single-cell RNA sequencing is used to identified effective
Matrix and Inflammation macrophages subsets of MSCs. Adoptively transferred CD45.1 bone
marrow cells is to further clarify the role of Fstl1 in macrophages
infiltration.
PP0731 Result: Here we observed that the serum baseline level of FSTL1 is
Molecular Characterization of PANoptosis-Related Genes significantly higher in cirrhosis patients who respond to stem cell therapy.
Associated with Immune Dysregulation in Liver Cirrhosis FSTL1 facilitates Ly6C−CX3CR1+ subset accumulation at 36-48 h
Jiahao Yuan1,2, Yu Wang1,2, Xu Fan1,2, Xinyan Zhao1,2, Jidong Jia1,2, after mesenchymal stem cell (MSC) fusion in fibrotic mice according to
Min Cong1,2 single‐cell RNA sequencing (scRNA‐seq). In addition, FSTL1 promotes
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical MSC-mediated early recruitment of inflammatory macrophages,
University, 2State Key Laboratory of Digestive Health and National which is essential for empowerment of MSCs and subsequent Ly6C−
Clinical Research Center of Digestive Disease CX3CR1+ macrophage remodelling. Fstl1 deficiency abrogates early
macrophage recruitment and effective Ly6C−CX3CR1+ macrophage
Background: Liver cirrhosis (LC) involves complex mechanisms,
accumulation, resulting in the poor antifibrotic effect of MSCs in mice.
including immune infiltration, necroinflammation, and fibrogenesis.
Mechanistically, host Fstl1 enhances rapid recycling of CCR2 to the
PANoptosis, a novel form of programmed cell death, is implicated in
membrane via activating CD14/TLR4/NF-kB/ATP6V1G2 axis, leading
various inflammatory diseases. This study aimed to identify differentially
to early recruitment of Ly6C+ monotyes / macrophages. Finally,
expressed PANoptosis-related genes (DE-PRGs) in LC and explore
recombinant FSTL1 protein restored the therapeutic efficacy of MSCs
their correlations with circulating immune cell profiles.
in CCl4-injured Fstl1+/ ̶� mice.
Method: RNA-seq data from the GEO database (GSE149601,
Conclusion: Taken together, our findings revealed that Fstl1 is a
GSE14323, GSE77627, and GSE171248) were analyzed using the
critical regulator of the fibrotic immune microenvironment and facilitates
limma R package to identify differentially expressed genes (DEGs;
subsequent stem cell therapy. Thus, these data suggest that Fstl1
|logFC| > 0.585, p < 0.05). PANoptosis-related genes (PRGs) were
could serve as a predictive biomarker of stem cell therapy response in
obtained from GeneCards, and intersecting DEGs were analyzed.
patients with liver cirrhosis.
Functional enrichment analysis was performed using clusterProfiler
Table and Figure:Figure 1.working model
for GO and KEGG pathways. LASSO regression and ROC analyses
were applied to develop and validate a diagnostic model, while
CIBERSORT was used to assess immune cell infiltration. Pearson PP0733
correlation analysis examined relationships between gene expression Neutrophil-specific MicroRNA-142 Restricts Liver Fibrosis by
and immune profiles. Limiting the Formation of Neutrophil Extracellular Traps
Result: A total of 4770 DEGs were identified in GSE149601, including Shujun Ge1, Shijia Ling1, Yawen Hao2,3, Ningning Ma2,3, Yong He2,3,1
87 DE-PRGs. Enrichment analysis revealed pathways such as PI3K- 1
School of Chinese Materia Medica, Nanjing University of Chinese
Akt and ECM-receptor interactions. Seven key DE-PRGs (TNFRSF25,
Medicine, Nanjing, China, 2State Key Laboratory of Drug Research,
ZBP1, IL18, CYCS, CCND1, HSP90AA1, and IGF1) were identified Shanghai Institute of Materia Medica (SIMM), Chinese Academy
of Sciences, Shanghai, China, 3University of Chinese Academy of PPZ was found to inhibit glycolysis of HSCs as evidenced by glucose
Sciences, Beijing, China consumption and lactate production. In an activity test for 3 key
Background: Neutrophil-mediated inflammation plays an important enzymes of glycolysis, PPZ inhibited phosphofructokinase activity, but
role in the development and progression of liver fibrosis. Previous not hexokinase and pyruvate kinase, suggesting PPZ probably inhibits
studies suggested that microRNA-142 (miR-142) to the regulation of glycolysis of HSCs via curbing phosphofructokinase.
haematopoiesis and immunity, however, whether and how neutrophilic Conclusion: PPZ showed preventive and therapeutic effects in murine
miR-142 affects liver fibrosis remain unknown. liver fibrosis induced by CCl4, CDAHFD, and BDL through inhibiting
Method: Neutrophil-specific miR-142 knockout mice (MRP8 Cre+ HSCs activation, which may partly be attributed to a decrease of
miR-142f/f, miR-142ΔNE) and neutrophil-specific miR-142 knock-in glycolysis via curbing phosphofructokinase. Our study adds to the
mice (MRP8 Cre+ miR-142KI/KI, miR-142ΔOE) were generated and growing body of evidence, that PPZ could be a potential effective drug
subjected to different experimental liver fibrosis models induced by for liver fibrosis.
the carbon tetrachloride (CCl4) injection or choline-deficient, L-amino
acid-defined, high-fat diet (CDAHFD) feeding. PP0735
Result: In this study, we demonstrated that neutrophils had higher
Nuclear factor I-B delays liver fibrosis by inhibiting chemokine
levels of miR-142 compared to other liver cells. Interestingly, miR-
ligand 5 transcription
142 was significantly elevated in liver fibrotic tissues in human and
Qianqian Chen1, Zhiwen Fan2, Hongju Yang3, Nan Geng1, Fajuan
mice. Importantly, miR-142ΔNE mice were more susceptible to the
Rui1, Wenjing Ni1, Yue Huan4, Chao Wu1, Shengxia Yin1, Wei An5,
development of experimental liver fibrosis compared to control mice
Qianwen Zhao1, Jie Li1
(miR-142f/f), while miR-142ΔOE mice were more resistant to liver
fibrosis. Furthermore, greater inflammatory cell infiltration and reactive
1
Department of Infectious Disease, Nanjing Drum Tower Hospital,
oxygen species (ROS) production were observed in miR-142ΔNE Affiliated Hospital of Medical School, Nanjing University,
mice in experimental fibrosis models. Mechanistically, miR-142 did not
2
DepartDepartment of Pathology, Nanjing Drum Tower Hospital,
Affiliated Hospital of Medical School, Nanjing University, 3Division of
appear to directly affect the activation of hepatic stellate cells (HSCs).
geriatric Gastroenterology, The First Afliated Hospital of Kunming
MiR-142 controlled neutrophil overactivation, specifically in response
Medical University, 4Jiangsu Key Laboratory of Oral Diseases, Jiangsu
to inflammatory stimulation and oxidative stress. Moreover, deletion
Province Engineering Research Center of Stomatological Translational
of miR-142 in neutrophils exhibited more neutrophil extracellular trap
Medicine, Department of General Dentistry Affiliated Hospital of
(NET) formation as demonstrated that miR-142 deficient neutrophils Stomatology, Nanjing Medical University, 5Department of Cell Biology,
had higher levels of Citrullinated Histone H3 (CitH3), a marker and Capital Medical University and the Municipal Key Laboratory for Liver
major histone of NETs. Expectedly, peptidylarginine deiminase 4 Protection and Regulation of Regeneration
(PAD4), a critical enzyme for NET formation, was also upregulated in
Background: Liver fibrosis is a vital pathophysiological process
neutrophils after deletion of miR-142.
in various liver-related diseases, with hepatic stellate cells (HSCs)
Conclusion: miR-142 limits neutrophil overactivation and the formation
activation being crucial in its development. Reduced expression of
of NETs through regulating PAD4-CitH3 signaling axis, eventually
nuclear factor I-B (NFIB) has been observed in patients with cirrhosis
ameliorating liver inflammatory response and fibrosis. Targeting miR-
and liver fibrosis of mice models. This study aims to investigate
142 could provide a novel therapeutic strategy to combat liver fibrosis.
whether restoring NFIB expression can alleviate liver fibrosis in mice
and elucidate its potential mechanism.
PP0734 Method: NFIB expression in HSCs was assessed in tissues from
Pantoprazole prevents the occurrence and progression of liver cirrhotic patients and liver fibrosis of mice models, by feeding a
fibrosis through inhibiting the activation of hepatic stellate cells choline-deficient l-amino acid defined diet (CDAA) and carbon
partly via a glycolysis decrease tetrachloride (CCl4) injection. The transcriptome was analyzed using
Jingguo Li1, Shun Yao1, Hai Jin1, Xuemei Liu1, Biguang Tuo1 RNA-sequencing. ChIP and luciferase reporter experiments were used
1
department of gastroenterology, affiliated hospital of zunyi medical to identify the potential target of NFIB during liver fibrosis.
university Result: Our study demonstrates that NFIB expression is
downregulated at both the transcriptional and protein levels in human
Background: Liver fibrosis is a major health problem worldwide and mouse tissues. Overexpression of NFIB in HSCs inhibited the
because of its rapidly increasing incidence and the lack of clinically progression of CDAA and CCl4-induced liver fibrosis. Furthermore,
satisfactory drugs. Here, we reported the effect of pantoprazole (PPZ), NFIB overexpression in HSCs reduced activation of HSCs, decreased
which demonstrated pleiotropic effects far more than proton pump oxidative stress, and attenuated cell inflammation. RNA-seq analysis
inhibitor previously, on liver fibrosis in a manner related to glycolysis. identified CCL5 as a key target of NFIB-induced changes in HSCs.
Method: CCl4-, bile duct ligation (BDL)- and choline-deficient, L-amino During liver fibrosis, NFIB bound to the CCL5 promoter and suppressed
acid-defined, high-fat diet (CDAHFD)-induced liver fibrosis models CCL5 expression. Further analysis showed that the transcriptional
were established in C57BL/6J male mice, and PPZ was administered inhibitory effect of NFIB on CCL5 was dependent on IRF3.
intraperitoneally at the dose of 1-10 mg/kg. The fibrosis markers in Conclusion: Our findings elucidate the mechanism of NFIB, and
murine liver tissues and hepatic stellate cells (HSCs) were examined by suggest that targeting the NFIB-IRF3-CCL5 axis could be a promising
qPCR, Western Blot, HE staining, Sirius red staining, Masson staining strategy for treating liver fibrosis.
and IHC. Glucose consumption, lactate production and enzymatic Table and Figure:Figure 1.A schematic model
activity were assessed by their Assay Kits.
Result: In both CCl4- and CDAHFD-induced murine liver fibrosis
models, the preventive and therapeutic administration of PPZ at 1-10 PP0736
mg/kg markedly attenuated the formation and progression of liver Microfibrillar-Associated Protein 4 from Hepatic Stellate Cells: A
fibrosis. In BDL-induced murine liver fibrosis model, the preventive Novel Target for Liver Fibrosis
administration of PPZ at 5 and 10 mg/kg, not 1 and 2 mg/kg, markedly Wenyue Wu1, Wen Zhang1, Hong Li1, Yameng Sun1, Ning Zhang1,
attenuated BDL-induced liver fibrosis, the therapeutic administration Xiaoning Wu1, Xuzhen Yan1, Aiting Yang1, Wei Chen1, Hong You1
of PPZ at the doses markedly ameliorated liver fibrosis. PPZ at 5 to 1
Beijing Friendship Hospital, Capital Medical University
80uM inhibited the TGFβ1-induced and spontaneous HSC activation.
In the liver tissues of PPZ-treated mice, the mRNA expression levels Background: Microfibril-associated glycoprotein 4 (MFAP-4) belongs
of inflammatory cytokines CXCL1, CCL2, CCL5, CCL6, CCL7, CCl20, to the fibrinogen-related protein superfamily and is a vital extracellular
and IL1β were reduced. PPZ at 5 to 80uM inhibited the mRNA matrix (ECM) protein. Serum MFAP-4 has been reported as a promising
expression levels of CXCL1, CCL2, CCL5, CCl20, IL1β, TGFβ, TGFBR, non-invasive biomarker for liver fibrosis. However, the role of MFAP-4 in
platelet-derived growth factor receptor (PDGFR) in HSCs. Additionally, the pathogenesis of liver fibrosis has yet to be elucidated.
Method: Liver biopsies from cirrhotic patients with various etiologies
and multiple mouse models of liver fibrosis were used to investigate the mechanisms of DIDS action need further investigation
expression pattern and cellular source of MFAP-4. The in vivo effects
of silencing Mfap4 in hepatic stellate cells (HSCs) were examined
PP0738
using an adeno-associated virus vector (serotype 6, AAV6) containing
short-hairpin RNAs targeting Mfap4, under the regulatory control of Atractylodes macrocephala polysaccharides inhibit cGAS/STING
U6 or glial fibrillary acidic protein (GFAP) promoter, in mouse models pathway to ameliorate liver fibrosis
of carbon tetrachloride (CCl4) or bile duct ligation (BDL)-induced liver Jiao Guo1, Jiali Wu1, Xianzhe Hu1, Jia Biao1, Yangpeng Li1
fibrosis. Histological, biochemical, bulk RNA-sequencing and in vitro 1
Guangdong Pharmaceutical University
analyses were conducted to elucidate the roles of MFAP-4 in liver Background: Liver fibrosis (LF) is a pathological process of liver self-
fibrogenesis. repair with abnormal proliferation of connective tissue caused by liver
Result: MFAP-4 was predominantly enriched in activated HSCs and injury factors, and metabolic disorders are common factors. There is
significantly upregulated in advanced liver fibrosis in both humans and still a lack of effective therapeutic drugs for LF. The ameliorative effects
mice. Histopathological analysis using H&E and Sirius Red staining of traditional herbs on LF have been commonly reported. Atractylodes
demonstrated that HSC-specific suppression of Mfap4 markedly macrocephala polysaccharides (AMPs) are the main active ingredient
alleviated fibrosis and intrahepatic inflammatory infiltration in both CCl4 of Atractylodes macrocephala Koidz.. It has demonstrated that AMPs
and BDL mouse models. Consistently, reverse transcription PCR and significant improved liver injury and NAFLD. However, the effect and
immunoblot analysis revealed reduced hepatic expression of fibrosis mechanism of AMPs in ameliorating LF are still unclear.
markers, including α-SMA, COL-1 and elastin, in Mfap4 knockdown Method: In this study, CCl4 , MCD diet and BDL surgery induced LF
mice subjected to CCl4 treatment or BDL operation. Furthermore, mice were treated with AMPs (100 mg/kg, 200 mg/kg) . The therapeutic
selective interference with Mfap4 in HSCs significantly decreased effects of AMPs were evaluated by serum biochemical analysis, liver
serum ALT and AST levels in both CCl4 and BDL mouse models. histopathology, qRT-PCR and western blotting. The potential regulatory
Additionally, RNA-sequencing identified notable downregulation of mechanism was performed by RNA-sequencing analysis. Afterwards,
pathways related to ECM remodeling, cell adhesion, cell junctions, analysis results were verified by ex vivo and in vivo experiments.
and focal adhesion in Mfap4 knockdown mice. In 3T3 cells, Mfap4 Result: Serum biochemical, liver inflammation and fibrosis markers
knockdown significantly inhibited the expression of fibrogenic markers, were significantly improved in LF mice after AMPs treatment.
while its overexpression notably promoted the expression of fibrogenic According to RNA-sequencing analysis results, we found the cGAS/
markers. STING signaling pathway as a potential mechanism for the anti-liver
Conclusion: A selective targeting MFAP-4 in HSCs represents a fibrosis of AMPs. Subsequently, validation experiments further showed
promising therapeutic strategy for the treatment of liver fibrosis. that AMPs significantly inhibited main markers of the cGAS/STING
However, the underlying molecular mechanisms involved require signaling pathway. Moreover, AMPs inhibited the release of mtDNA
further investigation. from injured hepatocytes, which can activate cGAS.
Conclusion: This study revealed that AMPs ameliorated liver injury,
PP0737 inflammation and fibrotic process by inhibiting cGAS/STING signaling
pathway.
DIDS EFFECTIVELY AMELIORATES LIVER FIBROSIS IN MICE
Shun Yao1, Hai Jin1, Guo Rong Wen1, Jia Xing Zhu1, Xue Mei Liu1, Bi
Guang Tuo1 PP0739
1
department of gastroenterology, affiliated hospital of zunyi medical The characteristics and metabonomics of gut microbiota in liver
university cirrhosis patients and the effect of S. Boulardii on it
Background: Liver fibrosis is a major health problem worldwide YU ZHU1, Wei Wei2
because of its rapidly increasing incidence and the lack of clinically 1
Tianjin Third Central Hospital , 2Tianjin Medical University Affiliated
satisfactory drugs to prevent the formation and progression of liver Second People‘s Hospital
fibrosis. In this study, we found that 4,4’-diisothiocyanostilbene-2,2’- Background: To investigate the characteristics and relationship of gut
disulfonic acid (DIDS) which is served as anion channel blocker can microbiota and metabolites in liver cirrhosis patients and explore the
effectively inhibit the development of liver fibrosis and ameliorate liver effect of Saccharomyces Boulardii on liver cirrhosis.
fibrosis in mice. Method: The characteristics of the gut microbiota in liver cirrhosis
Method: The study was performed in male C57BL/6 mice and human patients and healthy subjects from January 2019 to December 2020
normal hepatic stellate cells (HSCs) LX2 and rat HSCs HSC-T6. were analyzed using 16S rRNA sequencing technology, and the
CCl4-induced, bile duct ligation (BDL)-induced and choline-deficient, correlation between microorganisms and liver, ROC and function
L-amino acid-defined, high-fat diet (CDAHFD)-induced liver fibrosis prediction was analyzed. The metabolites in the fecal samples were
models were established in C57BL/6J male mice, and DIDS was analyzed using metabonomics, and the network and KEGG was
administered intraperitoneally at the dose of 2 mg/kg , 5mg/kg, 10mg/ analyzed. The effect of Saccharomyces boulardii on gut microbiota
kg,and 20mg/kg after model establishment. The fibrosis markers in and phenotype of 16 liver cirrhosis patients from January 2021 to
murine liver tissues and HSCs were examined by qPCR, Western Blot, August 2021 was analyzed.
HE staining, Sirius red staining, Masson staining and IHC. Result: We found that there was a low similarity and diversity of
Result: In the liver fibrosis models induced by CCl4 and CDAHFD, gut microbiota in liver cirrhosis compared with normal group. The
it was observed that DIDS (2 mg/kg, 5 mg/kg, 10 mg/kg, and 20 microorganism such as veillonella, streptococcus, blautia and
mg/kg) reduced the liver-to-body weight ratio, as well as ALT and faecalibacterium were significant correlation with liver function index,
AST levels. HE staining, Sirius red staining, Masson staining, and meanwhile, there was a well diagnostic efficiency for liver cirrhosis in
immunohistochemistry for α-SMA indicated that DIDS improved liver above-mentioned by receiver operating characteristic (ROC) analysis.
fibrosis in mice. qPCR and Western Blot showed that DIDS decreased It may be play an important role of abnormal amino acid biosynthesis
the expression of fibrosis markers α-SMA, Desmin, and TIMP2. and metabolism on liver cirrhosis progression by analyzed with
However, in the BDL-induced acute injury model, DIDS did not improve function prediction and metabonomics. The abnormal intestinal
liver fibrosis in mice. In HSCs, TGFβ induced HSC activation, and microorganism and serum ammonia was released in liver cirrhosis
subsequent treatment with DIDS (100 μM-400 μM) found that DIDS after Saccharomyces boulardii treatment.
reduced the expression of α-SMA and Col1a1. After treatment with Conclusion: We considered that the abnormal amino acid metabolism
DIDS (50 μM-800 μM) for 24 hours, CCK8 cell viability assays and and serum ammonia were induced by gut microbiota disorder in liver
ELISA for LDH content showed that DIDS had no cytotoxicity on HSCs. cirrhosis patients and probiotics treatment could rectified them.
Conclusion: DIDS can inhibit HSC activation and attenuate CCL4- Table and Figure:Figure 1.Figures
and CDAHFD-induced liver fibrosis in mice, implicating that DIDS is
a potential drug to prevent and treat liver fibrosis. But the detailed
 PP0740 varied significantly between different centers. The present study was
Itaconate ameliorates liver fibrosis by elevating GDF15 production designed to assess the application of pre-emptive TIPS in real clinical
practice.
Ningning Ma1, Jinming Zhang2, Yawen Hao1, Shijia Ling3, Yixin Li4
Method: This was a retrospective cohort study. From December 2019
1
Shanghai Institute of Materia Medica (SIMM), Chinese Academy to November 2022, cirrhotic patients with acute variceal bleeding
of Sciences, 2Department of Infectious Diseases, Ruijin Hospital,
admitted to West China Hospital who met the indication of pre-emptive
Shanghai Jiao Tong University School of Medicine, 3School of Chinese
TIPS were included. Those treated with TIPS were included in group
Materia Medica, Nanjing University of Chinese Medicine, 4Department
A, and the remaining patients were included in group B. The primary
of Cardiology, The First Affiliated Hospital of USTC, Division of Life
outcomes were 5-day treatment failure and 6-week mortality.
Sciences and Medicine, University of Science and Technology of
China (USTC) Result: A total of 709 patients with cirrhosis and acute variceal
bleeding were admitted to our hospital, among whom 126 patients
Background: Liver fibrosis is a common consequence of chronic (17.77%) met the criteria of high-risk. Twelve patients were child B >7
liver injury and is characterized by the deposition of extracellular points with endoscopic active bleeding, and 114 patients were child
matrix (ECM) mainly generated from activated hepatic stellate cells C (<14 points). TIPS was performed in only 37 patients (29.37%).
(HSCs) caused by chronic inflammatory damage. Although the TIPS was not carried out due to refusal by the patient or the relatives
expansive knowledge about the cellular and molecular biology of liver (n=42), hepatic encephalopathy (HE) (n=6) and poor liver function
fibrogenesis, its mechanisms remain obscure and effective therapies (n=10), hemodynamic instability (n=2), prior TIPS (n=2), hepocellular
are lacking. During the development of liver fibrosis, immune cells carcinoma (HCC) (n=22) and balloon-occluded retrograde
and HSCs synthesize and secrete various chemical mediators in transvenous obliteration therapy (n=5). Patients’ characteristics such
the presence of chronic liver injury, constituting a dynamic immune as age, sex ratio, etiology, ascites, and the proportion of patients with
microenvironment composed of immune cell-mediator-HSC network HE, ascites, and portal vein thrombosis were similar in the two groups.
system. As a highly heterogeneous group of immune cells in the Child-Pugh class varied significantly between these two groups, with
liver immune microenvironment, macrophages play a key role in the proportion of child B patients being 21.62% in group A and 7.87%
the occurrence and development of liver fibrosis. Itaconate is an in group B (P=0.03), but there was no significant difference in Child-
important anti-inflammatory and antioxidant substance produced by Pugh scores between the two groups (P=0.19). The proportion of
aconitic acid decarboxylase (ACOD1) in the tricarboxylic acid cycle patients with HCC is higher in group B (18.92% vs 41.57%, P=0.02).
of macrophages. Accumulating studies indicate that itaconate and The 5-day treatment failure were 24.32% in group A and 21.35% in
its derivatives have therapeutic potential in preclinical models of group B (P=0.82), and 6-week mortality were 10.81% and 33.71%
sepsis, viral infection, gout, ischemia/reperfusion injury and pulmonary in group A and B respectively (P=0.00). Multivariate analysis was
fibrosis. However, whether and how itaconate affects the development performed in 104 non-HCC patients, which found that TIPS (OR=0.08,
and progression of liver fibrosis remain largely unknown. 95% CI: 0.01-0.86, P=0.04), viral cirrhosis (OR=8.72, 95% CI: 1.36-
Method: Carbon tetrachloride (CCl4), bile duct ligation (BDL) and 55.80, P=0.02) and the 5-day treatment failure rate (OR=19.54, 95%
CDAHFD diet induced liver fibrosis models were used to evaluate CI: 2.30-165.97, P=0.00) were related to 6-week mortality.
the ameliorated effect of itaconate derivative 4-octyl itaconate (4-OI). Conclusion: The proportion of patients with high risk of treatment
Acod1 knockout (KO) mice and wild-type littermates were generated failure and mortality who received pre-emptive-TIPS was relatively low
and subjected to different experimental liver fibrosis models. Liquid in our cohort and TIPS can improve short-term survival in non-HCC
chromatography-mass spectrometry (LC-MS/MS) was performed to patients.
measure the serum amount of itaconate. The key roles of GDF15 in
itaconate in alleviating liver fibrosis was further explored by generating
different cell-specific Gdf15 deficient mice (Alb cre+GDF15f/f, Lrat PP0742
cre+GDF15f/f and Lyz2 cre+GDF15f/f). Clinical and Laboratory Characteristics and Features of Blood
Result: 4-OI and itaconate significantly inhibited HSC activation Oxygenation Indicators in Patients with Liver Cirrhosis and
and alleviated CCl4 and BDL-induced liver fibrosis. Acod1 deficient Pulmonary Complications
mice were more susceptible to liver fibrogenesis in three different Anastasiia Tsymbal1, Maria Karnauskina1, Olga Arisheva1, Lyubov
experimental models. Transcriptomic analysis indicated that itaconate Goreva1, Marina Markova1, Svetlana Avdoshina1, Zhanna Kobalava1
not only significantly inhibited the activation of TGF-β/Smad signaling 1
Moscow City Clinical Hospital No.64 (CCH named after V.V.
pathway, reduced the expression of various fibrosis-related genes, but Vinogradov)
also remarkedly upregulated the expression of growth differentiation
Background: To investigate the characteristics of liver cirrhosis
factor 15 (GDF15). Indeed, itaconate elevated GDF15 production in
(LC) with pulmonary complications (PC) and to characterize blood
HSCs via regulating ATF4, thereby suppressing HSC activation and
oxygenation indicators in this group of patients.
TGF-β/Smad signaling pathway.
Method: A total of 111 patients with LC of various etiologies (67.6%
Conclusion: In conclusion, we hypothesized that itaconate may
men, average age 50.3 ± 10.2 years) without cardiovascular diseases
ameliorate liver fibrosis by modulating the production of GDF15 and
and chronic lung diseases were included. The average score on the
affecting the TGF-β/Smad signaling pathway. To sum up, itaconate
Child-Pugh scale was 10 ± 2 points, and on the MELD — 20 ± 8.5
participates in the crosstalk of the immune system with HSCs and may
points. The average length of hospitalization was 9.97 ± 5.5 days. A
provide a promising option to treat liver fibrosis.
total of 101 patients (91.8%) were discharged, and 10 patients (8.2%)
Figure 2.Graphical Abstract
died. Two groups were formed: group 1 – patients with PC (n=71,
65%), group 2 – patients without PC (n=40, 35%). Hepatopulmonary
PP0741 syndrome was found in 34 (30.6%) patients, pulmonary hypertension
The prophylactic antibiotics do not influence the clinical outcomes in 37 (33.3%), and hepatic hydrothorax in 29 (26%). Only one PC
of patients with Child A cirrhosis and acute variceal bleeding. was observed in 46 patients (64.8%), a combination of two PCs in 24
Jiajia He1 (33.8%) patients, and a combination of three PCs in 2 (2.8%) patients.
