Background: Despite its status as a potential biomarker of hepatitis B virus (HBV) response to interferon treatment, the changes in hepatitis B surface antigen (HBsAg) levels over the natural course of HBV carriers have not been analyzed sufficiently.
Methods: A total of 101 HBV carriers were followed prospectively from 1999 to 2009. HBsAg level was measured yearly during the followed period.
Results: HBsAg levels at baseline ranged from -1.4 to 5.32 log IU/ml, with a median value of 3.2 log IU/ml. Lower HBsAg levels were significantly associated with higher age and lower HBV replication status. The rate of change of HBsAg levels showed two peaks, with a cut-off value of -0.4 log IU/year. Based on this, patients were tentatively classified into rapid decrease (rate of change <-0.4 log IU/year) and non-rapid decrease groups. All baseline levels of HBsAg, HB core-related Ag, and HBV DNA were lower in the rapid decrease group than in the non-rapid decrease group. Patients with persistently positive HBeAg were all classified into the non-rapid decrease group. In patients with persistently negative HBeAg, HBV DNA levels were significantly (P = 0.028) lower in the rapid decrease group than in the non-rapid decrease group.
Conclusions: Lower baseline HBsAg levels were significantly associated with older age and lower viral activity. Both a loss of HBeAg detection as well as inactive replication of HBV are suggested to be fundamental factors contributing to a rapid decrease in HBsAg over the natural course of HBV infection.