Characteristics and prediction of hepatitis B e-antigen negative hepatitis following seroconversion in patients with chronic hepatitis B


  • Conflict of interest: All authors declare no conflicts of interest.



We analyzed the characteristics of alanine aminotransferase (ALT) abnormality after achieving hepatitis B e-antigen (HBeAg) seroconversion (SC) and other factors associated with the occurrence of HBeAg negative hepatitis.


We followed 36 patients with chronic hepatitis B from 3 years prior to at least 3 years after SC (mean, 11.6 years) and examined ALT, hepatitis B virus (HBV) DNA, HB surface antigen, HB core-related antigen (HBcrAg) levels and mutations related to HBeAg SC.


ALT normalization (<31 IU/L for at least 1 year) was primarily observed until 2 years following SC, after which it became more infrequent. We next divided patients into abnormal (≥31 IU/L, n = 20) and normal (<31 IU/L, n = 16) groups based on integrated ALT level after the time point of 2 years from SC, and considered the former group as having HBeAg negative hepatitis in the present study. Although changes in median levels of ALT and HBcrAg differed significantly between the groups, multivariate analysis showed ALT normalization within 2 years after SC to be the only significant determining factor for this disease (P = 0.001). We then assessed the 19 patients whose ALT was normal at 2 years following SC, four of whom developed HBeAg negative hepatitis. Increased levels of HBV DNA (P = 0.037) and HBcrAg (P = 0.033) were significant factors of potential relevance.


ALT abnormality after 2 years of SC may be evaluated as HBeAg-negative hepatitis. ALT, HBV DNA and HBcrAg levels may be useful in predicting the outcome of patients who achieve HBeAg SC.