不同核苷（酸）类似物抗病毒治疗方案治疗失代偿期乙肝肝硬化的临床研究

目的 探讨核苷（酸）类似物初始联合治疗失代偿期乙型肝炎肝硬化的疗效及安全性。方法 回顾性分析2008年1月至2011年10月收治的116例乙型肝炎肝硬化患者的临床资料。按不同抗病毒方案分为恩替卡韦（ETV）组（n=38）,拉米夫定（LAM）＋阿德福韦酯（ADV）组（n=23）,替比夫定（LDT）＋ADV组（n=16）,未抗病毒治疗者作为对照组（n=39）。患者每3个月随访并收集其临床数据,分析各组Child-Pugh评分、病毒学指标、肝癌发生率、生存率及安全性。结果 各抗病毒治疗组在1年、2年时Child-Pugh评分较基线均显著下降（P〈0.05）;LDT＋ADV组在2年时e抗原（HBe Ag）阴转率（72.7%）高于ETV组（30.4%,P〈0.05）;ETV组（0.0%）、LAM＋ADV组（8.7%）、LDT＋ADV组（0.0%）的2年累积肝衰竭发生率均明显低于对照组（28.2%）;各抗病毒治疗组、对照组的2年累积耐药率、肝癌发生率、生存率的差异无统计学意义;各抗病毒治疗组在2年随访中均未出现严重肌病和肾功能损害。结论 LAM＋ADV及LDT＋ADV可改善失代偿期乙型肝炎肝硬化患者肝功能,LAM＋ADV及LDT＋ADV的2年疗效和安全性与ETV相似。

A clinical study on anti-viral therapy with different regimens of nucleos(t)ide analogues on HBV related decompensated cirrhosis

Objective To evaluate the efficacy and safety of combined antiviral therapy of nucleos（t）ide analogues in HBV related decompensated cirrhotic patients. Methods The patients with HBV related decompensated cirrhosis were enrolled and divided into 4 groups, ETV （n=38） naive, LAM＋ADV（n=23）, LDT＋ADV （n=16） and the control group（n=39）. The patients were followed up every 3 months and the clinical data were obtained. The Child-Pugh scores, virology indexes, hepatocellular carcinoma （HCC） incidence, survival and safety had been evaluated in the past 2 years. Results The Child-Pugh scores in each antiviral therapy group significantly decreased in the first year and the second year than the baseline scores （P 〈 0.05 ）. In the second year, the negative rate of HBeAg in the LDT＋ADV group was higher than that of the ETV group （72.7% vs. 30.4%, P 〈 0.05）. The cumulative incidence of liver failure in the ETV （0.0%）, LAM＋ADV （8.7%） and LDT＋ADV （0.0%） groups decreased significantly than that of the control group（28.2%, all P 〈 0.05）. There was no difference in survival, cumulative incidence of HCC and drug-resistant rate between each antiviral therapy group and the control group. No severe myopathy and renal injury were found in each antiviral therapy group during the 2-year follow-up. Conclusion Liver function can be improved by antiviral therapy with LAM＋ADV and LDT＋ADV in HBV related decompensated cirrhotic patients. The efficacy and safety of combination of LAM＋ADV or LDT＋ADV in the second year are similar to ETV monotherapy.