Hepatitis B core-related antigen: a novel and promising surrogate biomarker to guide anti-HBV therapy

Inoue, Takako; Watanabe, Takehisa; Tanaka, Yasuhito

doi:.0..

Review

Hepatitis B core-related antigen: a novel and promising surrogate biomarker to guide anti-HBV therapy

Takako Inoue¹, Takehisa Watanabe², Yasuhito Tanaka^2,3

¹Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
²Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
³Department of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Correspondence :

Yasuhito Tanaka ,
Tel: +81-96-373-5146, Fax: +81-96-371-0582, Email: ytanaka@kumamoto-u.ac.jp

Received: December 2, 2022 Revised: February 19, 2023 Accepted: March 7, 2023

ABSTRACT

The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 log U/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein.

KeyWords: hepatitis B core-related antigen (HBcrAg), covalently closed circular DNA (cccDNA), HBV reactivation, point-of-care testing (POCT), RNA destabilizer