Relative Roles of HBsAg Seroclearance and Mortality in the Decline of HBsAg Prevalence With Increasing Age

OBJECTIVES: Mortality and hepatitis B surface antigen ( HBsAg) seroclearance are the two extremes of prognostic destination of chronic hepatitis B virus (HBV) infection. Their relative roles in the decline of HBsAg prevalence with increasing age are unknown. METHODS: HBsAg-seropositive subjects with near normal alanine aminotransferase (ALT) were followed up every 3 to 12 months for >1 year. Serum HBsAg was assayed at entry and re-assayed at 3- to 5-year intervals. The morbidity and mortality data were obtained from hospital records, cancer registration, and the national mortality database. The mortality and HBsAg-seroclearance rates were examined by survival analysis. RESULTS: At entry, 1,386 subjects (20.9%) were hepatitis B e antigen (HBeAg) seropositive and 5,235 were HBeAg seronegative. The mean follow-up period was 13.6 +/- 5.4 years (median 13.2; range 1-29.1). HBsAg seroclearance occurred more frequently (555 cases, 8.4%) than mortality (97 cases, 1.5%; P<0.001; overall HBsAg seroclearance/mortality ratio: 5.6), of which only 40% were liver-related cases. Cox regression analysis revealed that male sex, HBeAg negativity, older age, low maximal ALT level, and hepatic steatosis were factors associated with HBsAg seroclearance. The estimated annual HBsAg seroclearance rate was around 1.05-1.61% after the age of 50 years, whereas the estimated mortality rate was quite low before the age of 60 and increased from 0.41% per year at ages 60-64 to 1.19% per year at ages 70-74 years. CONCLUSIONS: The HBsAg seroclearance over mortality rate was 5.6 in this cohort. This suggests that HBsAg seroclearance is the main reason for decreasing HBsAg prevalence with increasing age in the population.