Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy.
It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV.
Kuwahara
Reiichiro
R
The Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan. ray@med.kurume-u.ac.jp
Kumashiro
Ryukichi
R
Murashima
Shiro
S
Ogata
Kei
K
Tanaka
Kazuo
K
Hisamochi
Akiko
A
Hino
Teruko
T
Ide
Tatsuya
T
Tanaka
Eisuke
E
Koga
Yuriko
Y
Sata
Michio
M
D000328:Adult; D000368:Aged; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine