Background The seroclearance of hepatitis B e antigen (HBeAg) is usually associated with low HBV replication and slow disease progression. It is a favorable sign for patients with chronic hepatitis B. However, the mechanism of HBeAg seroclearance remains incompletely clear. The aim of this study was to examine factors associated with HBeAg seroclearance.
Methods There were 1526 HBsAg-seropositive and anti-HCV-seronegative men and women enrolled from seven townships in Taiwan between 1991 and 1992 in this analysis. Their serum samples at cohort entry were tested for HBeAg, ALT, HBV DNA level and genotype. The HBeAg status in last follow-up samples was also tested. Logistic regression analysis was used to derive multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for factors associated with HBeAg seroclearance.
Stratification analysis was used to evaluate the association of HBeAg seroclearance probability between different strata.
Result Follow-up period, HBV genotype and HBV DNA levels at study entry were significantly associated with HBeAg seroclearance. The multivariate-adjusted OR (95% CI) of HBeAg seroclearance was 6.30 (2.82-14.05) and 11.68 (5.52-24.71), respectively, for follow-up periods of 5-9 years and ≧10 years versus <5 years; 0.23 (0.13-0.41) for HBV genotype C versus genotype B; and 0.24 (0.07-0.77) for serum HBV DNA level at study entry ≧107 versus <105 copies/mL. The HBeAg seroclearance was not statistically significantly associated with gender, ALT level, HBV precore (G1896A) and basal core promoter (A1762T/G1764A) mutants. Genotype C showed a significantly lower HBeAg seroclearance probability than genotype B in male subjects （OR=0.14, 0.07-0.28）but not in female(OR=1.71, 0.51-5.72). Male gender showed a significantly lower HBeAg seroclearance probability than female in genotype C strata（OR=0.38, 0.20-0.74）, but not in genotype B strata（OR=2.09, 0.67-6.47）. The association between basal core promoter mutation and HBeAg seroclearance was modified by HBV DNA level. Genotype C had significantly lower HBeAg seroclearance probability than genotype B in age ≧35 participants(OR=0.35, 0.20-0.61).
Conclusion Longer follow-up period, HBV genotype B, and HBV DNA levels at study entry were associated with a significantly increased HBeAg seroclearance rate. However, no significant association with HBeAg seroclearance was observed for gender, ALT level, HBV precore (G1896A) and basal core promoter (A1762T/G1764A) mutants. In the subgroup analysis, we found the gender, genotype and basal core promoter effect of HBeAg seroclearance modified by genotype, age and HBV DNA level respectively.