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

The effect of lamivudine administration on the evolution of precore/core pr omoter mutation is unknown. The aim of this study was to determine the chan ges 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 ch ain 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 r eplaced 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). Mutatio ns in the core promoter appeared in only 1 of 10 patients (vs, before thera py; P = .021), However, precore and core promoter mutations appeared in 5 a nd 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had he patitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeA g-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene delet ions are not eliminated completely during prolonged therapy in 2 patients i n 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 r eappeared during prolonged therapy. HBeAg-negative wild-type precore hepati tis B virus could be selected after lamivudine withdrawal in patients who h ad HBeAg loss or seroconversion.