Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy

Authors

  • Sung Won Cho,

    Corresponding author
    1. Department of Gastroenterology, Laboratory of Liver and Digestive Disease, Ajou University School of Medicine, Suwon, South Korea
    • Department of Gastroenterology, Ajou University School of Medicine, San 5, Wonchon-dong, Paldal-gu, Suwon 442-749, South Korea. fax: (82) 31-219-5999
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  • Ki-Baik Hahm,

    1. Department of Gastroenterology, Laboratory of Liver and Digestive Disease, Ajou University School of Medicine, Suwon, South Korea
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  • Jin Hong Kim

    1. Department of Gastroenterology, Laboratory of Liver and Digestive Disease, Ajou University School of Medicine, Suwon, South Korea
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Abstract

The effect of lamivudine administration on the evolution of precore/core promoter mutation is unknown. The aim of this study was to determine the changes of precore/core promoter sequences in chronic type B hepatitis patients treated with lamivudine. Serial sera were obtained from 11 patients before, at the beginning of, and during therapy. Serum samples were polymerase chain reaction-amplified, and nucleotide sequences of hepatitis B virus (HBV) were analyzed. At baseline, precore and core promoter mutations were found in 6 and 4 of 11 patients, respectively. A precore stop codon mutant was replaced by a wild-type virus in all 6 patients infected with precore mutant at a median treatment of 12 months (vs. before therapy; P = .011). Mutations in the core promoter appeared in only 1 of 10 patients (vs. before therapy; P = .021). However, precore and core promoter mutations appeared in 5 and 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had hepatitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeAg-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene deletions are not eliminated completely during prolonged therapy in 2 patients in whom the HBV genomes had core gene deletions at baseline. In conclusion, lamivudine therapy resulted in reversion from precore/core promoter mutants to wild-type. However, mutations in the precore and core promoter region reappeared during prolonged therapy. HBeAg-negative wild-type precore hepatitis B virus could be selected after lamivudine withdrawal in patients who had HBeAg loss or seroconversion.

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