All patients underwent saturation levels (SpO2, %), partial pressure
1
Sichuan University West China Hospital
of oxygen in arterial blood (PaO2, mmHg), and maximum oxygen
Background: Acute variceal bleeding is a severe complication of consumption (Vo2 max, ml/min/kg) were measured.
portal hypertension in patients with cirrhosis. Patients who had a Result: Patients in group 1 were older than those in group 2 [51.00
Child-Pugh C (<14 points) or child B >7 points with active bleeding (44.0; 60.0), 46.00 (40.5; 49.0) years respectively, p=0.014], spent
at endoscopy were at high risk of treatment failure and mortality. Pre- more time in the hospital [9.5 (7.0; 12.25), 8.0 (6.0 – 10.0), days
emptive transjugular intrahepatic portosystemic shunt (pre-emptive respectively, p=0.01], and had a higher MELD score [21 (15 – 28), 17
TIPS) is indicated in these patients and widely recommended by (11 – 21) points, p=0.08]. There were no differences between groups
guidelines. However, the actual implementation of pre-emptive TIPS 1 and 2 regarding sex (p=0.532), etiology of LC (p=0.376), presence
of portal hypertension (p=0.529), weight at admission and discharge 1
Violeta Medical Center, 2Yerevan Medical Center, 3Yerevan State
(p=0.195, p=0.281 respectively), Child-Pugh scores (p=0.076), Medical University, 4Scientific-Research Institute of Spa Treatment and
bilirubin levels (p=0.570), albumin (p=0.718), INR (p=0.203), AST Physical Medicine
(p=0.230), ALT (p=0.095), or creatinine (p=0.824). Only in Group 1 Background: MASLD is a disease that affects multiple organs with
were phenomena such as platypnea, n=33 (45.8%), and orthodeoxia, a 30-40% prevalence. It is one of the global problems for worldwide
n=33 (45.8%) observed, p <0.001. The SpO2 value at rest in a sitting healthcare. The aims of the study is to research the changes in the
position was lower in patients of group 1 [95.0 (92.0 – 98.0), 97.0 (96.0 phospholipid (PL) spectrum of erythrocyte membranes (EM) in
– 98.0), p = 0.004], and the PaO2 was also lower in this group [84.75 patients with HCV associated liver cirrhosis and MASLD combined
(68.30 – 94.55), 92.5 (88.15 – 98.25) respectively, p<0.001]. It was HCV associated liver cirrhosis.
found that Vo2 max was significantly lower in group 1 (22.7 ± 0.96) Method: 88 patients were divided into two groups: HCV associated
ml/min/kg compared to group 2 (28.0 ± 1.05) ml/min/kg, p= 0.008. liver cirrhosis (n=54) and MASLD combined HCV associated liver
Nine patients (12.5%) from group 1 died in the hospital, while 1 (2.6%) cirrhosis (n=34). For these groups of patients, the relative PL contents
patient from group 2 died; however, no significant difference was found in EM were studied using thin-layer chromatography. Superoxide
(p=0.096). 29 (38.9%) patients from group 1 died significantly more Dismutase (SOD), ACT and ALT were also determined in all patients.
often within 6 months compared to patients from 2 group (n=10 (25%), 58 patients received antiviral therapy.
p= 0.028). Result: The changes in PL fractions manifested in monoinositide
Conclusion: Patients with LC who have PC were older and had a phospatides (MIP), lysophosphatidylcholine (LPC), phosphatidylserine
more severe course of LC. This group of patients was characterized (PS) and cardiolipins increase, on account of phosphatidylethanolamine
by worse blood oxygenation indicators and poorer prognosis over 6 (PE), phosphatidylcholine (PC) and sphingomyelin(SM) decrease,
months. which was more apparent in MASLD patients with HCV associated
liver cirrhosis during the whole study.MASLD cirrhosis patients MIP
PP0743 was significantly higher (13.8±0.16), than in HCV associated cirrhosis
patients (12.9±0.06, p≤0.01). For the patients who were given antiviral
Hepatocyte Growth Factor Upregulates Neuropilin-1 Expression
therapy (DAT) MIP levels gradually decreased, however staying
via Retinoic Acid Receptor Alpha, Exacerbating Liver Fibrosis
significantly over the norm (8.51±0.18) even after 12 weeks from the
Han Ding1,2, Huanran LV1,2, Songbo Zhao1,2, Le Wang1,2, Wanhua beginning of treatment which was normalized. Furthermore, MASLD
Ren1,2, Qiang Zhu1,2 patients had a double increase of LPC, whereas in HCV associated
1
Shandong Provincial Hospital Affiliated to Shandong First Medical liver cirrhosis index was 20.6±0.09% (p<0.001). Another significant
University, 2National medical center for infectious diseases result is that in patients who were given antiviral therapy (n=58)
Background: The hepatocyte growth factor (HGF)/c-Met pathway the rates of PL, ACT, ALT, SOD were normalized after 12 weeks of
plays a crucial role in chronic liver disease; however, its interaction treatment, whereas the patients who were not given antiviral therapy
with neuropilin-1 (NRP-1) in hepatocytes and its contribution to fibrosis (n=30) showed opposite trend (the rate of PL, ACT ALT SOD did not
exacerbation remain unclear. Therefore, we aim to investigate whether normalize even after 24-48 weeks).
the NRP-1 and HGF/c-Met pathways interact to drive liver fibrosis Conclusion: MASLD complicates the course of the disease in patients
progression. with HCV associated liver cirrhosis and slows the rate of clinical and
Method: We assessed the association between NRP-1 and liver fibrosis biochemical recovery which is linked, Pl spectrum imbalance leads to
using immunohistochemistry, quantitative real-time polymerase chain increase in membrane penetrability and necrotic inflammation,because
reaction, and western blotting. Hepatocyte-specific NRP-1 knockout of liver cell damage, which threatens to activate fibrogenesis and
mice were generated using the Cre-loxp system, with liver fibrosis oncogenesis in MASLD and HCV associated liver cirrhosis. To crown
induced by carbon tetrachloride (CCl4) injections and methionine- it all, it is lucid that all the biochemical rates and PL spectrum were
choline deficiency. The effects of hepatocyte NRP-1 on hepatic normalized after the antiviral treatment.
fibrosis and c-Met were evaluated by isolating primary liver cells and
performing western blotting. chromatin immunoprecipitation followed
PP0745
by quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays
were performed to analyze transcription factor binding to the NRP-1 New strategies for the staged diagnosis of liver cirrhosis.
promoter. Lilit Martin Arshakyan1
Result: Hepatocyte NRP-1 expression increased significantly during 1
STCOPC NAS RA
liver fibrosis and was positively correlated with HGF/c-Met expression Background: The multifactorial nature of liver cirrhosis, as well as
and fibrosis severity. In vivo, NRP-1 inhibition reduced extracellular the wide spectrum of consequences, render the illness incurable, as
matrix accumulation and abnormal angiogenesis in Alb-Cre NRP-1f/f indicated by projected increases in mortality over the next decade.
mice. In vitro, NRP-1 blockade inhibited c-Met activation and reduced This suggests that pathogenesis models, which would predict and
transforming growth factor-beta and vascular endothelial growth factor prevent the disease onset and development of complications, are still
secretion in hepatocytes. NRP-1 served as a co-receptor for HGF/c- incomplete. And in this context, it is very important to understand the
Met, with HGF upregulating NRP-1 expression at transcript and protein morphofunctional relationship of the liver with other interconnected
levels. NRP-1 promoted fibrosis through the Met/extracellular signal- organ systems in the dynamics of cirrhosis development.
regulated kinase pathway. Furthermore, HGF increased retinoic acid Although complex therapy for liver cirrhosis is gradually evolving in
receptor alpha (RARA) expression, promoting NRP-1 transcription. modern medicine, it is still regarded as an incurable disease because
Conclusion: HGF-induced upregulation of hepatocyte NRP-1, treatment begins when the illness is diagnosed. This work proposes a
mediated by RARA binding to its promoter, drives liver fibrosis study of the dynamics of cirrhosis development by identifying causal
through c-Met pathway activation, highlighting NRP-1 as a promising linkages.
therapeutic target in liver fibrosis. Aim:To research the gender-related morphofunctional damage chain
Table and Figure:Figure 1.Hepatocyte growth factor upregulates of the liver-lung-kidney three-organ system in the development of toxic
neuropilin-1 expression via retinoic acid receptor alpha, exacerbating liver cirrhosis.
liver fibrosis Method: Laboratory research on rats were conducted to modeling
toxic cirrhosis using the indicated tactical tactics. Biopsy samples from
PP0744 the animals’ liver, lungs, and kidneys were obtained for histological
investigation.
Metabolic Dysfunction Associated Steatotic Liver Disease in
Result: Research has shown that the lungs and kidneys are more
Patients with HCV Associated Liver Cirrhosis
affected shortly after the intoxication phase, during the pre-cirrhotic
Sona Sargsyan1, Violeta Sargsyan1, Hasmik Ghazinyan2, Vahe Yurii
stage, when pathological phenomena (inflammatory foci, lipid
Azatyan3, Anahit Gurgeni Isakhanyan4, Naira Gyulazyan 3
alterations, dystrophies, and so on) begin to emerge in the liver. and explore its potential therapeutic mechanism
It should be mentioned that because females’ liver regeneration Method: Fristly, by a retrospective case-control study on 88 AH
processes are more intense than males’, the kidneys receive the initial patients and 176 ALC patients, we found that an intestinal microbiota
blow (especially in females), as shown by their propensity to develop dysbiosis may be involved in the progression of ALD. Furthermore,
glomerulonephritis. However, there is more tissue bleeding and an animal experiment was desgined and performed to validate the
microscopic thrombosis in the livers of male, which leads to more lung potential role of FMT on the rectification of gut dysbiosis in mice with
injury and a higher risk of portal hypertension. ALD. After the treatment, 16sRNA, full-target metabolomics, short-
Following the intoxication stage, the pathophysiology of cirrhosis and chain fatty acid detection were used to analyze the polymorphism of
defense mechanisms develop in a gender-specific pattern. We are intestinal microbiota and the heterogeneity of transcriptome.
certain (an indication of the body’s defensive reflexes) that at some Result: As a result, we found that healthy human intestinal bacteria
point in the progression of disease, there be a period of harmony (like FMT significantly attenuated the pathological and histological damage
in life, between males and females) when pathological processes in ALD. In parallel, basic parameters including AST, TBIL, DBIL, and
manifest in the same way in both sexes. TG levels were attenuated. Moreover, this study exerted that human-
Conclusion: During the staged diagnosis of liver cirrhosis, it is FMT treatement was capable of suppressing the inflammation by
vital to analyze the liver-lung-kidney triplet organ concept based on reducing proinflammatory IL-6, IL-17A, LPS levels and increasing
gender principles and the causal links behind the organs’ functional anti-inflammatory IL-10. In addition, we found that improving intestinal
interactions, as well as to establish treatment choices based on and hepatic blood flow may contribute to the amelioration of ALD
the proposed innovative concept. We anticipate that, if our clarified progression. Mechanically, full-target metabolomics analysis showed
concepts are implemented, the damage to the aforementioned organs that healthy human FMT treatment improved the course of ALD through
will reveal the genesis of cirrhosis, and its application in practical the a-linolenic acid metabolic pathway and the short-chain fatty acid
medicine will enable for the identification and prevention of predicted pathway.
complication (diseases). Conclusion: Collectively, this study highlights that FMT treatment
ameliorates ALD via reshaping the gut microbiota and modulating the
metabolisms related to a-linolenic acid and short-chain fatty acids.
PP0746
SOFA Score in Patients with Decompensated Liver Cirrhosis: Role
in Assessing Severity and Prognostic Significance PP0748
Anastasiia Tsymbal1, Maria Karnaushkina1, Olga Arisheva1, Lyubov Ang1/Ang2 Dysregulation is associated with the development of
Goreva1, Marina Markova1, Svetlana Avdoshina1, Zhanna Kobalava1 liver fibrosis in mice models
1
Moscow City Clinical Hospital No.64 (CCH named after V.V. Minghua Lin1
Vinogradov) 1
Beijing Youan Hospital, Beijing Institute of Hepatology, Capital
Background: To investigate the associations between SOFA scores Medical University, Beijing 100069, China
and the severity of liver cirrhosis (LC), as well as to determine its role in Background: Introduction and Objectives: Hepatic angiogenesis is
predicting in-hospital mortality. closely associated with the
Method: The study included 111 patients with decompensated LC progression of fibrosis in chronic liver diseases (CLDs). The
of various etiologies (67.6% males, mean age 50.3 ± 10.2 years). angiopoietin (Ang)/Tie2
The mean Child-Pugh score was 10 ± 2 points, and the mean MELD system is a key regulator of pathological angiogenesis during
score was 20 ± 8.5 points. All patients underwent SOFA scoring upon inflammation. Binding of
hospital admission. The average SOFA score was 4 ± 2.1 points. Ang1 to Tie2 ensures vascular stability, whereas Ang2 exerts opposing
The mean length of hospital stay was 9.97 ± 5.5 days. A total of 101 effects. The
patients (91.8%) were discharged, while 10 patients (9.0%) died. aim of this study was to investigate the involvement of Ang/Tie2 system
Result: A correlational analysis was performed to assess the in mice liver
relationship between SOFA scores and Child-Pugh scores, as well fibrosis induced by CCl4 and the relationship between expression of
as between SOFA scores and MELD scores. A moderate positive Ang1/ Ang2 and
correlation was found between SOFA and Child-Pugh scores (r = pathological features of liver fibrosis.
0.486, p < 0.001) and between SOFA and MELD scores (r = 0.569, p Method: Material and methods: Liver fibrosis was induced in BALB/c
< 0.001). An increase of 1 point in the SOFA score was associated with mice by Carbon
an expected increase of 2.482 points in the MELD score (p < 0.001). tetrachloride (CCl4).Real time-PCR and Multiplexed
In deceased patients, the median SOFA score was 5 points (5.0–7.5), immunohistochemistry were
while for those who were discharged, it was 4 points (2.0–5.0) (p = applied to detect the expression and location of Ang1/ Ang2. Multiplex
0.003). The threshold SOFA score associated with in-hospital mortality staining images
was 5.0 points [OR = 7.22, 95% CI (0.615–0.960), p = 0.003], with a were analyzed by inForm image analysis software.
sensitivity of 80.0% and specificity of 65.3%. Result: In this study, we found that expression of Ang/ Tie2 system
Conclusion: Thus, the calculation of SOFA scores correlates with markedly increase
the severity of LC and potential outcomes during hospitalization. A as mice liver fibrosis development, and focus mainly on around
threshold SOFA score of 5 points was identified, which was associated damaged and fibrotic
with in-hospital mortality, with a sensitivity of 80.0% and specificity of liver tissue. We also observed that a significant increase of portal
65.3%. angiogenesis and
sinusoid capillarization. The expression of Ang2 mRNA is closely
associated with
PP0747
Colα1(Ⅰ) and CD31 mRNA.
Reshaping the gut microbiota by FMT ameliorates the alcoholic Conclusion: Conclusion: Ang/Tie2 system are activated during mice
liver disease via modulating a-linolenic acid metabolism and liver fibrosis induced by CCl4.
short-chain fatty acids Ang2 might represent a potential therapeutic target for liver fibrosis
Rong Su1, Shaoqi Yang1, Hao Wang2 Table and Figure:Figure 1.
1
.General Hospital of Ningxia Medical University, 2 Ningxia Medical
University
PP0749
Background: Alcoholic liver disease (ALD) is a disease with limited
Selective Targeting Hepatic Stellate Cell-derived THBS2 Mitigates
treatment methods and poor prognosis.This study was designed to
Liver Fibrosis by Inhibiting SPP1
investigate the effect of intestinal flora transplantation therapy on ALD
Hong Li1, Wenyue Wu2, Ning Zhang2, Wen Zhang2, Yameng Sun2,
Shuyan Chen2, Qi Han2, Xuzhen Yan1, Aiting Yang1, Hong You2, Wei months. T6MH and its early termination help to determine the functional
Chen1 status of the patient and can be used to assess the severity of LC and
1
Beijing Clinical Research Institute, Beijing Friendship Hospital, to predict mortality in patients during hospitalization and within three
Capital Medical University, Beijing 100050, China, 2Liver Research months after discharge.
Center, Beijing Friendship Hospital, Capital Medical University, Beijing
100050, China.
PP0751
Background: Thrombospondin-2 (THBS2) is significantly upregulated
Recurrent Upper Gastrointestinal Bleeding Secondary to
in fibrotic livers and correlated with fibrosis stages not perturbed by
Splenic Vein Sclerosis: A Case Report on Non-Cirrhotic Portal
any etiology. This study aimed to explore the role and mechanism of
Hypertension
hepatic stellate cells (HSCs)-derived THBS2 in HSC activation and
Chelsea Tauro Tantuco1, Joseph Cruz Bocobo1
liver fibrosis progression
Method: HSC-specific Thbs2 knock-out mice (Thbs2ΔHSC) and
1
St. Luke‘s Medical Center - Quezon City
HSC-specific human THBS2 knock-in mice (hTHBS2KI HSC) were A 50-year-old male, non-hypertensive and non-diabetic, non-alcoholic
subjected to intraperitoneal CCl4 injection and bile duct ligation (BDL) drinker, presented to the emergency room with hematemesis.
operation to induce liver fibrosis. The role of THBS2-SPP1 axis in liver He was diagnosed with gastritis five years prior during routine
fibrogenesis was investigated by intraperitoneal injection of inVivoMAb esophagogastroduodenoscopy (EGD) but had no symptoms and was
anti-mouse SPP1 in hTHBS2KI HSC mice and in vitro studies using managed medically. Workup was done revealing thrombocytopenia
LX-2 cells. and leukopenia, with no symptoms of bleeding. JAK2 assay was
Result: Histopathological analysis and immumohistochemical staining negative, and erythropoietin (EPO) and reticulocyte counts were
revealed that HSC-specific Thbs2 knock-out mice (Thbs2ΔHSC) in CCl4 normal. CT scan revealed splenomegaly. Further workup including
and BDL mice significantly decreased liver inflammation and fibrosis. bone marrow aspirate, autoimmune markers, tests for tuberculosis
In contrast, HSC-specific human THBS2 knock-in mice (hTHBS2KI and PET scan were unremarkable. EGD revealed large esophageal
HSC) promoted liver inflammation and fibrosis in both models. Thbs2 varices. Colonoscopy showed grade I internal hemorrhoids. A repeat
knockdown in HSCs significantly inhibited the expression of SPP1 that abdominal CT scan showed splenomegaly and signs of portal
is known as a profibrotic effector, while its overexpression in HSCs hypertension (dilated main portal vein and splenic and mesenteric
notably promoted SPP1 expression and secretion. THBS2-mediated veins). Liver elastography showed no fibrosis and liver enzymes were
liver fibrogenesis was blocked by intraperitoneal injection of inVivoMAb normal with slightly elevated bilirubin levels. Hepatitis profile showed
anti-mouse SPP1. previous hepatitis A infection. The patient was started on Carvedilol.
Conclusion: HSCs-derived THBS2 promoted liver fibrogenesis by Four weeks prior, the patient had elective laparoscopic
regulating SPP1 secretion. A selective targeting HSCs-derived THBS2 cholecystectomy. A week after the said procedure, he experienced
can mitigates liver fibrosis. Further studies are required to investigate severe epigastric pain and developed icteric sclerae, tea-colored
the specific mechanisms involved in the regulation of THBS2 on SPP1 urine, and acholic stools. MRCP showed non-dilated biliary tree and
in HSCs. marked splenomegaly. Tests for autoimmune hepatitis were negative.
Symptoms resolved after two days with supportive medications. On the
day of consult, he had two episodes of hematemesis, hence consult.
PP0750
On admission, EGD was done revealing large esophageal varices.
The Clinical and Prognostic Significance of Early Termination of Variceal ligations were then performed. The patient had recurrence
T6MH in Patients with Liver Cirrhosis of hematochezia and underwent a second gastroscopy showing no
Anastasiia Tsymbal1, Maria Karnaushkina1, Olga Arisheva1, Lyubov evidence of bleeding. Selective angiography was then done revealing
Goreva1, Marina Markova1, Svetlana Avdoshina1, Zhanna Kobalava1 tortuous portal vein and absent main splenic vein. The patient
1
Moscow City Clinical Hospital No.64 (CCH named after V.V. underwent splenectomy to which histopathology showed congestive
Vinogradov) splenomegaly with significant splenic vein sclerosis (>90% occlusion).
Background: To determine the significance of early termination of the The cause of the splenic vein sclerosis remains unclear, but is attributed
6-Minute Walk Test (6MWT) in assessing the severity and prognosis of to the blunt trauma to the patient’s epigastric area following a biking
liver cirrhosis (LC). accident which occurred years prior. As of this writing, the patient has
Method: A total of 111 patients with LC of various etiologies were been stable post-splenectomy with no recurrence of hematemesis.
included (67.6% men, mean age 50.3 ± 10.2 years, mean Child-Pugh This clinical case highlights the significance of having a high index
score 10 ± 2 points, MELD - 20 ± 8.5). Two groups were formed. of suspicion for splenic vein pathologies as a cause of non-cirrhotic
The first group consisted of patients who prematurely terminated the portal hypertension among patients presenting with gastric varices,
6MWT (n=19), and the second group included those who completed splenomegaly, thrombocytopenia and gastrointestinal bleeding. The
all 6 minutes (n=92). All patients underwent clinical-laboratory and prognosis of these patients vary depending on the underlying cause
instrumental examinations, as well as the 6MWT. The mean time for and the severity of portal hypertension, but is generally better than
early termination of the 6MWT was 135 ± 28.4 seconds, and the among patients with cirrhosis. When variceal bleeding is controlled, life
average distance covered was 181.6 ± 88.8 meters. Patients who expectancy is near normal. Splenectomy provides a good long term
completed the 6MWT walked a distance of 330.6 ± 99.9 meters. The outcome among patients.
endpoints were transfer to the intensive care unit, in-hospital mortality,
and mortality within 12 weeks after discharge. PP0752
Result: Patients in the first group were older than those in the second
Construction of diagnostic models for each stage of patients with
group (56 [46.50 – 63.50] vs. 47 [42.00 – 54.25] years, p=0.037), had
cirrhosis combined with portal hypertension respectively based
a higher Child-Pugh score (11 [9.50 – 12.50] vs. 10 [8.00 – 11.00],
on HVPG
p=0.014), and had a higher MELD score (26.76 ± 9.22 vs. 18.57
Wei Gou1
± 7.79, p<0.001). The groups did not differ in terms of the etiology
of the disease, duration of LC, gender, bilirubin, albumin, ALT, AST,
1
Department of metabolic liver disease, Qingdao public health clinical
creatinine, hemoglobin, platelets, or presence of portal hypertension center, Shandong Province, the people‘s Republic of China
signs. Patients in the first group exhibited higher in-hospital mortality Background: Ascites, esophageal varices, and hepatic
(n=8 (42%) vs. n=2 (2%), p<0.001), more frequent transfers to the encephalopathy are life-threatening complications in liver cirrhosis
intensive care unit (n=6 (32%) vs. n=8 (9%), p=0.027), as well as higher patients due to portal hypertension. HVPG is the main accurate
mortality within 3 months (n=11 (58%) vs. n=12 (13%), p<0.001). assessment tool; however, its invasiveness and limited availability
Conclusion: Thus, the premature completion of T6MH characterizes reduce patient compliance. HVPG normal range is 3-5 mmHg;
the severity of LC, its outcome during hospitalization, and within three >5 mmHg indicates portal hypertension, and ≥10 mmHg denotes
clinically significant portal hypertension (gold standard). HVPG 12- Focus on the practical application value of HVPG in patients with
20 mmHg indicates progression from decompensated to advanced liver cirrhosis
cirrhosis with increasing complication severity. Non-invasive models Wei Gou1
for accurate portal hypertension stratification in cirrhosis are lacking. 1
Department of metabolic liver disease, Qingdao public health clinical
Our team developed models for compensated (5-10 mmHg), clinically center, Shandong Province, the people‘s Republic of China
significant (≥10 mmHg), and decompensated cirrhosis based on
Background: As the gold standard for the diagnosis of portal
HVPG.
hypertension in patients with liver cirrhosis, HVPG is widely
Method: In this study, patients with liver cirrhosis who underwent HVPG
recommended worldwide. It is not only used to evaluate the degree
measurement in a multi center in Shandong Province were divided into
of portal hypertension, but also used to evaluate the condition of
three subgroups according to stages. Pearson correlation coefficient
patients with liver cirrhosis and portal hypertension, judge the stage
was used to explore the correlation between 19 clinical characteristics
of liver cirrhosis, predict the occurrence of decompensated events,
and portal vein pressure.
monitor the effect of drugs on reducing portal hypertension, and guide
Result: Results showed ALB, WBC, TBIL, and LN were negatively
individualized treatment.
correlated with HVPG, and liver stiffness (SLM) was positively correlated
Method: Methods the clinical data of 328 patients with liver cirrhosis
with HVPG in 5-10 mmHg compensated cirrhosis patients. Multivariate
determined by HVPG were retrospectively analyzed.
regression model: y=850.543-17.725*ALB+14.299*e-38.478*WBC-
Result: Currently, early cirrhosis is regarded as having no specific
4.102*TBIL-4.186*LN. AUC for significant portal hypertension
clinical symptoms or signs, with normal liver function, yet significant
(≥10 mmHg) was 0.75 (0.641-0.859). In ≥10 mmHg compensated
histological changes detectable by imaging. This explains the silent
subgroup, male gender, PT, and progression were positively
nature of early liver cirrhosis, and there is optimism about the potential
correlated. Multivariate model: y=-216.767+1.203*PT+2.135*sex
for reversal. However, our study revealed that over 57% of patients
(male=1, female=0). AUC for decompensated portal hypertension
with early cirrhosis had an HVPG >5 mmHg, with 18% indicating
diagnosis was 0.821 (0.726-0.916). In decompensated ≥10 mmHg
CSPH. Normal HVPG ranges from 1-5 mmHg. An HVPG of 6-9 mmHg
subgroup, major events (death, severe esophageal varices, red-
suggests portal hypertension, and ≥10 mmHg indicates clinically
colored biopsy) incidence compared. Excluding liver cancer and prior
significant portal hypertension, substantially increasing the risk of
decompensation, final results showed WBC, Hb, PT, INR, and four
ascites, varices, bleeding, and portal hypertensive gastropathy.
liver fibrosis markers correlated (correlation coefficient >0.2). Logistic
In the 2021 Baveno VII consensus, the 3-year risk of cirrhosis-related
regression found WBC and LN best predictive. Proposed non-invasive
events in chronic liver disease patients with LSM <10 kPa by TE was
model: y=0.65+0.003*WBC-0.31*LN. AUC for progression risk to
deemed very low. Our study found that among cirrhotic patients with
serious decompensated events was 0.778 (0.58-0.975).
LSM <10 kPa, 29% had HVPG <5 mmHg, 49% had HVPG 5-10 mmHg,
Conclusion: Portal hypertension exists in all stages of liver cirrhosis.
and 22% had HVPG >10 mmHg. This suggests that even with LSM
With the increase of portal vein pressure, the diagnosis and treatment
<10 kPa, there is a significant risk of high HVPG.
of liver cirrhosis become more and more difficult. The non modeling
In our study, we stratified the management of cirrhotic patients.
of cirrhotic portal hypertension is helpful for the diagnosis of portal
For those with decompensated cirrhosis and portal hypertension,
hypertension in patients with clinical cirrhosis, and improves the
decompensation events increased with rising HVPG, reaching 76.67%.
sensitivity of clinical diagnosis of portal hypertension.
Despite Child-Pugh scores indicating mild to moderate liver function
(A-B), there was no positive correlation between decompensated
PP0753 liver function and HVPG. Thus, we must consider HVPG in A-B level
Case Report – Esophageal Varices in Pregnancy decompensated cirrhosis, evaluating and intervening early. We
Sam Nogoy Fandood1 used carvedilol tablets for intervention. After 3-6 months, HVPG in
decompensated cirrhosis patients treated with carvedilol showed a
1
East Avenue Medical Center Quzeon City
downward trend, averaging a 23.86% decrease, with 2 cases dropping
BACKGROUND up to 50%. Carvedilol is recommended for patients where intervention
Esophageal variceal bleeding is one of the most severe complications or endoscopic treatment is not feasible, or for those who decline event-
that may occur during pregnancy in patients with liver cirrhosis. It based interventions, to lower portal vein pressure.
may result in death of the mother and the fetus. Pregnancy-induced Conclusion: To sum up, the results of this study show that HVPG
physiological changes exacerbate these risks, making timely diagnosis measurement is suitable for the diagnosis and disease evaluation
and management critical. This report presents a case of successful of patients with portal hypertension. There are differences in HVPG
management of a pregnant woman with esophageal varices. between different patients with portal hypertension, which has guiding
CASE SUMMARY significance for the selection of treatment options for liver cirrhosis and
We report a case of a 37/F female, G4P2 (1202) on her 27 2/7 weeks portal hypertension.
AOG who presented with hematemesis and melena. Laboratory
results showed anemia (Hgb: 7.1 g/dL), thrombocytopenia (Platelet:
155), coagulopathy (PT 14.40, INR 1.13, aPTT 38.30), jaundice PP0755
(TB 45.73 umol/L) and hypoalbuminemia (Albumin: 29 g/L). Whole To investigate the clinical diagnostic value of serum extra-spindle
Ultrasound showed normal sized liver with, exhibiting heterogenous pole-like protein 1 (ESPL1) detection for HBV-related liver fibrosis
and coarsened parenchymal echopattern with nodular and irregular process
boarders and splenomegaly. She underwent endoscopic band ligation Long Huang1, Hongqian Liang1, Aoli Ren1, Minghua Su1, Bobin
where 4 columns of tortuous violaceous vessels were banded. No Hu1, Qingmei Li1, Tumei Su1, Qianbing Yin1, Yanfei Feng1, Jianning
recurrence of bleeding noted. Delivery thru low transverse cesarean Jiang1,2
section (LTCS) was planned. growth scans and Doppler studies were 1
The First Affiliated Hospital of Guangxi Medical University, 2Key
conducted to assess for intrauterine growth restriction. AT 37 weeks, Laboratory of High-Incidence-Tumor Prevention and Treatment,
patient went into LTCS without complications. Patient was then started Ministry of Education
on non specific beta blocker and planned for repeat vatical screening.
CONCLUSION:
Pregnancies complicated by portal hypertension and esophageal PP0756
varices can achieve favorable outcomes with early identification, A Rare Complication of Decompensated Cirrhosis: Forward or
preventive strategies, and multidisciplinary management. Backward?
