Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients

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 pa- tients with chronic hepatitis B who underwent continu- ous 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 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i 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. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis 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.