Predictive value of serum HBcrAg in antiviral therapy for chronic hepatitis B

Chronic hepatitis B (CHB) remains a significant global public health challenge. The goals of its antiviral therapy are gradually shifting from long-term viral suppression toward achieving safer treatment discontinuation, more accurate risk stratification, and deeper functional cure. Traditional serological markers, such as HBV DNA and HBsAg, remain clinically important in CHB. However, their ability to reflect residual viral activity and long-term outcomes is limited after long-term nucleos(t)ide analog (NA) therapy, especially in patients with sustained virological suppression or marked HBsAg decline or clearance.In recent years, hepatitis B core-related antigen (HBcrAg), due to its capacity to reflect transcriptional activity of intrahepatic covalently closed circular DNA(cccDNA) and the state of the residual viral reservoir, has emerged as a notable novel biomarker in the field of CHB. Concurrently, with the development of pegylated interferon (Peg-IFN) add-on strategies and novel combination cure approaches, the potential of HBcrAg in selecting optimal patient populations and monitoring therapeutic efficacy is increasingly recognized. This review focuses on the biological basis of HBcrAg and its main predictive values in CHB antiviral therapy. It also summarizes and prospects its clinical application potential and existing challenges based on current research progress.