拉米夫定单药及其初始联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化的疗效比较

Efficacy of lamivudine monotherapy and combination therapy with adefovir dipivoxil for patients with hepatitis B virus-related decompensated cirrhosis

目的比较拉米夫定与阿德福韦酯初始联合或拉米夫定单药治疗失代偿期乙型肝炎肝硬化患者2年的疗效。方法60例失代偿期乙型肝炎肝硬化接受初始拉米夫定（LAM）与阿德福韦酯（ADV）联合抗病毒治疗，为初始联合组；55例接受拉米夫定（LAM）单药抗病毒治疗，为LAM单药组。每1～3个月检测患者肝功能、肾功能、甲胎蛋白、乙型肝炎病毒标志物、血清HBVDNA、凝血酶原时间（PT）、肝脏的超声或CT检查，分别在治疗12个月和24个月时比较疗效。组间均数比较用Mann-Whitney检验，相关性分析时采用Pearson双侧f检验。结果初始联合组45例治疗12个月时血清HBVDNA阴转率为51．1％（23／45），而40例LAM单药组HBVDNA阴转率为47．5％（19／40）；至24个月时，初始联合组HBVDNA阴转率达86．7％（39／45），LAM单药组为60．0％（24／40），两组间差异有统计学意义（P〈0．05）。初始联合组治疗24个月时，HBeAg血清学转换率为43．5％（10／23），LAM单药组HBeAg血清学转换率为30．0％（6／20），两组问差异有统计学意义（P〈0．05）。ALT复常率在初始联合组治疗12个月时为71．1％（32／45），LAM单药组为65．0％（26／40），至24个月时两组ALT复常率分别为88．9％（40／45）和75。0％（30／40），差异有统计学意义（P〈0．05）。初始联合组在治疗12个月和24个月时，分别有4．4％（2／45）和6．7％（3／45）发生病毒学突破，但均未检测到病毒学变异，LAM单药组在12个月和24个月时分别有22．5％（9／40）和37．5％（15／40）发生病毒学突破，并分别有17．5％（7／40）和32．5％（13／40）的患者中检测到病毒学变异，均较联合治疗组高（P〈0．05）。初始联合治疗更能改善肝功能，Child—Turcotte—Pugh评分和终末期肝病模型评分亦有更明显下降。随访24个月，LAM和ADV初始联合治疗组累计死亡或肝移植率为16．7％，LAM单药组累计死亡或肝移植发生率为20．0％。两组均未发现有血清肌酐超过正常值上限的病例。结论LAM与ADV初始联合治疗失代偿期乙型肝炎肝硬化患者能更明显抑制HBV复制，改善肝功能各项指标，降低病死率，值得临床应用。

Objective To compare the efficacy of Lamivudine （LAM） monotherapy and combination therapy with Adefovir Dipivoxil （ADV） for patients with hepatitis B virus （HBV） -related decompensated cirrhosis for 2 years. Methods A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study, among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM. The liver and kidney functions, I-IBV DNA, I4BV-M, AFE Ultrasond or CT scan of liver were tested every 1-3months. the treatment efficacy was evaluated by month 12 and 24. Results By month 12, the HBV DNA negative rates of combination therapy group and LAM monotherapy group were 51.1% （45 cases） and 47.5% （40 cases） respectively, by month 24 the rates were 86.7% and 60.0% respectively. By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0% respectively, with significant difference existed between the two therapy groups （P 〈 0.05）. By month 24, the ALT normalization rates of the two groups were 88.9% and 72.5% respectively. Viral breakthrough happened in 2 cases （4.4%） by month 12 and 3 cases （6.7%） by month 24 in LAM and ADV combination group, but no viral resistance observed. Viral breakthrough happened in 9 cases （22.5%） by month 12 and 15 cases （37.5%） by month 24 in LAM monotherapy group with viral resistance observed in 7 cases （17.5%） by month 12 and 13 cases （32.5） by month 24. Significant difference existed between the two groups （P 〈 0.05）. Improvement of liver function was more obviously in the combination group. The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group. No renal dysfunction observed in both groups. Conclusion LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.