恩替卡韦治疗慢加急性乙型肝炎肝衰竭疗效的Meta分析

doi:10.3969/j.issn.1672-5069.2015.05.011

摘要/Abstract

摘要： 目的系统评价恩替卡韦治疗慢加急性乙型肝炎肝衰竭的疗效和安全性。方法应用计算机检索PubMed、Cochrane Library、CBMdisc、CNKI、维普、万方等数据库公开发表的文献，检索年限均从2006年1月至2014年9月。纳入恩替卡韦与拉米夫定相比较治疗慢加急性乙型肝炎肝衰竭的随机对照试验。由两名评判员对纳入试验独立进行质量评价和资料提取，采用RevMan5.1软件进行Meta分析。结果经筛选共纳入7个随机对照试验，合计823例患者。Meta分析结果显示，恩替卡韦治疗6月以上的患者其病死率显著低于拉米夫定治疗患者[RR=0.75，95%CI（0.60，0.95），P＜0.05]；在治疗2～3 m和6 m以上评价，恩替卡韦治疗患者HBV DNA转阴率也显著高于拉米夫定治疗患者[RR=1.47，95%CI（1.29，1.68），P＜0.05；RR=1.48，95%CI（1.30，1.67），P＜0.05]，病毒学突破率也显著低于拉米夫定治疗组[RR=0.07，95%CI（0.01，0.54），P＜0.05]，且未出现严重不良反应。结论恩替卡韦治疗慢加急性乙型肝炎肝衰竭患者的远期病死率和病毒学突破率均显著低于拉米夫定，适合于长期抗病毒治疗。

关键词: 慢性乙型肝炎, 肝衰竭, 恩替卡韦, Meta分析

Abstract: Objective To evaluate the efficacy and safety of entecavir in treatment of patients with hepatitis B virus （HBV）-related acute-on-chronic liver failure. Methods All randomized controlled trials comparing the efficacy of entecavir versus lamivudine in patients with HBV-related acute-on-chronic liver failure published in January 2006 to September 2014 were collected by searching PubMed，Cochrane Library，CBMdisc，Chinese National Knowledge Infrastructure（CNKI），Chinese VIP database and WanFang database. The quality assessment of literatures and the extraction of information were accomplished by two independent reviewers. Statistical analyses were performed with RevMan 5.1 software. Results Seven eligible trials including 823 patients were included. According to the results of meta-analysis，the mortality rates of patients in entecavir groups were significantly lower than that of patients in lamivudine groups when the treatment lasted for more than 6 months [RR=0.75，95%CI （0.60，0.95），P<0.05]；the negative conversion rates of serum HBV DNA in patients of entecavir groups were significantly higher than that of patients in lamivudine groups when the treatment lasted for 2 to 3 months and more than 6 months[RR=1.47，95%CI（1.29，1.68），P<0.05;RR=1.48，95%CI（1.30，1.67），P<0.05]，and the virological breakthrough rate of patients in entecavir groups was significantly lower as compared to that of patients in lamivudine groups [RR=0.07，95%CI（0.01，0.54），P<0.05]. No serious adverse events were observed in the entecavir groups. Conclusion Entecavir leads to lower long-term mortality rate and virological breakthrough rate than lamivudine in patients with HBV-related acute-on-chronic liver failure，providing a better option for the long-term antiviral therapy.

Key words: Hepatitis B, Liver failure, Entecavir, Meta-analysis

毛海鹰，廖礼艳，胡秋菊，华杨，韩志超. 恩替卡韦治疗慢加急性乙型肝炎肝衰竭疗效的Meta分析[J]. 实用肝脏病杂志, 2015, 18(5): 491-495.

Mao Haiying，Liao Liyan，Hu Qiuju，et al.. Efficacy of entecavir in treatment of patients with hepatitis B virus-related acute-on-chronic liver failure: a Meta-analysis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(5): 491-495.

