Clinical utility of hepatitis B core-related antigen in chronic hepatitis B infection: diagnostic, prognostic, and therapeutic implications

Abstract

Abstract Background The hepatitis B core-related antigen (HBcrAg) is transforming the management of chronic hepatitis B (CHB) by providing a comprehensive biomarker that addresses the limitations of traditional diagnostic methods. Compared with the hepatitis B core antigen, e antigen, and a precore protein, HBcrAg uniquely correlates with covalently closed circular deoxyribonucleic acid (cccDNA), the persistent reservoir driving hepatitis B virus (HBV) chronicity and complications. Purpose HBcrAg’s clinical potential spans the entire HBV care continuum, enhancing diagnostic precision, identifying at-risk phases of infection, and predicting critical outcomes such as cirrhosis, hepatocellular carcinoma (HCC), and posttreatment relapse. Finding Unlike hepatitis B surface antigen (HBsAg) and HBV DNA, HBcrAg offers a detailed reflection of intrahepatic viral activity, even in scenarios of suppressed serum viral loads or undetectable HBV DNA. Breakthroughs in assay sensitivity, including high-sensitivity tests such as Immunoassay for Total Antigen including Complex via pretreatment (iTACT)-HBcrAg, enable earlier and more reliable detection, particularly in resource-limited settings. These advancements position HBcrAg as a cornerstone for therapy monitoring, guiding treatment decisions, and evaluating functional cure milestones. In addition to its clinical applications, HBcrAg has been used in cutting-edge research into HBV immune evasion mechanisms, therapeutic targets, and vaccine strategies to overcome cccDNA persistence. Conclusion By bridging the gap between traditional diagnostics and personalized HBV management, HBcrAg has accelerated progress toward a functional cure, reshaping global health outcomes in the fight against chronic HBV infection.