Key Words: Esophageal Varices; Pregnancy; Rubber band ligation Pengyue Zhang1, Zhenhua Zhang1, Yanyan Wei2
1
The Second Affiliated Hospital of Anhui Medical University, 2the First
PP0754 Affiliated Hospital of Anhui Medical University
A 56-year-old man was admitted with abdominal distention and Background: Differences in clinical characteristics and survival
progressive scrotal enlargement. The patient had an 8-year history outcomes between young and elderly cirrhosis remain to be
of HBV-related cirrhosis and had undergone endoscopic selective determined. We focused on assessing the clinical characteristics and
varices devascularization several times for upper gastrointestinal prognosis of hepatitis B cirrhosis in young population.
bleeding. Physical examination and ultrasound examination showed Method: A hospital-based retrospective cohort of young cirrhosis
that there was a large amount of fluid (30*20cm) in the scrotum were analyzed. Risk factors for serious complications during follow-up
and a positive transillumination test, but ultrasound examination were identified using multivariable analysis, and the Cox proportional-
showed minimal ascites. Enhanced computed tomography showed hazards model was used to analyze the prognosis of the young and
portal hypertension and venous thrombosis. Scrotal distension was elderly groups with hepatitis B cirrhosis. Prognostic analysis of hepatitis
rapidly relieved after scrotal puncture (Figure 1), and the property of B cirrhosis was performed and propensity score matching (PSM) was
testicular puncture fluid was similar to that of previous ascites, which used to adjust for differences between the two groups.
indirectly proved the source. Although a large amount of fluid was Result: The study included 177 patients with cirrhosis, of which 79
discharged every day, there was no significant retraction of scrotum were in the young group. Of the young group, 67.09% had cirrhosis
before transjugular intrahepatic portosystemic shunt (TIPS) (Figure 2). caused by the hepatitis B virus. Serum alanine aminotransferase
With the postoperative decrease of portal vein pressure, hydrocele (ALT) and albumin levels, as well as quantitative HBeAg and HBeAb
disappeared rapidly(Figure 3) and the urinary system disorder were tests, were higher in young cirrhotic patients than in the older group.
solved(Figure 4). Additionally, the proportion of HbsAg, HBeAg, and HBcAb-positive
Adult hydrocele is usually secondary. With the increasing use of combinations in the young group was significantly higher than in the
peritoneal cavity in peritoneal dialysis and ventriculoperitoneal shunt1, elderly group(39.62% vs 17.18%, P=0.011). All patients with hepatitis
2,the incidence rate of adult hydrocele is rising. However, ascites B cirrhosis were followed for 5.83±3.14 years. The Kaplan-Meier
in the abdominal cavity communicate with the tunica vaginalis and method revealed that the younger group had a higher survival rate(log-
cause massive hydrocele is rare. its pathogenesis may be related rank test, P= 0.035). There was no significant difference in prognosis
to hypoproteinemia and a patent processus vaginalis3. It has for survival after PSM. Additionally, the young age was an independent
demonstrated that TIPS is feasible and effective in the treatment of factor for the occurrence of gastrointestinal bleeding during the follow-
refractory ascites or variceal bleeding secondary to hepatic cirrhosis4. up process(odds ratio [OR] = 18.15, 95% confidence interval [CI]:
In this case, ultrasound-guided scrotal puncture and TIPS can rapidly 2.29 ~ 100.61, P < 0.01).Age and a high ALP level were independent
relieve local tension and clinical symptoms, but its long-term efficacy risk variables linked to survival, and the prognosis of hepatitis B
remains to be proved. cirrhosis could be predicted using the prediction model based on Cox
multivariable analysis.
PP0757 Conclusion: Even though the young hepatitis B cirrhosis and the
elderly group had significantly different clinical characteristics, there
The prevalence and mortality of stage 1, 2 and 3 of acute kidney was no statistically significant difference in prognostic survival time
injury in cirrhosis: a systematic review and meta-analysis. after PSM. For the young patients, particular attention should be given
Meng Yue Wan1 to serious complications like gastrointestinal bleeding during follow-up,
1
Kunming Medical University Second Hospital and prognostic survival can be reasonably predicted by combining
Background: Previous studies are discrepant on the prevalence age, ALP and other variables.
and mortality rates of different stages of acute kidney injury (AKI), Table and Figure:Figure 1.Clinical characteristics of cirrhosis in
and few studies have quantified the mortality risks across stage 1, 2 different ages
and 3 AKI.This systematic review and meta-analysis aims to evaluate Figure 2.Multivariable adjusted restricted cubic splines for the
the prevalence and mortality of stage 1, 2 and 3 AKI, and to explore relationship between age and mortality and prognostic prediction
predictors of mortality.
Method: Pubmed, Cochrane library, EMBASE, Scopus and Chinese PP0759
National Knowledge Infrastructure databases were searched.
The mortality risk of acute kidney injury stage 1A and 1B in
We pooled the incidence and mortality of stage 1,2 and 3 AKI and
cirrhosis: a systematic review and meta-analysis.
explored the mortality predictors in cirrhotic patients using a random-
effect model. Odds ratio (OR) with 95% confidence interval (CI) were Meng Yue Wan1
estimated.
1
Kunming Medical University Second Hospital
Result: 32 studies were included, enrolling 20,527 patients with Background: Acute kidney injury (AKI) stage1 in cirrhosis is divided
cirrhosis, which resulted into a pooled prevalence and mortality rate into 1A and 1B, which have greatly varied prevalence in different
of 26.1% and 29.8% for stage 1, 11.3% and 48.2% for stage 2, 11.2% studies. It remains controversial whether AKI stage 1A has increased
and 67.1% for stage 3 AKI, respectively. Compared to NAKI, stage 1, mortality risk over non-AKI (i.e. NAKI), and few studies quantified the
2 and 3 AKI increased the mortality risk by about 3.5 folds, 6 folds, and mortality risks across AKI stage1A, 1B and NAKI.This systematic review
11.5 folds, respectively. The presence of AKI and several liver function and meta-analysis aims to evaluate the prevalence and mortality risks
indices are significantly associated with mortality. of AKI stage1A and 1B.
Conclusion: AKI is a frequent and ominous complication of cirrhosis. Method: Pubmed, Cochrane library, EMBASE, Scopus and Chinese
The mortality of cirrhotic patients with AKI increases with AKI stages in National Knowledge Infrastructure databases were searched. Search
a stepwise manner. terms included: ‘acute kidney injury’, ‘cirrhosis’, ‘mortality’, and
Table and Figure:Figure 1.Figure 1A-D. Mortality risk of stage 1 corresponding synonyms. Comparisons across AKI stage 1A, 1B
AKI compared to NAKI: basic analysis (A), sensitivity analysis (B), and NAKI were included. Meta-analysis was conducted to estimate
publication bias analysis (C), subgroup analysis (D). the prevalence and mortality risk of AKI stage 1A and 1B in cirrhotic
Figure 2.Figure 2A-D. Mortality risk of stage 2 AKI compared to NAKI: patients.
basic analysis (A), sensitivity analysis (B), publication bias analysis Result: 11 studies were included, enrolling 2647 patients with AKI
(C), meta-regression analysis on study country (D) stage1A, 3052 with stage1B, and 1,395 without AKI, which resulted into
a pooled prevalence of 16.3% (95%CI:11.3-22.9%) for AKI stage 1A,
PP0758 and 15.7% (95%CI:9.3-25.3%) for 1B. Compared to NAKI, AKI stage
1A increased the mortality risk by about 2 folds (OR:1.98,95%CI:1.33-
Analysis of Clinical Characteristics and Prognosis in Young 2.97,P=0.004), and stage 1B increased it by 4.8 folds (OR:4.79,
Hepatitis B Cirrhosis: a Propensity Score Matching Study 95%CI:3.30-6.95, P<0.001). Compared to AKI stage 1A, AKI stage
Pengyue Zhang1, Wenjuan Zhang1, Xinlei Chen1, Xiaodan Hong1, 1B still increased the mortality risk by 1.6 folds (OR:1.55, 95%CI:1.03-
Zhenhua Zhang1 2.31, P<0.001).
1
The Second Affiliated Hospital of Anhui Medical University Conclusion: About one in six cirrhotic patients had AKI stage 1A and
1B, and both AKI stage 1A and 1B significantly increased the mortality status from normal to sarcopenic had worse outcomes in terms of
risks of cirrhotic patients. LT-free survival. Based on Cox and competing risk model analyses,
Table and Figure:Figure 1.Figure 1. Flow diagram of the study ∆SMI/year% was independently associated with poor survival. When
identification. separated by a cut-off of ∆SMI/year% -2.08 derived from the receiver
Figure 2.Figure 2A-C. Comparison of mortality risk across patients with operating characteristic (ROC) analysis, ∆SMI/year% < -2.08 was not
AKI stage 1A, 1B and NAKI: 1A vs. NAKI (A), 1B vs. NAKI (B), 1B vs. associated with age, but it did significantly discriminate the patients
1A (C). with decompensation, bacterial infection, and severe liver dysfunction
(P value<0.05).
Conclusion: SMI/year% may be an effective index for predicting
PP0760
poor long-term outcomes in patients with cirrhosis, independent of
Development and validation of a predictive nomogram for age. Early short-term monitoring of SMI could guide clinical decision-
sarcopenia in patients with decompensated cirrhosis making regarding nutritional interventions in cirrhosis.
Yangyang Zhou1, Yuhu Song1 Table and Figure:Figure 1.Figure 1 Longitudinal changes in sarcopenia
1
wuhan union hospital status associated with liver transplantation (LT)-free survival in
Background: Sarcopenia was a complication of cirrhosis and has cirrhosis. (A) Kaplan–Meier plot for LT-free survival on the basis of CT-
been validated as an independent prognostic factor in cirrhosis assessed sarcopenia at baseline. (B) Kaplan–Meier plot for LT-free
patients. However, current methods for assessing and diagnosing survival significantly stratified into four groups according to changes in
sarcopenia limited its application. In this study, we aimed to develop a sarcopenia status, NN, no sarcopenia to no sarcopenia; SN, sarcopenia
simple and reliable nomogram to predict the occurrence of sarcopenia to no sarcopenia; NS, no sarcopenia to sarcopenia; SS, sarcopenia to
in decompensated cirrhosis patients that could assist clinicians identify sarcopenia. (C) Receiver operating characteristic curves for long-term
and reverse sarcopenia patients early. LT-free survival in cirrhosis according to ΔSMI/yr%.
Method: A total of 462 patients with decompensated cirrhosis at Figure 2.Figure 2 Kaplan–Meier curves for CT scans of sarcopenia at
the Wuhan Union Hospital from January 2015 to August 2022 were different time points for the prediction of their relative future survival
included. They were randomly divided into either the development events free of liver transplantation: Sarcopenia at baseline to predict
cohort (n = 323) or the validation cohort (n = 139). Independent risk survival at (A) 1st year, (B) 3rd year and (C) end point after enrolment.
factors were screened for establishing the risk prediction nomogram Patients with cirrhosis who died or received liver transplantation were
of sarcopenia using multivariate logistic regression analysis. excluded and the sarcopenia status of the left patients at 1st year was
Discrimination, accuracy and clinical utility values were evaluated by used to predict survival at (D) 2nd year, (E) 3rd year and (F) end point
receiver operating characteristic, calibration curves, decision curve after enrolment; (G) patients with cirrhosis who died or received liver
analysis and clinical impact plots. transplantation were excluded and the sarcopenia status of the left
Result: Haematemesis, BMI, and FIB were effectively identified patients at the 3rd year was used to predict the survival outcomes at
to predict sarcopenia in decompensated cirrhosis patients. The the terminal point after inclusion.
nomogram showed the area under the curve of 0.719 and 0.784 in the
development and validation cohort. And the sensitivity, specificity, and PP0762
Youden index of the development cohort were 45.7% and 87.6%, and
Non-invasive assessment of liver fibrosis regression in patients
0.333, respectively. Calibration curves and decision curve analysis
with chronic hepatitis B
confirmed great accuracy and clinical utility.
Conclusion: We developed and validated a nomogram model to Qiang Li1, Professor Liang Chen research group
predict the risk of sarcopenia in decompensated cirrhosis patients,
1
1. Department of Liver Disease, Shanghai Public Health
which could be used for early identification and timely intervention. Clinical Center, Fudan University, Shanghai, China.
Background: Non-invasive tests (NITs) have been alternative methods
of liver biopsy for the cross-sectional assessment of liver fibrosis in
PP0761
patients with chronic hepatitis B (CHB). However, there are limited data
The impact of changes in skeletal muscle mass on the prediction on the longitudinal association between NITs and histological changes
of long-term survival in patients with liver cirrhosis of liver fibrosis. This study aimed to evaluate whether NITs can be used
Huiping Liang1, Chang Zhang1, Yuchao Wu2,3, Yingren Zhao2, Yuan to assess liver fibrosis regression (LFR) during anti-HBV treatment.
Yang2, Xiaoping Tang4,5 Method: This retrospective study included 337 patients with CHB who
1
Affiliated Cancer Hospital & Institute of Guangzhou Medical underwent contemporaneous NITs and liver biopsy at baseline and
University, Guangzhou China., 2Department of Infectious Diseases followed by a repeated liver biopsy and NITs assessment. LFR was
and Hepatopathy, First Affiliated Hospital of Xi’an Jiaotong University, defined as fibrosis regression by ≥ 1 stage assessed by METAVIR-
China, 3 Affiliated Cancer Hospital & Institute of Guangzhou Medical Scoring-System.
University, Guangzhou China., 4Department of Infectious Diseases, Result: The median interval between the two paired assessment was
Guangzhou Eighth People‘s Hospital, Guangzhou Medical University, 31 months (IQR: 24-45). At the first liver biopsy, the fibrosis stage
5
Guangzhou Medical University was F2 in 159, F3 in 68 and F4 in 110 patients. At the second liver
Background: Sarcopenia is the progressive loss of muscle mass biopsy, patients with F0-1, F2, F3, and F4 was 102, 106, 63, and 66,
that worsens the clinical outcomes of cirrhosis. Here, we aimed respectively. Namely, at follow up liver biopsy, 169 patients (50.1%)
to investigate the changes in skeletal muscle mass (ΔSMI) over an had LFR, 128 patients (38.0%) had no change in fibrosis stage, and
intermediate period of time to comprehensively elucidate its prognostic 40 patients (11.9%) had fibrosis progression on histology. A decrease
value for long-term mortality in cirrhosis. in liver stiffness measurement (LSM) by 25% is the optimal cutoff for
Method: This retrospective cohort study included patients with cirrhosis predicting LFR. Patients with a ≥ 25% decrease in LSM had more LFR
who underwent abdominal computed tomography (CT) between than those with a < 25% decrease in LSM (78.1% vs 22.9%, p < 0.001).
January 2012 and December 2021. SMI was obtained from annual CT Conclusion: LSM might be used to monitor regression of liver fibrosis
scans at the third lumbar vertebra. The effect of the first three years of during antiviral treatment using NUCs in patients with CHB
the annual rate of change in SMI (∆SMI/year%) was calculated and its
prognosis at the next long-term follow-up was analyzed. PP0763
Result: Overall, 384 patients who underwent at least two CT
examinations during the first three years were enrolled. Here, 120 men Case report: POEMS syndrome with portal hypertension
(31.3%) and 44 women (11.5%) had sarcopenia at baseline. At an Xiaotong Xu1, Qinghua Meng1, Jianjun Li1
average follow-up of 71.52 months, 257 (66.9%) patients were with 1
Interventional Therapy Center for Oncology, Beijing Youan Hospital,
liver transplantation (LT)-free. Sarcopenia defined status at 1–3 years Capital Medical University, Beijing, China
tended to be a prognostic factor. Patients with a change in sarcopenia
A 70-year-old male patient developed abdominal distension without an for non-linearity=0.004). LogCV predicted AKI with an AUC of 0.645.
obvious cause 11 months prior and was diagnosed with liver cirrhosis ROC and DCA indicated LogCV had higher predictive power and
at a local hospital. Albumin supplementation and diuretic treatment clinical decision-making efficacy for AKI than blood glucose and mean
alleviated symptoms to some extent. One-month prior, the patient glucose. Moreover, subgroup analysis showed a robust relationship
experienced abdominal distension accompanied by shortness of between CV and AKI (all P< 0.05).
breath. After symptomatic treatment, the discomfort persisted. Then Conclusion: High glycemic variability is an independent risk for AKI
the patient sought medical attention at our hospital. in non-diabetic cirrhotic patients. This study highlights potential clinical
He denied a history of alcohol use. The typical signs of liver cirrhosis, significance of maintaining glycemic stability in non-diabetic cirrhotic
including spider haemangioma, engorged paraumbilical veins, or palm patients for prevention of AKI.
erythema, were all negative. Cognitive function appeared normal. He Table and Figure:Figure 1.Logistic regression analysis of the
presented with coarse breathing sounds in both lungs and weak vocal relationship between GV and AKI in non-diabetic cirrhotic patients
resonance in the right lung. The liver and spleen were not palpable, but Figure 2.ROC analysis of the diagnostic efficiency of LogCV, LogGlu_
shifting dullness was detected. Both lower limbs were free of oedema. avg, LogGlu_first, SOFA, and MELD to predict the risk of AKI in non-
The patient has no special medication history, and hepatitis B, diabetic cirrhotic patients
hepatitis C, autoimmune indicators, and genetic metabolism related
liver diseases have been excluded.Given the refractory hydrothorax
PP0765
and ascites and the advanced age, a transjugular intrahepatic
portosystemic shunt (TIPS) was applied, and a transjugular liver Meta-analysis of the safety of non-selective β-blockers in the
biopsy was performed to determine the cause of the condition(Non treatment of cirrhotic patients with ascites
cirrhotic portal hypertension). After TIPS , the patient was discharged Jiansong Wan1
without any discomfort. 1
First People‘s Hospital of Fuzhou
One and a half months after TIPS, the patient was referred to our Background: The use of non-selective beta-blockers (NSBB) to
hospital again due to nausea, fatigue, abdominal distension, and decrease the danger of variceal bleeding is widespread, yet there
shortness of breath. Computed tomography showed no thrombosis is still a dearth of conclusive proof as to whether NSBB should be
or stenosis in the TIPS stent.Blood ammonia levels were normal and continued in those with cirrhotic ascites.
consciousness was normal. After symptomatic treatment, the patient’s Method: PubMed, Embase, Web of science,Cochrane Library,CBM,
condition improved slightly. Considering the persistent recurrent Wanfang, VIP, CNKI, and Chinese/American Clinical Trial Registry were
pleural and abdominal fluid accumulation after TIPS placement and searched by computer using subject words and free words from the
concomitant, lower limb weakness but lack of hepatic encephalopathy, establishment of the database to March 2023.Employing a search
the patient’s medical history was traced again. One-year prior, the tactic of subject headings and free words, the search terms were liver
patient had developed weakness in both lower limbs, and in May of cirrhosis, ascites, non-selective β-blockers, propranolol, carvedilol,
this year, melanin deposition appeared on the skin of both feet. One nadolol and labetalol.The criteria for inclusion and exclusion were
and a half months after TIPS placement, the weakness in both lower adhered to, the literature was examined, its excellence was appraised,
limbs gradually worsened, and hydrothorax and ascites recurred. and finally the valid data was drawn out.The safety of NSBB in those
However, the patient did not experience significant relief after reducing with liver cirrhosis and ascites was assessed through the utilization of
portal pressure. RevMan5.3 software.
Based on the above symptoms, relevant examinations of the blood Result: A total of 20 articles were included, including 12467 patients,
system improved (Electrophysiological manifestations of multiple of which 6 were Randomized controlled trials (RCTs) and 14 were
peripheral nerve damage, Monoclonal immunoglobulin type(IgA-λ observational studies. Adverse reactions were reported in 4 RCTS.
type), abnormal sex hormone and abnormal thyroid function testing), The control groups received other interventions or placebo to prevent
and the diagnosis of POEMS syndrome with portal hypertension variceal bleeding. The NSBB group’s mortality risk was only 85% of
was ultimately confirmed. Subsequently, bortezomib combined with the control group’s (RR=0.85, 95%CI=0.75-0.96, P=0.008<0.05),
glucocorticoids was administered for treatment. After two courses of according to the results. In the observational study group, the use
treatment, the patient died due to pneumonia and infection. of NSBB was found to have a minimal effect on the risk of death in
cirrhotic ascites, with a risk of death in the NSBB group only 79% of
PP0764 that of the control group (RR=79%,95%CI=0.69-0.91, P=0.0010.05).
Subgroup analysis, taking into account the presence or absence
Association between glycemic variability and risk of acute kidney
of refractory ascites, race in different regions, drug type and dose,
injury in non-diabetic cirrhotic patients: analysis of the MIMIC-IV
and follow-up time, further revealed that NSBB did not increase the
database
all-cause mortality of those with cirrhotic ascites or even refractory
Yaxin Li1, Huiguo DING1 ascites. At 12 and 24 months, no augmentation of all-cause mortality
1
Beijing Youan Hospital, Capital Medical University was observed in those suffering from cirrhotic ascites. No noteworthy
Background: Acute kidney injury (AKI) is a common complication with divergence in the occurrence of adverse responses between the two
poor prognosis in cirrhotic patients. The relationship between glycemic groups was observed (RR=0.87,95%CI=0.67-1.14, P=0.31>0.05).
variability and AKI in non-diabetic cirrhotic patients is unknown. We Conclusion: NSBB use in those with cirrhotic and ascites does not
aimed to investigate the link between glycemic variability and AKI. lead to a rise in mortality from all causes or an increase in adverse
Method: This retrospective cohort study screened patients with non- reactions, and it is not essential to discontinue NSBB even in cases of
diabetic cirrhosis from the Medical Information Mart for Intensive refractory ascites.
Care IV (MIMIC-IV) database. Glycemic variability was defined as
the coefficient of variation (CV), and the relationship between CV and
PP0766
AKI in non-diabetic cirrhotic patients was assessed using multivariate
logistic regression model, and the non-linear relationship was explored FibroScan Predicts Liver Fibrosis Progression in Chronic HBV
by restricted cubic spline. The predictive power of CV for AKI was Infection Patients Without Antiviral Therapy
judged by plotting the receiver operating characteristic (ROC) curve, Qiang Li1, Professor Liang Chen research group
and the net clinical benefit was assessed using the decision curve 1
1. Department of Liver Disease, Shanghai Public Health
analysis (DCA). Finally, the consistency of the relationship between CV Clinical Center, Fudan University, Shanghai, China.
and AKI in different subgroups was explored. Background: Chronic hepatitis B virus (HBV) infection patients who do
Result: 1848 participants were included. Multivariate logistic not fulfill the typical treatment indications should be followed up. This
regression revealed LogCV was an independent risk for AKI in non- study aimed to evaluate the risk of liver fibrosis progression (LFP), and
diabetic cirrhotic patients (OR, 2.468; 95% CI, 1.859-3.300), and there assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring
was a non-linear relationship between LogCV and the risk of AKI (P
LFP in these patients. NCT-A positive patients
Method: 116 patients with active HBV replication, persistently normal
or minimally elevated alanine aminotransferase (ALT) levels, and no or
PP0768
mild hepatic necroinflammation or fibrosis based on liver biopsy tests
at baseline and followed by a repeated liver biopsy assessment during Mitochondrial membrane potential of CD8+ T cells predicting
follow-up. LFP was defined as increase in METAVIR fibrosis score by infection and acute-on-chronic liver failure within 90 days in
1 score or more. cirrhotic patients
Result: Among 116 patients, 40 patients (34.5%) progressed by at Xixuan Wang1, Shuling Chen1, Jing Fan1, Yuxiang Gong1, Hongli Liu1,
least one fibrosis stage, 16 patients (13.8%) progressed by at least Lili Wang2, Xiaoning Feng3, Hui Zhou3, Wenquan Zeng3, Changhua
two fibrosis stages at a median follow-up interval of 27 months (IQR: Yi4, Caiyun Zhang2, Qingfang Xiong3, Hao Ren3, Yongfeng Yang1
12-36). Multivariate analysis confirmed the significant association 1
Department of Hepatology, The Second Hospital of Nanjing, Affiliated
of an increase in liver stiffness measurement (LSM) value with LFP Southeast University, 2Clinical Research Centre, The Second Hospital
on histology [p =0.005]. The AUROC of LSM value increase rate is of Nanjing, Affiliated to Nanjing University of Chinese Medicine,
significantly higher than that of serum-based NITs of liver fibrosis for
3
Department of Hepatology, The Second Hospital of Nanjing, Affiliated
the prediction of LFP (p < 0.05). An increase in LSM by 20% is the to Nanjing University of Chinese Medicine, 4Department of Biobank,
optimal cutoff for the prediction of LFP. The Second Hospital of Nanjing, Affiliated to Nanjing University of
Conclusion: LFP is non-negligible in patients with active HBV Chinese Medicine
replication, persistently normal or minimally elevated ALT, and initially Background: People with cirrhosis are at increased risk of bacterial
no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests infection (BI), which is the most common precondition for acute-
would be more reliable in identifying LFP than serum-based NITs, and on-chronic liver failure (ACLF). We aimed to evaluate the ability of
easier to obtain than serial liver biopsy tests. mitochondria-related indicators (mitochondrial mass and mitochondrial
membrane potential, MMP) of T cells in peripheral blood to predict BI
and ACLF within 90 days in cirrhotic patients.
PP0767
Method: We prospectively studied mitochondria-related indicators
Study of the sleep quality and psychological state of patients with of various T cells of 235 cirrhotic patients at the Second Hospital of
hepatitis B liver cirrhosis Nanjing. The outcomes were BI and ACLF.
Aili Fan1, Jiawen Feng1, Qing Ye2 Result: The restricted cubic spline showed that the MMP of CD8+
1
The Third Central clinical college of Nankai University, Tianjin, PR T cells had a linear relationship with the risk of BI and ACLF (both
China, 2Department of Gastroenterology and Hepatology, Tianjin Third P<0.001). The multivariable Cox regression model showed that the
Central Hospital, Tianjin, PR China MMP of CD8+ T cells was independent risk factor for BI and ACLF (BI:
Background: Hepatitis B liver cirrhosis is a long-term chronic disease, hazard ratio (HR) 0.96, 95% CI 0.94-0.98; P<0.001; ACLF: HR 0.94,
accompanied by complications such as ascites, esophageal variceal 95% CI 0.90-0.97; P<0.001). The MMP of CD8+ T cells had a better
bleeding, and hepatic coma in the course of disease progression; diagnostic efficacy than the traditional index in predicting BI (C index:
moreover, the population with hepatitis B liver cirrhosis is at a high risk 0.75). The MMP of CD8+ T cells combined with the traditional models
for liver cancer . Therefore, the patients may suffer from issues such as (CTP and MELD score) could improve their diagnostic efficiencies in
psychological stress, pain, and economic burden for a long-term. With predicting BI and ACLF. The MMP of CD8+ T cells was significantly
an altered medical model, the phenomena of chronic physical diseases lowly correlated with inflammation-related markers (P<0.05). The
accompanied by psychological disturbances, such as anxiety and mitochondria damage and abnormally-activated mitochondrial
depression, have attracted widespread attention. However, systematic autophagy were observed in CD8+ T cells of cirrhotic patients with
studies on the sleep quality and psychological states of patients with low MMP.
hepatitis B liver cirrhosis are yet lacking.We aimed to investigate the Conclusion: The MMP of CD8+ T cells could be a valuable predictor
sleep quality, mild hepatic encephalopathy, anxiety and depression of BI and ACLF within 90 days for cirrhotic patients.
in patients with hepatitis B cirrhosis by using a variety of scales and
questionnaires. PP0769
Method: A cohort of 341 patients with hepatitis B liver cirrhosis were
Gut microbiome composition in patients with liver cirrhosis with
categorized by Child-Pugh grading (A, B, and C) in this cross-sectional
and without hepatic encephalopathy: A systematic review and
study. Pittsburgh Sleep Quality Index (PSQI), Number Connection
meta-analysis
Test-A (NCT-A), and Hospital Anxiety and Depression (HAD) evaluated
the questionnaires and statistically analyzed the intrinsic correlation. Xiaotong Xu1, Qinghua Meng1, Jianjun Li1
The control group included 50 healthy individuals.
1
Department of Oncology, Beijing Youan Hospital, Capital Medical
Result: 213/341 patients presented PSQI index>5 points. The PSQI, University, Beijing, China, 3Interventional Therapy Center for
NCT-A, Anxiety scale (HAD) (a) and depression scale (HAD) (d) of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing,
the patients were significantly different. The NCT-A positive patients China
revealed 214 cases of maybe minimal hepatic encephalopathy (MHE) Background: The gut microbiome is associated with hepatic
during a preliminary screening of patients. PSQI score of NCT-A encephalopathy (HE), but research results on the gut microbiome
positive patients was significantly elevated as compared to NCT-A characteristics of patients with liver cirrhosis with and without HE are
negative patients (P<0.001) . HAD (a) and HAD (d) were significantly inconsistent.We aimed to study the gut microbiota characteristics of
different between the NCT-A positive and the NCT-A negative groups, patients with liver cirrhosis with and without HE.
