本文關(guān)鍵詞：恩替卡韋對乙肝后失代償性肝病或肝衰竭患者臨床療效的Meta分析，由筆耕文化傳播整理發(fā)布。

        背景：2012年歐洲肝臟病學(xué)會(huì)最新版《慢性乙型病毒性肝炎感染臨床管理指南》指出：世界上約1/3的人口有乙肝病毒感染的證據(jù),每年約50-100萬人死于乙肝或乙肝相關(guān)性疾病。2010年《中國慢性乙肝防治指南》中提到“2006年我國乙型肝炎流行病學(xué)調(diào)查數(shù)據(jù)顯示,全國1-59歲一般人群HBsAg攜帶率為7.18%”。據(jù)此推算,我國現(xiàn)有慢性乙肝感染者接近1億人。乙肝患者進(jìn)展為乙肝后失代償性肝病或肝衰竭,五年內(nèi)的生存率小于20%,多數(shù)在兩年內(nèi)死亡。因此選擇有效的乙肝后失代償性肝病及肝衰竭的治療方法至關(guān)重要。恩替卡韋(entecavir, ETV)是抑制核苷類逆轉(zhuǎn)錄酶的抗病毒藥物,于2005年在美國批準(zhǔn)上市,同年在中國批準(zhǔn)上市。從2005年至今國內(nèi)外專家學(xué)者對ETV的研究方興未艾。雖然國內(nèi)外有不少針對ETV用于乙肝后失代償性肝病及肝衰竭的臨床療效的隨機(jī)對照的研究,但是目前尚無關(guān)于ETV用于乙肝后失代償性肝病或肝衰竭臨床療效較全面的Meta分析。目的：評價(jià)ETV對乙肝后失代償性肝病或肝衰竭患者的臨床療效。對象與方法：通過系統(tǒng)檢索Cochrane Library (central,2013), Pubmed(1966-2013.4), Embase(1974-2013.4),中國知網(wǎng)(1978-2013.4),萬方數(shù)據(jù)庫(1998-2013.4),中文科技期刊數(shù)據(jù)庫(1989-2013.4)和中國生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(1978-2013.4)中使用ETV治療乙肝后失代償性肝病及肝衰竭患者的隨機(jī)對照試驗(yàn)(random control trials, RCTs),獲得符合納入標(biāo)準(zhǔn)的文獻(xiàn),對獲得的文獻(xiàn)進(jìn)行質(zhì)量評估及篩選,然后采用RevMan5.1軟件對文獻(xiàn)進(jìn)行Meta分析,并根據(jù)GRADE指南對Meta分析的結(jié)果進(jìn)行質(zhì)量評價(jià),并獲得相關(guān)結(jié)論。結(jié)果：本研究總共納入了8篇RCTs文獻(xiàn),769個(gè)患者。Meta分析顯示：HBV DNA轉(zhuǎn)陰率的評價(jià)中大部分分析顯示合并文獻(xiàn)異質(zhì)性大,且獲得的證據(jù)質(zhì)量極低,其中分析亞組二3)(納入文獻(xiàn)數(shù)目n=2)發(fā)現(xiàn)納入的文獻(xiàn)之間沒有明顯異質(zhì)性,試驗(yàn)組與對照組相比HBV DNA轉(zhuǎn)陰率顯著增加(P<0.00001),證據(jù)質(zhì)量為中等；分析丙氨酸轉(zhuǎn)氨酶(Alanine Aminotransferase, ALT)恢復(fù)正常的概率(n=3)發(fā)現(xiàn)納入各研究之間異質(zhì)性明顯,試驗(yàn)組與對照組相比ALT恢復(fù)正常的概率沒有明顯差異(P=0.07)；分析亞組A(n=2)發(fā)現(xiàn)納入各研究間沒有明顯異質(zhì)性,試驗(yàn)組與對照組相比ALT恢復(fù)正常的概率顯著增加(P<0.0001),證據(jù)質(zhì)量為低質(zhì)量；分析亞組B(n=2)發(fā)現(xiàn)各研究之間無明顯異質(zhì)性,試驗(yàn)組與對照組相比ALT恢復(fù)正常的概率沒有顯著差異(P=0.12),證據(jù)質(zhì)量為中等；分析死亡率(n=7)發(fā)現(xiàn)各研究之間沒有明顯異質(zhì)性,試驗(yàn)組與對照組相比死亡率顯著降低(P<0.0001),證據(jù)等級為中等。結(jié)論：單純內(nèi)科綜合治療與加用ETV或加用其他核苷類似物相比較,有中等質(zhì)量證據(jù)證明,在治療乙肝后失代償性肝病或肝衰竭方面,ETV可以提高HBVDNA遠(yuǎn)期(96周左右)轉(zhuǎn)陰率,提高ALT較遠(yuǎn)期恢復(fù)正常的概率(48周左右)和降低患者死亡率。但是,由于本研究納入文獻(xiàn)數(shù)量較少,入組病例數(shù)較少且文獻(xiàn)的質(zhì)量不高,尚不能得出一個(gè)確切的結(jié)論,所以仍需要大型隨機(jī)對照試驗(yàn)對結(jié)果進(jìn)一步驗(yàn)證。

    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.

恩替卡韋對乙肝后失代償性肝病或肝衰竭患者臨床療效的Meta分析

目錄4-5CONTENTS5-6中文摘要6-8英文摘要8-9符號(hào)說明10-11前言11-14資料與方法14-21結(jié)果21-26討論26-32結(jié)論32-33附表33-44附圖44-49參考文獻(xiàn)49-56致謝56-58學(xué)位論文評閱及答辯情況表58

  本文關(guān)鍵詞：恩替卡韋對乙肝后失代償性肝病或肝衰竭患者臨床療效的Meta分析，由筆耕文化傳播整理發(fā)布。