Mutations of polymerase, precore and core promoter gene in hepatitis B virus during 5-year lamivudine therapy.
OBJECTIVE
The effects of long-term lamivudine therapy on changes in polymerase and precore/core promoter mutations are unknown. The aim of this study was to determine the changes in these regions in patients with chronic hepatitis B virus (HBV) infection treated with lamivudine for 5 years.


METHODS
Serum samples obtained from 16 patients at the beginning of and during therapy were polymerase chain reaction-amplified, and nucleotide sequences of HBV analyzed.


RESULTS
By the end of 5-year therapy, mutations in YMDD motif emerged in ten patients. Mutations in L526M, M550V and M550I in polymerase were found in seven, six and six patients, respectively. The L526M mutant was found at the time or after detection of M550V/I mutant in six of seven patients. At baseline, precore and core promoter mutations were found in eight and 12 of 16 patients, respectively. Mutants of precore and core promoter were replaced by wild-type virus in each of three patients infected with mutants at 1 year. However, at 5 years of treatment, precore and core promoter mutations reappeared in some patients.


CONCLUSIONS
Our data showed that lamivudine initially selected from precore/core promoter mutants to wild-type virus, but precore mutation reappeared during prolonged therapy.
Suzuki
Fumitaka
F
Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. fumitakas@toranomon.gr.jp
Suzuki
Yoshiyuki
Y
Tsubota
Akihito
A
Akuta
Norio
N
Someya
Takashi
T
Kobayashi
Masahiro
M
Saitoh
Satoshi
S
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004334:Drug Administration Schedule; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D014758:Viral Core Proteins / Q000235:genetics*
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins; D019259:Lamivudine; D000410:Alanine Transaminase; D004259:DNA-Directed DNA Polymerase