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.
Loriot
M A
MA
Unité de Recherches de Physiopathologie Hépatique, Hôpital Beaujon, Clichy, France.
Marcellin
P
P
Talbodec
N
N
Guigonis
V
V
Gigou
M
M
Boyer
N
N
Bezeaud
A
A
Erlinger
S
S
Benhamou
J P
JP
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002908:Chronic Disease; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000032:analysis*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes / Q000235:genetics; D014775:Virus Activation
D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D015345:Oligonucleotide Probes