title: Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg-positive chronic hepatitis B patients receiving lamivudine therapy.
abstract: OBJECTIVE
  Lamivudine is effective in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but the relapse rate after cessation of treatment is high. The evolution of viral genome may contribute to the viral replication under antiviral pressure of lamivudine. We therefore determined the evolution of hepatitis B virus (HBV) precore/basal core promoter and polymerase genes in HBeAg-positive chronic hepatitis B patient during lamivudine therapy.
  
  
  METHODS
  Thirteen patients with HBeAg-positive chronic hepatitis who had received short-term lamivudine therapy (mean, 30 weeks) during 1999-2001 were enrolled. The precore/basal core promoter region and polymerase gene were amplified and directly sequenced before, during and post lamivudine treatment.
  
  
  RESULTS
  HBeAg loss or seroconversion occurred in 11, but eight relapsed after stopping therapy and five had reversion of HBeAg. Before treatment, basal core promoter mutation was found in 1. In the first 3 months of therapy, a rapid decline of serum HBV DNA level accompanied with basal core promoter mutation appeared in 11 of 13 patients (vs. before therapy; P=0.003). However, this mutant was replaced by wild-type virus in four of eight patients who relapsed after treatment. There was no significant change of precore sequences before and during therapy.
  
  
  CONCLUSIONS
  Lamivudine therapy may result in the rapid development of basal core promoter mutation of HBV, but this mutation may revert to wild type gradually after cessation of therapy.
authors.affiliation: Department of Gastroenterology, Taipei Municipal Jen-Ai Hospital, Taipei, Taiwan.
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liao
authors.forename: Chaur-Shine
authors.initials: CS
authors.lastname: Wang
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000187:drug effects / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase