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Meeting the Challenge of Eliminating Chronic Hepatitis B Infection
Open AccessReview

The Role of Hepatitis B Core-Related Antigen

Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya 467-8602, Japan
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Author to whom correspondence should be addressed.
Genes 2019, 10(5), 357;
Received: 2 April 2019 / Revised: 2 May 2019 / Accepted: 6 May 2019 / Published: 9 May 2019
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. View Full-Text
Keywords: hepatitis B core-related antigen (HBcrAg); covalently closed circular DNA (cccDNA); hepatitis B virus (HBV); chronic hepatitis B (CHB); HBV DNA hepatitis B core-related antigen (HBcrAg); covalently closed circular DNA (cccDNA); hepatitis B virus (HBV); chronic hepatitis B (CHB); HBV DNA
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Inoue, T.; Tanaka, Y. The Role of Hepatitis B Core-Related Antigen. Genes 2019, 10, 357.

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