Low rate of YMDD motif mutations in polymerase gene of hepatitis B virus in chronically infected patients not treated with lamivudine.
BACKGROUND
Lamivudine is used for the treatment of chronic hepatitis B (CH-B), and exhibits excellent antiviral activity. However, longterm administration increases the likelihood of the emergence of resistant viruses, with an accompanying relapse of hepatitis. However, recent studies have reported lamivudine-resistant viruses in patients with CH-B before such treatment. The aim of this study was to investigate whether YMDD mutants occur in nature.


METHODS
The existence of lamivudine-resistant viruses was examined in 20 asymptomatic carriers of hepatitis B virus (ASC), 10 patients who lost hepatitis B surface antigen (HBsAg) during follow-up and in 20 lamivudine-treated patients with and without breakthrough hepatitis. Both polymerase chain reaction (PCR) restriction fragment length polymorphism and SMITEST hepatitis B virus (HBV)-YMDD mutation detection methods were used to detect resistant viruses.


RESULTS
No YMDD mutants were detected in the sera of the 20 ASC at the initial and final medical examinations, nor were YMDD mutants detected in sera collected at the initial medical examination, about 6 months before, or immediately after the loss of HBsAg in the 10 patients. In the 20 patients treated with lamivudine, YMDD mutants were not detected in any of them before treatment, whereas mutants were detected in the sera of 10 patients during treatment.


CONCLUSIONS
Our results suggest that lamivudine-resistant YMDD mutant viruses were present in a few patients with HBV infection before they have been treated with lamivudine.
Matsuda
Marie
M
Research Institute for Hepatology, Toranomon Branch Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki 213-8587, Japan.
Suzuki
Fumitaka
F
Suzuki
Yoshiyuki
Y
Tsubota
Akihito
A
Akuta
Norio
N
Hosaka
Tetsuya
T
Someya
Takashi
T
Kobayashi
Masahiro
M
Saitoh
Satoshi
S
Arase
Yasuji
Y
Satoh
Junko
J
Takagi
Kimiko
K
Kobayashi
Mariko
M
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012194:RNA-Directed DNA Polymerase / Q000235:genetics
D000998:Antiviral Agents; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase