Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg-positive chronic hepatitis B patients receiving lamivudine therapy.
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.
Lin
Chih-Lin
CL
Department of Gastroenterology, Taipei Municipal Jen-Ai Hospital, Taipei, Taiwan.
Liao
Li-Ying
LY
Wang
Chaur-Shine
CS
Chen
Pei-Jer
PJ
Lai
Ming-Yang
MY
Chen
Ding-Shinn
DS
Kao
Jia-Horng
JH
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
D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase