HCC in the Setting of Hepatitis B:

Key Issues for Clinicians Providing Care for

Liver Diseases

This program is supported by an educational grant from Gilead Sciences, Inc.

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Faculty
Norah Terrault, MD, MPH Paul Y. Kwo, MD
Professor of Medicine Professor of Medicine
Chief of Gastrointestinal and Liver Director of Hepatology
Diseases Stanford University School of
University of Southern California Medicine
Los Angeles, California Palo Alto, California
Faculty
Robert S. Brown, MD, MPH
Gladys and Roland Harriman Professor of Medicine
Vice Chair, Mentorship and Academic Development
Clinical Chief, Division of Gastroenterology and Hepatology
Weill Cornell Medicine
New York, New York
Faculty Disclosures
Norah Terrault, MD, MPH, has reported that she has received consulting fees
from Dova Pharmaceuticals, and has received funds for research support from
AbbVie, Bristol Myers Squibb, Gilead Sciences, and Merck & Co.
Paul Y. Kwo, MD, has disclosed that he has received consulting fees
from AbbVie, Aligos, Ambys, Dova, Gilead, Mallinckrodt, Shionogi, and
Surrozen; funds for research support from Allergan, Arrowhead, Assembly,
Bristol-Myers Squibb, Eiger, Gilead, and Janssen; other financial or material
support from Generon and Janssen; and has ownership interest in Durect.
Robert S. Brown, Jr, MD, MPH, has reported that he has received consulting
fees from Bristol Myers Squibb, and Gilead Sciences, and has received funds for
research support from Gilead Sciences.
Program Outline
 Assessing HCC risk in patients with hepatitis B
‒ Patient case 1 is a 52-yr-old Black male diagnosed with HBV infection 6 yrs
ago
 HCC screening and surveillance in patients with hepatitis B
‒ Patient case 2 is a 57-yr-old Asian male with chronic HBV who has a lesion
discovered by ultrasound surveillance
 Management of HCC: Liver specialists as leaders of the multidisciplinary
team
‒ Patient case 3 is a 65-yr-old Russian male with chronic HBV, recently
diagnosed with hepatocellular carcinoma
Slide credit: clinicaloptions.com
Assessing HCC Risk in Patients With HBV
Patient Case 1
 A 52-yr-old African-American male Parameter Result
diagnosed with HBV infection 6 yrs Liver function tests
 Total bilirubin, mg/dL 0.8
ago  Albumin, g/L 4.0
 ALT, IU/L 82
‒ Therapy was not recommended by  AST, IU/L 60
PCP  AFP, ng/mL 4.8

 Nonsmoker, no alcohol use Virology

 HBsAg/anti-HBs Positive/negative
 Anti-HBc Positive
 Experiencing mild fatigue  HBeAg/anti-HBe Positive/negative
 HBV DNA, IU/mL 1,600,000
 No HIV, HCV, or HDV coinfection
Platelets, n x 109/L 170
Fibroscan, kPa 13.2

Slide credit: clinicaloptions.com

 HCC Surveillance: Patients at Highest Risk

Threshold Incidence for

Population Group, % per Yr Efficacy of Surveillance, Incidence of HCC
> 0.25 LYG (%)
Hepatitis C cirrhosis 1.5 3-5
Hepatitis B cirrhosis 0.2-1.5 3-8
Asian male hepatitis B carriers
> 40 yrs of age 0.2 0.4-0.6

Asian female hepatitis B carriers

> 50 yrs of age 0.2 0.3-0.6

Marrero. Hepatology. 2018;68:723. Slide credit: clinicaloptions.com

 REVEAL: Risk of HCC Among Patients With Chronic
Hepatitis B
 3653 untreated HBsAg-positive adults in Taiwan followed for mean of 11.4 yrs;
85% HBeAg negative at entry
Incidence of HCC Without vs With Cirrhosis Incidence of HCC by HBV DNA Levels at Entry
7.0
1.4 < 300
6.0 300-9999
1.2 10,000-99,999
5.0
1.0 100,000-
% per Yr

4.0 999,999

% per Yr
0.8 ≥ 1 million
3.0
0.6
2.0 0.4
1.0 0.2
0 0
No Cirrhosis HBV DNA (copies/mL)
Cirrhosis
Chen. JAMA. 2006;295:65. Slide credit: clinicaloptions.com
 HCC Screening Recommendations for
HBsAg-Positive Patients
 Screen whether or not on anti-HBV treatment:
‒ Anyone with cirrhosis
‒ Asian males > 40 yrs of age
‒ Asian females > 50 yrs of age
‒ Black males > 40 yrs of age
‒ Persons with positive family history of cirrhosis or HCC in
first-degree relative
‒ HDV coinfection

Terrault. Hepatology. 2018;67:1560. Slide credit: clinicaloptions.com

 Incidence of HCC Among African-Americans
 VA study of 8320 patients with chronic hepatitis B; 39% African-American,
95% male, followed for 7.1 yrs
‒ Risk of HCC is highest among Asian-Americans, followed by Whites and
African-Americans
Incidence of HCC per Yr by Race and Age
1 AA
HCC Incidence, % per Yr 0.9
White
0.8 Asian-Am
0.65
0.61
0.6 0.57
0.45
0.4
0.4

0.2 0.14 0.14

0.03
0
All Participants ≤ 40 Yrs of Age ≥ 40 Yrs of Age

Mittal. Clin Gastroenterol Hepatol. 2018;16:252. Slide credit: clinicaloptions.com

 Country of Origin and Patients With HCC at Age < 40 Yrs
 59,907 US patients with HCC from Adjusted OR for
P
2000-2012; median age at diagnosis Characteristic HCC at Age < 40
Value
yrs [95% CI]
62 yrs
Race
 29% of US patients with HCC are  White (ref)
 Black 1.84 [1.53-2.20] < .01
foreign born  API 1.92 [1.55-2.37] < .01
‒ ~ 5% Black Area of birth
 West Africa 16.3 [9.15-27.9] < .01
‒ ~ 85% Asian-Pacific Islanders (API)  East Africa 3.48 [1.54-6.82] < .01
 Central/ South 11.0 [4.45-23.7] < .01
 Certain regions in Africa strongly Africa
 North Africa 1.15 [0.19-3.62] .59
associated with onset of HCC at
< 40 yrs of age

Yang. Cancer. 2017;123:81. Slide credit: clinicaloptions.com

 Risk of HCC and Family History of HCC
Risk of HCC by Family History of HCC Age Distribution of HCC Onset Within Families
0.18 and HBsAg Serostatus Parents
20
Sons
Cumulative incidence of HCC (%)

0.16 Family hx (-)/HBsAg (-)

Daughters

Number With ≥ 1 First-degree

Family hx (+)/HBsAg (-)

Relative With HCC (n = 44)

0.14 Family hx (-)/HBsAg (+)
Family hx (+)/HBsAg (+) 15
0.12
0.10
0.08 10

0.06
0.04 5
0.02
0
0
0 2 4 6 8 10 12 14 16 18 10-19 20-29 30-39 40-49 50-59 60-69 70-79
Follow-up Time (Yrs) Age Interval (Yrs)

Loomba. Clin Gastroenterol Hepatol. 2013;11:1636. Tong. Hepatol Int. 2013;7:1019. Slide credit: clinicaloptions.com
 HCC Risk:
HBV and HDV Coinfection vs HBV Monoinfection
Sensitivity No. of Coinfection + P
Analyses Studies Patients (N) HCC Pooled Value
HBV and HDV OR [95% CI]
coinfection 1.28
Overall 93 98,289 [1.05-1.57] .01

1.31
Full text 85 92,613 [1.06-1.63] .01

VS 1.26
English only 86 96,965 [1.02-1.55] .03

Matched or 2.07
HCC adjusted 12 64,360 [1.48-2.90] <. 001
studies
Prospective 2.77
HBV mono- studies 11 7065 [1.79-4.28] < .001
infection

