Persistence of viral replication after anti-HBe seroconversion during antiviral therapy for chronic hepatitis B.
OBJECTIVE
Hepatitis B virus genome mutants may be selected during the immune-mediated clearance of infection or during long-term nucleoside analog administration and may escape both antiviral pressures. The pattern of anti-HBe seroconversion was analyzed in patients receiving new nucleoside analogs, lamivudine or famciclovir, in comparison with patients treated with interferon alpha.


METHODS
Eighteen consecutive patients who seroconverted to anti-HBe were included in the study. Serial serum samples were studied with the quantitative determination of HBV DNA by the branched DNA assay (Chiron) and by a quantitative PCR assay (Roche diagnostics), determination of pre-S1 Ag, the genetic analysis of the viral genome with the determination of pre-core promoter or pre-core region mutations with a line probe assay (Innogenetics) and, in selected samples of polymerase gene mutations.


RESULTS
The quantitative PCR assay was found to be more sensitive than the bDNA assay, allowing a 25-log decrease in viral DNA levels to be demonstrated after anti-HBe seroconversion. Viral persistence after anti-HBe seroconversion induced by interferon, lamivudine or famciclovir, was often associated with circulating HBV genomes harboring mutations in the precore promoter. The clinical significance of these findings was demonstrated by the observation of reversion to HBeAg in two patients treated with interferon and one with lamivudine.


CONCLUSIONS
Persistence of significant levels of viremia that are not detected by the branched DNA assay may be observed after anti-HBe seroconversion. A precise monitoring of viremia levels with more sensitive assays and HBV mutant strains is warranted in patients undergoing antiviral therapy.
Pichoud
C
C
INSERM Unit 271, Hôtel Dieu, Lyon, France.
Berby
F
F
Stuyver
L
L
Petit
M A
MA
Trépo
C
C
Zoulim
F
F
D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000032:analysis*; D000998:Antiviral Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000077595:Famciclovir; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
D000914:Antibodies, Viral; D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir