Serum hepatitis B surface antigen levels in the natural history of chronic hepatitis B infection

Background The production of hepatitis B surface antigen (HBsAg) may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The impact of age on HBsAg production remains unclear. Aim To determine the age-specific distribution patterns of HBsAg and related factors during the natural course of CHB infection. Methods Seven hundred and sixty-eight untreated HBsAg carriers were enrolled in the study. The parameters and distribution patterns of HBsAg were evaluated in relation to age and immune phases. Results The HBsAg levels were significantly lower in the HBeAg-negative stage, with the lowest levels in inactive carriers. The HBsAg tended to decrease from hepatitis to cirrhosis and to hepatocellular carcinoma, and from Child-Pugh class A to B and to C. Age and HBV DNA were independently associated with HBsAg levels. In HBeAg-positive patients, the HBsAg levels were distributed in a triphasic-like decline pattern by 2 logs across age strata. For HBeAg-negative patients, the titres in inactive carriers exhibited a 2-log reduction, but remained unchanged over age strata in patients with HBeAg-negative hepatitis. The ratios of HBsAg/HBV-DNA were highest, but steadily decreased with age in inactive carriers, whereas the levels remained largely unchanged over the entire age strata in patients with HBeAg-negative hepatitis. Conclusions Age and HBV DNA levels are independent parameters of HBsAg levels. During the natural course of CHB infection, HBsAg levels decrease with age and disease progression, but the patterns are significantly different between the immune phases of CHB. This information may contribute to our understanding of the immunopathogenesis of chronic hepatitis B and management involving HBsAg quantification.