Initial viral response is the most powerful predictor of the emergence of YMDD mutant virus in chronic hepatitis B patients treated with lamivudine.
OBJECTIVE
Lamivudine (LAM) has been widely used to treat chronic hepatitis B (CHB) patients, but the emergence of a LAM-resistant virus greatly limits its therapeutic efficacy. In this study, we tried to identify factors affecting the emergence of a LAM-resistant virus in CHB patients treated with LAM.


METHODS
The subjects were 190 CHB patients in continuous LAM therapy (139 males, mean age 50 years, 87 HBeAg-positive). The mean duration of follow-up was 39 months (range 12-104). The initial viral response (IVR) was defined as HBV DNA < 4.0 logcopies/mL, and the initial biochemical response (IBR) as normalization of alanine aminotransferase (ALT) (<40 IU/L) at 6 months.


RESULTS
IVR was positive in 86% of the patients. The cumulative emergence rates of LAM-resistant virus were 10% at 1 year, 30% at 2 years and 46% at 3 years. In univariate analysis, factors contributing to the emergence of LAM-resistant virus were baseline HBV DNA > 6.5 logcopies/mL (P = 0.0044), HBeAg-positivity (P = 0.0062), IBR (P = 0.01) and IVR (P < 0.0001). The cumulative emergence rates of LAM-resistant virus in IVR-positive and -negative patients were 4% and 41% at 1 year, and 41% and 79% at 3 years. In multivariate analysis, only IVR was an independent factor affecting the emergence of LAM-resistant virus (P < 0.0001).


CONCLUSIONS
IVR is a useful factor for predicting the emergence of LAM-resistant virus in CHB patients treated with LAM. For IVR-negative patients, therapeutic options other than LAM monotherapy should be used because of the high incidence of the emergence of LAM-resistant virus.
Osaka University, Osaka, Japan.
Nao
N
Kurashige
Naoki
N
Hiramatsu
Kazuyoshi
K
Ohkawa
Tsugiko
T
Oze
Yuko
Y
Inoue
Mika
M
Kurokawa
Takayuki
T
Yakushijin
Takumi
T
Igura
Shinichi
S
Kiso
Tatsuya
T
Kanto
Tetsuo
T
Takehara
Shinji
S
Tamura
Akinori
A
Kasahara
Masahide
M
Oshita
Taizo
T
Hijioka
Kazuhiro
K
Katayama
Harumasa
H
Yoshihara
Eijirou
E
Hayashi
Yasuharu
Y
Imai
Michio
M
Kato
Norio
N
Hayashi