Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B

Background & Aims: Predictors of reactivation of hepatitis B following hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B have rarely been reported before and deserve further study. Methods: A total of 133 HBeAg-positive asymptomatic carriers who have undergone HBeAg seroconversion were studied. Reactivation of hepatitis B was defined as elevation of alanine aminotransferase >2 x upper normal limit accompanied by serum hepatitis B virus DNA detectable by hybridization assays. Results: The samples consisted of 75 men and 58 women, and the mean age at entry was 28.2 +/- 6.9 years. One hundred eight subjects had genotype B, and 25 had genotype C. The maximal alanine aminotransferase levels during the HBeAg-positive phase were <2, 2-5, and > 5 x upper normal limit in 49, 40, and 44 subjects, respectively. HBeAg seroconversion occurred after a mean follow-up of 4.6 +/- 3.7 years. During a mean follow-up of 5.8 +/- 4.6 years following HBeAg seroconversion, reactivation of hepatitis B occurred in 26 patients at 3.3% per year. Multivariate analyses demonstrated that reactivation of hepatitis B correlated significantly with genotype C (P =.003), male sex (P =.03), alanine aminotransferase levels >5 x upper normal limit during the HBeAg-positive phase (P =.02), and age at HBeAg seroconversion >= 40 years (P =.002). Conclusions: At baseline, genotype C and male sex are independent factors predictive of reactivation of hepatitis B. Additionally, the likelihood of reactivation of hepatitis B is increased if more rigorous immune-mediated hepatocytolysis or more prolonged immune clearance phase is necessary to eliminate the virus.