Persistence of viral replication after anti-HBe seroconversion during antiviral therapy for chronic hepatitis B

Background/Aims: Hepatitis B virus genome mutants may be selected during th e immune-mediated clearance of infection or during long-term nucleoside ana log administration and may escape both antiviral pressures, The pattern of anti-HBe seroconversion was analyzed in patients receiving new nucleoside a nalogs, lamivudine or famciclovir, in comparison with patients treated, wit h interferon alpha, Methods: Eighteen consecutive patients who seroconverted to anti-HBe were i ncluded in the study. Serial serum samples were studied with the quantitati ve determination of HBV DNA by the branched DNA assay (Chiron) and by a qua ntitative PCR assay (Roche diagnostics), determination of pre-Si Ag, the ge netic analysis of the viral genome with the determination of pre-core promo ter 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 2-5-log decrease in viral DNA levels to be demonstr ated after anti-HBe seroconversion, Viral persistence after anti-HBe seroco nversion induced by interferon, lamivudine or famciclovir, was often associ ated with circulating HBV genomes harboring mutations in the precore promot er, The clinical significance of these findings was demonstrated by the obs ervation of reversion to HBeAg in two patients treated with interferon and one with lamivudine, Conclusion: Persistence of significant levels of viremia that are not detec ted 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.