阿德福韦酯联合拉米夫定治疗YMDD变异慢性乙型肝炎的临床研究

Clinical study of adefovir dipivoxil combined with lamivudin in treatment of chronic hepatitis B with YMDD mutation

目的:对经拉米夫定治疗出现YMDD变异的慢性乙型肝炎患者采用阿德福韦酯联合拉米夫定治疗48周,观察其疗效及不良反应,探讨慢性乙型肝炎YMDD变异后的治疗方案。方法:将72例患者随机分为3组,A组单用阿德福韦酯治疗48周;B组采用阿德福韦酯与拉米夫定联合治疗12周,后单用阿德福韦酯治疗36周;C组采用阿德福韦酯与拉米夫定联合治疗48周。结果:3组治疗12周内ALT水平进一步反弹升高的患者比例分别为29.2%(7/24)、12.5%(3/24)、4.2%(1/24)(P<0.05),A组1例患者出现重型肝炎;治疗12周3组患者YMDD变异株检测阳性率分别有17.4%、0、0。治疗48周与治疗前比较3组患者血清ALT水平均显著下降(P<0.05);但3组之间比较差异均无显著性意义(P>0.05),HBV DNA水平较基线值显著下降(P<0.05),均未检测出YMDD变异株;治疗48周3组间e抗原阳性患者血清转换率比较,差异均无显著性意义(P>0.05);C组患者HBV DNA转阴率与A组比较,差异有显著性意义(P<0.05),3组患者的HBV DNA反弹率分别为8.3%(2/24)、4.2%(1/24)、0。A组2例耐药患者测序结果为rtN236T变异,B组rtA181V+rtN236变异和rtN236T变异各1例。结论:YMDD变异后采用阿德福韦酯与拉米夫定联合治疗更安全有效。

Objective： To observe the efficacy and adverse events of adefovir dipivoxil （ADV） combined with lamivudin （LAM） therapy in patients with chronic hepatitis B who had YMDD mutation during the course of treatment with LAM and explore the treatment prescription. Methods： Seventy two patients were randomly assigned into three groups. Group A received ADV for 48 weeks. Group B received ADV in combination with LAM during the first 12 week period and received ADV only for 36 weeks in the second period. Group C received ADV＇in combination with LAM for 48 weeks. Results： The further rebound rate of alanine aminotransferase （ALT） in three groups were 29. 2% （7/24）, 12. 5 % （ 3/24 ）, 4. 2% （1/24） （ P 〈 0. 05 ） respectively during the first 12 week period and one patient appeared with severe hepatitis in group A, while the positive rate of YMDD mutation were 17.4%, 0, 0 respectively. After 48 weeks of treatment, patients of three groups, ALT and HBV DNA level all showed significantly reduced than before treatment （ P 〈 0. 05）, but there was no significant difference among three groups in the level of ALT and seroconversion rate of HBeAg/HBeAb after 48 weeks treatment （ P 〉 0. 05 ） . However, HBV DNA was PCR- negative rate in significantly more patients of group C than group A. Patients with virological breakthrough were 8. 3% （2/24）, 4. 2% （1/24）, 0 respectively in three groups. Two patients had rtN236T mutation in group A, and in group B one patients had rtN236T mutation and the other one had rtA181V and rtN236T mutation. Conclusion： ADV in combination with LAM are more safe and effective therapy for the patients of chronic hepatitis B with YMDD mutation.