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Initial viral response is the most powerful predictor of the emergence of YMDD mutant virus in chronic hepatitis B patients treated with lamivudine.
Authors:Nao Kurashige  Naoki Hiramatsu  Kazuyoshi Ohkawa  Tsugiko Oze  Yuko Inoue  Mika Kurokawa  Takayuki Yakushijin  Takumi Igura  Shinichi Kiso  Tatsuya Kanto  Tetsuo Takehara  Shinji Tamura  Akinori Kasahara  Masahide Oshita  Taizo Hijioka  Kazuhiro Katayama  Harumasa Yoshihara  Eijirou Hayashi  Yasuharu Imai  Michio Kato  Norio Hayashi
Affiliation:Osaka University, Osaka, Japan.
Abstract:Aim: 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). Conclusion: 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.
Keywords:chronic hepatitis B    initial viral response    lamivudine monotherapy    lamivudine-resistant virus
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