Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure.

Hepatitis B virus (HBV) infection is a global health concern. The current sequential endpoints for the treatment of HBV infection include viral suppression, hepatitis B e antigen (HBeAg) seroconversion, functional cure, and covalently closed circular DNA (cccDNA) clearance. Serum hepatitis B core-related antigen (HBcrAg) is an emerging HBV marker comprising three components: HBeAg, hepatitis B core antigen, and p22cr. It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serological testing. There is a strong correlation, and a decrease in its level corresponds to sustained viral suppression. In patients with chronic hepatitis B (CHB), serum HBcrAg levels are good predictors of HBeAg seroconversion (both spontaneous and after antiviral therapy), particularly in HBeAg-positive patients. Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion, which may serve as a good surrogate option for treatment endpoints. In this review, we summarize the role of serum HBcrAg in the treatment of CHB. Therefore, long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen, making it a promising marker for monitoring HBV cure.