P=0.002 and P=0.006, respectively. Univariate Pearson’s correlation Method: We searched the PubMed, Web of Science, EMBASE, and
analysis found that NCT-A and HAD (a) were positively correlated with Cochrane databases using two keywords, hepatic encephalopathy,
PSQI, P<0.001 and P=0.045, respectively; however, Child-Pugh score and gut microbiome. According to the inclusion and exclusion criteria,
and HAD (d) were not correlated with PSQI, P=0.061 and P=0.059, suitable literature was screened to extract data on the diversity and
respectively. composition of the fecal microbiota in patients with liver cirrhosis with
Conclusion: These results indicated that patients with hepatitis B liver and without HE. The data were analyzed using RevMan and STATA.
cirrhosis have a disturbed sleep, which might be an MHE symptom, Result: Seventeen studies were included. 1. A meta-analysis of 7
further causing considerable anxiety. Thus, the evaluation of the sleep studies revealed that the Shannon index in liver cirrhosis patients with
quality and psychological state of patients with hepatitis B liver cirrhosis HE was significantly lower than that in patients without HE (-0.20, 95% CI
necessitates further investigation to guide the positive intervention. -0.28, -0.13, I²=20%). 2. The relative abundances of Lachnospiraceae
Table and Figure:Figure 1.Table 2. PSQI, NCT-A, and HAD in each (-2.73, 95% CI -4.58, -0.87, I²=38%) and Ruminococcaceae (-2.93,
group 95% CI -4.29, -1.56, I²=0%) in liver cirrhosis patients with HE was
Figure 2.Table 3. Sleep quality and anxiety as well as depression of significantly lower than those in patients without HE. 3. In patients
with HE, Enterococcus, Proteobacteria, Enterococcaceae, and non-infectious liver disease in different years
Enterobacteriaceae proportions increased, but Ruminococcaceae, Figure 2.Comparison of liver tissue inflammation grade and fibrosis
Lachnospiraceae, Prevotellaceae, and Bacteroidetes proportions stage in patients with different diseases
decreased. 4. Differences in the fecal metabolome between liver
cirrhosis patients with and without HE were detected. 5. Differential gut
PP0771
microbiomes may serve as diagnostic and prognostic tools.
Conclusion: The gut microbiomes of patients with liver cirrhosis with New subtype of recompensation (intermittent recompensation) in
and without HE differ. Some gut microbiomes may distinguish liver patients with HBV-related decompensated cirrhosis
cirrhosis patients with or without HE and determine patient prognosis. Shuai Xia1, Zhiying He1, Jialing Zhou1, Zhongjie Hu2, Yan Huang3,
Table and Figure:Figure 1.Comparison of alpha diversity indices Chunqing Zhang4, Yanqin Hao5, Wei Rao6, Jing Wang7, Yongfeng
between patients with hepatic encephalopathy (HE) and without YANG8, Xinyu Zhao9, Xiaojuan Ou10, Jidong JIA9, Xiaoning Wu1,
hepatic encephalopathy (non-HE) in cirrhosis Bingqiong Wang9, Hong YOU10
Figure 2.Alpha diversity indices of patients with liver cirrhosis with 1
Beijing Friendship Hospital, Capital Medical University, 2Beijing
or without HE. A: The Shannon index results; B: The Simpson index You‘an Hospital, Capital Medical University, 3Xiangya Hospital Central
results; C: Chao 1 index results South University, 4Provincial Hospital Affiliated to Shandong First
Medical University, 5The First Hospital of Shanxi Medical University,
6
The Affiliated Hospital of Qingdao University, 7The Second Affiliated
PP0770 Hospital of Baotou Medical College, 8The Second Hospital of
Analysis of pathological diagnosis and clinical diagnosis in 1752 Nanjing, Affiliated to Medical School of South East University, 9Beijing
cases undergoing routine liver biopsy Friendship Hospital, 10Beijing Frienship Hospital
Airong Hu1, Suwen Jiang1, Jialan Jiang2, Menghan Jin3, Ken Lin3, Ying Background: The Baveno VII consensus has proposed a definition
Fan4, Haojin Zhang4, Shiyang Fang4, Shiqi Yang2 of “recompensation”, which has been validated in studies enrolled
1
Liver Diseases Center, Ningbo Institute of Liver Diseases, Ningbo patients with only once decompensation. However, whether achieving
No. 2 Hospital, 2Graduate School, Wenzhou Medical University, recompensation interweaved with multiple episodes of decompensation
3
Ningbo University Health Science Center, 4School of Medicine, represents a distinct subtype and its clinical significance remain
Shaoxing University unclear. In this study, we investigated the clinical implications of new
Background: To investigate the histopathological diagnosis, subtypes of recompensation and the subsequent prognosis in patients
clinicopathological features and etiological components of liver with decompensated cirrhosis.
puncture, and to provide guiding value for clinical diagnosis and Method: Patients with HBV-related decompensated cirrhosis
treatment. who experienced first decompensated events were enrolled, and
Method: The clinicopathological data of 1,752 patients who underwent clinical data were retrospectively collected over 5 years. Hepatic
liver biopsy in Ningbo No. 2 Hospital from January 2015 to December recompensation was defined based on Baveno VII criteria, including
2023 were included in this study. The consistency of demographic the resolution of ascites (off diuretics) and hepatic encephalopathy (off
traits, clinical diagnosis, pathological diagnosis, and the severity of lactulose/ rifaximin), absence of variceal bleeding, and improved liver
liver histopathology were analyzed. function.
Result: Among the 1,752 patients, 1,589 (90.70%) had a definite Result: In total, 394 patients with HBV-related decompensated cirrhosis
diagnosis of the disease, and the top three were hepatitis B virus were enrolled (age: 58.1 years [IQR: 51.3-66.2]; 69.5% male; Child-
(HBV) infection (45.04%), metabolic dysfunction-associated steatotic Pugh score: 8 [IQR: 7-10]; MELD score: 13 [IQR: 10-17]) and followed
liver disease (MASLD) (12.61%), autoimmune liver disease (11.64%), for a median time of 5.3 (IQR:4.4-5.8) years after first decompensation.
and 163 cases (9.30%) without a clear disease diagnosis, involving Among them, 93 patients (23.6%) never achieved recompensation
22 diseases. Multiple liver illnesses were present concurrently, such and experienced repeated episodes of decompensation through their
as autoimmune liver disease and drug-induced liver damage (DILI), clinical course. The remaining 301 patients achieved recompensation,
autoimmune liver disease and MASLD, HBV infection and MASLD, of whom 204 patients (51.8%) remained free of further decompensation
etc. and with HBV infection combined with MASLD being the most events, while 97 patients (24.6%) occurred further decompensation
predominant (67.14%). Hepatic occupations were mainly liver primary after achieving recompensation. Therefore, we identified two distinct
or metastatic malignant tumors of the liver (3.82%). The patients with patterns of recompensation: the first type was “stable recompensation,”
HBV infection, concomitant combination of two or more liver diseases, characterized by achieving recompensation immediately after the first
and liver primary or metastatic malignant tumors were mainly males, decompensation and never experiencing further decompensation;
while the patients with MASLD, autoimmune liver disease, DILI, and and the other type was “intermittent recompensation”, characterized
undiagnosed diseases were mainly females, and the composition by achieving recompensation interweaved with decompensation
was statistically significant (P < 0.001), and the statistical differences after first events (Figure 1 A). Importantly, patients achieving stable
between the two were significant (P < 0.05). There was a significant recompensation and intermittent recompensation had a lower 5-year
statistically significant difference in age between the groups (P < rate of HCC/Death compared to patients without recompensation (6.3%
0.001), with the lowest age of patients with HBV infection and the vs. 13.2% vs. 24.3%, P<0.001). However, patients with intermittent
highest age of patients with primary or metastatic hepatic malignancies. recompensation were significantly worse prognosis compared to
Except for 2017, the composition of diseases was dominated by HBV stable recompensation. (Figure 1 B)
infection until 2021, whereas the composition ratio of non-infectious Conclusion: The long-term prognosis in patients who had achieved
liver diseases showed a yearly increasing trend from 2022 onwards, recompensation was much better than patients who had never
reaching 96.82% in 2023 (especially for MASLD, which reached achieved recompensation. However, intermittent recompensation
44.09%). The autoimmune liver disease group had the most severe differed from stable recompensation, as it was associated with a higher
hepatic pathological damage, including the mean Ridit value of liver risk of HCC/Death.
inflammation grade and fibrosis stage, and the composition ratio of Table and Figure:Figure 1.Figure 1
significant hepatic inflammation (≥ G2)/significant hepatic fibrosis (≥
S2)/cirrhosis (S4), especially in patients with autoimmune hepatitis- PP0772
primary biliary cholangitis overlap syndrome.
The correlation between the ratio of ALT to qHBsAg and the
Conclusion: The etiology and clinicopathological features of liver
recompensation of HBV-related patients with cirrhosis: A
diseases are highly heterogeneous, and the demand for liver
retrospective cohort study based on the Baveno VII criteria
pathology caused by HBV infection is gradually decreasing, while liver
pathological diagnosis is necessary for non-infectious liver diseases, Ya Ping Xu1, Yan Wang1
especially autoimmune liver diseases.
1
Department of Infectious Diseases and Hepatology, The Second
Table and Figure:Figure 1.Figure 1 Distribution of HBV infection versus Hospital of Shandong University,
Background: Patients with decompensated cirrhosis related to Table and Figure:Figure 1.Area under the receiver operating curve of
hepatitis B have the potential for recompensation. The ratio of ALT to XGBoost model predicting EVB rebleeding in (A) the Training cohort
qHBsAg is a newly proposed effective predictor for the clearance of and (B) the Validation cohort.
hepatitis B surface antigen. We aim to study whether this ratio can also
be used to predict the recompensation of hepatitis B-related cirrhosis PP0774
based on the latest Baveno VII criteria.
Method: In this retrospective study, HBV-related patients with Assessments of sarcopenic obesity and its predictors based on
decompensated cirrhosis were enrolled and treated with first-line CT imaging in patients with cirrhosis: a large-scale retrospective
nucleos(t)ide analogues therapy for at least 12 months. Participants study
were classified into 2 groups: decompensated group and Yuteng Yang1, Changjie Tie1, Tingyang Wei1, Zixing Wang2, Rui
recompensated group according to Baveno VII criteria. Multivariate Huang2
regression models and propensity score matching were used to 1
School of Basic Medical Sciences, Peking University Health Science
identify the predictors of HCC. Logistic regression analysis was used Center, No.38 Xueyuan Avenue, Beijing, 10038, China, 2Peking
to investigate the predictors for recompensation at baseline. University People’s Hospital, Institute of Hepatology Peking University
Result: Of the 136 patients recruited, during a median follow-up of 44.5 Background: Sarcopenic obesity (Sa-O) has been proven associated
months (interquartile range 26.8, 57.0 months), 80 (58.8%) patients with poor prognosis in liver cirrhosis (LC), and Computed Tomography
acquired hepatic recompensation. In the univariate analysis, sex, age, (CT) based body composition parameters offer diagnostic value of
levels of ALT, levels of AST, HBV DNA, qHBsAg and ALT/logqHBsAg Sa-O. However, large-scale studies on its incidence and influencing
were associated with hepatic recompensation. In the logistic factors in patients with cirrhosis are limited. This study aims to assess
multivariate analysis, transferase, and HBV DNA. In the multivariate the incidence and predictors of Sa-O and develop a predictive model
analysis, higher ALT/logqHBsAg level was associated with a higher for this condition in cirrhotic patients.
likelihood of recompensation in the fully adjusted model (OR=0.99, Method: This study is a part of a single-center retrospective study
95% CI=0.98~1; p=0.027) , and when ALT/logqHBsAg was treated (NCT06531200) which involved adult patients diagnosed with cirrhosis
as a categorical variable, ALT/logqHBsAg >23.48 was associated from November 2008 to September 2022. We chose patients who
with a higher likelihood of recompensation in the fully adjusted model were aged 18 years or older, possessed comprehensive medical
( OR=0.29, 95% CI=0.12~0.73, p=0.011). In the subgroup analysis, records and underwent a CT scan. Body composition parameters
the correlation between the ALT/logqHBsAg and recompensation was were assessed from L3-level CT scans. Patients with end-stage liver
consistent across all five pre-specified subgroups defined by sex, disease with skeletal muscle index (SMI) < 38 cm2/m2 for women
age, HBeAg status, HBV-DNA, Child-Pugh grade and MELD score. and < 42 cm2/m2 for men, and visceral adipose tissue area (VATA)
Conclusion: The higher ratio of ALT to qHBsAg could be used to > 100 cm2 were diagnosed as Sa-O. Univariable and multivariable
predict a higher likelihood of recompensation of hepatitis B-related analysis were employed to identify potential predictors of Sa-O. The
cirrhosis based on the latest Baveno VII criteria. nomograph was plotted by selected predictors.
Result: A total of 769 patients with cirrhosis were included in the
PP0773 analysis, with 281 (36.5%) diagnosed with Sa-O. Compared to patients
without Sa-O, those with Sa-O were older (≥ 60 years: 60.5% vs.
Machine Learning Model for Predicting Rebleeding Risk after
42.5%, P = 0.0002), had a lower body mass index (BMI) (BMI < 24kg/
Endoscopic Variceal Ligation in Esophageal Variceal bleeding: A
m2: 69.8% vs. 52.7%, P < 0.001), and exhibited a higher prevalence
Chinese multicenter cohort study
of hypertension (39.5% vs. 25.6%, P = 0.0013) as well as diabetes
Junyi Zhan1, Yongping Mu1 (29.5% vs. 20.9%, P = 0.0341) (Table 1). Univariable analysis identified
1
Shuguang Hospital Affiliated to Shanghai University of Traditional age (OR 2.069, 95% CI 1.406-3.045, P = 0.0002), BMI (OR 0.077, 95%
Chinese Medicine CI 0.019-0.319, P = 0.0011), alcohol-related liver disease (OR 1.967,
Background: Rebleeding is a severe complication following recovery 95% CI 1.200-3.224, P = 0.0300), hypertension (OR 1.898, 95% CI
from esophageal variceal bleeding (EVB), with limited predictive tools 1.278–2.817, P = 0.0015), and diabetes (OR 1.577, 95% CI 1.032–
for assessing post-treatment risk after endoscopic variceal ligation 2.409, P = 0.0352) as significant predictors of Sa-O. Multivariable
(EVL) therapy. This study aimed to develop and externally validate analysis confirmed age (OR 1.813, 95% CI 1.210-2.718, P = 0.0040),
a rebleeding risk prediction model for EVB patients using machine BMI ≥ 28 (OR 0.076, 95% CI 0.018-0.317, P = 0.0011), baseline
learning (ML) algorithms and multidimensional clinical data. alcohol-related liver disease (OR 1.685, 95% CI 1.078–2.634, P =
Method: Two independent cohorts were included: a retrospective 0.0220) and hypertension (OR 1.801, 95% CI 1.184-2.739, P = 0.0059)
cohort (n=392) for model development and a prospective cohort as independent predictors of Sa-O in patients with cirrhosis. The
(n=100) for external validation, with a one-year rebleeding endpoint. nomogram (Figure 1A) was constructed based on these predictors,
Predictors were identified through Recursive Feature Elimination enabling individual risk prediction by assigning points to each variable.
(RFE), and eight ML algorithms were evaluated. Each algorithm was Stratified analysis (Figure 1B) demonstrated distinct separation among
optimized using 5-fold cross-validation. The model with the highest three groups by their total points, with significant differences in Sa-O
predictive accuracy was selected as the final model, with performance probabilities (P < 0.0001).
assessed via AUC, accuracy, and other relevant metrics. SHAP plots Conclusion: Sa-O is a significant complication in cirrhosis, with distinct
facilitated feature interpretation, and an online platform was developed clinical predictors such as age, BMI, hypertension, and alcohol-
based on the final model. related liver disease. The nomogram developed in this study provides
Result: RFE identified seven key predictors, including concentrations a practical tool for risk stratification and personalized prognosis
of albumin, alanine aminotransferase, aspartate aminotransferase, and assessment of Sa-O in clinical practice.
uric acid, as well as the presence of ascites, portal vein thrombosis, Table and Figure:Figure 1.Baseline characteristics of patients with
and bleeding signs. In the training cohort, all eight machine learning cirrhosis by sarcopenic obesity (n = 769).
models demonstrated strong predictive performance, with AUC Figure 2.Nomograph and stratified analysis of ABA scoring
exceeding 0.85. In the external validation cohort, XGBoost achieved
the highest predictive accuracy (AUC = 0.894, 95% CI: 0.819–0.969), PP0775
with ascites identified as the most influential predictor. Leveraging the
feature importance and AUC of the XGBoost model, an online platform Study on the active components of Fuzheng Huayu formal and
was developed to assess 1-year rebleeding risk in EVB patients. their anti-fibrotic mechanisms
Conclusion: The XGBoost-based model, incorporating seven Jiamei Chen1,2, Wei Liu1,2, Ping Liu1,2,3
accessible clinical features, demonstrates robust predictive accuracy 1
Shuguang Hospital affliated to Shanghai University of Traditional
for EVB rebleeding risk. The platform supports clinicians in 1-year risk Chinese Medicine, 2Key Laboratory of Liver and Kidney Diseases
assessment, aiding informed decision-making. (Ministry of Education), 3Institute of Interdisciplinary Medicine,
Shanghai University of Traditional Chinese Medicine DCA, C16:1, C20:4, ω3-C22:5, MELD, and neutrophil-to-lymphocyte
Background: To investigate the the main active components/ ratio (NLR), with a model sensitivity, specificity, and positive and
ingredients and their underlying mechanism and targets of a traditional negative predictive values of 75.0, 92.1, 83.3%, and 87.5%.
Chinese medicine formula, Fuzheng Huayu formula (FZHY) against Conclusion: Serum levels of 5 DAMs may characterize metabolomic
liver fibrosis. changes and help to predict the 28-day prognosis of ACLF.
Method: The quantitative analysis of the compound in FZHY extracts,
and the dynamic changes of exposure in portal vein blood, jugular PP0777
vein blood and liver tissue of rats after intragastric administration of
Dose-response relationship between serum N-glycan markers and
FZHY, as well as the uniform design and the evaluation of efficacy
liver fibrosis in chronic hepatitis B
of components and ingredients in rodent models, the analysis of key
Chi Zhang1, Yiqi Liu1, Hong Zhao2, Guiqiang Wang2
targets of main components and their mechanisms in vivo and in vitro
were performed.
1
Peking university first hospital, 2Peking University First Hospital,
Result: Salvianolic acid B (Sal B), schisantherin A (Sin A), and Beijing, 100034, China
amygdalin, which had the highest content in the FZHY decoction, Background: Background Evaluation of liver fibrosis played a
plasma, and liver, respectively, were selected to evaluate the anti- monumental role in the diagnosis and monitoring of chronic hepatitis
hepatic fibrosis effects in vivo and in vitro. We further found that Sal B(CHB). We aimed to explore the value of serum N-glycan markers in
B significantly attenuated liver fibrosis in carbon tetrachloride (CCl4)- liver fibrosis.
induced mice, and suppressed erastin- or CCl4-induced hepatocyte Method: Methods This multi-center(33 hospitals) study recruited
ferroptosis in vitro. In addition, extracellular matrixprotein 1 (Ecm1) 760 treatment-naïve CHB patients who underwent liver biopsy.
interacted with the solute carrier family 7 member 11 (SLC7A11, xCT) Serum N-glycan markers were analyzed by DNA sequencer-assisted
to regulate hepatocyte ferroptosis. ECM1 deletion in hepatocytes fluorophore-assisted with capillary electrophoresis(DSA-FACE)
abolished the antifibrotic effect of Sal B in vivo and in vitro, suggesting technology. First, we explore the relationship between 12 serum
that Sal B protected against hepatocyte ferroptosis by upregulating N-glycan markers and the fibrosis stage. Then, we developed a Px
Ecm1. Sin A significantly ameliorated bile acid metabolism, ductular score for diagnosing significant fibrosis using the LASSO regression.
reaction, inflammation and fibrosis in both DDC-induced and Mdr2- Next, we compared the diagnostic performances between Px, LSM,
/- mice through bounding directly to the PPARα protein to improve APRI, and FIB-4. Finally, we explored the relationships between
the stability of the PPARα protein and activate PPARa. Amygdalin not glycosyltransferase gene and liver fibrosis with RNA-transcriptome
only alleviated inflammation and hepatic fibrosis in CCl4-induced liver sequencing.
fibrosis mice, but also ameliorated inflammation, lipid deposition, and Result: Results We included 622 CHB participants: male-
hepatic fibrosis in a metabolic dysfunction-associated steatohepatitis dominated(69.6%); median age 42.0(IQR 34.0-50.0); 287 with
(MASH) mouse model induced by high fat and high sugar diet, and normal ALT; 73.0% with significant fibrosis. P5(NA2), P8(NA3),
its mechanism is related to the inhibition of CDK9 signaling pathway. and P10(NA4) were opposite to the degree of fibrosis, while other
Interestingly, we have identified a novel active ingredient from cultured profiles(except for P0[NGA2]) increased with the degree of fibrosis.
mycelia of C.sinensis, named CO2, with potent anti-hepatic fibrosis Seven profiles(P1[NGA2F], P2[NGA2FB], P3[NG1A2F], P4[NG1A2F],
and anti-MASH effects by using the method of LC/GC-MS combined P7[NA2FB], P8[NA3], and P9[NA3Fb]) were selected into Px score.
with activity oriented component separation. Further research Px score was associated with an increased risk of significant fibrosis
demonstrated that CO2 inhibited macrophages polarization to M1 (for per Px score increase, the risk of significant fibrosis was increased
type and inflammation by suppressing cGAS/Sting signaling, thereby by 3.54 times(OR=4.54 [2.63-7.82]) in the fully-adjusted generalized
alleviating liver fibrosis in both CCl4- and DMN-induced mice. linear model. P for trend was <0.001. The diagnostic performance
Conclusion: Sal B, amygdalin, Sin A and C02 are the main ingredients of the Px score was superior to others. Glycosyltransferase
of FZHY against liver fibrosis through protecting hepatocyte from genes were overexpressed in liver fibrosis, and glycosylation and
damage, anti-hepatic sinusoidal endothelial cell injury, inhibition glycosyltransferase-related pathways were significantly enriched.
of inflammatory response and activation of hepatic stellate cells Conclusion: Conclusions Serum N-glycan markers were positively
separately. In addition, ECM1, CDK9, PPARα and cGAS/Sting are the correlated with liver fibrosis. Px score had good performance in
key targets of these ingredients. distinguishing significant fibrosis.
Table and Figure:Figure 1.Figure 1 The value of 12 N-glycan peaks
in different liver fibrosis stage. (A) representative N-glycan peaks
PP0776
of different liver fibrosis stages; (B) structure of 12 N-glycan peaks;
Metabolomics in 28-day prognosis of acute-on-chronic liver failure (C) N-glycan profiles abundances between different liver fibrosis
Ying Xiao1, Yan Liu1, Caiyan Zhao1, Yadng Wang1 stages. Fibrosis stages were evaluated by Ishak scoring system, and
1
Hebei Medical University Third Hospital significant fibrosis was defined as F ≥ 3. The data in figure C was
Background: Liver failure is a severe liver injury caused by many represented as the median (interquartile range), and student t-test
factors, which leads to severe dysfunction or decompensation of (Gaussian distribution) or Kruskal-Wallis H-test (skewed distribution)
liver synthesis, detoxification, metabolism and biotransformation. We were used to detect the differences among fibrosis stage.
aimed to analyze the differences in metabolite expression between Figure 2.Figure 5 Relationship between glycosyltransferases and liver
patients with acute-on-chronic liver failure (ACLF) at different 28-day fibrosis. (A) Volcano plot of genes differentially expressed between
prognoses. significant fibrosis and mild fibrosis in the GSE84044 dataset. Blue
Method: This noninterventional observation case-control study nodes represent down-regulation in significant fibrosis; red nodes
involved 58 patients with ACLF in a Chinese hospital between July represent up-regulation; and gray nodes represent no significant
2023 and March 2024. Serum specimens were analyzed using difference between them. (B) Intersection of differentially expressed
targeted metabolomics. The basic features of groups were compared, genes (DEGs) in the GSE84044 and glycosyltransferases-related
while the possible risk factors afecting the 28-d mortality rate of ACLF genes (C) Expression of 3 representative glycosyltransferase genes
were analyzed. (CHST4, SLC51B, and TUSC3) in different fibrosis stage; (D) GO
Result: The levels of Hb, ALB, ALT, AST, TBil and the model for end- enrichment analysis of glycosyltransferases-related DEGs; (E) KEGG
stage liver disease (MELD) score in the artificial extracorporeal liver enrichment analysis of glycosyltransferases-related DEGs.
support group (n = 23) were higher than those in the medical treatment
group (n = 35). Fifteen significant differentially accumulated metabolites PP0778
(DAMs) between different 28-d prognosis groups were screened by
univariate and multivariate analysis. Multivariate logistic regression
analysis revealed that the predictor afecting patient outcomes were Ile,
Prevention of hepatic encephalopathy following transjugular regression analyses ultimately identified age and liver function as the
intrahepatic portosystemic: lactulose plus rifaximin vs. lactulose influencing factors of CBT1 in the cirrhotic population. The ROC AUC
monoprophylaxis for CBT1, using PHES as the gold standard, was 0.799 (0.724, 0.873)
Shu Du Mei1 (Figure 2A and Table 1). In terms of convenience, CBT1 (9.55±0.80)
1
West China Hospital of Sichuan University also significantly outperformed PHES (8.81±1.57).
Conclusion: Compared to PHES, CBT1 demonstrates superior
Background: Hepatic encephalopathy (HE) is the most common
diagnostic efficacy, with good sensitivity and specificity, making it
complication after transjugular intrahepatic portosystemic shunt (TIPS).
a rapid, effective, simple-to-score, highly patient-acceptable, and
Rifaximin and lactulose are effective in preventing HE in patients with
clinically feasible new method for diagnosing CHE, which warrants
cirrhosis and TIPS. There is a lack of evidence concerning whether
further application in clinical practice.
a combination of rifaximin and lactulose is better than lactulose
Table and Figure:Figure 1.Figure 1. CBT1 population differences, ROC
monoprophylaxis. The present aims to compare the efficacy of
curve and convenience differences
lactulose plus rifaximin with lactulose monoprophylaxis in preventing
Figure 2.Table1. ROC characteristics
post-TIPS HE.
Method: Consecutive patients with cirrhosis who underwent TIPS
successfully from May 2019 to May 2024 in our center were included PP0780
in the study. Patients were divided into group A and group B (A: Analysis of Risk Factors for Portal Thrombosis after Endoscopic
lactulose monoprophylaxis; B: lactulose plus rifaximin). Propensity Treatment in Cirrhotic Patients with Severe Gastroesophageal
score matching (PSM) was performed to control potential confounding Varices
variables at baseline, and the Child-Pugh score, MELD score, PT and Jiamei Zhou1, Tao HAN2, Huiling Xiang3, Feng Zhang1, Huizhe Wang1,
age were defined as covariates. Patients were prescribed rifaximin 600 Baiguo Xu3
mg two times daily and lactulose 15 ml three times daily (the starting 1
Department of Gastroenterology, Baoding Second Central
dose) or lactulose 15 ml three times daily for six months after TIPS Hospital, Hebei Zhuozhou, China, 2Department of Hepatology and
placement. Gastroenterology, Tianjin Union Medical Center affiliated to Nankai
Result: 608 patients were included in this study, 527 patients treated University, Tianjin, China, 3Department of Gastroenterology ,Tianjin
with lactulose, and 81 patients treated with lactulose plus rifaximin. Third Central Hospital, Tianjin, China
After PSM, there were 74 fuzzy-matched patients in group A and group
Background: Endoscopic therapy is commonly used to treat patients
B. The Child-Pugh score was 10.5, and MELD score was 7.0 in group
with cirrhosis complicated with severe gastroesophageal varices or
A versus 9.8 and 7.0, respectively, in group B (p=0.943; p=1.000).
ruptured bleeding. At present, there are few studies on the predictors
The median follow-up was 22 (12-35) and 7 (6-9) months in groups
of PVT during treatment. This study was conducted to investigate the
A and B, respectively. The 1-year cumulative rate of overt HE was
risk factors for portal vein thrombosis (PVT) in cirrhotic patients with
comparable between the two groups (22.0% vs. 22.4%, Grays test,
severe gastroesophageal varices within one year after endoscopic
p=0.537). 58.0% and 64.2% of patients had only one episode of overt
treatment and the influence of PVT on the long-term prognosis for
HE in groups A and B. No statistically significant difference was found
cirrhotic patients.
in the 1-year cumulative rate of transplant-free survival (80.6% vs.
Method: The clinical data from 755 patients with severe
90.0%, Grays test, p=0.269).
gastroesophageal varices or rupture bleeding in cirrhotic patients
Conclusion: Our data show that adding rifaximin to lactulose
without PVT treated under endoscope for the first time were
monoprophylaxis is not effective in the prevention of overt HE following
retrospectively analyzed in Tianjin Third Central Hospital from January
TIPS.
2014 to December 2017. The occurrence of PVT within one year was
observed, and the influencing factors of PVT were analyzed by Binary
PP0779 Logistic Regression. The survival analysis was conducted.
