Research progress on hepatitis B surface antigen decline and clearance.

Chronic hepatitis B (CHB) remains a major global cause of liver cirrhosis and hepatocellular carcinoma (HCC), particularly in China. With ongoing advances in antiviral therapy, the therapeutic objective for CHB has evolved from sustained suppression of hepatitis B virus replication toward achievement of a functional cure, defined by hepatitis B surface antigen (HBsAg) loss with or without anti-HBs seroconversion. Increasing evidence suggests that HBsAg clearance is strongly associated with reduced hepatic inflammation, regression of fibrosis, and a substantially lower risk of HCC, thereby serving as a critical indicator of long-term clinical prognosis in patients with CHB. Drawing upon recent domestic and international advances, this review summarizes the biological characteristics and pathogenic significance of HBsAg, its dynamic changes during antiviral therapy, and its associations with virologic responses and clinical outcomes. Particular emphasis is placed on the integrated immunologic mechanisms underlying HBsAg decline and clearance, including the interplay between innate and adaptive immune responses, cytokine networks, and immune reconstitution during functional cure. In addition, emerging predictive models and potential therapeutic strategies targeting HBsAg clearance are discussed, together with future research directions aimed at advancing standardized management and precision treatment strategies for CHB.