肝硬化患者YMDD变异后治疗的临床研究

Clinical studies on the treatment of liver cirrhosis with YMDD mutation

目的评价经拉米夫定（IAM）治疗后出现YMDD变异的代偿期乙型肝炎肝硬化患者采用阿德福韦酯（ADV）单药或与LAM联合治疗的疗效及不良事件发生率。方法将66例患者随机分为3组，A组采用ADV治疗48周，B组采用ADV与LAM联合治疗12周后，再用ADV治疗36周；C组采用ADV与LAM联合治疗48周。结果3组治疗12周内出现ALT水平进一步反弹率分别为33．3％（8／24）、5．0％（1／20）和4．5％（1／22）（P〈0．05），其中A组2例患者出现重型肝炎。3组治疗48周ALT水平下降均显著，但3组之间比较差异均无统计学意义（P〉0．05）；C组ALT复常率、HBVDNA转阴率与A、B组相比，差异有统计学意义（P〈0．05），A组与B组之间差异无统计学意义（P〉0．05）。3组病毒学突破或反弹发生率分别为13．6％、10．0％、0，A组出现rtA181V和rtN236T变异各1例，B组rtN236T变异1例。结论肝硬化患者出现YMDD变异后采用ADV与LAM联合治疗更安全有效。

Objective To evaluate the efficacy and adverse events of adefovir dipivoxil（ADV） or in combination with lamivudine（LAM）in the treatment of liver cirrhosis with YMDD mutation. Method 66 patients were randomly assigned into three groups. In group A, patients received ADV for 48 weeks. In group B, patients received ADV in combination with LAM during the first 12-week period and received ADV for 36 weeks only in the second period. In group C, patients received ADV in combination with LAM for 48 weeks. Results The rebound rates of ALT were 33.3 % （8/24）, 5.0 % （1/20）, 4.5 % （ 1/22） during the first 12-week period in three groups, respectively （ P 〈 0.05）. Two patients appeared severe hepatitis in group A. The level of ALT reduced remarkably in three groups and there was no significant difference between them after 48- week treatment （ P 〉 0.05 ）. At week 48, there was significant difference between group C and A, and also between groups C and B in the ALT nonnalization rate and HBV DNA negative rate （ P 〈 O. 05）, but there was no significant difference between group A and B. Patients with virological breakthrough or reboundrate were 13.6%, 10.0% ,0 respectively in three groups. One patient had rtA181V mutation and another patient had rtN236T mutation in group A, and one patient in group B had rtN236T mutation. Conclusions ADV in combination with LAM is safe and effective for the liver cirrhosis patients with YMDD mutation.