Chopsticks Challenge: Innovating CHE Diagnosis with the Result: 43 patients developed PVT among the 755 patients within one
1-Minute Clamping Soybean Test year and the incidence was 5.70%. Esophagogastric variceal bleeding
Yilong Liu1, Xiaolin Li1, Weifen Xie1, Pingfang Hu1 and serum albumin were independent risk factors for the occurrence
of PVT (P<0.05). The number of liver disease-related deaths in the PVT
1
Department of Gastroenterology, Changzheng Hospital, Naval
Medical University, 415 Fengyang Road, Shanghai group was higher than that in the non-PVT group and the cumulative
survival rate in the PVT group was lower than that in the non-PVT
Background: Covert hepatic encephalopathy (CHE) is often seen in group, all with statistical significance (P<0.05).
patients with cirrhosis, affecting 20-80% globally. It greatly impacts Conclusion: A history of esophagogastric variceal bleeding and
quality of life, work, and driving, so early diagnosis is crucial. In China, serum albumin are independent risk factors for PVT within one
PHES is used for CHE diagnosis but is limited by its complexity and year after endoscopic treatment in cirrhotic patients with severe
poor patient compliance. There’s a need for a better screening method. gastroesophageal varices and PVT has a negative impact on the long-
Chopsticks use involves fine motor skills and cognition, which could term prognosis of cirrhotic patients.
indicate CHE. The 1-minute clamping soybean test (CBT1) is a new
test based on chopstick use, tested in healthy and cirrhotic patients to
establish norms and assess its potential for diagnosing CHE, offering PP0781
a new clinical approach. LSM decreased in on-treatment CHB patients led to remarkably
Method: This study employed a two-center, cross-sectional design, high false negative rates of advanced liver fibrosis or cirrhosis
collecting data from all individuals who underwent CBT1 testing from evaluated by pre-treatment thresholds
September 2023 to June 2024. A PHES score of less than -4 was Xiaoning Wu1, Jialing Zhou1, Yameng Sun1, Bingqiong Wang2, Shuyan
used as the diagnostic criterion for CHE. We constructed the Receiver Chen1, Chenghai Liu3, Hongxin Piao4, Huiguo DING5, Shuai Xia1,
Operating Characteristic Curve (ROC) and calculated the ROC Area Tongtong Meng2, Luqi Tang1, Xiaojuan Ou1, Hong You1, Jidong Jia1
Under the Curve (AUC) to evaluate the diagnostic capability of CBT1. 1
Beijing Friendship Hospital, Capital Medical University, 2Beijing
Result: A total of 144 healthy individuals and 113 patients with Friendship Hospital, Capitial Medical University, 3Shuguang Hospital,
cirrhosis were included in the study. The range of CBT1 scores in the Shanghai University of Traditional Chinese Medicine, 4Affiliated
normal population was 30.48±4.38. The CBT1 scores in the normal Hospital of Yanbian University, 5Beijing Youan Hospital, Capitial
population were influenced by higher levels of education (more than Medical University
12 years of schooling) and older age (50 years or above), but not by Background: Liver stiffness measurement (LSM) is the most
gender. Statistical differences in CBT1 scores were observed among extensively accepted non-invasive method to evaluate liver fibrosis.
healthy individuals, those with CHE (21.26±5.37), and those without LSM decreases after CHB patients initiate antiviral treatment. However,
CHE (27.79±5.41) (Figure 1A). Univariate and multivariate linear in on-treatment CHB patients, the reason for and effect of the LSM
decrease in liver fibrosis evaluation are unknown. The cut-off values at the maximum Youden index were determined
Method: Adult CHB patients who had liver biopsy and LSM on the to be 95.5 for PLT and 56.25 for SA. For practical application, cut-off
same day before and during antiviral treatment were enrolled. LSM values of 100 for PLT and 55 for SA were selected. The corresponding
was performed with FibroScan (Echosens, Paris, France) or Fibrotouch sensitivity, specificity, and false negative rates for predicting HRV were
(Wuxi Hisky Medical Technology Co., Ltd., Wuxi, China). Liver fibrosis 75.0%, 76.5%, and 25.0% for PLT, and 95.5%, 70.6%, and 4.5% for
regression was defined as the Ishak score decreased by at least 1 SA, respectively.
point, and inflammation improvement was defined as the HAI score Conclusion: This study gathering a total of 78 patients with PSVD
decreased by at least 1 point. LSM decrease was defined as a showed that 100 × 109/L or SA ≥ 55 cm2 identifies patients with PSVD
reduction of ≥ 30% of pre-treatment. The Spearman correlation was and portal hypertension with a probability of HRV < 10%, in whom
used to analyze the correlation of LSM decrease with fibrosis reversion screening endoscopy can be spared.
or inflammation improvement. The sensitivity, specificity, and accuracy Table and Figure:Figure 1.Efcacy of PLT and SA in predicting HRV
were used to describe the performance.
Result: In our study, 264 patients were enrolled. About 46.6%
PP0783
(123/264) of patients had liver fibrosis reversion, and 54.5% (144/264)
had inflammation improvement. LSM decreased significantly during Meta-analysis: Global Prevalence of Bacterial Infections in
antiviral treatment (P<0.001) with a median (Q1-Q3) of -3.9 (-0.9, -8.6) Patients with Liver Cirrhosis
kPa. There were 56.4% (149/264) of patients had LSM decreased Yuxin Tian1, Baiyun Wu1, Qi An1, Yinping Wu1, Jing Zuo1, Yuchen
≥30%. Fan1
In the fibrosis reversion group, LSM decreased from 12.0 (8.6, 17.6) 1
Department of Hepatology, Qilu Hospital of Shandong University
kPa to 6.8 (5.5, 8.8) kPa (P<0.001), in the non-reversion group LSM Background: Bacterial infections (BIs) are common and severe
decreased from 10.6 (7.3, 17.6) kPa to 6.9 (5.6, 9.8) kPa (P<0.001), complications in patients with liver cirrhosis. Here, we aimed to
there was no significant difference between groups (P=0.278). In the evaluate the global prevalence of BIs in patients with liver cirrhosis.
inflammation improvement group, LSM decreased from 12.7 (9.4, 18.2) Method: We systematically searched PubMed, EMBASE, Web of
kPa to 7.2 (5.6, 9.3) kPa (P<0.001); in the non-improvement group, LSM Science, and the Cochrane Library for eligible studies published
decreased from 8.9 (7.1, 14.5) kPa to 6.7 (5.4, 9.4) kPa (P<0.001), LSM without language restrictions until 3 December 2024. The main
decreased more significantly in patients with inflammation improvement outcome was defined as the prevalence of BIs in patients with liver
(P<0.001). No significant interaction effects were observed between cirrhosis.
fibrosis reversion and inflammation improvement. Result: Fifty-five studies including 808,901 patients with cirrhosis were
As evaluated by the previous representative diagnostic criteria such as analysed. The pooled prevalence of BIs (29 studies) was 37.2%, with
proposed by Marcellin et al., the false negative rates (FNR) were 37.9%, a 95% CI of 30.7 to 44.2. The prevalence of E. coli, Streptococcus
49.5%, and 80.0%, and the diagnostic accuracy rates were 65.6%, spp., Klebsiella spp., Staphylococcus spp., Pseudomonas spp.,
46.8%, and 28.9% in patients with≥F2, ≥F3, and F4 respectively. Using Enterococcus spp., Acinetobacter spp., and Proteus spp. were 3.8%
the EASL_ALEH criteria classified with ALT level, the false negative (2.5–5.2), 1.5% (0.8–2.6), 1.3% (0.9–1.8), 2.0% (1.0–4.0), 0.3% (0.2–
rates were 36.8% and 60.5% in patients with normal ALT and elevated 0.6), 1.3% (0.6–2.8), 0.9% (0.4–1.8) and 0.6% (0.2–1.4), respectively
ALT, and the diagnostic accuracy was 75.7% and 69.4%. (I2 > 90%). The pooled prevalence of multidrug-resistant (MDR)
Conclusion: LSM decrease in on-treatment CHB patients is a bacteria was 6.8% (95% CI: 4.0–11.3). The most common BI sites
comprehensive response to both fibrosis reversion and/or inflammation were the gastrointestinal tract, followed by ascites, the urinary tract,
improvement. Remarkably high false negative rates of advanced liver the respiratory tract, skin and soft tissue. The prevalence of BIs varied
fibrosis or cirrhosis evaluated by pre-treatment thresholds demand considerably across geographic regions, with the greatest prevalence
cut-off updates. in Europe. The highest prevalence of BIs was observed in patients with
acute-on-chronic liver failure, with a prevalence of 50.4%.
PP0782 Conclusion: BIs are highly prevalent in patients with liver cirrhosis,
especially in the population with acute-on-chronic liver failure.
Platelets Count and Spleen Area for ruling out High Risk Varices in
Table and Figure:Figure 1.Global prevalence of Bis, which varies
patients with Porto-Sinusoidal Vascular Disease
across different regions. The map uses various colours to indicate
Li Li Zhao1, Ping Han, Yuanyuan Zhao, Jie Liu, Jia Li the prevalence rates in different countries. Significant variations in the
1
1.Department of Gastroenterology and Hepatology, Tianjin Second prevalence of BIs were identified among different countries
People’s Hospital, Tianjin, China Figure 2.Forest plot demonstrating the pooled prevalence of BIs in
Background: The guidelines recommend that all patients with liver patients with cirrhosis by subgroup: Clinical status
cirrhosis should undergo esophagogastroduodenoscopy (EGD) to
determine whether there are high risk varices (HRV) requiring primary
PP0784
prevention of bleeding. Conversely, screening EGD is required in all
patients with Porto-Sinusoidal Vascular Disease (PSVD). The Baveno Changing spectrum and disparities of etiology of liver cirrhosis in
VII consensus proposed that patients with compensated liver cirrhosis male and female patients in Tianjin, China
could safely avoid esophagogastroduodenoscopy (EGD) when Li Li Zhao1, Ping Han, Yuanyuan Zhao, Jie Liu, Jia Li
platelets count (PLT) > 150 × 109/L and liver stiffness (LS) < 20 kPa 1
1.Department of Gastroenterology and Hepatology, Tianjin Second
(B7C) for low HRV missed rate. But B7C is not apply to patients with People’s Hospital, Tianjin, China
PSVD. This study aimed to develop a new criteria for ruling out HRV in Background: Liver cirrhosis remains a major health concern globally,
patients with PSVD. but its etiology evolve with time. However, the changing pattern in
Method: We conducted a retrospective analysis of 78 patients with etiology for patients with cirrhosis are not fully elucidated. In particular,
PSVD, of whom 56% (44/78) were identified as having HRV. Univariate spectral changes and etiological differences in male and female
logistic regression was used to evaluate whether PLT, spleen thickness, cirrhosis have not been elucidated. Herein, our aim was to characterize
spleen diameter, and spleen area (SA) are risk factors for HRV. For risk the temporal trend of the etiological and analyze the clinical
factors significantly associated with HRV in the univariate analysis, we characterize of patients with cirrhosis and to explore the etiology and
constructed ROC curves, calculated the area under the curve (AUC), changes of cirrhosis in male and female patients in Tianjin.
identified cut-off values using the Youden index, and assessed the Method: Clinical profiles of patients with cirrhosis who were
diagnostic performance of these cut-off values for detecting HRV. hospitalized for the first time in 9 hospitals in Tianjin from January 2016
Result: Univariate regression analysis revealed that PLT (P<0.001), and December 2023 were retrospectively collected and analyzed. The
spleen length (P < 0.001), spleen width (P < 0.001), and SA (P < 0.001) spectral changes and etiological differences of cirrhosis in the overall
are independent risk factors for HRV. ROC curves were generated for population, male and female were calculated.
PLT and SA (Figure 1), with AUCs of 0.756 and 0.834, respectively.
Result: A total of 5018 cirrhotic patients were included. The Which Non-Invasive Test Is More Useful in the Assessment of
predominant cause was hepatitis B virus (HBV), followed by hepatitis C Liver Fibrosis in Patients Receiving Methotrexate?
virus (HCV), autoimmune-related and Alcohol-related increases yearly. Taylan METİN1, Seydi ERÖZCAN2, Orhan ZENGİN3, Sezgin
From 2016 to 2023, in the overall proportion of HBV‐related cirrhosis BARUTÇU1, Ayhan BALKAN1, Mehmet Ali ŞAHAN1, Mehmet
decreased from 72.56% to 28.11%. Meanwhile, the proportions of KARAÇALI2, Murat Taner GÜLŞEN1
autoimmune-related cirrhosis and Alcohol-‐related cirrhosis increased 1
Gaziantep University School of Medicine, Department of
from 3.17% to 9.36 % and 7.12% to 12.02%, respectively. In male Gastroenterology, 2Gaziantep University School of Medicine,
patients, HBV‐related cirrhosis decreased from 79.50% to 44.00%, Department of Internal Medicine, 3Gaziantep University School of
HCV‐related cirrhosis is the second cause of cirrhosis. Alcohol-related Medicine, Department of Rheumatology
cirrhosis increased from 10.88% to 14.14 %, and autoimmune-related
Background: Methotrexate (MTX) has been used for many years in the
cirrhosis increased from 1.26% to 5.14 %. But in female patients,
treatment of many rheumatologic diseases. Although it is well tolerated
HBV‐related cirrhosis decreased from 79.50% to 44.00%, HCV‐related
at the beginning of treatment, liver fibrosis may develop with long-term
cirrhosis decreased from 25.00% to 16.63%, and autoimmune-related
use. For detection of liver fibrosis, liver biopsy is invasive and can lead,
cirrhosis increased from 6.43% to 10.25 %.
even if rarely, to severe complications. Non-invasive methods such as
Conclusion: HBV remained a common cause of liver cirrhosis but
transient elastography (TE; Fibroscan), Fibrosis-4 (FIB-4) , aspartate
gradually decreased. The etiological changes of liver cirrhosis in male
aminotransferase (AST)/platelet ratio index (APRI) and Zeugma score
and female patients are differences. The main cause of cirrhosis in male
((Gama glutamyl transferase×Globulin×100) / ( Albumin×Platelet)) are
was HBV, but the Alcohol-related cirrhosis increases. The difference is
used safely in the detection of hepatic fibrosis.
that autoimmune-related cirrhosis increases in female.
Method: Fifty patients (43 with rheumatoid arthritis (RA), 7 with
Table and Figure:Figure 1.Changing spectrum and disparities of
psoriatic arthritis (PsA)) receiving MTX and 50 healthy adults were
etiology of liver cirrhosis from 2016 to 2023
included. Viral hepatitis, ethanol use, non-alcoholic steatohepatitis and
other hepatic pathologies were excluded. Evaluation of fibrosis by TE
PP0785 method, and the cutoff value of 7.1 kPa (kilopascal) was considered
A study of clinical characteristics in 43 patients with porto- abnormal. TE was performed by a single experienced operator.
sinusoidal vascular disease Result: Liver stiffness and steatosis value in TE were found to be
significantly higher in the group receiving MTX compared to the healthy
Chengjian Wu1, Yi Shen1, Xuefeng Luo1
group (p:0.001). When the group receiving MTX was divided into two
1
Department of Gastroenterology and Hepatology, Laboratory of
groups as kPa ≥ 7.1 and below, it was determined that the cumulative
Gastrointestinal Cancer and Liver Disease, West China Hospital,
dose of MTX and duration of drug use were significantly higher in the
Sichuan University, Chengdu, Sichuan Province, China
group with high fibrosis (p:0.009). When the patients were divided
Background: Since the introduction of the term ‘Porto-sinusoidal into three groups according to the cumulative MTX dose: 0-1499 mg,
vascular disease’ (PSVD) in 2019, understanding of this disease has 1500-4999 mg, 5000 mg and above, the kPa value measured by TE
been limited. It has been reported that PSVD patients have a higher risk was found to be significantly higher in patients receiving 5000 mg and
of developing portal vein thrombosis (PVT), but it is unclear whether above MTX compared to other doses. (p:0.036). In patients receiving
PVT affects the progression of PSVD. MTX, the APRI, FIB-4 and Zeugma score after treatment was found
Method: This study retrospectively included patients diagnosed with to be significantly higher than before treatment (p:0,001) (p:0,013)
PSVD at West China Hospital, Sichuan University, from 2019 to 2024. (p:0,001). When patients receiving MTX were compared with healthy
All patients were confirmed not to have liver cirrhosis through liver individuals, it was determined that the APRI, FIB-4 and Zeugma score
biopsy. Patient medical records were obtained through the electronic score was significantly higher in patients receiving MTX than in healthy
medical record system, collecting basic information, laboratory individuals (p: 0,001) (p:0,001) (p:0,001).
tests, imaging examinations, gastroenterological endoscopy, and Conclusion: There are two types of noninvasive methods in the
pathological examination data, as well as treatment and prognosis evaluation of fibrosis. The first is the imaging method in which liver
information. Patients were divided into two groups based on the stiffness is evaluated. This includes transient elastography (FibroScan).
presence or absence of PVT: (1) PVT group, (2) non-PVT group, and TE can be used as an effective method to detect liver fibrosis due to
then the clinical characteristics of the two groups were compared. MTX use. The second is the serological method in which various serum
Result: A total of 43 PSVD patients were included in this study, with biomarkers and formulas obtained with biochemical parameters are
26 males (60.5%) and 17 females (39.5%), and the average age was used. Some of the methods used are APRI, FIB-4 and Zeugma score.
46±17 years. Among them, 11 (25.6%) patients had PVT. Comparing The APRI, FIB-4 and Zeugma score are novel noninvasive test, a useful
the two groups of patients with and without PVT, we found no statistically and easy tool to evaluate liver fibrosis in patients using MTX. Finally,
significant differences in age, total bilirubin, transaminase, alkaline non-invasive markers with comparable ability to predict liver-related
phosphatase, and γ-glutamyl transpeptidase levels. Additionally, outcomes may be used instead of liver biopsy in patients at high risk
there were no significant differences in the manifestations of portal of complications.
hypertension or pathological manifestations between the two groups.
Patients with PVT tended to have longer spleen lengths (16.08±3.97cm,
14.16±2.63cm, P=0.097), and pathological examinations found a PP0787
higher proportion of non-regional sinusoidal dilation (72.7%, 40.6%, Case Report of Acquired Hepatocerebral Degeneration: An
P=0.088). Interestingly, we found that the proportion of males in the Underrecognized Complication of Advanced Liver Disease
PVT group was significantly higher (90.9%, 50%, P=0.029), and the Hasmik Ghazinyan1, Aram Mirijanyan1, Lusine Navoyan2, Ashkhen
albumin levels in this group of patients were lower than those without Keryan1, Tatevik Shahinyan3
PVT (32.3±12.2g/L, 40.4±6.9g/L, P=0.011), while the INR levels 1
Yerevan MSC, 2Independent Clinical Researcher , 3LLC Ecosense
were higher (1.30±0.16, 1.16±0.15, P=0.020). A total of 13 patients
Background/Aims: Acquired hepatocerebral degeneration (AHD),
underwent transjugular intrahepatic portosystemic shunt surgery, but
also known as “Parkinsonism in cirrhosis” is an underdiagnosed
there was no difference in the proportion of patients between the two
neurological complication of advanced liver disease, particularly in
groups, with 5 (45.5%) in the PVT group and 8 (25%) in the non-PVT
patients with portosystemic shunts. The pathogenesis of AHD remains
group, P=0.262. There have been no deaths in either group to date.
poorly understood, but it is believed to result from chronic exposure
Conclusion: We found that PSVD patients with PVT are predominantly
of the brain to neurotoxic substances, especially manganese,
male, and these patients have lower serum albumin levels and higher
bypassing the liver. Although historically considered irreversible,
INR levels, suggesting a potentially more severe condition.
patients with AHD can benefit from liver transplantation. This report
aims to emphasize the importance of recognizing AHD and proposes
PP0786 a diagnostic approach.
Case presentation: A 63-year-old woman with HBV-associated Liver Cirrhosis, State Key Lab of Digestive Health, National Clinical
cirrhosis and a history of two sessions of esophageal varices ligation Research Center of Digestive Diseases, Beijing, China
presented with mild cognitive impairment, including attention and Background: Blood-based biomarkers are commonly used in the
psychomotor speed deficits, along with hyperkinetic movement diagnosis and monitoring of HBV-related cirrhosis. Most of these
disorder (i.e., involuntary movements involving the face, neck, trunk biomarkers may change after initiation of antiviral therapy in chronic
and limbs). Abdominal ultrasound revealed signs of liver cirrhosis, hepatitis B (CHB) patients. However, the diagnostic performance
portal hypertension, and ascites. Considering the possibility of ADH in change of these biomarkers before and during antiviral treatment is
the context of advanced liver disease, brain MRI was performed, which unknown.
demonstrated T1 hyperintensity in the globus pallidus and substantia Method: Adult CHB patients who had liver biopsy and corresponding
nigra, indicative of manganese accumulation due to liver dysfunction, clinical data of PLT, liver function test (ALT, AST, ALB), and coagulation
consistent with AHD. These imaging findings, alongside the patient’s test of INR before or during antiviral treatment were enrolled. Liver
advanced HBV-associated cirrhosis, supported the diagnosis of AHD. cirrhosis was defined as stage 5/6 by the Ishak scoring system.
Conclusion: The liver-brain relationship is well-established, with hepatic Logistic regression was used to identify diagnostic biomarkers and
encephalopathy being the most recognized neurological manifestation AUROC was used to describe the performance of diagnosing liver
of chronic liver disease. However, AHD is underdiagnosed, and early cirrhosis.
diagnosis, including brain MRI in patients with suggestive symptoms, Result: A total of 960 patients were enrolled in our study, 268 patients
is crucial to provide potential treatment opportunities and improving were untreated and 692 patients were on-treatment. In untreated
patient outcomes. Additionally, prospective follow-up will offer valuable patients, 8.2% (22/268) were diagnosed with liver cirrhosis. About
insights into disease progression and enable the development of more 70.1% (188/268) of the untreated patients were male with a median
effective therapeutic strategies age was 38.0 (30.0, 46.8). In on-treatment patients, 33.2% (230/692)
were diagnosed with liver cirrhosis. About 80.3% (556/692) of the on-
PP0788 treatment patients were male with a median age was 46.0 (38.0, 52.0)
and the median duration of antiviral treatment was 13.0 (11.0, 30.0)
Porto-Sinusoidal Vascular Disease: A group of portal hypertension
months.
Different from Liver Cirrhosis
In the untreated patients, univariate logistic regression analysis
Jie Liu1, Lili Zhao1, Yuying Jin2, Yuhang Yu2, Jia Li1
showed that PLT was negatively associated with liver cirrhosis having
1
Tianjin Second People’s Hospital, 2Clinical School of the Second a coefficient of -0.015 (p=0.001); ALT, AST, ALB, and INR were not
People’s Hospital, Tianjin Medical University significantly associated with liver cirrhosis. The AUROC of PLT
Background: Porto-sinusoidal vascular disease (PSVD) is was 0.725 (95% CI: 0.667,0.777) with a cut-off of 155 ×109/L . The
characterized by the absence of cirrhotic sensitivity and specificity were 81.8% and 60.6% respectively. The
modification of the liver parenchyma but can manifest as portal positive predictive value (PPV) was 13.5% (95% CI:11.0%, 16.6%), the
hypertension (PH). PSVD is often misdiagnosed as cirrhosis negative predictive value (NPV) was 97.4% (95% CI: 93.8%, 98.9%).
emphasizing the need to improve PSVD diagnosis strategies.This In the on-treatment patients, univariate logistic regression analysis
study aimed to compare the clinical and biochemical features between showed that PLT and INR were significantly associated with liver
the PSVD and that of liver cirrhosis to evaluate the accuracy diagnostic cirrhosis. In multivariate logistic regression, PLT and INR had
model to discriminate PSVD from cirrhosis in patients with signs of PH. coefficients of -0.013 (p<0.001) and 2.737 (p=0.004) respectively.
Method: Retrospective case-control study of patients with PSVD The AUROC of PLT combined with INR was 0.730 (0.695, 0.762) while
matched cirrhosis patients in a 1:3 ratio by age and sex. A logistic the AUROC of PLT alone was 0.724 (0.689, 0.757) , no significant
regression model was used to study factors predicting risk of PSVD. difference between them. The PLT cut-off for diagnosis of liver cirrhosis
The area under the receiver operating characteristic curve(AUROC) was 131×109/L with a sensitivity of 64.3% and a specificity of 70.1%.
assess the diagnostic performance The PPV was 33.2% (29.7%, 36.9%) and the PPV was 79.8% (76.7%,
Result: In total, 55 PSVD patients and 165 cirrhosis patients with PH 82.6%).
were included. Liver cirrhosis patients showed higher LSM levels Conclusion: PLT was an independent blood biomarker for diagnosis
(15.4 (8.8, 24.6) vs. 8.75 (6.675,13.825) , p < 0.001 ) than the PSVD of liver cirrhosis both in untreated and on-treatment patients with CHB;
patients. PSVD patients showed longer spleen size and lower platelet the on-treatment cut-off is lower than in the untreated patients.
count level (136 (120.25,156.25) vs. 120(103.5,142); 100 (60,127)
vs. 119(79.5,167.5) ,both p < 0.001) but Showed better liver reserve
PP0790
function. 90.9% of the patients with PSVD and signs of PH had LSM
<20 kPa.The presence or absence of characteristic pathological Diagnostic value of Liver biopsy in Evaluation of Liver Disease- 50
manifestations and their number were not correlated with PH (P Case Study
= 0.252) .The AUC of LSM, PLT, and combined model LSM-PLT for Abul Hayat Manik1, Faroque Ahmed1
predict the PSVD were respectively 0.731, 0.638, and 0.805. 1
Dhaka Medical College Hospital
Conclusion: PSVD patients with PH are prone to misdiagnosis, and Background: Liver biopsy is a well-known method for the diagnosis
the characteristic liver pathology can only be used for diagnosis, and evaluation of chronic diffuse liver diseases, especially among
independent of portal hypertension. Baveno VI criteria should not patients with abnormal liver function test or portal hypertension without
be used in patients with PSVD.For patients with portal hypertension, radiological evidence of cirrhosis.
LSM and platelet values should be combined for comprehensive Method: It was a cross sectional observational study among patients
identification. presented in hepatology department of DMCH with chronic diffuse
Table and Figure:Figure 1.Patient characteristics liver disease with unknown etiology having portal hypertension but
Figure 2.Predict the area under ROC curve of different models of PSVD no radiological evidence of cirrhosis. Total 50 patients were enrolled
and undergone liver biopsy (n=50, Male 22, Female 28). Then
PP0789 determine whether histological diagnosis lead to a specific diagnosis
and prebiopsy laboratory variables and clinical features correlate the
PLT was an independent blood biomarker for diagnosis of HBV-
histological etiology.
related cirrhosis before and during antiviral therapy
Result: Liver biopsy lead to confirmatory diagnosis in 90% patients.
Yizhou Liu1, Jialing Zhou1, Yameng Sun1, Bingqiong Wang1, Shuyan
Histopathological features of autoimmune hepatitis were in 16 cases,
Chen1, Tongtong Meng1, Qiushuang Guan1, Tongtong Wang1, Shuai
steatohepatitis in 10 cases, autoimmune hepatitis-primary biliary
Xia1, Luqi Tang1, Qiannan Jiang1, Xiaojuan Ou1, Hong You1, Xiaoning
cirrhosis overlap syndrome 3 cases, porto-sinusoidal vascular disease
Wu1
in 9 cases, non cirrhotic portal hypertension 7 cases, 2 cases are
1
Liver Research Center, Beijing Friendship Hospital, Capital Medical chronic hepatitis, 2 cases are inconclusive and 1 case found cavernous
University, Beijing Key Laboratory of Translational Medicine on
hemangioma. Method: Using a retrospective study, patient cases diagnosed with
Conclusion: Liver biopsy is safe and valuable for diagnosis hepatitis B cirrhosis at our hospital from January 2010 to December
hepatopathy of unknown etiology. Porto-sinusoidal vascular disease 2021 were collected. Eligible patients received antiviral therapy, and
should be kept in mind when dealing with non cirrhotic portal based on the use of traditional Chinese medicine, they were divided
hypertension. Clinical features may be helpful for suggesting the into a combination therapy group and a western medicine-only group
cause, however liver biopsy and histological examination is essential to compare the impact of different treatments on prognosis.
for disease diagnosis and prognosis assessment. Result: A total of 42,795 hepatitis B cirrhosis patients were selected
from our hospital’s database, with 35,317 inpatients and 7,478
PP0791 outpatients. After propensity score matching, 94 patients were
included in both the combined TCM and Western medicine group and
One case report of the upper gastrointestinal bleeding as the first the Western medicine-only group, with no significant differences in
manifestation of polycythemia vera gender, age, or treatment time.
Xiwei Yuan1, Lei Liu1, Qianqian Li1, Qing Ye1 Liver cancer incidence: 8/94 in the TCM + Western medicine group
1
Tianjin Third Central Hospital and 25/94 in the Western medicine-only group (P=0.001). AFP before
The patient, male, 73 years old, was admitted to hospital due to and after treatment: TCM + Western medicine group P=0.022, Western
“intermittent black stool for more than 1 month and hematemesis for medicine-only group P=0.078. Survival analysis showed better survival
2 weeks”. History of hypertension over 20 years; Denied chronic liver in the TCM + Western medicine group (P=0.004).
disease history. Physical examination: normal face, liver palm (-), spider Liver fibrosis: Significant differences in FIB-4/APRI and E in the TCM +
naevi (-), skin sclera without yellow staining, eyelid conjunctiva without Western medicine group (P<0.01), and in E in the Western medicine-
pallor, cardiopulmonary examination without abnormality, abdomen only group (P=0.019). No significant differences between groups.
flat and soft, no tenderness and rebound pain, liver and spleen not Blood routine: PLT increased significantly in the TCM + Western
reached under the ribs, positive mobility dullness, and no edema medicine group (P=0.009), with HGB rising significantly (P<0.001). No
in both lower limbs. After admission, relevant laboratory tests were significant changes in the Western medicine-only group.
completed: liver and kidney function: ALB 33.2g/L, no other obvious Liver function: ALT, AST, and γ-GT decreased, ALB increased
abnormalities were found; Coagulation routine: PT-ses 22.9, PTA 37%, significantly in the TCM + Western medicine group (P<0.001). ALB
INR 2.04; Blood routine: WBC 17.55×109/L, N 82.2%, HGB 135g/L, showed no significant change in the Western medicine-only group.
PLT 456×109/L; PCT: <0.5ng/ml; CRP: 3.70ug/ml; Ascites examination: Significant differences in ALB, CHE between groups (P<0.05).
fluid leakage, no infection. Upper abdominal CT plain scan + enhanced Coagulation: Significant improvement in PT% and HS PT in the TCM +
scan: 1. Liver morphology is not regular; 2. Thrombosis in the portal Western medicine group (P<0.05), with no significant changes in the
vein and spleen vein, accompanied by spongy transformation of the Western medicine-only group.
portal vein, varicose veins in the deformed area of the splenic vein HBV markers and DNA: Both groups showed significant reductions
and around the stomach and spleen, considering the formation of (P<0.001), with greater reductions in the TCM + Western medicine
gastrorenal shunt; 3. Enlarged spleen 4. Ascites. After admission, he group (P<0.01).
was given comprehensive treatment measures such as portal pressure Conclusion: The combined TCM and Western Medicine group
reduction, hemostasis, acid inhibition, anti-infection, fluid rehydration, showed significant effects in increasing hemoglobin, serum albumin,
blood pressure control, enteral nutrition, diuresis and vitamin K1 to and cholinesterase levels compared to the Western Medicine-only
improve coagulation. Gastroscopy showed severe gastric variceal group, indicating that traditional Chinese medicine improves liver
rupture and bleeding. At the same time, gastric variceal tissue glue synthetic function. The combined TCM and Western Medicine group
and laurel alcohol combined sclerotherapy were given. also had a clear advantage in reducing liver cancer incidence,
Further improvement of the examination of thrombolysis showed that improving overall survival rate, and extending median survival time,
protein S, protein C and antithrombin III were decreased. Further suggesting that patients receiving TCM treatment have better survival
improvement of bone marrow biopsy showed that the possibility rates, with the difference becoming more pronounced as treatment
of bone marrow proliferation tumor was not excluded. Decreased duration increases.
erythropoietin; Genetic test showed JAK2/V617F positive. The Table and Figure:Figure 1.The median survival time of the two groups
diagnosis was polycythemia vera (PV). PV is a clonal chronic of patients.
myeloproliferative disease of hematopoietic stem cells. The onset Figure 2.Comparison of survival curves between the two groups
and slow progression of PV are panhemopenia, extramedullary (0 represents the Combined TCM and Western Medicine group, 1
hematopoietic, hepatosplenomegaly, hyperplenism and myelofibrosis. represents the Western Medicine Only group)
Bleeding and thrombosis are the two main clinical manifestations of
PV. Subsequently, the patient was discharged from the hospital after PP0793
improvement, and was followed up in a blood specialist hospital.
Shugan Xiaozhi formula improved inflammatory injury in MCD-
Long-term oral hydroxyurea maintenance treatment was performed.
induced NASH mice model by regulating HMGB1/NF-κB/NLRP3
Reexamination results four months after discharge were as follows:
mediated pyroptosis
blood routine: WBC 11.7×109/L, N 61.4%, HGB 160g/L, PLT 268×109/L,
HCT 47.3%. Patients are generally in good condition. Final diagnosis Ruili Du1,2,3, Wang Shuai1,3,4, Kaili Ge1,3, Guangdong Tong1,3,4, Lidan
of this patient: 1. polycythemia vera 2. prehepatic portal hypertension Luo1,3
with gastric variceal rupture hemorrhage 3. Thromboembolism.
1
Department of Hepatology, the Fourth Clinical Medical College of
Guangzhou University of Traditional Chinese Medicine, Shenzhen,
China, 2The First Clinical Medical College of Henan University of
PP0792 Chinese Medicine, Henan, China, 3Shenzhen Key Laboratory of Liver
Retrospective Exploration of the Impact of Traditional Chinese Diseases of Traditional Chinese Medicine, Shenzhen, China, 4Faculty
Medicine Antifibrotic Treatment on the Prognosis of Hepatitis B of Chinese Medicine and State Key Laboratory of Quality Research
Cirrhosis Based on the Real World in Chinese Medicine, Macau University of Science and Technology,
YANG LIU1, XIUHUI LI1 Taipa, Macau, China
1
Beijing Youan Hospital, Capital Medical University Background: Non-alcoholic steatohepatitis (NASH) is the fastest
growing cause of liver cancer deaths globally, with complex
Background: Based on a real-world retrospective study, this research
pathogenesis and lack of practical drug therapy. Shugan Xiaozhi
explores the impact of traditional Chinese medicine’s antifibrotic
formula (SGF) has been used clinically to treat NASH with proIn this
treatment on the prognosis of hepatitis B cirrhosis, providing clinical
study, we would like to investigate the intrinsic connection between
evidence-based treatment rationale for reducing the incidence of liver
HMGB1 and pyroptosis in the mechanism of SGF treating NASH.ven
cancer.
efficacy without in-depth pharmacological research.
Method: For in vivo experiments, C57BL/6J mice were fed methionine PP0795
and choline-deficient (MCD) diet for 6 weeks to establish NASH mice The effective ingredients identification and pharmacodynamics
model, and were administered graded concentrations of SGF (2.5, 5, 10 exploration of the Qu-Tan-Huo-Xue Formula in the treatment of
g/kg/day) by gavage or GL (50 mg/kg/day) by intraperitoneal injection Non-Alcoholic Fatty Liver Disease
for 4 weeks. For in vitro experiments, the inflammatory response was
Qinghua Peng1, Xiaoning Zhu 1, Jing Wang1
induced in RAW264.7 cells by stimulation with LPS (1000 ng/mL) for
24 hours. Then, gradient concentrations of SGF (0.1, 1, 10 μg/mL) or
1
The Affiliated Traditional Chinese Medicine Hospital of Southwest
Medical University No. 182 Chunhui Road, Longmatan District,
GL (100 μM) were separately co-treated with LPS (1000 ng/mL) for
Luzhou City, Sichuan Province, China
24 hours. UPLC-ESI-MS and Network pharmacology was applied to
predict the active ingredients and the signaling pathways associated Background: The Qu-Tan-Huo-Xue (QTHX) Formula has shown
with HMGB1 in the co-targets of SGF for NASH treatment, which were significant benefits in the clinical symptoms of patients with non-
validated in subsequent in vitro and in vivo experiments and molecular alcoholic fatty liver disease (NAFLD). The mechanisms of the efficacy
docking. include improving glucose and lipid metabolism, reducing systemic
Result: First, we found that both SGF and HMGB1 inhibitor GL were inflammation, and decreasing body weight and liver fat degeneration.
able to ameliorate pathological injury, liver function abnormalities and However, its effective components remain unclear. This study aims
lipid metabolism disorders in MCD-induced NASH mice model. Then, to identify the in vitro effective components and in vivo metabolic
the results of UPLC-ESI-MS combined with network pharmacological components using mass spectrometry, and it explores the initial
analysis showed that the intrinsic mechanism of SGF treatment for pharmacodynamic research and molecular mechanisms.
NASH might be related to the HMGB1-regulated pyroptosis pathway. Method: The chemical components of the QTHX Formula were
Finally, the results of in vivo experiments with WB, IHC, ELISA and analyzed using mass spectrometry. Twelve male SD rats were
TUNEL staining collectively showed that SGF was able to ameliorate randomly divided into the Normal Control (NC) and Treatment (TCM)
NASH by inhibiting the extracellular release of HMGB1 and the groups. Blood samples, urine and fecal samples were collected to
subsequent inflammatory cascade as well as the activation of the identify metabolic components using liquid chromatography-mass
pyroptosis pathway. Meanwhile, in vitro experimental results also spectrometry. HE staining was performed to observe the degree of
verified this speculation. And molecular docking results also showed hepatic fat degeneration, while immunohistochemistry (IHC) was
that ursolic acid and dioscin, the active chemical components of SGF, used to assess the expression levels of inflammatory factors in liver
have good binding ability to HMGB1 and pyroptosis-related proteins cells. Active components and target genes of the QTHX Formula
such as NLRP3, IL-1β and IL-18. were sourced from the Traditional Chinese Medicine Systems
Conclusion: SGF ameliorate MCD induced-NASH by regulating Pharmacology Database and Analysis Platform (TCMSP), HERB,
HMGB1/NF-κB/NLRP3 mediated pyroptosis, indicating HMGB1 is a and ETCM databases. Genes related to NAFLD were extracted from
potential target in SGF intervention on NASH. the GeneCards and OMIM databases, and the data were visualized
using Cytoscape software to construct active component-gene-target
networks, PPI (protein-protein interaction) networks, and conduct GO
PP0794 and KEGG enrichment analyses.
Metabolic differences among patients with cirrhosis using Q Result: Initially, 156 chemical components were identified in the QTHX
ExactiveTM hybrid quadrupole Orbitrap mass spectrometry Formula, primarily flavonoids, including baicalin, naringin, limonin,
technology and chlorogenic acid. Secondly, twelve chemical components were
Ying Xiao1, Jie Lu1, Suyan Xu2, Zhinian Wu1, Wei Wang1, Ru Ji1, identified from blood samples, seventeen were detected in urine
Tingyu Guo1, Zeqiang Qi1, Hua Tong1, Yadong Wang1, Caiyan Zhao1 samples, and nineteen were identified in fecal samples. Next, HE
1
the Hebei Medical University Third Hospital, 2Affiliated Hospital of staining revealed that the TCM group can reduce fat degeneration and
Hebei Engineering University fewer lipid droplets, and IHC analysis showed a significant decrease
Background: Disease progression assessment is critical for decision- in the expression of inflammatory factors TNFα, TGFβ, INFγ, IL4, and
making for liver cirrhosis (LC) patients. We aimed to help define clinical IL10 in the liver tissue. Then, 52 core genes and 261 intersecting
stage and better target interventions by detecting the expression and genes were identified as correlating with QTHX Formula and NAFLD.
levels of specific metabolites in patients with different stages of LC via Ultimately, PPI network analysis and GO/KEGG enrichment analysis
Q ExactiveTM hybrid quadrupole Orbitrap mass spectrometry (UPLC- indicated that the formula may treat NAFLD by improving inflammation
Q-Exactive) technology. and lipid metabolism.
Method: This non-interventional observation case-control study Conclusion: The vitro and vivo chemical components of the QTHX
involved 139 patients with LC or acute-on-chronic liver failure (ACLF) Formula were identified, such as flavonoids, terpenoids, and phenolic
in a Chinese Hospital between October 2022 and April 2023. Among acids, et al. QTHX Formula significantly reduced inflammation and
them, 112 with LC included 32, 51, and 29 cases of Child-Turcotte improved hepatic fat degeneration by regulating multiple signaling
Pugh (CTP) classes A (CTP-A group), B (CTP-B group), and C (CTP-C pathways, including IL-17, AGE-RAGE, HIF-1, and PI3K-Akt pathways.
group), respectively, and 27 with ACLF. Serum specimens were
analyzed for multiple metabolite levels using UPLC-Q-Exactive. Data PP0796
were processed and combined with the KEGG database to screen The mechanism of Fuzheng Huayu capsule improves metabolic
for differentially accumulated metabolites (DAMs). Short time-series dysfunction-associated steatohepatitis induced liver fibrosis by
expression miner (STEM) analysis and enrichment analysis were regulating ATF3 to inhibit scar-associated macrophages
performed to assess cirrhosis progression biomarkers.
Chen Zou1,2, Xiao Xu1,2, Qian Huang1,2, Ping Liu1,2, Yiyang Hu1,2, Xin
Result: Following univariate and multivariate analyses, 220, 72, and
Xin1,2, Qing Feng1,2,3
216 significant DAMs were selected; a Venn diagram indicated 9 in 1
Shuguang Hospital Affiliated to Shanghai University of Traditional
common among groups. STEM analysis showed 8’-hydroxyabscisic
Chinese Medicine/Institute of Liver Disease, Shanghai University of
acid, HDCA, pyruvate-3-phosphate, indospicine, eplerenone, and
Traditional Chinese Medicine, Shanghai 201203, 2Key Laboratory
DEHP as significant; their levels first peaked (CTP-B peaked) and then
of Hepatorenal Diseases (Ministry of Education), Shanghai 201203,
decreased with CTP grade aggravation. Significant differences among 3
Central Laboratory, Shuguang Hospital Affiliated to Shanghai
8’-hydroxyabscisic acid, eplerenone, and DEHP were observed University of Traditional Chinese Medicine, Shanghai 201203, China
among LC comorbidities and between subgroups.
Conclusion: Serum levels of six DAMs were significantly associated Background: Previous studies have reported that a novel
with disease progression in patients with LC. These indicators may subpopulation of macrophages marked by cluster of differentiation 9
characterize metabolomic changes and determine the severity of LC (CD9) and triggering receptor expressed on myeloid cells 2 (Trem2),
and predict the development of ACLF. known as scar-associated macrophages (SAMs), can activate
Table and Figure:Figure 1.Graphical Abstract hepatic stellate cells, which promotes the progression of metabolic
dysfunction-associated steatohepatitis (MASH) induced liver fibrosis. eosin (HE) and reticular fiber staining. The hepatocyte mortality rates
It has been varified that the anti-fibrotic traditional Chinese medicine, were determined by cell counting kit-8 (CCK-8) assay, cytotoxicity
Fuzheng Huayu Capsule, effectively alleviates liver inflammation. In assay, and propidium iodide nucleic acid stain assay. Additionally, the
this study, we aim to investigate the molecular mechanisms underlying expression of key proteins of PANoptosis was analyzed by Western
the therapeutic effects of Fuzheng Huayu Capsule on MASH induced blot.
liver fibrosis, with a particular focus on the regulation of SAMs. Result: JDNW formula ameliorated the hepatic and renal functions,
Method: Twenty-four male mice were randomly divided into a control blood ammonia, and coagulation functions, decreased the levels
group (CON), a model group (HFD+ CCL4), and a Fuzheng Huayu of TNF-α and IFN-γ in serum and liver tissue, and alleviated liver
Capsules group (FZHY). The HFD+ CCL4 and FZHY groups were pathological damage in ACLF rats. JDNW formula reduced hepatocyte
given a high-fat diet combined with carbon tetrachloride (CCL4) mortality rate and down-regulation of the expression of proteins
intraperitoneal injection for 6 weeks to establish a MASH induced liver PANoptosis pathways.
fibrosis model. The FZHY group was administered 4.8 g/kg of Fuzheng Conclusion: The findings indicate that the JDNW formula protects the
Huayu Capsules by gavage. After 5 weeks, serum liver enzymes, ACLF rats and L02cells by inhibiting PANoptosis signaling pathways,
hepatic TG, and hydroxyproline (HYP) levels were measured. Three implying that these pathways might be a potential therapeutic target
liver tissue samples from the HFD+ CCL4 and FZHY groups were for ACLF treatment.
subjected to RNA-seq. The expression of SAMs markers, CD9 and
Trem2, as well as the upstream regulatory molecule activating
PP0798
transcription factor 3 (ATF3), were detected in liver tissues. BMDMs
were isolated in vitro and activated with LPS combined with TGF-β1, Shenge Formula reduces hepatic lipid deposition in patients with
and the effects of Fuzheng Huayu drug-containing serum on cell Metabolic-Dysfunction-Associated Fatty Liver Disease (MAFLD):
Trem2 and ATF3 protein and/or gene expression were detected by A Randomized, Placebo-Controlled, Double-Blinded Clinical Trial
Immunofluorescence and Western blot. Rongjie Zhang *1,2,3, Jia Lv *1, Longshan Ji *1,2,3, Yanxi Zheng1, Xin
Result: The levels of liver enzymes, hepatic TG, and HYP content Zhang1,2,3, Yating Gao1,2,3, Xuehua Sun #1,2,3, Man Li #1,2,3, Yueqiu Gao
in the FZHY group were significantly reduced. RNA-seq analysis #1,2,3
revealed that DEGs were primarily enriched in the chemokine 1
Department of Hepatopathy, Shuguang Hospital Affiliated to
signaling pathway. Additionally, The expression levels of surface Shanghai University of Traditional Chinese Medicine, 2Laboratory of
markers CD9 and TREM2 of SAMs, as well as ligands associated Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese
with SAMs, including SPP1, GPNMB, TGF-β, PDGFβ, Tnfsf12, VEGFα, Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University
and receptors CSF1R and NOTCH2 were significantly decreased in of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney
the FZHY group. Moreover, RNA-seq analysis further showed that Diseases (Shanghai University of Traditional Chinese Medicine),
the gene expression level of ATF3—an upstream regulatory molecule Ministry of Education, 3Institute of Infectious Diseases of Integrated
of SAMs—was also significantly downregulated in the FZHY group. Traditional Chinese and Western Medicine, Shanghai Institute of
Fuzheng Huayu Capsules significantly reduced the protein and gene Traditional Chinese Medicine
expression levels of SAMs markers CD9 and Trem2, as well as the Background: Shenge Formula (SGF), as the experimental traditional
upstream regulatory molecule ATF3 in mouse liver tissues . Fuzheng Chinese medicine, is widely used to treat MAFLD. However, high-level
Huayu Capsules significantly reduced Trem2 protein expression and clinical evidence for evaluating the potential reducing hepatic lipid
ATF3 protein and mRNA levels in activated BMDM. deposition properties of SGF are lacking.
Conclusion: Fuzheng Huayu Capsules have significant effects on Method: A double-blind, placebo-controlled randomized clinical trial
anti-MASH induced liver fibrosis in mice, and its mechanism of action involving 154 MAFLD patients was conducted from December 2020
may be related to the downregulation of ATF3 expression inhibiting of to December 2023. Patients are recruited from Shuguang hospital
SAMs. affiliated to Shanghai University of Traditional Chinese Medicine.
Table and Figure:Figure 1.Schematic diagram showing the mechanism Participants were randomized 1:1 to receive either oral SGF (21.4g/
of Fuzheng Huayu capsule inhibiting MASH induced liver fibrosis time, 2 times/day, n=77) or placebo for 12 weeks. The primary endpoint
Figure 2.Workflow of this study was the change in MRI-PDFF value. Secondary outcomes included
changes in hepatic function index, blood lipid level and the Chinese
medicine symptom complex score. (Clinical Trials Registration:
PP0797
ChiCTR2000040993).
The Jieduan-Niwan Formula in treating acute-on-chronic liver Result: Seventy-five patients (97.40%) in the SGF group and 66
failure based on PANoptosis-mediated regulation of hepatocytic patients (85.71%) in the control group completed the study. The SGF
death group showed significant reduction in MEI-PDFF value post-treatment
Ye Qianling1, Zheng Yihao1, Wang Hanjing1, Du Yuqiong1, Ma compared with the control group [37.18 (IQR, 17.84 to 50.93) vs 4.07
Chongyang1, Zhang Qiuyun1 (IQR, -13.94 to18.15), P<0.05]. In addition, the reduction of Chinese
1
Capital Medical University medicine symptom complex score in the SGF group was more
Background: The pathogenesis of Acute-on-chronic liver failure remarkable than that in the control group. However, no significant
(ACLF) involves several forms of cell death, such as pyroptosis, changes were observed in hepatic function index and blood lipid level.
apoptosis, and necroptosis, which consisits of PANoptosis. Jieduan- Conclusion: SGF treatment reduces hepatic lipid deposition in
Niwan (JDNW) formula, a traditional Chinese medicine (TCM), has MAFLD patients.
shown remarkable clinical efficacy in ACLF treatment. However, # Corresponding authors: Yueqiu Gao, Man Li and Xuehua Sun.
whether the formula can inhibit the PANoptosis of ACLF has not been * Rongjie Zhang, Jia Lv and Longshan Ji contributed equally to this
determined. work as co-first authors.
Method: The ACLF rat model was established using carbon
tetrachloride-induced liver cirrhosis, followed by D-galactosamine and PP0799
lipopolysaccharide joint acute attacks. The TNFα and IFN γ induced Electroacupuncture Attenuates Hepatic Steatosis by Activating
L02 cell injury. The ACLF rat was treated with JDNW formula and Hepatic Vagal Nerve in High-Fat Diet-Induced Metabolic Associated
dexamethasone. The serum alanine aminotransferase (ALT), aspartate Fatty Liver Disease Mice
aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Blood
Yuge Zhou1, Liyue Lu1, Xuehua Sun1, Xiaoni Kong1
urea nitrogen (BUN), creatinine (CRE) and NH3 were quantified
to investigate the Hepatic and Renal Functions, Blood Ammonia
1
Central Laboratory, Shuguang Hospital Affiliated to Shanghai
University of Traditional Chinese Medicine, Shanghai 201203, China
and Coagulation Function. ELISA kits were used to determine the
expression levels of IFN-γand TNFα in the serum and hepatic tissue Background: Metabolic associated fatty liver disease (MAFLD)
samples. The liver pathological injury was observed by hematoxylin- is a multi-system metabolic disorder characterized primarily by
hepatic steatosis, resulting from multiple contributing factors. The Yin-chen Wu-ling powder inhibits MAPKs/CXCL1/CXCR2-induced
global prevalence of MAFLD is currently 30.05%, reaching 32.9% neutrophil infiltration to alleviate LPS/D-GalN-induced acute liver
in China, where it is now the leading cause of chronic liver disease. failure
Electroacupuncture (EA), a safe and effective acupoint stimulation Liyue Lu1, Jiacheng Lin1, Xiaoni Kong1
method, is a crucial component of traditional Chinese medicine with a 1
Shuguang Hospital Affiliated to Shanghai University of Traditional
long history and wide clinical application. However, its mechanism in Chinese Medicine, 528 Zhangheng Road, Shanghai, China, 201203
treating MAFLD remains unclear. Therefore, we conducted a study to
Background: Acute liver failure (ALF) is the result of progression from
investigate the efficacy and mechanism of EA in high-fat diet (HFD)-
acute liver injury with high mortality, and novel treatments are needed.
induced MAFLD mice.
Yin-chen Wu-ling powder (YWP), a traditional herbal medicine in
Method: We measured body weight, liver weight, body fat
China, has been used for treating acute liver injury for thousands of
percentage, and serum levels of alanine aminotransferase, aspartate
years. However, the mechanism of YWP is unknown.
aminotransferase, triglyceride, total cholesterol, high-density
Method: We established an LPS/D-GalN-induced ALF mouse model
lipoprotein, and low-density lipoprotein in mice. Glucose metabolic
and in vitro system to evaluate the effect of YWP. We characterized
parameters were also assessed. Immunohistochemistry was used to
YWP’s chemical composition via UHPLC-Q-Exactive Orbitrap HRMS.
evaluate the histomorphology of liver and adipose tissues in the mice.
Enzyme-linked immunosorbent assay, hematoxylin and eosin staining,
Liquid chromatography-tandem mass spectrometry (LC-MS)-based
immunohistochemistry and immunofluorescence, flow cytometry,
quantification, real-time quantitative PCR, western blotting analysis
qPCR, Western blot were used to discover key mechanisms both in
and immunofluorescence staining were used to assess the activation
vitro and in vivo.
of hepatic vagal.
Result: YWP alleviated liver dysfunction and liver necrosis. YWP
Result: Our results showed that EA at ST36 effectively reduced body
reduced hepatocyte death and inflammatory responses. Importantly,
weight, liver weight, hepatosomatic index, and body fat percentage
YWP markedly inhibited neutrophil infiltration into the liver. We
in HFD-induced MAFLD mice. Furthermore, EA improved serum liver
examined key chemokines that contribute to neutrophil recruitment.
function, lipid profiles, and glucose metabolic capacity, and attenuated
The results showed that YWP inhibited CXCL1, which is sourced from
hepatic steatosis and lipid droplet formation in MAFLD mice. The
inflammation-activated hepatocytes. In addition, YWP inhibited TNF-
mechanism may be related to the increased release of acetylcholine
α-induced CXCL1 transcription via the inhibition of MAPKs signalling
from hepatic vagal nerve endings.
in vitro. Furthermore, the anti-ALF effect of YWP was weakened when
Conclusion: Electroacupuncture effectively ameliorates hepatic
CXCL1/CXCR2 signalling was suppressed.
steatosis in HFD-induced MAFLD mice, offering a novel therapeutic
Conclusion: YWP could inhibit neutrophil infiltration into the liver,
approach for MAFLD.
alleviating inflammatory injury in ALF. The effect of YWP might be
attributed to the regulation of the MAPKs/CXCL1/CXCR2 axis. We
PP0801 suggest that YWP is a potential anti-inflammatory treatment for ALF.
Discussion on the pathogenesis and treatment of metabolism-
related fatty liver disease based on the theory of “Xuqi (虚气) - PP0804
Kenang (窠囊) ”and the evolution of pathogenesis and treatment of
Modulation Hepatic Farnesoid X Receptor and Gut Microbiota of
metabolic fatty liver disease
Puerarin in High-Fat Diet-Induced Obese Mice
Guangqin ZHU1, Jinrong ZHANG1, Jiping ZHANG1, Yike SUN1, Sunlin
Tzung Yan Lee1
HU1, Shuran MA1 1
Chang Gung University
1
Beijing University of Chinese Medicine
Background: Obesity is associated with alterations in lipid metabolism
Background: As a complex metabolic chronic disease, Metabolic
and gut microbiota dysbiosis.
dysfunction-Associated Fatty Liver Disease (MAFLD) has a
Method: This study investigated the effects of puerarin, a bioactive
pathogenesis that involves the imbalance of qi, blood and fluids, as
isoflavone, on lipid metabolism disorders and gut microbiota in high-fat
well as abnormalities in the functions of the liver and the spleen, and
diet (HFD)-induced obese mice.
its development is similar to the hidden onset of Xuqi and Kenang, with
Result: Supplementation with puerarin reduced plasma alanine
deficiency and stasis being trapped in the Kenang, and prolonged
aminotransferase, liver triglyceride, liver free fatty acid (FFA), and
and difficult to treat.
improved gut microbiota dysbiosis in obese mice. Puerarin’s beneficial
Method: Starting from the theory of Xuqi-Kenang, the article proposed
metabolic effects were attenuated when farnesoid X receptor (FXR) was
that MAFLD started from the retention of Xuqi and progressed to
antagonized, suggesting FXR-mediated mechanisms. In hepatocytes,
the detention of Kenang, which showed the dynamic pathological
puerarin ameliorated high FFA-induced sterol regulatory element-
characteristics of stasis due to deficiency, and further deficiency
binding protein (SREBP) 1 signaling, inflammation, and mitochondrial
caused by stasis. We analyze the evolution and dynamic progression
dysfunction in an FXR-dependent manner. In obese mice, puerarin
of Xuqi and Kenang in the pathogenesis, and divide the disease
reduced liver damage, regulated hepatic lipogenesis, decreased
process into three overlapping stages: Xuqi retention, phlegm and
inflammation, improved mitochondrial function, and modulated
stasis generation and Kenang retention.
mitophagy and ubiquitin-proteasome pathways, but was less effective
Result: The disease process was divided into three superimposed
in FXR knockout mice. Puerarin upregulated hepatic expression of
phases of pathogenesis, and the basic therapeutic idea of taking qi as
FXR, bile salt export pump (BSEP), and downregulated cytochrome
the pivot, attacking and tonifying was further proposed, emphasizing
P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP),
that, on the basis of tonifying the spleen qi, taking into account
indicating modulation of bile acid synthesis and transport. Puerarin
expelling blood stasis and pounding the areoles and nourishing the
also restored gut microbial diversity, the Firmicutes/Bacteroidetes
liver and kidneys, the treatment was carried out in phases with a view
ratio, and the abundance of Clostridium celatum and Akkermansia
to providing a new way of thinking and methodology for the diagnosis
muciniphila. This study demonstrates that puerarin effectively
and treatment of MAFLD in Chinese medicine.
ameliorates metabolic disturbances and gut microbiota dysbiosis in
Conclusion: As a syndrome characterized by a predominance of
obese mice, predominantly through FXR-dependent pathways.
deficiency and a mixture of deficiency and excess, the therapeutic
Conclusion: These findings underscore puerarin’s potential as a
approach for MASLD should primarily focus on benefiting qi as the
therapeutic agent for managing obesity and enhancing gut health,
main method, while also incorporating secondary measures of
highlighting its dual role in improving metabolic functions and
resolving stasis and eliminating the root cause. By prioritizing qi, this
modulating microbial communities.
approach integrates supportive and corrective strategies.

PP0805
PP0803
Schisantherin A attenuates biliary fibrosis by targeting PPARα in were conducted using the STRING database, Metascape platform
mice and Cytoscape software to identify potential biological processes and
Zheng Zhang1, Enqi Tang1, Yue Liang1, Xiaohan Yu1, Wei Liu1, signaling pathways. Finally, the indexes related to hepatic inflammation,
Gaofeng Chen1, Yongping Mu1, Ping Liu1, Jiamei Chen1 apoptosis and the AKT/NF-κB signal pathway were assessed.
