Initial viral response is the most powerful predictor of the emergence of YMDD mutant virus in chron

April 24, 2008

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1872-034X.2007.00292.x

Hepatology Research 38 (5) , 450–456 doi:10.1111/j.1872-034X.2007.00292.x

Abstract

Original Article

Initial viral response is the most powerful predictor of the emergence of YMDD

mutant virus in chronic hepatitis B patients treated with lamivudine

Nao Kurashige,11Osaka University, Naoki Hiramatsu,11Osaka University, Dr Naoki

Hiramatsu, Department of Gastroenterology and Hepatology, Osaka University

Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.

Email: hiramatsu@... Kazuyoshi Ohkawa,11Osaka University,

Tsugiko Oze,11Osaka University, Yuko Inoue,11Osaka University, Mika

Kurokawa,11Osaka University, Takayuki Yakushijin,11Osaka University, Takumi

Igura,11Osaka University, Shinichi Kiso,11Osaka University, Tatsuya

Kanto,11Osaka University, Tetsuo Takehara,11Osaka University, Shinji

Tamura,11Osaka University, Akinori Kasahara,11Osaka University, Masahide

Oshita,22Osaka Police Hospital, Taizo Hijioka,33National Organization Osaka

Minami Medical Center, Kazuhiro Katayama,44Osaka Kouseinenkin Hospital, Harumasa

Yoshihara,55Osaka Rousai Hospital, Eijirou Hayashi,66Kinki Central Hospital,

Hyogo, Japan Yasuharu Imai,77Ikeda City Hospital, Michio Kato88National Hospital

Organization Osaka National Hospital, Osaka, and and Norio Hayashi11Osaka

University, 1Osaka University, 2Osaka Police Hospital, 3National Organization

Osaka Minami Medical Center, 4Osaka Kouseinenkin Hospital, 5Osaka Rousai

Hospital, 7Ikeda City Hospital, 8National Hospital Organization Osaka National

Hospital, Osaka, and 6Kinki Central Hospital, Hyogo, Japan

Dr Naoki Hiramatsu, Department of Gastroenterology and Hepatology, Osaka

University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka

565-0871, Japan. Email: hiramatsu@...

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) ( 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.

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April 24, 2008