参考文献

[1] 李晨. 核苷类似物治疗慢加急性乙型肝炎肝衰竭的研究进展.实用肝脏病杂志，2010，13（4）:306-309.
[2] 王宇明，李兰娟. 《肝衰竭诊治指南（2012年版）》治疗进展的解读与探讨. 中华临床感染病杂志，2013，6（2）:77-80.
[3] 中华医学会感染病学分会肝衰竭与人工肝学组和肝病学分会重型肝病与人工肝学组.肝衰竭诊疗指南. 实用肝脏病杂志，2006，9（6）：321-324.
[4] 叶非，过建春，裘云庆，等. 恩替卡韦、拉米夫定治疗HBeAg阴性乙型肝炎相关慢加急性肝衰竭12周疗效比较. 中华实验和临床病毒学杂志，2014，28（3）:209-212.
[5] 赵文革，马艳丽. 恩替卡韦和拉米夫定治疗乙型慢加急性肝衰竭3年疗效的对比研究. 中国医药，2012，7（2）:169-171.
[6] Zhang Y，Hu XY，Zhong S，et al. Entecavir vs lamivudine therapy for naive patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. World J Gastroenterol，2014，20（16）:4745-4752.
[7] 文彬，袁静，胡敏冬，等.恩替卡韦与拉米夫定治疗乙肝病毒所致慢加急性肝功能衰竭疗效的对比研究.热带医学杂志，2010，10（2）:183-185.
[8] 蔡文辉，王大伟，施翠芬.恩替卡韦与拉米夫定治疗乙型肝炎病毒所致慢加急性肝功能衰竭的疗效比较.中国医药指南，2011，9（36）:303-304.
[9] 胡瑾华，王慧芬，何卫平，等.核苷类似物治疗早中期HBV-ACLF患者随机对照临床研究.中华实验和临床病毒学杂志，2010，24（3）:205-208.
[10] 何兵.拉米夫定和恩替卡韦治疗乙型肝炎慢性加急性肝功能衰竭近期疗效比较. 河北医药，2013，35（5）:661-663.
[11] 姜立胜，李用国，陈姝，等. 抗病毒治疗对乙型肝炎相关慢加急性肝衰竭近期及远期疗效的影响.临床肝胆病杂志，2013，29（2）:110-113.
[12] 王淼，李用国. 核苷（酸）类似物治疗慢加急性肝衰竭研究进展.临床肝胆病杂志，2012，28（5）:391-394.
[13] 中华医学会感染病学分会肝衰竭与人工肝学组，中华医学会肝病学分会重型肝病与人工肝学组.肝衰竭诊治指南（2012年版）. 中华肝脏病杂志，2013，21（3）:177-183.
[14] Seifer M，Hamatake RK，Colonno RJ，et al. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob Agents Chemother，1998，42（12）:3200-3208.
[15] Colonno RJ，Genovesi EV，Medina I，et al. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J Infect Dis，2001，184（10）:1236-1245.
[16] Marion PL，Salazar FH，Winters MA，et al. Potent efficacy of entecavir（BMS-200475） in a duck model of hepatitis B virus replication. Antimicrob Agents Chemother，2002，46（1）:82-88.
[17] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志，2011，14（2）：81-89.
[18] Tenney DJ，Rose RE，Baldick CJ，et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology，2009，49（5）:1503-1514.
[19] Lok AS，McMahon BJ. Chronic hepatitis B: update 2009. Hepatology，2009，50（3）:1-36.
[20] European Association For The Study Of The Liver. EASL clinical practice guidelines:Management of chronic hepatitis B virus infection. J Hepatol，2012，57（1）:167-185.
[21] Lange CM，Bojunga J，Hofmann WP，et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. Hepatology，2009，50（6）:2001-2006.
[22] Cui YL，Yan F，Wang YB，et al. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci，2010，55（8）:2373-2380.
[23] 毛海鹰，康涛，邱邦东，等. 乙型肝炎肝硬化失代偿期应用恩替卡韦并发乳酸酸中毒1例.中国医院药学杂志，2013，33（15）:1297-1298.