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 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.
Cho
S W
SW
Department of Gastroenterology, Laboratory of Liver and Digestive Disease, Ajou University School of Medicine, Suwon, South Korea. sung-woncho@hotmail.com
Hahm
K B
KB
Kim
J H
JH
D000328:Adult; D005260:Female; D017353:Gene Deletion; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014758:Viral Core Proteins / Q000235:genetics*
D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins; D019259:Lamivudine