Alfaiate. J Hepatol. 2020;73:533. Slide credit: clinicaloptions.com

 Other Risk Cofactors of Potential Importance in
Development of HCC
 Alcohol misuse
Cumulative HCC Incidence by NA Therapy in Propensity
 Diabetes/metabolic syndrome/fatty liver Score-Matched Patients With HBV and Cirrhosis
delete
 HBV genotypes 50 delete

Cumulative Incidence (%)

ETV vs control P < .001 Control
‒ C vs B in Asians [1] 40 ETV vs LAM P = .043 38.9 n = 316

‒ F1 in Alaskan Natives[2] 30 28.5

LAM
20.9 22.2
 Lack of or inadequate antiviral therapy[1] 20
19.7 n = 182

11.4 12.2
‒ Analysis of propensity-matched cohorts 10
of treatment-naive patients with 4.8 7.0
ETV
7.0
4.3 n = 182
cirrhosis receiving ETV vs LAM vs control 0 2.8
(no treatment) showed reduced HCC risk 0 1 3 5
with ETV Treatment Duration (Yrs)

Hosaka. Hepatol. 2013;58:98. Grounder. J Pediatr. 2016;78:206. Slide credit: clinicaloptions.com

 HCC Risk Reduction: Tenofovir DF vs Entecavir for HBV
 Systematic review and meta-analysis of 15 studies of TDF (n = 16,101) vs ETV (n = 45,686) in
reducing incidence of HCC among patients with chronic hepatitis B
 Overall, treatment with TDF vs ETV associated with lower risk of HCC: HR = 0.80 (95% CI: 0.69-0.93;
P = .003, I2 = 13%); effect persisted in propensity score-matched cohorts and cirrhosis subcohorts
Propensity Score-Matched Cohorts Receiving TDF vs ETV
Study Log [HR] SE HR HR 95% CI Weight (%)
Kim BD 2018 -0.63 0.4378 0.53 0.22-1.25 7.0
Choi J 2019 -0.39 0.1916 0.68 0.47-0.99 19.6
Kim SU 2019 0.02 0.1428 1.02 0.77-1.35 24.1
Yip TC 2019 -0.94 0.3915 0.39 0.18-0.84 8.3
Hsu YC 2019 -0.26 0.3732 0.77 0.37-1.60 8.9
Lee SW 2019 0.03 0.1952 1.03 0.70-1.51 19.3
Chang KC 2019 -0.58 0.2855 0.56 0.32-0.98 12.9

Random effects model 0.75 0.58-0.97 100.0%

Heterogeneity: I2 = 46%, T2 = 0.0491, P = .09
0.2 0.5 1 2 5
Choi. Clin Gastroenterol Hepatol. 2021;19:246. Slide credit: clinicaloptions.com
Summary Points: HCC Risk Assessment in Patients who
are HBsAg Positive
 The risk factor mostly strongly associated with HCC is advanced fibrosis/cirrhosis
‒ Important that all patients have severity of fibrosis assessed
 Other groups at elevated risk for HCC:
‒ Family history of first-degree family member with HCC
‒ Asian or Black men > 40 yrs of age
‒ Asian women > 50 yrs of age
‒ Persons coinfected with HDV (screen for HDV)
 Emerging risk cofactors: alcohol misuse, NAFLD, certain HBV genotypes
 Antiviral therapy with sustained HBV DNA suppression reduces risk of HCC
Slide credit: clinicaloptions.com
HCC Screening and Surveillance
in Patients With HBV
Patient Case 2
 A 57-yr-old Asian male with chronic Parameter Result
hepatitis B; on tenofovir DF for Liver function tests
 Total bilirubin, mg/dL 0.8
anti-HBV therapy  Albumin, g/L 4.0
 Social alcohol use  ALT, IU/L 31
 AST, IU/L 20
 Normal LFTs and alpha-fetoprotein  AFP, ng/mL 4.0
Virology
(AFP)  HBsAg/anti-HBs Positive/negative
 Anti-HBc Positive
 Surveillance ultrasound (US)  HBeAg/anti-HBe Negative/negative
revealed a single 2.5-cm  HBV DNA, IU/mL Undetectable
hypoechoic lesion Platelets, n x 109/L 268

