The Role of Hepatitis B Core-Related Antigen

Genes (Basel). 2019 May 9;10(5):357. doi: 10.3390/genes10050357.

Abstract

Hepatitis B virus (HBV) cannot be completely eliminated from infected hepatocytes due to the existence of intrahepatic covalently closed circular DNA (cccDNA). Serological biomarkers reflect intrahepatic viral replicative activity as non-invasive alternatives to liver biopsy. Hepatitis B core-related antigen (HBcrAg) is a novel biomarker that has an important role in chronic hepatitis B (CHB), because it correlates with serum HBV DNA and intrahepatic cccDNA. In clinical cases with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with promising outcomes for CHB patients. HBcrAg can predict spontaneous or treatment-induced hepatitis B envelope antigen (HBeAg) seroconversion, persistent responses before and after cessation of nucleos(t)ide analogues, potential HBV reactivation, HBV reinfection after liver transplantation, and risk of hepatocellular carcinoma progression or recurrence. In this review, the clinical applications of HBcrAg in CHB patients based on its virological features are described. Furthermore, new potential therapeutic anti-HBV agents that affect intrahepatic cccDNA are under development, and the monitoring of HBcrAg might be useful to judge therapeutic effects. In conclusion, HBcrAg might be a suitable surrogate marker beyond other HBV markers to predict the disease progression and treatment responses of CHB patients.

Keywords: HBV DNA; chronic hepatitis B (CHB); covalently closed circular DNA (cccDNA); hepatitis B core-related antigen (HBcrAg); hepatitis B virus (HBV).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / etiology
  • Hepatitis B Core Antigens / blood*
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / therapy
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / etiology
  • Liver Transplantation

Substances

  • Antiviral Agents
  • Biomarkers
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens