拉米夫定初始联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化1年的疗效评价

One-year combination therapy de novo of adefovir dipivoxil and lamivudine for decompensated cirrhosis related to HBV

目的观察拉米夫定（LMV）初始联合阿德福韦酯（ADV）治疗失代偿期乙型肝炎肝硬化1年的疗效和可能的肾功能异常。方法36例无核苷类似物治疗史的乙型肝炎肝硬化失代偿期患者，随机分为2组，对照组（n=18）给LMV 100mg／d单药抗病毒，观察组（n：18）给LMV 100mg／d＋ADV10mg／d，同时均予常规护肝及对症、支持治疗，疗程1年；观察治疗前后肝功能、Child-Pugh评分和血清肌酐变化，病毒学应答率和病毒学反弹发生率，统计学比较组间差异。结果（1）基线时两组患者性别、年龄、HBeAg状况、HBV载量、血肌酐和Child．Pugh评分均无统计学差异（P〉0．05）。（2）治疗结束时2组均无死亡发生，自身前后对比肝功能改善、Child-Pugh评分下降、HBV-DNA水平显著下降，观察组疗效优于对照组（P〈0．01）、病毒学应答率高于对照组（88．89％VS66．67％，P〈0．05）。（3）观察组无病毒学反弹发生，对照组3例（16．67％）发生病毒学反弹，HBVP区基因测序均系rtM204V变异。（4）2组患者均无血肌酐增高发生。结论乙型肝炎肝硬化失代偿期LMV初始联合ADV1年治疗在肝功能改善、病毒学应答和HBV耐药变异等方面均优于LMV单药治疗，且肾脏安全性良好。

Objective To evaluate the efficacy and potential renal impairment of one-year combination therapy de novo of adefovir dipivoxil （ADV） and lamivudine（LMV） for decompensated cirrhosis related to HBV. Methods A total of 36 patients with decompensated cirrhosis related to HBV, nobody had nucleos（t）ide analogs （NAs） treatment history, were recruited and were divided into two group（ control group and observation group） randomly. A monotherapy of LMV （100 mg per day） was selected to individuals in control group（ n = 18） , in contrast, a combination therapy de novo of ADV （ 10 mg per day） and LMV （ 100 mg per day） was applied to those in observation group （n = 18 ）. Basic approaches including liver protection, symptom-driven intervention, and supporting therapy, were given to all of the individuals. A course of one year was applied to all. Liver function, Child-Pugh score, serum ereatinine（sCr） level, virological response（VR） rate, and virological breakthrough rate were observed pro- and post- treatment, differences between the two populations were analysed statistically. Results （ 1 ） The averages of gender, age, HBeAg status, HBV viral load, sCr level, and Cbild-Pugb score were all compatible in the two groups at baseline（P 〉 0. 05 for all）. （2）At the endpoint of treatment, none of deaths was reported. Comparing with the status before treatment in each group itself, liver function, Child-Pugh score, and viral load were improved statistically （ P 〈 0.01 for all） , especially in observed group（ P 〈 0. 01 for all variables, vs control group） , as for VR rate, result is significant superior to that of control group too（88.89% vs 66.67% , P 〈 0.05）. （3） Virological breakthrough occurred to none in observed group and three cases （16.67%） incontrol group, all of them were confirmed to be rtM204V variant in the following detection of direct sequencing. （4） Elevated level of sCr didn＇ t arised at the end of treatment in two groups. Conclusion Present study reveals that in populations with decompensated cirrhosis related to HBV, one-year combination therapy de novo of ADV and LMV is superior to monotherapy of LMV, and the renal safety is favorable within one year.