Slide credit: clinicaloptions.com

Ultrasound: Right Hepatic Lobe

What’s next?
Slide credit: clinicaloptions.com
Liver MRI

Arterial Phase Portal Venous Phase

2.1 cm LI-RADS 5 lesion in segment 6

Slide credit: clinicaloptions.com
 Screening vs Surveillance
 Screening: One-time application of diagnostic tests, imaging, or
procedures in apparently healthy patients
 Surveillance: Serial application of blood-based tests, imaging, or
procedures in an at-risk patient population
 Since the underlying risk for HCC is usually identifiable, patients who
are at risk for HCC development are highly encouraged to enroll in
surveillance programs for early detection of HCC

Frennette. Mayo Clin Proc Inn Qual Out. 2019;3:302. Slide credit: clinicaloptions.com
 AASLD Guidance on HCC Screening and Surveillance in
Patients Who Are HBsAg Positive
 HBsAg-positive patients with cirrhosis are  Insufficient data to identify high-risk groups
at high risk for HCC: screen/surveil with for HCC in HBsAg-positive children;
US every 6 mos, with or without AFP reasonable to screen children with advanced
fibrosis (F3), cirrhosis, or first-degree family
 Among HBsAg-positive patients without member with HCC, with US every 6 mos,
cirrhosis, screen/surveil high-risk subgroups with or without AFP
(based on age, sex, viral coinfections, family
history) with US every 6 mos, with or without  American and European guidelines consider
AFP: US most appropriate surveillance test[1,2]
‒ Asian or Black men > 40 yrs of age ‒ Some experts do not recommended AFP in
patients with active liver inflammation, as the
‒ Asian women > 50 yrs of age 6% to 8% gain in the detection rate may not
counterbalance the increase in false-positive
‒ Persons coinfected with HDV results[2]
‒ Persons with first-degree relative with HCC

1. Terrault. Hepatology. 2018;67:1560. 2. EASL CPG. J Hepatol. 2018;69:182. Slide credit: clinicaloptions.com
 Imaging Modalities for HCC Surveillance

Imaging Modality Advantages Disadvantages

 Highly operator and technique dependent—

 Noninvasive directly proportional to operator skill and experience
US  Nearly ubiquitous  Low sensitivity in obese patients and certain other
 Low cost disease states
 Soft tissue assessment

 High sensitivity
 Risk of high radiation
CT  Moderate to high
 High cost
resolution

 High sensitivity  Limited availability

MRI
 High resolution  Extremely high cost
 Gadolinium accumulation

Sherman. Semin Liver Dis. 2010;30:3. Slide credit: clinicaloptions.com

 Sensitivity of Imaging Modalities

Lesions Detected US Sensitivity, CT Sensitivity, MRI Sensitivity,

n/N (%) n/N (%) n/N(%)
Per nodule 92/200 (46) 123/194 (65) 126/175 (72)

< 2 cm 20/96 (21) 35/88 (40) 33/70 (47)

2-4 cm 44/71 (62) 59/74 (80) 66/77 (86)

≥ 4 cm 28/33 (85) 32/32 (100) 27/28 (96)

Per patient 88/138 (64) 113/149 (76) 99/117 (85)

Yu. Clin Gastroenterol Hepatol. 2011;9:161. Slide credit: clinicaloptions.com

 A Proposed Ultrasound Algorithm for HCC Surveillance

Poor/fair quality US
or abnormal Contrast-enhanced MRI or CT
biomarkers

Liver-dedicated
surveillance US
+ Negative MRI or CT
HCC biomarkers in
high-risk* patients
Good/excellent
US surveillance Abnormal US
quality US and
every 6 mos with or
normal HCC
biomarkers increasing biomarkers
biomarkers

*Per AASLD HCC guidance.

Gish. Gasterenterol Hepatol. 2014;10:121. Slide credit: clinicaloptions.com

 Diagnostic Algorithm for Suspected HCC
Liver nodule

< 1 cm > 1 cm

4-phase CT/dynamic
Repeat US at 3 mos
contrast-enhanced MRI

Arterial hypervascularity AND

Growing/changing character Stable
venous or delayed phase washout

Re-investigate according Other contrast enhanced

Yes No
to new size study (CT or MRI)

Arterial hypervascularity AND

HCC Biopsy
venous or delayed phase washout

Yes No
Bruix. Hepatology. 2011;53:1020. Slide credit: clinicaloptions.com
 FDA-Approved HCC Risk Biomarkers: AFP and AFP-L3
 AFP: alpha-fetoprotein
‒ Elevated in patients with hepatic injury or
cancer AFP-L1

 AFP-L3: Lens culinaris agglutinin-reactive

subfraction of alpha-fetoprotein
‒ A fucosylated isoform of AFP
Fucose
‒ AFP-L3% is ratio of AFP-L3 to total AFP (AFP-
L1 plus AFP-L3)
AFP-L3
‒ Elevated levels highly specific for/occur
early in HCC

Gish. Gastroenterol Hepatol (N Y). 2014;2:121. Slide credit: clinicaloptions.com

 FDA-Approved HCC Risk Biomarker: DCP/PIVKA-II
 Normal hepatocytes post- Prothrombin
DCP Prothrombin
translationally carboxylate precursor

prothrombin precursors, prior to CH2 CH2 CH2

secretion CH2 CH2 CH2

 Serum des-gamma-carboxy COOH COOH HOOC COOH

Glutamic acid Glutamic acid γ- carboxy Glutamic acid
prothrombin (DCP) an immature, non- (Glu) (Glu) (Glu)
carboxylated form of prothrombin γ- carboxy glutamic acid
(Glu)
‒ Also known as “proteins induced by
vitamin K absence-II” or PIVKA-II
‒ Elevated in absence of vitamin K Reduced vitamin K Oxidized vitamin K
dependent carboxylase, such as in Vitamin K–Dependent Carboxylation of
HCC[1] (also diminished in vitamin K DCP and Prothrombin Precursors[2]
deficiency or warfarin use)
1. Gish. Gastroenterol Hepatol (N Y). 2014;2:121. 2. Fukikawa. Acta Med Okayama. 2009;6:299. Slide credit: clinicaloptions.com
 A New Approach to Application of Biomarkers to
HCC Surveillance and Diagnosis: the GALAD Model
 Statistical model developed with data G – Gender
from 670 patients at a medical center
in UK A – Age
‒ 331 with HCC, 339 with chronic liver L – AFP-L3
disease
A – AFP
 Predicts probability of developing HCC
in persons with chronic liver disease D – DCP

‒ Validated internally and externally in  GALAD Score Z = -10.32 + 0.10 x [Age]

data sets from independent cohorts;
prospective studies needed + 1.39 x [Gender] + 2.43 x log[AFP]
+ 0.040 x [AFP-L3] + 1.45 x log[DCP]
 Probability of HCC = exp(Z)/[1+ exp(Z)]
‒ Gender: male = 1, female = 0
Johnson. Cancer Epidemiol Biomarkers Prev. 2014;23:144. Slide credit: clinicaloptions.com
 Validation of GALAD
 Validation of GALAD in 6834 patients Japanese Cohort
from Japan, Hong Kong, and Germany (Within Milan Criteria)
1.00
GALAD:
‒ 2430 with HCC, 4404 with CLD AUROC 0.91
0.75
 Performance of GALAD at AFP:

Sensitivity
AUROC 0.87
discriminating between pts with HCC
0.50 DCP:
and CLD vs pts with CLD alone, AUROC 0.78
quantified by area under the receiver
AFP-L3:
operating curve (AUROC) 0.25
AUROC 0.71
‒ AUROC > 0.90 for all cohorts 0
0 0.25 0.50 0.75 1.00
 Combination of risk biomarkers
1-Specificity
outperforms each individual biomarker,
in large retrospective cohorts
Berhane. Clin Gastroenterol Hepatol. 2016;14:875. Slide credit: clinicaloptions.com
Non-Contrast Liver MRI: HCC With HBV, No Cirrhosis
T2 T1 in phase T1 out of phase