1
Institute of Liver Diseases, Key Laboratory of Liver and Kidney Result: The data demonstrated that CAT effectively ameliorated
Diseases (Ministry of Education), Shuguang Hospital Affiliated to hepatic fibrosis in both CCl4-induced mice and DMN-induced rats.
Shanghai University of Traditional Chinese Medicine Network pharmacology analysis revealed that CAT systematically
inhibited the progression of hepatic fibrosis by suppressing hepatic
Background: Schisantherin A (Sin A), the natural compound from
inflammation and apoptosis. In vivo experiments confirmed that CAT
Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis
alleviated hepatic inflammation and apoptosis via suppressing the
effects, but the efficacy and underlying mechanism in treating biliary
AKT/NF-κB signal pathway.
fibrosis is poorly understood.
Conclusion: The study findings suggest that CAT has the potential
Method: In this study, two mouse models, including
to ameliorate hepatic fibrosis, inflammation and apoptosis through
3,5-Diethoxycarbonyl-1,4-Dihydro-2,4,6-Collidine (DDC)-induced and
suppressing the AKT/NF-κB signal pathway.
Mdr2-/- spontaneous biliary fibrosis, and the peroxisome proliferator-
activated receptor alpha (Pparα) gene knockout (Pparα-/-) mice were
used to investigate the therapeutic effect and mechanisms of Sin A. PP0807
Furthermore, proteomics and RNA-sequencing analyses, luciferase Clinical Observation on Efficacy and Safety of Fushui Paste in the
reporter assay, as well as drug affinity responsive target stability Treatment of Hepatitis B-related Liver Cirrhosis with Moderate and
(DARTS), cellular thermal shift assay (CESTA) and surface plasmon Severe Ascites: A Propensity Score Analysis
resonance (SPR) experiments were performed. Degradation of the Xiaoya Yang1, Yangyang Xue1, Kaili Ge1, Chunshan Wei1,2
PPARα protein was measured after the treatment of cycloheximide 1
The Fourth Clinical Medical College of Guangzhou University of
(CHX) with or without Sin A at the indicated time points in vitro.
Chinese Medicine , 2 Shenzhen Traditional Chinese Medicine Hospital
Result: Treatment with Sin A significantly ameliorated the cholestasis-
related disorder of bile acid metabolism, liver injury, ductular reaction Background: The survival rate of cirrhotic patients with ascites is
(DR), inflammation and fibrosis in both DDC-induced and Mdr2- significantly lower than that of patient without ascites. This study
/- mice. Proteomics and RNA-sequencing analyses of both DDC- intends to observe the efficacy and safety of using Fushui Paste to
induced liver and Mdr2-/- liver samples before and after treatment treat patients with ascites in hepatitis B-related cirrhosis through a
with Sin A suggested that Sin A activated PPAR signaling. Further retrospective study.
validation revealed that Sin A significantly up-regulated hepatic Method: Patients with moderate-to-severe ascites in hepatitis B
PPARa protein expression in these two mice models. Subsequently, cirrhosis who were hospitalized between January 2020 and December
luciferase reporter assay revealed that Sin A significantly activated 2022 were retrieved and were divided into the control group and the
PPARa. DARTS and CETSA experiments indicated that Sin A inhibited Fushui Paste group. The propensity score method (PSM) was used to
the PPARα degradation caused by pronase and the temperature- reduce the influence of confounding factors.
induced denaturation in AML12 cell lysates, thereby implying a direct Result: After PSM, a total of 53 patients were finally included: 32
interaction between herpetrione and PPARα. SPR analysis validated patients in the Fushui Paste group and 21 patients in the control
the interaction of Sin A with PPARα, demonstrating an equilibrium group, and the two groups were comparable at baseline. Intergroup
dissociation constant (KD) of 63.26 μM. The results of degradation comparison of the two groups showed that the effective rate of the
of the PPARα protein with CHX showed that Sin A weakened PPARα Fushui Paste group was higher than that of the control group (96.9%
degradation compared to the control group. These results revealed vs. 71.4%, P<0.05). After treatment, the Chinese medicine evidence
that Sin A bound directly to the PPARα protein to improve the stability of points, abdominal circumference and ultrasound depth of ascites
the PPARα protein and activate PPARa. Furthermore, PPARa deletion in the Fushui Paste group decreased compared with those in the
abolished the anti-biliary fibrotic effect of Sin A in DDC-induced mice, control group ( 4 (2,6) vs. 6 (4,8), 85.38±8.28cm VS. 90.29±9.07cm,
suggesting that Sin A alleviated cholestasis, bile acid metabolism, DR 43.00 (28.75,63.75)mm VS. 53.00 (41.50,98.00)mm, P<0.05), and
and inflammation in mice by targeting up-regulation of PPARα, thereby the 24-h urine volume increased compared with those in the control
alleviating biliary fibrosis. group (2055.63±427.71ml VS. 1690.48±503.35ml, P<0.05). Liver
Conclusion: Our findings provided compelling evidence for Sin A function comparison (ALT, AST, GGT, TB, ALB), coagulation function
treatment in biliary fibrosis, as well as the broader prospects for biliary comparison (PT, PTA) revealed that there was no statistical difference
fibrosis treatment by targeting PPARα. between the two groups. In comparing before and after treatment of
heart rate, blood pressure, renal function, and electrolytes, there was
no statistically significant difference between the Fushui Paste group
PP0806 and the control group before and after treatment.
Catalpol ameliorates liver fibrosis through suppressing AKT/NF- Conclusion: Compared with conventional traditional Chinese and
κB signal pathway in rodent models western medicine treatment, combined with Fushui Paste in the
Liang Yue1, Cheng Tianyu1, Pu Jiaying1, Zhang Zheng1, Ma Wanyu1, treatment of patients with moderate to severe ascites of hepatitis B
Liu Wei1, Mu Yongping1, Zhang Hua1, Jiamei Chen1, Liu Ping1 cirrhosis can improve the clinical efficiency, relieve the symptoms of
1
Shuguang Hospital affliated to Shanghai University of Traditional patients, reduce abdominal circumference, increase the 24-hour urine
Chinese Medicine volume of patients, and reduce the depth of ascites. And Fushui Paste
has better safety, which is worthy of popularization and application.
Background: Hepatic fibrosis is a complex disease characterized by
the accumulation of extracellular matrix and hyperplasia of connective
tissue. Recent studies have demonstrated that catalpol (CAT), the PP0808
major compound found in Rehmannia glutinosa, exhibits anti-fibrotic The Mechanism of Icaritin in Liver Fibrosis: Insights from
and anti-informatory effects. However, there is currently insufficient Metabolomics and Gut Microbiota
information regarding the mechanisms of CAT in treating hepatic Yuqin Li1,2, Wentao Kuai3,2,4, Yuqiang Mi3,2,4, Liang Xu3,2,4
fibrosis. 1
Clinical School of the Second People’s Hospital, Tianjin Medical
Method: The liver fibrosis models both in mice induced by carbon
University, 2Tianjin Second People‘s Hospital, 3Department of
tetrachloride (CCl4) and in rats induced by dimethylnitrosamine Hepatology, Tianjin Second People’s Hospital, 4Tianjin Institute of
(DMN) were used to investigate the effect and underlying mechanism Hepatology
of CAT at varying doses. Potential targets associated with CAT and
hepatic fibrosis were gathered from databases. Protein-protein Background: The mechanism of Icaritin (ICT) in inhibiting liver
interaction network analysis and GO & KEGG enrichment analysis fibrosis is unclear. This study aims to explore its effects and potential
mechanisms. Background: Pien Tze Huang (PTH), a prominent traditional
Method: Forty-four healthy female SD rats were randomly assigned Chinese medicine compound, has demonstrated anti-hepatic fibrosis
to a blank control group (10 rats) and a CCl4-induced liver fibrosis properties in vitro and animal models, but the randomized clinical trials
model group (34 rats). After 4 weeks of CCl4 injection, liver fibrosis for evaluating anti-hepatic fibrosis of PTH are lacking. Chronic hepatitis
was confirmed by histology in two rats from each group. The control B (CHB) is a leading cause of hepatic fibrosis in China. This study
model and ICT treatment groups (1, 4, and 16 mg/kg/day) were then aimed to assess the efficacy of PTH in improving hepatic fibrosis in
established, with 8 rats per group, and treated for 4 weeks. Serum ALT CHB patients.
and AST levels were measured, and liver fibrosis was assessed using Method: We conducted a randomized, double-blind, placebo-
H&E and Masson’s staining. At the study endpoint, fecal samples controlled clinical trial involving 144 CHB patients with hepatic fibrosis.
were collected for metagenomic sequencing and liver tissues were This study was carried out from September 2020 to April 2023. Patients
analyzed by untargeted metabolomics. Spearman correlation analysis are recruited from 10 hospitals across China. Participants were
was performed to assess the relationship between gut microbiota and randomized 1:1 to receive either oral PTH (0.6 mg, three times daily)
metabolic changes. or placebo for 48 weeks, in addition to entecavir (0.5 mg/day). The
Result: (1) Compared to the normal group, the liver surface in primary endpoint was the change in Ishak score. Secondary outcomes
the model group was rough and yellowish, while increasing ICT included changes in Knodell HAI score, LSM, APRI score, FIB-4 index
concentrations made the liver surface smoother. The model group and hepatic function index.
exhibited a significant reduction in body weight (P < 0.001) and liver- Result: Of the 144 randomized patients, 142 patients (71 in the PTH
to-body weight ratio (P < 0.01) compared to the normal group. After group and 71 in the placebo group) were included in the primary
4 weeks of ICT treatment, the 16 mg/kg group showed a significant analysis. The PTH group exhibited lower Ishak score compared
decrease in liver coefficient (P < 0.01), with a 23.2% improvement. ICT to the control group. Notably, in treatment-naive patients, the PTH
also significantly reduced ALT and AST levels (P < 0.01). Histological group showed significant improvement in Ishak score post-treatment
analysis confirmed that ICT treatment reduced liver fibrosis, with compared with the control group. However, no significant changes
Masson’s trichrome staining showing a marked reduction in fibrotic were observed in these parameters among patients already receiving
areas. antiviral therapy.
(2) Metagenomic analysis revealed that ICT increased the relative Conclusion: PTH in combination with entecavir improves hepatic
abundance of Firmicutes in the gut microbiota compared to the model fibrosis in Chinese CHB patients, particularly in treatment-naive
group (P = 0.015). In the CCl4-induced liver fibrosis model, Lactobacillus individuals.
rhamnosus and Lactobacillus johnsonii significantly decreased, while Table and Figure:Figure 1.Graphical Abstract
Lactobacillus entericus, Akkermansia muciniphila, and Rubuinidae
significantly increased after ICT treatment. Notably, ICT restored gut
PP0810
microbiota balance, particularly enhancing Lactobacillus johnsonii
abundance (P = 0.002). Spearman correlation analysis showed that Total Sanghuangporus vaninii extract attenuates liver fibrosis by
Lactobacillus johnsonii abundance was negatively correlated with inhibiting hepatocyte ferroptosis via Nrf2-GPX4 signaling pathway
liver fibrosis (r = 0.173, P = 0.420), while Akkermansia muciniphila (r = Siqi Gao1, Qiuying Xu1, Lumeng Yao1, Xingxing Wang1, Jianjun Wu1,
0.439, P = 0.032) and Rubuinidae (r = 0.578, P = 0.003) were positively Luping Qin1
correlated with fibrosis severity. 1
School of Pharmaceutical Sciences, Zhejiang Chinese Medical
(3) Untargeted liver metabolomics analysis revealed that ICT primarily University, Hangzhou 311402, China
affected metabolites involved in unsaturated fatty acid biosynthesis, Background: Sanghuangporus, the dried fruiting body of
linoleic acid metabolism, and arachidonic acid metabolism. Sanghuangporus vaninii (Ljub) L.W.Zhou et Y.C.Dai, is the main
Conclusion: Icaritin significantly reduces liver fibrosis caused by species of Sanghuang in Zhejiang Province. As a traditional medicinal
carbon tetrachloride in rats and alters intestinal microbiota and liver and edible macrofungus known for its hepatoprotective properties, its
metabolites. This provides a basis for discovering new liver fibrosis potential efficacy and mechanism in liver fibrosis have yet to be fully
treatments and is valuable for translational research. elucidated. This study aimed to explore firstly evaluate the efficacy and
Table and Figure:Figure 1.Icaritin Improves Biochemical Functions in underlying mechanism on liver fibrosis mice.
Carbon Tetrachloride-Induced Rats Method: Total Sanghuangporus vaninii extract (TSH) was prepared
by ethanol extraction, and liver fibrosis was induced by CCl4 in mice
PP0809 and treated with TSH or sorafenib in vivo. Besides, erastin-induced
hepatocyte ferroptosis model with TSH or ferrostatin-1 were evaluated
Pien Tze Huang plus entecavir improves hepatic fibrosis in
in vitro. Potential targets were validated using network-pharmacology
Chinese patients with chronic hepatitis B
analysis and molecular docking. The 16S rDNA sequencing and
Xin Zhang1, Liwen Zhang1, Longshan Ji1, Suthat Liangpunsakul 2, untargeted metabolomics analysis were applied to investigate the role
Jinghao Zhang1, Fei Hong3, Hua Lyu4, Seonghwan Hwang5, Chunyan of TSH in gut microbiome.
Gou6, Yuyong Jiang7, Xiaorong Chen8, Qin Li9, Guangdong Tong10, Result: TSH treatment significantly ameliorated serum indicators of
Anna Zhang11, Jing Wang12, Xiaodong Li13, Mingxin Zhang14, Xuehua liver injury in CCl4-induced fibrosis mice, reduced HSCs activation
Sun1, Man Li1, Yueqiu Gao1 and collagen deposition. Notably, hepatocyte ferroptosis with lipid
1
Department of Hepatopathy, Shuguang Hospital Affiliated to peroxidation was also attenuated with TSH treatment in vivo and in vitro,
Shanghai University of Traditional Chinese Medicine , 2Division of in which liver iron and MDA contents were decreased. In particular,
Gastroenterology and Hepatology, Department of Medicine, Indiana network-pharmacology analysis and molecular docking suggested
University School of Medicine, 3Fujian Pien Tze Huang Enterprise Nrf2 as the potential target. TSH was demonstrated to activate the
Key Laboratory of Natural Medicine Research and Development,
Nrf2-GPX4 signaling pathway to protect hepatocytes from ferroptosis,
Zhangzhou Pien Tze Huang Pharmaceutical Co.,Ltd, 4National
especially contributing Nrf2 nuclear transcription. Furthermore,
Monitoring Center for Medical Services Quality of TCM Hospital,
TSH exerted an effect of remodelling gut microbiota and improving
5
College of Pharmacy, Pusan National University, 6Beijing You An
intestinal metabolic disorders, while the abundance of Parasutterella
Hospital, Capital Medical University, 7Beijing Ditan Hospital, Capital
Medical University, 8Shanghai Public Health Clinical Center, Fudan and Olsenellas enriched by TSH had a significantly positive correlation
University, 9Mengchao Hepatobiliary Hospital of Fujian Medical with the increase of phosphatidylcholines of linoleic acid metabolism,
University, 10Shenzhen Hospital of Traditional Chinese Medicine , with the negative correlation with the reduction of fatty acyls. And the
1
1Henan Infectious Disease Hospital, 12The Affiliated Traditional enrichment of intestinal linoleic acid metabolism presented a negative
Chinese Medicine Hospital of Southwest Medical University, Luzhou, correlation in the reduction of liver fibrosis biomarkers.
1
3Hubei province Hospital of Traditional Chinese Medicine, 14The First Conclusion: TSH exerts a significantly protective impact on liver
Affiliated Hospital of Xi‘an Medical University fibrosis in mice by ameliorating hepatic injury and ferroptosis damage,
inhibiting HSCs activation and collagen deposition, and remodelling
gut microbiota homeostasis and metabolic imbalance. Notably, TSH Prevalent western medicine having limitations about CLD, patients
attenuated hepatocyte ferroptosis in liver fibrosis via contributing Nrf2 do visit Ayurveda physicians. The objective of present study was to
nuclear transcription to activating the Nrf2-GPX4 signaling pathway. determine the safety of Ayurvedic formulations in patients with CLD
Our study provided more effective and unreported evidence of TSH in who consumed these medicines for minimum period of 3 months.
anti-fibrosis activity. Method: Data capture was conducted of 30 CLD patients via
retrospective chart review in our speciality Ayurvedic clinic. A
self-developed algorithm was used to determine the sum total of
PP0811
metals Sulphur(S), Mercury(Hg), Gold(Au), Silver(Ag), Iron(Fe) and
Yiqi Huoxue Lishui Decoction regulates Nrf2/GPX4 signaling Cupper(Cu) used in various Ayurvedic formulations which were
pathway to inhibit ferroptosis and improve liver fibrosis in rats consumed by the patients during the study period. Thirty patients who
Jingjing Liu1, Qi Dai2 had CLD and consumed Ayurvedic formulations for a mean duration of
1
Jiangxi University of Traditional Chinese Medicine, 2Affiliated Hospital 26.43(±20.79) months. Liver function tests, haemoglobin, total bilirubin,
of Jiangxi University of Traditional Chinese Medicine SGOT, SGPT, Alkaline Phosphatase, total protein, serum creatinine and
Background: HF is a kind of injury-repair reaction caused by various blood urea nitrogen (BUN) were performed before, during, and after
causes of liver injury, which leads to abnormal activation of hepatic treatment/till last follow-up of patient was used for analysis.
stellate cells (HSC), resulting in a large amount of extracellular matrix Result: These investigations showed rise in the levels of haemoglobin
accumulation and destruction of the normal structure of the liver . The amounting to 10.93 ±2.51 vs 12.26± 2.95 (p < 0.01) and total bilirubin
continuous development of liver fibrosis will transform into irreversible decreased significantly 2.79(±2.42) vs 1.91±1.43 (p < 0.05). No
cirrhosis, and even develop into liver cancer , so it is particularly significant changes were observed in the Alkaline Phosphatase,
important to carry out anti-liver fibrosis treatment in time to block its SGOT, SGPT, total protein, serum creatinine or BUN (p> 0.05).
further development. Traditional Chinese medicine (TCM) has its Conclusion: It is pertinent to mention use of metals or minerals in
specific advantages in anti-liver fibrosis. In recent years, TCM has Ayurveda undergoes exhaustive manufacturing processes which
been widely used in the prevention and treatment of liver diseases and involves plants and physical processes. This makes these metals
has good curative effect. Yiqi Huoxue Lishui Decoction is a clinical or minerals completely different than chemical form of such metals
summary of Professor Chen Kunshan’s research on liver fibrosis/ or minerals. In the group of study patients with CLD treatment with
cirrhosis. It has been confirmed in previous studies that Yiqi Huoxue formulations containing metals did not showed any adverse outcomes
Lishui decoction can effectively treat liver fibrosis , but its mechanism in liver or kidney functioning. Improvement in liver functions was noted.
of action is still unclear. However, since this was a retrospective study with a small number of
Method: Forty SD rats were randomly divided into 5 groups: HF subjects, additional larger prospective studies are needed to further
model group, Yiqi Huoxue Lishui Decoction group, Yiqi Huoxue Lishui validate these findings.
decoction + ferroptosis inhibitor (Fer-1) group, and Yiqi Huoxue Lishui
decoction +Fer-1+ autophagy inhibitor (3-MA) group. Yiqi Huoxue PP0813
Lishui Decoction was given by gavage (2ml/100g), and Fer-1 and 3-MA
Unveiling Transient Portal Hypertension: A Rare Complication of
were given by intraperitoneal injection (1mg/kg, 15mg/kg). The control
EBV Infection
group and the model group were given the same amount of normal
saline. The contents of AST, ALT, TNF-a, SOD, MDA and iron ion were Lianhui Zhao1, Ke Xu1, Gang Wang1, Huajun Zhao2
detected by biochemical kits. Hematoxylin-eosin (HE) and Masson
1
Department of Infectious Disease, Qilu Hospital, Cheeloo College of
staining; Western blotting was used to detect the protein expression of Medicine, Shandong University, 2Institute of Immunopharmaceutical
ferroptosis-related proteins SLC7A11, Nrf2, GPX4, and Beclin-1. Sciences, School of Pharmaceutical Sciences, Shandong University
Result: Compared with the control group, the pathological changes Introduction Epstein-Barr virus (EBV) infection is commonly associated
of liver tissue were obvious, the collagen volume was significantly with infectious mononucleosis and rarely manifests with complications
increased (P<0.05), the contents of ASL, ALT, MDA, TNF-a, liver iron ion such as transient portal hypertension (PH). This report presents a
and Bclin-1 protein levels were significantly increased, and the protein case of EBV-induced transient PH, contributing to the limited existing
expressions of Nrf2 and GPX4 were significantly decreased. The literature.
expression of SOD and SLC7A11 protein decreased (both P<0.05). Case Presentation A 34-year-old male presented with a 1-month
Compared with the model group, the protein levels of ASL, ALT, MDA, history of fever and a 3-week history of abdominal pain and distension.
TNF-a and Bclin-1, liver iron ion content and collagen volume in the Physical examination revealed hepatosplenomegaly. Laboratory
treatment groups were decreased to varying degrees (all P<0.05). findings showed neutrophil predominance (81%), lymphopenia
SOD level, Nrf2, GPX4 and SLC7A11 protein expression levels were (0.54×10^9/L), thrombocytopenia (17×10^9/L), and elevated liver
increased in different degrees (all P<0.05). enzymes (ALT 117 U/L, AST 127 U/L). Serum EBV DNA levels were
Conclusion: Yiqi Huoxue Lishui Decoction inhibits ferroptosis of significantly elevated (2.20×10^6 copies/mL in mononuclear cells.
hepatocytes to improve liver fibrosis through Nrf2/GPX4 signaling Imaging studies demonstrated hepatomegaly, splenomegaly, ascites,
pathway, and its effect may be affected by autophagy signaling. and signs of portal hypertension. The portal vein width was 1.7
Table and Figure:Figure 1.HE staining results cm. FibroScan revealed a liver stiffness value of 7.8 kPa. Infectious
Figure 2.Results of serum biochemical tests metagenomic sequencing identified 2269 reads of human herpesvirus
type 4 (EBV), while bacterial, fungal, and parasitic pathogens were
not detected. Further evaluations, including bone marrow biopsy,
PP0812
excluded malignancies.
Safety of chronic consumption of Ayurvedic Formulations in Management and Outcomes The patient was treated with antibiotics,
Chronic Liver Disease (CLD): A Retrospective Study antivirals, corticosteroids, hepatoprotective agents, and supportive
Yogesh Bendale1, Ketaki Jagtap1, Avinash Kadam1, Anjali Pote1 measures. Then, he received intravenous immunoglobulin (IVIG),
1
Rasayu Ayurved Clinic Ruxolitinib (JAK inhibitors), and antiviral therapy (Ganciclovir), leading
Background: The composition of Ayurveda formulations includes to symptom alleviation.At 3-month follow-up, the patient’s liver stiffness
minerals, which raise safety concerns among the physicians and values normalized, the portal vein width returned to normal, and all
the patients, especially those with liver diseases. In spite of this, a signs of portal hypertension resolved. These findings supported the
lot of Ayurvedic formulations given for the purpose of improving liver hypothesis of a temporary inflammatory response related to EBV
function in chronic liver disease (CLD) have minerals present in them. infection.
In spite of its human consumptions for hundreds of years, it appears Discussion EBV infection can rarely lead to transient portal
that little information is available in the research literature regarding the hypertension. The mechanism may involve immune dysregulation and
safety of these formulations in CLD patients. inflammation. Early recognition and management, including antivirals
and immunomodulatory therapy, can lead to favorable outcomes. This
case highlights the need for further studies on its pathophysiology and life.
clinical implications. Conclusion: This systematic review underscores the diversity in
Conclusion Acute infections may lead to transient portal hypertension. therapeutic strategies for CPH, with beta-blockers as the mainstay
In cases of unexplained portal hypertension, infection-related factors of treatment and promising new directions from emerging agents.
should be thoroughly considered. Despite progress, variability in trial phases and limited long-term
follow-up necessitate larger, harmonized trials across all phases to
refine HVPG-guided therapies for CPH.
PP0814
Table and Figure:Figure 1.Regional Distribution of Clinical Trials
Registry Clinical Trials on Treatment of Cirrhotic Portal Figure 2.Focus Areas of Primary Outcomes in Clinical Trials
Hypertension Evaluated by Hepatic Venous Pressure Gradient: A
Systematic Review
Lianhui Zhao1, Huajun Zhao2
PP0815
1
Department of Infectious Disease, Qilu Hospital, Cheeloo College of Avatrombopag for the treatment of immune checkpoint inhibitor/
Medicine, Shandong University, 2Institute of Immunopharmaceutical targeted therapy?related thrombocytopenia in patients with
Sciences, School of Pharmaceutical Sciences, Shandong University hepatocellular carcinoma: A prospective, multicenter, single-arm
trial
Background: Cirrhotic portal hypertension (CPH) is a significant
complication of chronic liver disease, and hepatic venous pressure Wang Yong Shuai1, Luo Da Yong2, Wang Ji Zhou1
gradient (HVPG) remains the gold standard for evaluation. This
1
The First Affiliated Hospital of University of Science and Technology
systematic review categorizes clinical trials by pharmacological of China, 2No.2 People’s Hospital of Fuyang City
mechanisms, trial phases, and outcomes to assess the therapeutic Background: Immune checkpoint inhibitor?related thrombocytopenia
landscape. (ICIRT) or targeted therapy?related thrombocytopenia (TTRT) is one of
Method: Trials were identified through ClinicalTrials.gov, the Chinese the common adverse reactions to antineoplastic drugs.
Clinical Trial Registry, and the European Clinical Trials Register. Data Method: This prospective, multicenter, single-arm trial enrolled ICIRT
on drug mechanisms, trial phases, study designs, funding sources, or TTRT in patients with HCC in two centers from June 2022 to February
and outcomes were extracted and analyzed. 2024. The primary endpoint was the proportion of responders (patients
Result: Drug Classification by Pharmacological Mechanism: with platelet count ≥75×109/L or increased ≥25×109/L or increased
Beta-blockers (30%): Including carvedilol and by ≥100% from the baseline and not received rescue therapy for
propranolol, targeting portal pressure reduction. bleeding) before the next targeted/immunotherapy cycle (21 days).
Vasodilators (15%): Agents like doxazosin and Result: A total of 52 patients were included. The number of responders
nitrates targeting vascular resistance. who met the primary endpoint (any criteria) was 46 (86.54%), of which
Anti-metabolic agents (10%): Metformin targeting 36 (69.23%) patients met PLT counts ≥75×109/L, 37 (71.15%) patients
hepatic insulin sensitivity. met PLT counts increased ≥25×109/L and 31 (59.62%) patients met
Gut microbiota modulators (10%): Rifaximin and PLT counts increased by ≥100% from the baseline. There were no
probiotics improving gut-liver interactions. serious AEs occurring during treatment and no patients discontinuing
Experimental agents (15%): Emerging therapies treatment due to AEs. There were also no bleeding-related or
such as BI 685509. thrombosis-related AEs. The most common AEs were nausea (n=5,
Others (20%): Combination therapies and agents 9.62%), pyrexia (n=5, 9.62%), abdominal pain (n= 4, 7.69%), fatigue
like taurine. (n=3, 5.77%), headache (n=2, 3.85%) and peripheral edema (n=1,
Study Classification by Trial Phase: 1.92%).
Phase I: 5 trials (10%), focusing on safety and Conclusion: Avatrombopag is safe and effective in the treatment of
dosage. ICIRT or TTRT in patients with HCC.
Phase II: 12 trials (24%), evaluating efficacy and Table and Figure:Figure 1.
safety.
Phase III: 8 trials (16%), confirming efficacy in
PP0816
larger populations.
Phase IV: 6 trials (12%), focusing on post-market Establishment of Novel Mouse Model of Dietary NASH Rapidly
surveillance. Progressing into Liver Cirrhosis and Tumors
Observational Studies/Other: 19 studies (38%), Qianqian Zheng1, NAOKI TANAKA2
exploring mechanisms and outcomes without interventional protocols. 1
Department of Hepatic Disease Research, Integrating Traditional
Control Measures: Chinese and Western Medicine, Third hospital of Hebei medical
Placebo-Controlled: 25% of trials. university, 2Department of Global Medical Research Promotion
Carvedilol-Controlled: 18% of trials. International Relations Office, Shinshu University School of Medicine
Single-Arm or Combination Therapy: 57% of trials. Background: Non-alcoholic steatohepatitis (NASH), which is the most
Study Status: severe manifestation of non- alcoholic fatty liver disease (NAFLD), has
Completed: 40%. been recognized as a major hepatocellular carcinoma (HCC) catalyst.
