Brief Article
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World J Gastroenterol. Jun 28, 2011; 17(24): 2945-2952
Published online Jun 28, 2011. doi: 10.3748/wjg.v17.i24.2945
Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients
Masayuki Murata, Norihiro Furusyo, Mami Unno, Eiichi Ogawa, Kazuhiro Toyoda, Hiroaki Taniai, Hachiro Ohnishi, Jun Hayashi
Masayuki Murata, Norihiro Furusyo, Mami Unno, Eiichi Ogawa, Kazuhiro Toyoda, Hiroaki Taniai, Hachiro Ohnishi, Jun Hayashi, Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, 812-8582, Japan
Norihiro Furusyo, Mami Unno, Jun Hayashi, Department of Environmental Medicine and Infectious Disease, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
Author contributions: Murata M and Furusyo N performed the majority of the experiments; Unno M, Ogawa E, Toyoda K, Taniai H and Ohnishi H provided clinical serum samples from patients for the study; Murata M and Furusyo N designed the study; Murata M analyzed data and wrote the manuscript; Hayashi J reviewed the manuscript in addition to providing financial support for this study.
Correspondence to: Masayuki Murata, MD, PhD, Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. mmurata@gim.med.kyushu-u.ac.jp
Telephone: +81-92-6425909 Fax: +81-92-6425916
Received: August 28, 2010
Revised: February 15, 2011
Accepted: February 22, 2011
Published online: June 28, 2011
Abstract

AIM: To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate (YMDD) mutants (reverse transcription; rtM204I/V) and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus (HBV) infection.

METHODS: The data of 61 consecutive Japanese patients with chronic hepatitis B who underwent continuous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo (mean, 50.8 mo; range, 24-90 mo).

RESULTS: A mixed mutant-type (YMDD + tyrosine-isoleucine-asparatate-asparatate: YIDD or tyrosine-valine-asparatate-asparatate: YVDD) or a mutant-type (YIDD or YVDD) were found in 57.4% of 61 patients at 1 year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 (92%) had mixed mutant- or a mutant-type. Only 5 (8%) had no mutants at each observation point. Virological breakthrough was found in 26 (46.4%) of 56 patients with YMDD mutants, 20 of whom had a hepatitis flare-up: the remaining 30 (53.6%) had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment.

CONCLUSION: Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.

Keywords: Tyrosine-methionine-asparatate-asparatate mutant; Hepatitis B virus; Lamivudine; Drug resistance