恩替卡韦与拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化失代偿期患者48周疗效Meta分析

摘要

目的：评价恩替卡韦（ETV）与拉米夫定（LAM）联合阿德福韦酯（ADV）治疗乙型肝炎肝硬化失代偿期患者48 w的疗效。方法检索MEDLINE、EMBASE、CENTRAL、Cochrane图书馆、中国期刊全文数据库、中国生物医学文献数据库、中国万方数据库、中国维普数据库建库至2015年5月的资料，纳入ETV与LAM联合ADV治疗乙型肝炎肝硬化失代偿期患者48 w的临床随机对照试验（RCT），采用Revman5.2软件进行Meta分析。结果共纳入9个RCT，包括联合组311例，ETV组305例。Meta分析结果显示，在治疗48 w时，联合治疗组在改善肝功能方面未见明显优于ETV治疗组，其白蛋白升高、胆红素下降、PT缩短、Child-Pugh评分下降幅度的标准化均差（SMD）分别为-0.10（95%CI-0.31~0.12，P=0.39）、-0.00（95%CI -0.58~0.57，P=1.0）、0.19（95%CI -0.01~0.40，P=0.07）、-0.03（95%CI -0.24~0.18，P=0.76）；在治疗48 w时，联合治疗组病死率、血清HBV DNA转阴率、HBeAg 血清学转换率和病毒学突破率分别为5.3%、68.8%、24.1%和5.0%，与ETV治疗组的4.5%、74.8%、23.4%和2.8%比，无统计学差异（P=0.83、P=0.19、P=0.96、P=0.39）。结论恩替卡韦与拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化失代偿期患者具有相似的短期疗效，但其远期疗效如何尚需大样本长疗程的临床随机对照试验进一步观察。%Objective To evaluate the effectiveness of entecavir (ETV) monotherapy versus lamivudine (LAM) combined with adefovir dipivoxil (ADV) in patients with hepatitis B-associated decompensated cirrhosis after 48 weeks of treatment. Methods All randomized control trials (RCTs) of ETV monotherapy versus LAM combined with ADV for 48 week treatment of patients with hepatitis B-associated decompensated cirrhosis published before May 2015 were collected by searching Cochrane Library,MEDLINE,EMBASE,CENTRAL,Chinese National Knowledge Infrastructure (CNKI),Wan-Fang database and VIP database. Meta-analysis was carried out with RevMan 5.2 software. Results A total of 9 RCTs involving 311 cases in the combination therapy group and 305 in the monotherapy group were included. The Meta analysis showed that as compared with patients in ETV group,there were not greater improvement in hepatic functions in combined group at 48 weeks treatment,and the standard mean differences (SMDs) for elevation of albumin levels,reduction of bilirubin levels,reduction of prothrombin time,and,reduction of Child-Pugh-score were -0.10(95%CI-0.31~0.12,P=0.39),-0.00(95%CI -0.58~0.57,P=1.0),0.19 (95%CI -0.01~0.40,P=0.07),-0.03 (95%CI -0.24~0.18,P=0.76),respectively;The mortality, undetectable rate of serum HBV DNA,HBeAg seroconversion rate,and viral breakthrough rate in patients in combined groups at 48 weeks treatment (5.3%,68.8%,24.1%,5.0%) were not higher than those in ETV groups (4.5%,74.8%,23.4%,2.8%;P=0.83,P=0.19,P=0.96,P=0.39,respectively). Conclusion ETV and LAM combined with ADV had similar short-term effectiveness for patients with hepatitis B-associated decompensated cirrhosis at 48 weeks treatment,and their long-term efficacy needs further study.