Recruiting: 35%. However, the molecular mechanism of NASH-liver fibrosis-HCC
Not Yet Recruiting/Unknown: 25%. sequence remains unclear and a specific and effective treatment for
Enrollment: NASH has not yet been established. The progress in this field depends
Total enrollment was 3,273 participants, with a on the availability of reliable preclinical models which show the steady
median sample size of 76 per trial. progression to NASH, liver cirrhosis, and HCC. However, most of the
Geographical Distribution: NASH mouse models that have been described to date develop NASH
Trials conducted in China (40%), United States generally for more than 24 weeks and there is an uncertainty of HCC
(30%), and European countries (20%). development. To overcome such shortcomings of experimental NASH
Funding Sources: studies, we established a novel NASH-HCC mouse model with very
Investigator-Initiated Trials (IITs): 65%. high reproducibility, generality, and convenience.
Industry-Sponsored Trials: 35%. Method: We treated male C57BL/6J mice with a newly developed
Primary and Secondary Outcomes: choline-deficient and methionine-restricted high-fat diet, named OYC-
Primary Outcomes: HVPG reduction, variceal NASH2 diet, for 60 weeks.
bleeding prevention, and mortality. Result: Treatment of OYC-NASH2 diet for 3 weeks revealed marked
Secondary Outcomes: Liver function improvement, steatosis, lobular inflammation, and fibrosis, histologically diagnosed
esophageal variceal grade, heart rate, and patient-reported quality of
as NASH. Liver cirrhosis was observed in all mice with 48-week the only effective treatment for end-stage liver disease. However, the
treatment. Liver nodules emerged at 12 weeks of the treatment, > 2 limited availability of donors, post-transplant immune rejection, and
mm diameter liver tumors developed in all mice at 24 weeks of the high costs limit its widespread clinical application. Mesenchymal
treatment and HCC appeared after 36-week treatment. stem cell (MSC) transplantation has shown potential for improving
Conclusion: In conclusion, our rapidly progressive and highly liver function in liver disease. This study conducted an exploratory
reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical histological evaluation of human umbilical cord-derived mesenchymal
development and research on the pathogenesis of human NAFLD- stem cells (hUC-MSCs) for the treatment of hepatitis B cirrhosis.
NASH-HCC. Our mouse model would be useful for the development of Method: Following informed consent, 20 patients with compensated
novel chemicals for NASH-HCC-targeted therapies. hepatitis B cirrhosis were randomly divided into two double-blind
Table and Figure:Figure 1.Time course of gross appearance and groups: the experimental group (10 patients) and the control group
nodule formation in livers of C57BL/6J mice fed OYC-NASH2 diet. (10 patients). The experimental group received MSC therapy through
Figure 2.Time course of histopathological features in non-tumorous intravenous infusion of hUC-MSCs in addition to oral tenofovir for viral
liver tissues of C57BL/6J mice fed OYC-NASH2 diet. suppression and Anluohuaxian pills for anti-fibrosis. The control group
received tenofovir and Anluohuaxian pills along with a placebo (hUC-
MSC blank suspension). Both hUC-MSC injection solution and placebo
PP0817
were supplied by Zhongyuan Concord Cell Storage Service Co., Ltd.,
Timing of Endoscopic Intervention and Its Impact on the Prognosis Tianjin, China (identical in appearance). Based on patient weight, a
of Patients with Liver Cirrhosis and Esophageal-Gastric Variceal single dose was calculated at 1 × 10^6 cells/kg. Treatment included
Bleeding five infusions administered at baseline, weeks 2, 4, 16, and 24.
Shenan Huang1, Zhili Wen1, Chaomin Ruan1 Liver biopsy was conducted before the first and final MSC treatments,
1
The Second Affiliated Hospital of Nanchang University and liver tissue pathology was assessed via histopathology and
Background: To investigate the impact of different endoscopic electron microscopy. Two pathologists evaluated liver tissue changes
intervention times on the prognosis and other outcomes of patients using the Ishak score and semi-quantitative scoring system (SSS = P
with liver cirrhosis accompanied by esophageal and gastric fundal + L + 2(N * W)).
varices. Result: In the MSC-treated group (n=10), improvements were
Method: A retrospective study was conducted to analyze 266 observed as follows: periportal interface inflammation improved in
patients with liver cirrhosis and esophageal-gastric variceal bleeding 1 case, bridging necrosis improved in 1 case, portal inflammation
who presented with symptoms like hematemesis and melena and improved in 3 cases, and focal (dot necrosis), apoptosis, and focal
underwent endoscopic intervention at the Second Affiliated Hospital inflammation improved in 4 cases, with the Ishak total score improving
of Nanchang University from January 2019 to November 2023. Patient in 6 cases.
data included general information, biochemical indicators, and In the placebo group (n=10), improvements were as follows: periportal
outcomes such as all-cause mortality, rebleeding, ICU admission, red interface inflammation improved in 3 cases, bridging necrosis
blood cell transfusion volume, and length of stay within 30 days. GBS, improved in 1 case, portal inflammation improved in 2 cases, and focal
MELD, CHILD, and AIMS65 scores were calculated. Patients were (dot necrosis), apoptosis, and focal inflammation improved in 2 cases,
categorized into emergency (≤6h), early (>6h, ≤24h), and late (>24h) with the Ishak total score improving in 3 cases.
endoscopic intervention groups based on the time from admission to SSS scores showed a decrease of >2 points in 6 cases in the MSC-
intervention. The study assessed the impact of intervention timing on treated group, while 3 cases in the placebo group showed a similar
clinical outcomes and identified risk factors for all-cause mortality and improvement.
rebleeding. Conclusion: MSC treatment improved liver histopathology scores
Result: The three groups showed no significant difference in 30-day in 6 out of 10 patients with hepatitis B cirrhosis, while placebo
all-cause mortality (P=0.097) or average hospital stay (P=0.074), treatment (tenofovir and Anluohuaxian pills) improved scores in 3 out
but varied significantly in rebleeding rate (P=0.032). The emergency of 10 patients. These findings suggest that MSCs may modulate the
endoscopic intervention group (≤6 hours) had a higher rebleeding hepatic immune environment and inhibit hepatic stellate cell activation,
rate (18.6%) than the early (7.1%) and late (8.2%) groups. Significant warranting further exploration.
differences were also found in average blood transfusion volume
(P<0.05) and ICU admission rate (P<0.05) among the groups. PP0819
Specifically, the emergency and early groups had higher blood
High-sensitivity troponin T and N-terminal pro-B-type natriuretic
transfusion volumes and ICU admission rates than the late group.
peptide, but not coronary artery disease, may be associated with
Conclusion: 1.The timing of endoscopic intervention does not
further decompensation and death in liver cirrhosis
significantly influence the 30-day all-cause mortality in patients with
cirrhosis and esophageal-gastric variceal bleeding (EGVB). To Liyan Dong1,2, Yao Xiao1,3, Yibing Li1, Yong He1,4, Yu Liu1, Xingshun
mitigate the risk of recurrent bleeding in EGVB patients, endoscopic Qi1, Huishan Wang1
intervention may be considered after an interval of six hours following
1
General Hospital of Northern Theater Command, 2China Medical
hospital admission. University, 3Liaoning University of Traditional Chinese Medicine,
2.Age and heart rate are identified as independent risk factors for
4
Shenyang Pharmaceutical University
both 30-day all-cause mortality and recurrent bleeding in patients with Background: Currently, coronary artery disease (CAD) is very
EGVB, whereas systolic blood pressure acts as a protective factor common worldwide, and N-terminal pro-B-type natriuretic peptide
against these adverse outcomes. (NT-Pro BNP) and high-sensitivity troponin T (hs-TNT) are major serum
biomarkers for cardiac dysfunction. However, the association between
CAD, NT-Pro BNP, and hs-TNT with prognosis of patients with cirrhosis
PP0818
remains unclear.
Exploratory Evaluation of Hepatic Tissue Changes in Hepatitis Method: Patients with cirrhosis who were consecutively admitted to
B Virus-Related Compensated Cirrhosis Treated with Human the Department of Gastroenterology of our hospital from June 2020
Umbilical Cord-Derived Mesenchymal Stem Cells to January 2024 were retrospectively screened. Kaplan-Meier and
Yingan Jiang1,2, Zhi Zeng1,3, Jingmin Zhao4,5, Pingji Liu1,2 Nelson-Aalen cumulative risk curves as well as competing risk and
1
Renmin Hospital of Wuhan University, 2Department of infectious Cox regression analyses were used to estimate the associations
disease, 3Department of Pathology, 4The Fifth Medical Center of PLA of CAD, NT-Pro BNP, and hs-TNT with further decompensation and
General Hospital, 5Center of Pathology Diagnosis and Research death, if appropriate.
Background: Hepatitis B virus-related cirrhosis can progress to liver Result: Overall, 601 cirrhotic patients were included. hs-TNT>14 ng/L
failure and hepatocellular carcinoma, with liver transplantation being and NT-Pro BNP≥300 pg/ml, but not CAD, were significantly associated
with higher cumulative incidence of further decompensation and
death in Kaplan-Meier (hs-TNT for further decompensation: P<0.001, PP0821
for death: P<0.001; NT-Pro BNP for further decompensation: Safety and feasibility of transjugular intrahepatic portosystemic
P=0.006, for death: P=0.003) and Nelson-Aalen (hs-TNT for further shunt in elderly patients with liver cirrhosis and esophagogastric
decompensation: P<0.001, for death: P<0.001; NT-Pro BNP for further variceal bleeding.
decompensation: P=0.017, for death: P=0.005) curves. Additionally,
Botao Wu1
hs-TNT>14 ng/L was significantly associated with increased risk
of further decompensation and death in multivariate competing risk
1
[email protected]
analyses (further decompensation: P=0.012; death: P=0.001), and hs- Background: Investigate safety and feasibility of elderly patients with l
TNT>14 ng/L was an independent predictor of death in multivariate iver cirrhosis and esophagogastric variceal bleeding with Viatorr stent
Cox regression analyses (P=0.017). However, NT-Pro BNP and CAD to
were not independently associated with further decompensation or enable early assessment, prevention, and intervention
death in multivariate competing risk and Cox regression analyses. Method: A retrospective study analyzed 211 patients with cirrhosis and
Conclusion: hs-TNT and NT-Pro BNP, but not CAD, should be esophageal variceal bleeding who underwent TIPS with Viatorr stents
incorporated in the prognostic model of liver cirrhosis. (Oct 2018–Oct 2022). After excluding 63 cases with incomplete data,
Table and Figure:Figure 1.Graphical Abstract 92 patients (46 elderly, 46 non-elderly) matched by age were included.
Follow-up at 1, 3, 6, and 12 months assessed hepatic function, HE
incidence, rebleeding, and mortality. The primary endpoint was HE
PP0820
incidence; secondary endpoints included rebleeding and mortality
Evaluation of Percutaneous Microwave Ablation of the Spleen rates.
Combined with Splenic Artery Occlusion for Treating Secondary Result: Portal Vein Pressure:
Hypersplenism: A Single-Arm Study TIPS significantly reduced portal vein pressure in both groups.
Xing Li1, Huikai Li1, Yong Xu1, Tongguo Si1, Rui Xia1, Mao Yang1, Elderly group: Preoperative = 38.5 ± 7.94 mmHg; postoperative =
Rentao Li1, Yang Liu1 26.14 ± 5.32 mmHg (P = 0.000).
1
Tianjin Cancer Hospital Airport Hospital Non-elderly group: Preoperative = 39.67 ± 9.32 mmHg; postoperative
Background: Portal hypertension, often caused by cirrhosis, is a = 27.76 ± 7.08 mmHg (P = 0.000).
common complication in liver cancer patients, leading to obstruction No significant difference in postoperative pressure reduction between
of splenic vein outflow, increased splenic pressure, and secondary groups (P = 0.214).
hypersplenism. Traditional surgical treatments for hypersplenism are Liver Function:
highly invasive, and many patients are not suitable candidates. Splenic Total and indirect bilirubin levels increased postoperatively in both
artery embolization, while effective, may carry significant side effects. groups, peaking early and then declining (P < 0.05).
This study aims to evaluate the safety and efficacy of percutaneous ALT increased in the elderly group at 6 months (P < 0.05) and in the
microwave ablation as a less invasive treatment option. non-elderly group at 1 and 3 months (P < 0.05).
Method: This study collected data from 40 patients with cirrhosis- Creatinine decreased significantly at various postoperative points in
induced secondary hypersplenism who underwent percutaneous both groups (P < 0.05).
microwave ablation of the spleen. Preoperative assessments included HE Incidence:
complete blood count, liver and kidney function tests, coagulation Within 3 months, HE incidence was higher in the elderly group.
studies, and abdominal imaging. The ablation procedure involved No significant difference in HE rates at 6 and 12 months.
splenic artery balloon occlusion, artificial pleural effusion, evaluation Risk Factors for HE:
of splenic artery blood flow velocity, moving-shot and fixed-needle Positive correlation: Ascites, ALT, creatinine, and hemoglobin.
microwave techniques, and contrast-enhanced ultrasound to assess Negative correlation: Albumin.
ablation volume. Multivariate analysis confirmed ascites, ALT, and creatinine as risk
Result: A total of 40 patients were treated, with a mean age of 58.0 factors, while albumin was protective.
years (range: 37-72 years), including 24 males (60%) and 16 females Conclusion: TIPS effectively reduces portal vein pressure and
(40%). Among them, 28 patients (70%) had Child-Pugh Class A rebleeding risk, with similar efficacy in elderly and non-elderly patients.
liver function, while 12 (30%) were classified as Child-Pugh Class B. Hepatic function may worsen temporarily but recovers over time. TIPS
Preoperative blood tests showed: White blood cell count: (7.85±6.92) is safe for elderly patients, and age is not a decisive factor for treatment
×10⁹/L; Red blood cell count: (2.88±0.68) ×10¹²/L; Platelet count: eligibility.
(51.55±16.86) ×10⁹/L. Changes in Platelet Counts Post-Ablation: At 7
days: increased to (77.33±37.25) ×10⁹/L; At 1 month: increased further PP0822
to (113.7±81.44) ×10⁹/L; At 3 months: peaked at (215.53±147.88) The efficacy and safety of painless gastroscopy assisted
×10⁹/L; At 6 months: decreased to (159.47±118.46) ×10⁹/L. Although esophageal and gastric variceal ligation for secondary prevention
platelet counts peaked at 3 months, they remained significantly higher of variceal bleeding in patients with liver cirrhosis
than pre-ablation levels at all time points (P<0.05). White blood cell
Rui Zhang1
counts initially increased post-ablation but returned to baseline levels
by 6 months, showing no significant difference from pre-ablation levels
1
[email protected]
(P>0.05). Red blood cell counts showed minimal changes throughout Background: Endoscopic variceal ligation (EVL) is the main treatment
the study period (P>0.05). Immediate ultrasound and MRI evaluations of esophagogastric variceal bleeding (EGVB). We aimed to investigate
post-ablation indicated that the average ablated volume accounted the effectiveness and safety of painless gastroscopy assisted EVL
for (78.30±12.45)% of the total spleen. MRI follow-ups at 1-3 months treatment in secondary prophylactic treatment of EGVB patients with
showed that the ablated volume averaged (79.65±18.22)% of the liver cirrhosis is effective and safe.
spleen in 6 patients. No ablation-related deaths were reported Method: We retrospectively analyzed 651 EGVB patients who received
among the 40 patients; however, 5 patients (12.5%) experienced secondary prophylactic EVL treatment at the Second Hospital of Hebei
complications: 3 cases of bleeding, 1 case of renal failure, and 1 case Medical University from June 2018 to June 2023. After excluding
of splenic vein thrombosis. those with incomplete data, a total of 363 patients were included. The
Conclusion: Percutaneous microwave ablation of the spleen enrolled patients were divided into the sedation EVL group and the
combined with splenic artery occlusion shows promising short-term ordinary EVL group. The two groups were matched using propensity
efficacy and has the potential to be an effective alternative for patients score matching method, and ultimately included 107 people in the
with hypersplenism. Further studies are warranted to evaluate long- each group.
term outcomes. Result: 1. Among the selected patients with EGVB with cirrhosis,
Table and Figure:Figure 1.The balloon blocked the splenic artery there were no significant differences in gender, age, etiology of
Figure 2.The effect of spleen ablation was evaluated by enhanced MRI cirrhosis,Child-Pugh grade, bilirubin, ALT, AST and Cr(P>0.05);
2. There is no significant difference in the treatment effect of varicose in liver fibrosis. The levels of p62, HSP-27 and HSP70 were reduced in
veins between the two groups of patients (χ2=2.610, P=0.271), the both the YAP-HKO and VP group, while MFGE8 levels were icreased.
procedure time required for sedation EVL group was shorter than that Our findings provide valuable insights into the role of YAP in liver
of the ordinary EVL group (6.16±1.73 minutes VS 8.37±3.7 minutes, fibrosis and may contribute to find novel biomarkers for the disease.
P=0.00), and the satisfaction of visual fields was better than in the Table and Figure:Figure 1.RNA sequencing and proteomic analysis of
ordinary EVL group( χ2=8.165, P=0.043). During sequential treatment, liver tissues from wild, YAP-HKO and treated with VP mice with liver
23 patients (33.8%) in the ordinary EVL group still chose ordinary fibrosis.
gastroscopy, 45 patients (66.2%) refused ordinary gastroscopy and Figure 2.Expression of HSP27, HSP70, MFGE8 and p62 in liver tissue
chose painless gastroscopy. 76 patients (97.4%) in the sedation EVL of mice.
group received painless gastroscopy again, while only 2 patients
(2.6%) refused painless gastroscopy and chose ordinary gastroscopy.
PP0824
3. Compared with the ordinary EVL group, there were no significant
differences in nausea, vomiting, rebleeding, chest and abdominal pain, Resting-State fMRI Global Small-World Network as a Mediator
bloating, diarrhea, fever, dizziness, aspiration pneumonia, and hepatic Between Glymphatic System and Cognitive Function in Patients
encephalopathy in the sedation EVL group post of EVL (P>0.05); with Minimal Hepatic Encephalopathy
Conclusion: Painless gastroscopy assisted esophageal and gastric Qian Zhang1, Zhenliang Xiong1, Ming Zhong1, Hong Peng1
variceal ligation treatment for liver cirrhosis combined with EGVB 1
Guizhou Provincial People’s Hospital
bleeding can shorten procedure time, improve the satisfaction of Background: Minimal hepatic encephalopathy (MHE) significantly
visual fields, not worsen liver and kidney function damage, and not impairs quality of life and cognitive function in patients with cirrhosis.
increase the incidence of adverse events. Given the higher comfort Despite its clinical importance, the pathogenesis of MHE remains
of performing painless gastroscopy, more and more patients are incompletely understood. Exploring the interplay between glymphatic
choosing to undergo it, which is relatively safe and effective for liver system dysfunction and brain network inefficiency may provide novel
cirrhosis patients. therapeutic targets. This study investigates the roles of glymphatic
function and brain network efficiency in the cognitive impairment
PP0823 associated with MHE.
Method: A total of 67 patients with decompensated cirrhosis were
Unraveling the Molecular Mechanism of YAP Gene Knockout
enrolled and categorized into non-hepatic encephalopathy (non-HE,
in Liver Fibrosis: A Multi-Omics Approach Integrating
n = 36) and MHE (n = 31) groups. All participants underwent the
Transcriptomics and proteomics
Psychometric Hepatic Encephalopathy Score (PHES) assessment
Siyuan Wang1, Shihui Liu1, Chuanmiao Liu1, Wen Zhao1 to evaluate cognitive function. Diffusion tensor imaging was used to
1
The First Affiliated Hospital of Bengbu Medical University, Bengbu measure glymphatic function via the perivascular space activity index
Background: This study investigates the role of the yes-associated (ALPS index), while resting-state functional MRI (fMRI) was utilized to
protein (YAP) gene in the development of liver fibrosis, utilizing a multi- assess brain network efficiency.
omics approach. Result: No significant differences were observed between the two
Method: A total of 24 male C57BL/6 mice were divided into four groups in terms of age, sex, education level, or Child-Pugh scores.
groups: control group, a liver fibrosis model induced by carbon However, the MHE group exhibited significantly lower ALPS index
tetrachloride (CCl4), a YAP knockout in hepatocytes (YAP-HKO) liver values (1.15 ± 0.12) compared to the non-MHE group (1.42 ± 0.10,
fibrosis group, and a group treated with verteporfin (VP). Histology, p < 0.05), indicating impaired glymphatic activity. Additionally,
immunohistochemistry (IHC), and western blotting were performed functional brain network metrics were compromised in MHE patients,
to evaluate the role of YAP in liver cirrhosis. RNA sequencing (RNA- as evidenced by reduced small-world network parameters: Gamma
Seq) and proteomic analysis of liver tissues from all four groups (0.748 vs. 0.849, p = 0.016) and Global Efficiency (Eg) (0.253 vs. 0.254,
were conducted to explore the underlying mechanism of YAP in the p = 0.014). Correlation analysis demonstrated a moderate positive
regression of liver fibrosis. IHC and western blotting were also detected association between the ALPS index and PHES scores (r = 0.549, p
to verify the expression of differential expression genes (DEGs) in liver < 0.001). PHES scores were also positively correlated with Gamma (r
tissue of YAP-HKO mice and VP-treated mice. Expression of DEGs in = 0.386, p = 0.001), while the ALPS index correlated with Gamma (r
plasma was assessed by ELISA to further evaluate their roles in liver = 0.308, p = 0.011). Mediation analysis revealed that Gamma partially
cirrhosis. mediated the effect of glymphatic dysfunction on cognitive impairment
Result: Compared with the CCl4 group, YAP-HKO group exhibited in MHE, with an indirect effect of 1.695, accounting for 13.99% of the
more pronounced inflammation, necrosis and collagen fiber total mediation effect.
deposition, while these features were ameliorated in the VP group. Conclusion: This study highlights the dual contributions of reduced
Additionally, the protein levels of α-SMA were similar in the YAP-HKO glymphatic system activity and diminished brain network efficiency to
group, while they were downregulated in the VP group compared to cognitive dysfunction in MHE. The identification of Gamma as a partial
the CCl4 group. Expression of YAP was reduced in the YAP-HKO and mediator between glymphatic dysfunction and cognitive impairment
VP groups. RNA-Seq analysis and proteomic analyses revealed 27 underscores the potential of targeting brain network efficiency and
molecules with significant changes at both the transcript and protein glymphatic function in developing novel therapies for MHE. These
levels among the control, CCl4 and YAP-HKO group, and 88 molecules findings may pave the way for improved management strategies,
with significant changes among the control, CCl4 and VP groups. Of enhancing patient outcomes and quality of life.
these, 12 molecules were commonly differentially expressed across all Table and Figure:Figure 1.Graphical Abstract
three group. Notably, CTSO, p62, MFGE8, Hspb1 (HSP27), Hspa1b
(HSP70) and Cyp2a5 were found to be positively correlated with YAP.
PP0825
IHC and western blotting analysis of liver tissue from the mice revealed
that HSP27, HSP70 and p62 were elevated in CCl4 group and reduced Reducing the occurrence of decompensated events and improving
in both the YAP-HKO and VP group. Furthermore, plasma levels of liver function in post-TIPS cirrhotic patients by selective COX-2
p62, HSP27 and HSP70 were progressively increased in patients inhibitors: A retrospective study
with chronic hepatitis B (CHB) and HBV-related cirrhosis compared Zhu Yang1, Jinhang Gao2, Chengwei Tang1
to healthy controls, while MFGE8 levels were gradually decreased. 1
Department of Gastroenterology, West China Hospital of Sichuan
Spearman correlation analysis showed that p62, HSP27 and HSP70 University, 2Lab of Gastroenterology and Hepatology, West China
were positively correlated with α-SMA and YAP, while MFGE8 showed Hospital of Sichuan University
a negative correlation with both α-SMA and YAP. Background: Liver cirrhosis is associated with high morbidity,
Conclusion: Loss of YAP in hepatocytes accelerated the progression mortality and medical costs worldwide. In addition to etiology, portal
of liver fibrosis, whereas inhibiting YAP using VP led to improvements
hypertension as a major pathophysiological determinant exacerbates factor for recurrent decompensation events after TIPS in patients with
haemodynamic disorders and systemic inflammation in the sustainable liver cirrhosis. However, there was no statistically significant difference
development of cirrhosis. Systemic inflammation is a major determinant in mortality between the recurrent decompensated event group and
in the progression of decompensated cirrhosis. Up-expression of the non-recurrent decompensated event group (12.24% vs 5.41%,
cyclooxygenase-2 (COX-2) in liver and intestinal tract has been P=0.48).
reported in the cirrhotic patients. This retrospective clinical study Conclusion: 1. Serum Na<137.5mmol/L is an independent risk factor
aimed to evaluate the effects of selective COX-2 inhibitors (COX-2-I) for recurrent decompensation events after TIPS in patients with liver
on the occurrence of decompensated events in the cirrhotic patients cirrhosis, esophageal and gastric variceal bleeding.
who underwent transjugular intrahepatic portosystemic shunt (TIPS). 2. The mortality rate within 12 months in the group of patients with
Method: Cirrhotic patients underwent TIPS were enrolled recurrent decompensation after TIPS was slightly higher than that of
retrospectively. The cohort was divided into the TIPS and TIPS+COX- patients without relapse loss.
2-I group according to whether taking COX-2-I due to comorbidity of Table and Figure:Figure 1.
rheumatoid arthritis (RA) or osteoarthritis (OA). The primary outcome Figure 2.
was the occurrence of decompensated events. The second outcome
was the change of liver function measured by the albumin-bilirubin
PP0827
(ALBI) score and modified ALBI (mALBI) grade.
Result: A total of 140 patients were recruited retrospectively, 89 and Application of speckle tracking echocardiography in cirrhotic
51 patients were allocated to the TIPS and TIPS+COX-2-I cohort cardiomyopathy patients: a single center observational study.
respectively. The cumulative occurrence of decompensated events Jiakun Liu1, Cuncao Wu1, Xiaoxiao Hu1, Rui Huang1,2,3
yielded a lower incidence in the TIPS+COX-2-I group than in the TIPS 1
Peking University People‘s Hospital, 2Peking University Hepatology
group (5.88% vs. 21.35%, p=0.016). ALBI scores were reduced in the Institute, 3Infectious Disease and Hepatology Center of Peking
TIPS+COX-2-I group (p<0.001) at the end of treatment (-2.41) than at University People‘s Hospital
the baseline (-2.16) without adverse drug reactions. Cox regression Background: Cirrhotic cardiomyopathy (CCM) often eludes
analysis demonstrated that COX-2-I was an independent protective detection through conventional cardiovascular imaging modalities.
factor for occurrences against clinic events. Consequently, more sensitive echocardiography indices, such as
Conclusion: Selective COX-2 inhibitor as an independent protective speckle tracking echocardiography (STE), have emerged as valuable
factor significantly reduced occurrences of decompensated events tools for identifying subclinical myocardial dysfunction in cirrhotic
and improved liver function in the post-TIPS patients with safety. patients. However, the available data on Global Longitudinal Strain
Table and Figure:Figure 1.Table 1 (GLS) and other STE-measured parameters in cirrhotic patients are
Figure 2.Figure currently limited. This study aims to provide a critical evaluation of the
current evidence regarding the use of STE in patients with LC.
PP0826 Method: In this prospective observational study, cirrhotic patients
admitted from July 2023 to May 2024 in Peking University People’s
To explore the risk factors for transjugular intrahepatic
Hospital were enrolled. We excluded patients with known cardiac
portosystemic shunt in the treatment of esophageal and gastric
disease, chronic lung disease, severe renal insufficiency. Laboratory
variceal bleeding and recurrent decompensation events
information, including liver function, serum creatinine, N-terminal pro-
LIU Yu Hui1, Jiang Xiang2, You Yu2 B-type natriuretic peptide (NT-proBNP) and high sensitivity-C-reactive
1
Department of Pharmacology, School of Pharmacy, Jiangxi University protein (hs-CRP). Tissue Doppler echocardiography combined with
of Traditional Chinese Medicine, 2Department of Gastroenterology, two-dimensional speckle-tracking echocardiography was performed.
The First Affiliated Hospital of Nanchang University The left ventricular end-diastolic diameter, left ventricular systolic
Background: To investigate the risk factors for recurrent diastolic diameter, interventricular septal thickness and left ventricular
decompensation events in patients with cirrhosis and esophageal ejection fraction (LVEF) were measured from the parasternal long-axis
and gastric variceal bleeding treated with transjugular intrahepatic section. The early diastolic transmitral flow velocity (E) and late diastolic
portosystemic shunt (TIPS). transmitral flow velocity (A), early diastolic mitral annulus velocity
Method: A retrospective analysis was performed for 86 patients with (e’), left atrial volume index and peak tricuspid regurgitation velocity,
esophageal and gastric variceal bleeding who received TIPS treatment were measured. Left ventricular GLS and left atrium strain (LAS) was
in the First Affiliated Hospital of Nanchang University from January calculated. Then we measured the peak atrial longitudinal strain at the
1, 2014 to March 31, 2023. The patients were divided into recurrent end of the reservoir phase from atrial longitudinal strain curves. CCM
decompensated event group and non-recurrent decompensated were defined according to redefining CCM criteria in 2019.
event group according to whether there was another cirrhosis related Result: Among the 54 patients diagnosed with cirrhosis, data on
decompensation event during the follow-up period, and the risk factors their cirrhosis causes, gender, age, medical history, MELD score,
affecting recurren