 Noncontrast imaging:
‒ T2 bright
‒ DWI

T2 fat sat DWI

‒ Can have fat (not in
this case)

Slide credit: clinicaloptions.com

Contrast-Enhanced Liver MRI: HCC
T1 pre-contrast Late arterial Portal venous

 Contrast imaging
‒ Arterial hyper-enhancement (central, mass-like)
‒ Portal venous washout (lesion is less enhancing than the liver)
‒ Enhancing capsule on portal venous/delayed phase

Slide credit: clinicaloptions.com

 LI-RADS Reporting System
 A radiologic reporting system to assess Category Interpretation
probability that a hepatic lesion is LI-RADS 1 Benign
HCC, in patients with:
LI-RADS 2 Probably benign
‒ Cirrhosis LI-RADS 3 Intermediate probability for HCC
‒ Chronic hepatitis B LI-RADS 4 Probably HCC
‒ Current or prior HCC LI-RADS 5 Definite HCC
LI-RADS M Non-HCC malignancy
‒ Post liver transplant
LI-RADS TIV Tumor in vein
 Not suitable for patients:
LI-RADS NC Noncategorizable
‒ < 18 yrs of age
‒ With cirrhosis from congenital hepatic
fibrosis or vascular disorders
Marrero. Hepatology. 2018;68:723. Slide credit: clinicaloptions.com
 HCC Surveillance and Diagnostic Algorithm
Surveillance ultrasound with or without AFP
SURVEILLANCE Interpretation
Multiphase CT or MRI in
select patients*
Negative Subthreshold Positive
(< 10 mm lesions) (≥ 10 mm lesions or AFP ≥ 20 mg/mL)

Repeat US in 6 mos, Repeat US in 3-6 mos,

with or without AFP with or without AFP

DIAGNOSIS Diagnostic imaging for HCC with multiphase CT or MRI

Interpretation

No observation Categorize each

detected observation detected

Negative LI-RADS NC LI-RADS 1 LI-RADS 2 LI-RADS 3 LI-RADS 4 LI-RADS 5 LI-RADS M

No observation Noncategorizable Definitely Benign Probably Benign Intermediate Probably HCC Definitely HCC Malignant, not definitely HCC

Return to Recommend Recommend

multidisciplinary multidisciplinary
Repeat or surveillance Repeat or
Return to Return to discussion for tailored discussion for tailored
alternative imaging in 6 mos alternative workup that may workup that may
surveillance surveillance include biopsy (select
HCC confirmed
diagnostic imaging Consider repeat diagnostic imaging include biopsy (most
in 6 mos imaging in 6 mos cases), or repeat or cases), or repeat or
in ≤ 3 mos diagnostic imaging in 3-6 mos
alternative diagnostic alternative diagnostic
in ≤ 6 mos imaging in ≤ 3 mos imaging in ≤ 3 mos
*Depending on body habitus (eg, obesity), visibility of liver on If biopsy If biopsy
ultrasound, whether awaiting liver transplant, and other factors.
Marrero. Hepatology. 2018;68:723. Slide credit: clinicaloptions.com Pathology diagnosis Pathology diagnosis
LI-RADS Major Features
 Arterial enhancement  Washout
‒ HCC neoangiogenesis has increased ‒ Decreased PV blood supply, increased
arterial supply from nonhepatic triad tumor cellularity with low
arteries extracellular space, and enlarged
extracellular space in cirrhotic liver
‒ Non-rimlike enhancement of part
or entire lesion ‒ Some patients with preserved liver
function (eg, HBV without cirrhosis)
 Size may have an early transitional phase
that overlaps with PV phase
‒ Benign cirrhotic nodules rarely
> 15 mm  Enhancing capsule appearance
‒ HCC can be very small ‒ Either true capsule or compressed
parenchyma
Slide credit: clinicaloptions.com
Management of HCC: Liver Specialists as Leaders
of the Multidisciplinary Team
Patient Case 3
 65-yr-old Russian male recently Parameter Result

diagnosed with HCC, diagnosed Liver chemistries

 Total bilirubin, mg/dL 0.8
with HBV 25 yrs ago  Albumin, g/L
 ALT, IU/L
3.7
34
 AST, IU/L 40
 Retired software engineer with Virology
2 children  HBsAg/anti-HBs
 Anti-HBc
Positive/negative
Positive
 HBeAg/anti-HBe Negative/positive
 Nonsmoker  HBV DNA, IU/mL 1800 IU/L
AFP, ng/mL 84.8
 Feels well Platelets, n x 109/L 156
Ultrasound 2 cm mass in segment 3
 No family history of chronic liver MRI
Confirms lesion is
LI-RADS 5, OPTN 5b
disease

