Meta-Analysis
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World J Gastroenterol. Oct 21, 2013; 19(39): 6665-6678
Published online Oct 21, 2013. doi: 10.3748/wjg.v19.i39.6665
Effects of entecavir and lamivudine for hepatitis B decompensated cirrhosis: Meta-analysis
Xiao-Guang Ye, Qi-Min Su
Xiao-Guang Ye, Qi-Min Su, Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
Author contributions: Su QM did data acquisition, analysis and interpretation, and drafted the manuscript; Ye XG conceived and designed the study, and revised the article critically for important intellectual content, and both authors have read and approved the final version to be published.
Supported by The Chinese Foundation for Hepatitis Prevention and Control, Fund of “Guanghui” No. 2012208
Correspondence to: Dr. Xiao-Guang Ye, Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China. yexiaoguang@126.com
Telephone: +86-20-34152236 Fax: +86-20-34153982
Received: June 7, 2013
Revised: July 18, 2013
Accepted: August 13, 2013
Published online: October 21, 2013
Processing time: 87 Days and 22.8 Hours
Abstract

AIM: To compare the effects of entecavir (ETV) and lamivudine (LAM) for the treatment of hepatitis B decompensated cirrhosis using a meta-analysis.

METHODS: We conducted a literature search for all eligible studies published prior to May 30, 2013 using PUBMED, MEDLINE, EMBASE, the China National Knowledge Infrastructure (CNKI), the VIP database, the Wanfang database and the Cochrane Controlled Trial Register. Randomized controlled trials (RCTs) comparing ETV with LAM for the treatment of hepatitis B decompensated cirrhosis were included. The data were analyzed with Review Manager Software 5.0.2. We used RR as an effect measure, and reported its 95%CI. The meta-analysis was performed using either a fixed-effect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data independently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, HBV DNA level, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) level, albumin level, total bilirubin (TBIL) level, prothrombin time activity (PTA) level, Child-Turcotte-Pugh (CTP) score, mortality, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics and the therapeutic effects of the two agents.

RESULTS: Thirteen eligible trials (873 patients in total) were included and evaluated for methodological quality and heterogeneity. Of these studies, all had baseline comparability, 12 of them reported baseline values of the two treatment groups in detail. Following various treatment durations (12, 24, 36, 48 and > 48 wk), both ETV and LAM significantly reduced HBV DNA level, however, reductions were greater in the ETV group (MD = -0.66, 95%CI: -0.83-0.50, P < 0.00001), (MD = -0.93, 95%CI: -1.36-0.51, P < 0.0001), (MD = -1.4, 95%CI: -1.78-1.01, P < 0.00001), (MD = -1.18, 95%CI: -1.90-0.46, P = 0.001), (MD = -0.14, 95%CI: -0.17-0.11, P < 0.00001, respectively). At 12, 24 and 48 wk of treatment, ETV had a significant effect on the rate of HBV DNA undetectability (RR = 1.55, 95%CI: 1.22-1.99, P = 0.0004), (RR = 1.25, 95%CI: 1.13-1.38, P < 0.0001), (RR = 1.2, 95%CI: 1.10-1.32, P < 0.0001, respectively). Although HBeAg seroconversion in the ETV group was more pronounced than that in the LAM group at 24 wk (27.90% vs 26.19%) and 48 wk (31.52% vs 25.00%) of treatment, there was no statistically significant difference between them (RR = 1.49, 95%CI: 0.98-2.28, P = 0.07), (RR = 1.27, 95%CI: 0.98-1.65, P = 0.07, respectively). Following various treatment durations, both the ETV group and the LAM group showed significantly improved liver function (ALT, AIB, TBIL, PTA and CTP levels) and reduced mortality (ETV 6.37%, LAM 7.89%). The effects in the ETV group (0.33%) were statistically lower than those in the LAM group (14.33%) regarding the rate of drug-resistance (RR = 0.1, 95%CI: 0.04-0.24, P≤ 0.00001). In addition, no severe adverse reactions were observed in the two treatment groups.

CONCLUSION: ETV and LAM significantly improved liver function and reduced mortality. Both drugs produced similar serological responses, and were safe and well tolerated. However, ETV resulted in a better virological response and lower drug-resistance, but is more expensive.

Keywords: Hepatitis B; Decompensated cirrhosis; Entecavir; Lamivudine; Randomized controlled trial; Meta-analysis.

Core tip: This meta-analysis was conducted to compare the effects of entecavir (ETV) and lamivudine (LAM) in the treatment of hepatitis B associated decompensated cirrhosis. The results suggested that ETV and LAM significantly improved liver function and reduced mortality. Both drugs produced similar serological responses, and were safe and well tolerated. However, LAM had higher drug-resistance and is therefore unsuitable for the long-term treatment of patients with hepatitis B decompensated cirrhosis. ETV can be used as the first-line drug for long-term treatment of patients with hepatitis B decompensated cirrhosis as it has stronger anti-viral activity and extremely low drug-resistance.