Low frequency of precore hepatitis B virus mutants in anti‐hepatitis B e—positive reactivation after loss of hepatitis B e antigen in patients with chronic hepatitis B

The objective of this study was to evaluate the role of hepatitis B virus (HBV) precore mutations in patients with anti‐HBe—positive chronic hepatitis B with or without previous known HBe antigen (HBeAg) viremic phase, and to assess the potential implication of precore mutants in HBeAg—negative reactivation after loss of HBeAg. Nineteen patients were studied: 7 had a previous HBeAg‐positive phase and had spontaneous or therapeutically induced loss of HBeAg (group A); 12 had no previous HBeAg‐positive phase (group B). Direct sequencing of PCR products was performed on serum collected during the anti‐HBe—positive phase in the two groups. In group A, precore sequencing showed that 5 patients were infected by wild‐type virus, 1 patient was infected with a precore mutant, and 1 patient was found to be infected by a mixture of wild‐type and precore mutant viruses. In group B, precore sequencing showed that only 1 patient was infected with wild‐type virus and that 11 were infected with precore mutants. In a few patients, the presence of HBeAg within immune complexes may explain HBeAg negativity. In conclusion, our results show that, in patients with anti‐HBe—positive chronic hepatitis B: (1) precore mutations creating a stop codon are more frequently found in those without known previous HBeAg positivity; (2) after loss of HBeAg, the patients who have anti‐HBe—positive reactivation are infected by wild‐type virus, which suggests that reactivation is not related to precore mutations; (3) HBeAg negativity may be caused by immune complexes formation.