Slide credit: clinicaloptions.com

Liver MRI

T1 Arterial T1 Delayed Images

Slide credit: clinicaloptions.com

 HCC Treatment Options

Early Intermediate Advanced Terminal

Surgical Therapy Locoregional Therapy Systemic Therapy Best Supportive Care

Resection Chemoembolization Sorafenib Palliative care

Ablation Radioembolization Lenvatinib Hospice
Transplantation Stereotactic radiation Atezolizumab/
Bevacizumab
Nivolumab
Regorafenib
Cabozantinib
Ramucirumab
Marrero. Hepatology. 2018;86:723. Portions reproduced courtesy of Renu Dhanasekaran. Slide credit: clinicaloptions.com
 Multidisciplinary Approach in Patients With
HBV and HCC
Palliative care Radiology

Tumor Primary care

registry provider
Hepatology

Radiation
Nursing oncology

Clinical Our
research Surgery Patient
Naugler. Clin Gastroenterol Hepatol. 2015;13:827. Slide credit: clinicaloptions.com
 Survival Following Surgical Resection for HCC
 Best outcomes: single lesions < 5 cm, preserved hepatocellular function, no vascular invasion

100
Probability of Survival (%)

N = 77
80 Log-rank = .00001
No portal hypertension
60 (HVPG < 10 mm Hg)

40 Portal hypertension
+ bilirubin < 1 mg/dL
20
Portal hypertension
0 + bilirubin > 1 mg/dL
0 12 24 36 48 60 72 84 96
Postoperative Month
Llovet. Hepatology. 1999;30:1434. Slide credit: clinicaloptions.com
MRI Reveals Multiple New Lesions

Slide credit: clinicaloptions.com

 NCCN Guidance for Early Unresectable HCC
CLINICAL PRESENTATION TREATMENT SURVEILLANCE
 Refer to liver
transplant  Imaging every
center 3-6 mos for 2 yrs,
Transplant  Consider Transplant then every 6-12
candidate
bridge mos
therapy, as  AFP every 3-6 mos
indicated for 2 yrs, then every
Unresectable
 Inadequate 6-12 mos
Evaluate whether
 See relevant
hepatic patient is a
pathway in NCCN
reserve candidate for
 Tumor Options: guidance if disease
transplant
 If locoregional therapy recurs
location
preferred:
─ Ablation Progression
Not a ─ Arterially directed on or after
transplant
therapies systemic
candidate ─ Radiation therapy therapy
 Clinical trial
 Best supportive care
 Systemic therapy

Benson. J Natl Compr Canc Netw. 20019;17:302. Slide credit: clinicaloptions.com

 Example of Steps in Liver Transplant Evaluation
 Financial clearance  Liver imaging (CT/MRI/US of liver
vessels/bile ducts for vessels)
 Review previous history/etiology/
severity of liver disease/frailty  If hepatoma present, is it treated and
or within Milan criteria to obtain
 Current examination at transplant
MELD exception points
center by hepatologists/surgeons
 Psychosocial evaluation for support
 Multiple diagnostic tests of all organ
evaluation
systems (ie, renal, cardiac, and
pulmonary, with appropriate consults)  Meeting with nurse coordinator and
transplant social worker
 Laboratory testing
 Education of patient and family

Courtesy of Paul Kwo. Slide credit: clinicaloptions.com

 Multidisciplinary Approach in Patients With
HBV and HCC
Palliative care Radiology

