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-valineasparatate-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. 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 ) 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- valineasparatate-asparatate: YVDD) or 57.6% 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. (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.