IMPORTANT&
N OV EL
BIOMARKER FOR
HEPATITIS
dr. Weny Rinawati, SpPK(K), MARS, FISQua
2. Standard liver function test panel
Screening
Results should only be
interpreted after review of
• CBC • Previous results
Initial • Bilirubin • Past medical history
investigation • AST/ALT • Current medical condition
for potential • Albumin
liver disease • ALP
The extent of liver blood test
• PT
abnormality is not
necessarily a guide to clinical
significance
Method
Test Method
CBC Automatic cell counter
Urinalysis Automated:
• Semiautomated chemistry analyzers
• Fully automated chemistry analyzers
• Automated urine cell microscopy
analyzers
• System that are completely automated
Bilirubin Colorimetric assay (diazo)
AST/ALT Colorimetric assay
Albumin Colorimetric assay (bromcresol green)
ALP Colorimetric
PT Coagulometry
Diagnosis
Helpful in distinguishing:
• Pattern of injury (hepatocellular vs cholestatic)
• Aminotransferase enzymes
• ALP
• Chronicity of injury (acute vs chronic)
• Albumin
• Severity of injury (mild vs severe)
• PT
• Factor V
Rifai N et al. Tietz 6th ed. 2012. p.1348-96
Method
ELISA/ECLIA/ ELISA/ECLIA/rapid ELISA/ECLIA/ ELISA/ECLIA/
rapid test test rapid test rapid test
PCR
Lameson JL et al. Harrison 20thed. 2018. p.2338-41
4. Test principle
Qualitative
Quantitative
• Whether present or not • Measure the amount of the
• Result: "detected" or "not
hepatitis virus in the blood.
detected
• The result will be an exact
• Qualitative test: positive
number
Quantitative: no detectable
• Viral load tests are used to
→ a very low level of virus that
confirm active hepatitis
can be detected only with the
infection and are used during
qualitative test
treatment to help determine
response
• Used to monitor a patient
who is currently on treatment
6. Current challenges in viral hepatitis testing
Most people infected with HBV and/or HCV remain unaware of their
infection → frequently present with advanced disease
Low rate of hepatitis testing in LMICs
• Limited facilities or services for hepatitis testing
• Lack of effective testing policies or national standards due to weak or
non-existent hepatitis surveillance programmes to inform regional
epidemiology and testing policies
• Costly and complex diagnostic assays and algorithms
https://www.who.int/publications
6. Current challenges in viral hepatitis testing
Most people infected with HBV and/or HCV remain unaware of their
infection → frequently present with advanced disease
Low rate of hepatitis testing in LMICs
• Poor laboratory capacity and infrastructure
• Use of poor-quality test kits and reagents
Patients have the right to accurate and high quality testing to ensure that
those requiring treatment are identified and initiated, while those who are
negative or not in need of treatment are not inappropriately treated.
https://www.who.int/publications
6. Current challenges in viral hepatitis testing
The foundation of accurate testing includes:
• Provision of reliable
• High quality
• Regulatory approved test kits
• Qualified, trained, competent and supported testing personnel
• Quality-assured testing environment that addresses quality (process)
control, equipment management and maintenance, accurate
recordkeeping and documentation (standard operating procedures (SOPs),
and external quality assessment (EQA) schemes.
https://www.who.int/publications
8. Chronichepatitis parameter
Souza R & Foster G. Soc Med 2004;97:318–321
10/12/20. Establish serummarkers of liver fibrosis and
cirrhosis
Nallagangula KS et al. Future Sci. OA (2017) FSO250
14. HCCdiagnosis
https://www.who.int/publications
14. HCCdiagnosis
14. HCCdiagnosis
DCP/PIVKA-II
Des-gamma-carboxyprothrombin (DCP)/a
protein induced by vitamin K absence or
antagonist II (PIVKA-II)
• Abnormal form of prothrombin.
• In normal liver, prothrombin precursors
undergo post-translated carboxylation
(addition of carboxylic acid group) by
gamma-glutamyl carboxylase before being
released into peripheral blood.
• Carboxylase-dependent vitamin K which is
responsible for carboxylation is not found in
HCC, leading to the secretion of abnormal
prothrombin
14. HCCdiagnosis
DCP/PIVKA-II
Cut-off level of 140.85 mAU/mL:
dx HCC in in cirrhotic patients
Sensitivity 93.33%
Specificity 75%
PPV 73.68%
NPV 93.75%
16. Monitoring for treatment
The foundation of accurate testing includes:
• Provision of reliable
• High quality
• Regulatory approved test kits
• Qualified, trained, competent and supported testing personnel
• Quality-assured testing environment that addresses quality (process)
control, equipment management and maintenance, accurate
recordkeeping and documentation (standard operating procedures (SOPs),
and external quality assessment (EQA) schemes.
https://www.who.int/publications
16. Monitoring for treatment
https://www.who.int/publications
10/18. M2BPGi biomarker
• Produced by various cell types, including hepatocytes, and changes in its
glycosylation pattern in the setting of liver disease
• Glycosylation isoform of Mac-2 binding protein that correlated with liver
fibrosis in patients with chronic hepatitis C virus (HCV) infection
• Serum M2BPGi levels were measured from archived sera using an
automated analyzer applying the lectin-antibody sandwich immunoassay
https://www.who.int/publications
10/18. M2BPGi biomarker
https://www.who.int/publications
10/18. M2BPGi biomarker
M2BPGi performed significantly
better among:
• HBV (36.3% cirrhosis) >
HCV (87.6% cirrhosis)
(AUROC, 0.84 vs 0.51; P <
0.001).
• HBV overall > HBV with
cirrhosis (AUROC, 0.84
versus 0.69; P = 0.02)
20. Establish serummarkers of liver fibrosis and cirrhosis
Nallagangula KS et al. Future Sci. OA (2017) FSO250
