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Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA

Danny Ka-Ho Wong1,2, Wai-Kay Seto1,2, Ka-Shing Cheung1

  • 1Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Liver International : Official Journal of the International Association for the Study of the Liver
|December 20, 2016
PubMed

Insights

Serum hepatitis B core-related antigen (HBcrAg) reliably indicates the amount of covalently closed circular DNA (cccDNA) in the liver, serving as a valuable surrogate marker for chronic hepatitis B infection persistence.

Area of Science:

  • Hepatology
  • Virology
  • Biomarker Discovery

Background:

  • Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) drives persistent infection.
  • Serum hepatitis B core-related antigen (HBcrAg) is a novel marker for HBV disease.

Purpose of the Study:

  • To determine if serum HBcrAg can serve as a surrogate marker for intrahepatic cccDNA.
  • To assess the correlation between HBcrAg levels and cccDNA during antiviral therapy.

Main Methods:

  • Analysis of 305 liver biopsies and sera from 138 patients treated with nucleos(t)ide analogues.
  • Measurement of serum HBcrAg, HBV DNA, HBsAg, and intrahepatic HBV DNA and cccDNA.
  • Longitudinal analysis of paired biopsies and sera over 6-12 years of treatment.

Main Results:

  • Serum HBcrAg strongly correlated with intrahepatic cccDNA (r=.70) and HBV DNA (r=.67-0.69).
  • HBcrAg remained detectable and correlated with cccDNA even when serum HBV DNA was undetectable.
  • HBcrAg reduction mirrored cccDNA reduction during long-term therapy.

Conclusions:

  • Serum HBcrAg is a reliable surrogate marker for intrahepatic cccDNA.
  • HBcrAg can sensitively reflect cccDNA content and disease persistence, even below detection limits.
Abstract

Keywords:
covalently closed circular DNAhepatitis Bhepatitis B core-related antigenhepatitis B serum markersintrahepatic HBV DNA

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