The influence of hepatitis B virus genotype on the development of lamivudine resistance during long-term treatment.
OBJECTIVE
Genotype-dependent development of lamivudine resistance in hepatitis B virus (HBV) has not been reported.


METHODS
We determined the cumulative rate of emergence of YMDD motif mutant in 213 Japanese patients with chronic hepatitis B infected with genotype A, B, or C and treated with lamivudine for more than 1 year.


RESULTS
The emergence rate of lamivudine resistance was independent of the genotype (A, B, and C). In contrast, the emergence rate was significantly higher in the Ba ("a" stands for Asia) subgroup of HBV than in Bj ("j" for Japan) subgroup (P<0.05). For genotype C (HBV/C), the emergence rate in hepatitis B e antigen (HBeAg)-positive was significantly higher than in HBV/C-HBeAg-negative (P<0.05), but the rate in HBV/B-HBeAg-positive was similar to HBV/B-HBeAg-negative. Only four patients with HBV/C developed severe acute exacerbation of hepatitis accompanied by emergence of YMDD mutant, but none of the patients with other genotypes developed such complication.


CONCLUSIONS
Our results suggest that lamivudine resistance in HBV does not seem to depend on the genotype but rather on the subgroup of HBV/B. The results also suggest that lamivudine resistance according to HBeAg state might be different between HBV/B and HBV/C. Large-scale prospective studies of each genotype should be conducted in the future to confirm these findings.
Akuta
Norio
N
Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-0001, Japan. akuta-gi@umin.ac.jp
Suzuki
Fumitaka
F
Kobayashi
Mariko
M
Tsubota
Akihito
A
Suzuki
Yoshiyuki
Y
Hosaka
Tetsuya
T
Someya
Takashi
T
Kobayashi
Masahiro
M
Saitoh
Satoshi
S
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs / Q000235:genetics; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy* / Q000503:physiopathology; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D012720:Severity of Illness Index
D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine