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Review
. 2023 Apr;29(2):263-276.
doi: 10.3350/cmh.2022.0448. Epub 2023 Jan 19.

The role of different viral biomarkers on the management of chronic hepatitis B

Lung-Yi Mak  1   2 , Rex Wan-Hin Hui  1 , James Fung  1   2 , Wai Kay Seto  1   2 , Man-Fung Yuen  1   2
Affiliations
Review

The role of different viral biomarkers on the management of chronic hepatitis B

Lung-Yi Mak et al. Clin Mol Hepatol. 2023 Apr.

Abstract

Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.

Keywords: Chronic hepatitis B; Hepatitis B core antigen; Treatment outcome; Viremia.

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Conflict of interest statement

Conflicts of Interest

LY Mak is an advisory board member for Gilead Sciences. WK Seto received speaker’s fees from AstraZeneca and Mylan, is an advisory board member of CSL Behring, is an advisory board member and received speaker’s fees from AbbVie, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. MF Yuen serves as advisor/consultant for AbbVie, Assembly Biosciences, Aligos Therapeutics, Arbutus Biopharma, Bristol Myer Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Hoffmann-La Roche and Springbank Pharmaceuticals, Vir Biotechnology and receives grant/research support from Assembly Biosciences, Aligos Therapeutics, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Immunocore, Merck Sharp and Dohme, Hoffmann-La Roche, Springbank Pharmaceuticals and Sysmex Corporation. The remaining authors have no conflict of interests.

Figures

Figure 1.
Figure 1.
Viral cycle of hepatitis B virus. Those highlighted in asterisks are detectable in the bloodstream and can be used as viral biomarkers. These include HBsAg, HBeAg, HBcrAg, HBV DNA and pgRNA. cccDNA, covalently closed circular DNA; dslDNA, double-stranded linear DNA; HBV, hepatitis B virus; HBcAg, hepatitis core antigen; HBcrAg, hepatitis B core related antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; mRNA, messenger RNA; NTCP, sodium taurocholate co-transporting polypeptide; pgRNA, pre-genomic RNA; rcDNA, relaxed circular DNA. *Detectable in the bloodstream.
Figure 2.
Figure 2.
Treatment endpoints in the cascade of cure in chronic hepatitis B infection. cccDNA, covalently closed circular DNA; HBsAg, hepatitis B surface antigen; mRNA, messenger RNA; pgRNA, pre-genomic RNA; rcDNA, relaxed circular DNA; HBV, hepatitis B virus; DNA, double-stranded deoxy-ribonucleic acid.
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