Tumor Primary care

registry provider
Hepatology

Radiation
Nursing oncology

Our
Clinical Interventional Surgery Transplant
research radiology surgery Patient
Naugler. Clin Gastroenterol Hepatol. 2015;13:827. Slide credit: clinicaloptions.com
Treatment Options for Early and Intermediate HCC
Depend on Local Expertise

HCC: Post-Microwave Ablation

HCC: Transarterial Chemoembolization (TACE)

Pretreatment Post-treatment

Slide credit: clinicaloptions.com

Treatment Options for Early and Intermediate HCC
Depend on Local Expertise

Stereotactic Body Radiation Therapy (SBRT)

Y90 (Radioembolization)

Slide credit: clinicaloptions.com

Infiltrative HCC With Portal Vein Invasion and Lung
Metastases

Slide credit: clinicaloptions.com

 Multidisciplinary Approach in Patients With
HBV and HCC
Medical oncology
Palliative care Radiology

Tumor Primary care

registry provider
Hepatology

Radiation
Nursing oncology

Our
Clinical Interventional Surgery Transplant
research radiology surgery Patient
Naugler. Clin Gastroenterol Hepatol. 2015;13:827. Slide credit: clinicaloptions.com
 Multivariate Analysis of Factors Influencing All-Cause
Mortality in Patients With HCC
 VA cohort of 3988 HCC patients with HCC
 Associated with better overall survival: specialist (medical oncology, hepatology, surgery)
seen within 30 days of HCC diagnosis, and multidisciplinary tumor board review
Provider Factors HR for Mortality 95% CI P Value

Specialist within 30 days

 Hepatology 0.70 0.63-0.78 < .001
 Medical oncology 0.82 0.74-0.91 < .001
 Surgery 0.79 0.71-0.89 < .001
 Gastroenterology 1.02 0.93-1.13 .673
 Palliative care 2.10 1.87-2.36 < .001
 No specialist 0.89 0.65-1.21 .447

Evaluation by > 1 specialist 1.09 0.96-1.23 .187

Multidisciplinary tumor board 0.83 0.77-0.90 < .001

Serper. Gastroenterology. 2017;152:1954. Slide credit: clinicaloptions.com

 Modified BCLC Staging System, T Classifications, and
Treatment Strategies
HCC in cirrhotic liver

Advanced stage (C)

Very early stage (0) Early stage (A) Intermediate stage (B) Terminal stage (D)
Prognostic Portal invasion/
T1: Single < 2 cm Single or 2-3 nodules < 3 cm Multinodular, unresectable Not transplantable HCC
extrahepatic spread
stage Preserved liver function, Preserved liver function, Preserved liver function,
Preserved liver function, PS
End-stage liver function,
PS 0, T1 PS 0 PS 0 PS 3-4
1-2

2-3 nodules
Solitary
≤ 3 cm; T2

Optimal surgical
candidate

Transplant
Yes No
candidate

Yes No

Treatment Ablation Resection Transplant Ablation Chemoembolization Systemic therapy BSC

Survival > 5 yrs > 2.5 yrs ≥ 10 mos 3 mos

EASL Clinical Practice Guidelines: Management of Hepatocellular Carcinoma. J Hepatol. 2018;69:182.
Minagawa. Ann Surg. 2007;245:909. Slide credit: clinicaloptions.com
Take-home Points
 Hepatologists play a key role in managing patients with HBV and HCC
‒ Effective surveillance will identify those with early-stage HCC
 Both subspecialty care and multidisciplinary care associated with
improved survival
 Develop a relationship with a multidisciplinary team/tumor board
 See the patient regularly to monitor viral disease and response to
therapy
 Hepatologists may guide the care of patients with HBV and HCC to
ensure all options are considered
Slide credit: clinicaloptions.com
 Go Online for More CCO
Coverage of HCC in the Setting of HBV!
Quick-Reference Guide for easy-to-access information on screening and surveillance in
patients with hepatitis B
Additional CME/CE-certified video module on HCC risk assessment, screening, and
management with expert faculty interaction and discussion
Clinical Thought commentaries drafted by expert faculty on
issues of clinical importance

clinicaloptions.com/hepatitis/programs/hcc-and-hbv