Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

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Abstract
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. J. Med. Virol. 72:26–34, 2004.