恩替卡韦对乙肝后失代偿性肝病或肝衰竭患者临床疗效的Meta分析

  本文关键词：恩替卡韦对乙肝后失代偿性肝病或肝衰竭患者临床疗效的Meta分析，由笔耕文化传播整理发布。

        背景：2012年欧洲肝脏病学会最新版《慢性乙型病毒性肝炎感染临床管理指南》指出：世界上约1/3的人口有乙肝病毒感染的证据,每年约50-100万人死于乙肝或乙肝相关性疾病。2010年《中国慢性乙肝防治指南》中提到“2006年我国乙型肝炎流行病学调查数据显示,全国1-59岁一般人群HBsAg携带率为7.18%”。据此推算,我国现有慢性乙肝感染者接近1亿人。乙肝患者进展为乙肝后失代偿性肝病或肝衰竭,五年内的生存率小于20%,多数在两年内死亡。因此选择有效的乙肝后失代偿性肝病及肝衰竭的治疗方法至关重要。恩替卡韦(entecavir, ETV)是抑制核苷类逆转录酶的抗病毒药物,于2005年在美国批准上市,同年在中国批准上市。从2005年至今国内外专家学者对ETV的研究方兴未艾。虽然国内外有不少针对ETV用于乙肝后失代偿性肝病及肝衰竭的临床疗效的随机对照的研究,但是目前尚无关于ETV用于乙肝后失代偿性肝病或肝衰竭临床疗效较全面的Meta分析。目的：评价ETV对乙肝后失代偿性肝病或肝衰竭患者的临床疗效。对象与方法：通过系统检索Cochrane Library (central,2013), Pubmed(1966-2013.4), Embase(1974-2013.4),中国知网(1978-2013.4),万方数据库(1998-2013.4),中文科技期刊数据库(1989-2013.4)和中国生物医学文献数据库(1978-2013.4)中使用ETV治疗乙肝后失代偿性肝病及肝衰竭患者的随机对照试验(random control trials, RCTs),获得符合纳入标准的文献,对获得的文献进行质量评估及筛选,然后采用RevMan5.1软件对文献进行Meta分析,并根据GRADE指南对Meta分析的结果进行质量评价,并获得相关结论。结果：本研究总共纳入了8篇RCTs文献,769个患者。Meta分析显示：HBV DNA转阴率的评价中大部分分析显示合并文献异质性大,且获得的证据质量极低,其中分析亚组二3)(纳入文献数目n=2)发现纳入的文献之间没有明显异质性,试验组与对照组相比HBV DNA转阴率显著增加(P<0.00001),证据质量为中等；分析丙氨酸转氨酶(Alanine Aminotransferase, ALT)恢复正常的概率(n=3)发现纳入各研究之间异质性明显,试验组与对照组相比ALT恢复正常的概率没有明显差异(P=0.07)；分析亚组A(n=2)发现纳入各研究间没有明显异质性,试验组与对照组相比ALT恢复正常的概率显著增加(P<0.0001),证据质量为低质量；分析亚组B(n=2)发现各研究之间无明显异质性,试验组与对照组相比ALT恢复正常的概率没有显著差异(P=0.12),证据质量为中等；分析死亡率(n=7)发现各研究之间没有明显异质性,试验组与对照组相比死亡率显著降低(P<0.0001),证据等级为中等。结论：单纯内科综合治疗与加用ETV或加用其他核苷类似物相比较,有中等质量证据证明,在治疗乙肝后失代偿性肝病或肝衰竭方面,ETV可以提高HBVDNA远期(96周左右)转阴率,提高ALT较远期恢复正常的概率(48周左右)和降低患者死亡率。但是,由于本研究纳入文献数量较少,入组病例数较少且文献的质量不高,尚不能得出一个确切的结论,所以仍需要大型随机对照试验对结果进一步验证。

    Background:In the latest clinical practice guidelines made by European association for the study of the liver(EASL), approximately one third of the word’s population has serological evidence of past or present infection with hepatitis B virus (HBV) and HBV-related end stage liver diseases or hepatocellular carcinoma(HCC) are responsible for over0.5-1million deaths per year. The guideline of prevention and treatment for chronic hepatitis (2010version) of China points that about7.18%of the population aged1to59years old in China are chronic HBV surface antigen(HBsAg) carriers, according to the epidemiological investigate nationwide. Now, there are about0.1billion people who are HBsAg carriers based on the epidemiological studies. Morbidity and mortality in chronic hepatitis (CHB) are linked to peristence of viral replication. Entecavir(ETV) is a nucleoside analog(more specifically, a guanosine analogue) that inhibits reverse transcription, DNA replication and transcription in the viral-eplication process, which was approved by the U.S.FDA in March2005, and approved by SFDA in the same year. There are many random control trials on ETV used for patients with hepatitis B decompensated liver disease or liver failure, but system review and Meta-analysis are rare.Objective:To assess the treatment outcomes of ETV in participants with lepatitis B decompensated liver disease or liver failure. Search methods and Data collection:A computerized search of The Cochrane Library (CENTRAL,2013), PubMed(1966-April2013), EMbase (1974-April2013), CNKI (1978-April2013), WANFANG (1998-2013.4),VIP (1989-2013.4), CBM (1978-2013.4) databases was conducted. Studies were selected according to prespecified inclusion and exclusion criteria and then subjected for quality assessment and data extraction. Meta-analysis was performed using the statistical software (RevMan5.1.1) provided by the Cochrane Collaboration and the evidence quality was evaluated by Grading of Recommendations Assessment, Development and Evaluation’s(GRADE) guideline.Results:A total of8studies, all of which were randomized clinical trials (RCTs), involving769patients with severe hepatitis B were included. Subgroup analyses by control group and treatment duration were conducted. The quality of the evidence was classified from very low to moderate by the GRADED approach for all the included RCTs. Meta-analysis showed that patients were significantly more likely to experience HBV-DNA loss(P<0.00001), have normalized alanine aminotransferase levels(ALT)(P<0.0001) and have a low mortality ratez(P<0.0001) when treated with entecavir versus control groups for either48or96weeksConclusion:Entecavir appeared to be more effective than other therapies in reducing serum HBV-DNA load, normalizing ALT and reducing mortality in patients with severe hepatitis B. However, the small sample size, short period of follow-up, and high risk of bias in the included trials limited the credibility ofresults. Therefore, adequately powered randomised trials with low risk of bias and long periods of follow-up and assessing all of the important outcomes for patients and professionals were in great need.

恩替卡韦对乙肝后失代偿性肝病或肝衰竭患者临床疗效的Meta分析

目录4-5CONTENTS5-6中文摘要6-8英文摘要8-9符号说明10-11前言11-14资料与方法14-21结果21-26讨论26-32结论32-33附表33-44附图44-49参考文献49-56致谢56-58学位论文评阅及答辩情况表58

  本文关键词：恩替卡韦对乙肝后失代偿性肝病或肝衰竭患者临床疗效的Meta分析，由笔耕文化传播整理发布。