A Meta-analysis Of Comparative Efficacy Of Entecavir And Lamivudine For Treatment Of HBeAg Positive Chronic Hepatitis B

Objective: To systematically evaluate the effects of entecavir (ETV) andLamivudine（LAM） in treatment of hepatitis B e antigen (HBeAg)-positivechronic hepatitis B by meta-analysis.Methods: We conducted a literature search using these index words suchas Entecavir(ETV), lamivudine (LAM), Randomized controlled trials（RCT）andHBeAg-positive chronic hepatitis B on the PubMed, MEDLINE, EMBASE, theCBMdisk，the China National Knowledge Infrastructure（CNKI）, the Wan-fang database and the VIP database, for all relevant articles published fromJanuary1,2005to June1,2012. Randomized controlled trials (RCTs)comparing ETV with LAM for treatment of HBeAg-positive chronic hepatitis B wereincluded. The data was analyzed with Review Manager Software5.0. We usedrelative risk (RR) as an effect measure, and reported its95%CI.Meta-analysis was performed using either a fixed-effect orrandom-effect model, based on the absence or presence of significantheterogeneity which was assessed with Cochran’s Q test(Chi-square χ2test) and I2test.Two reviewers assessed the risk of bias and extracted data independently and induplicate. The analysis was executed using the main outcome parameters includinghepatitis B virus (HBV) DNA undetectability, alanine aminotrans ferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adversereactions. Subgroup analyses were conducted to reduce the heterogeneity betweenthese RCTs.Results: Seven eligible Randomized controlled trials were included, whichcontain1436patients，734patients adopted entecavir and702patients adoptedlamivudine. In various treatment durations of4wk,8wk,12wk,24wk,48wk and96wk, the rates of HBV DNA undetectability was higher in the ETV group than thatin the LAM group，there were statistical significance differences in the twogroups，respectively(RR5.09,95%CI1.99,13.02, P=0.007; RR3.54,95%CI1.99,6.31, P <0.0001; RR1.84,95%CI1.40,2.41, P <0.0001; RR1.45,95%CI1.24,1.70, P <0.0001; RR1.46,95%CI1.27,1.67, P <0.00001; RR1.36,95%CI1.12,1.64, P=0.002）; In various treatment durations of4wk,8wk,12wk,24wkand48wk, the rates of ALT normalization was higher in the ETV groupthan that in the LAM group，there were statistical significance differences inthe two groups，respectively（RR,1.99,95%CI1.20,3.29, P=0.008; RR2.03,95%CI1.44,2.84, P <0.0001; RR1.61,95%CI1.09,2.38, P=0.02; RR1.34,95%CI1.06,1.70, P=0.01; RR1.23,95%CI1.12,1.34, P <0.0001），while at96wk ofthe treatment, there were no significant difference in the rate of ALTnormalization between the two groups. At12wk,24wk,48wk and96wk of thetreatment, HBeAg loss and HBeAg seroconversion were similar in the two groups,without statistical significant differences. The rate of drug resistance was higherin the LAM group than in the ETV group, there were significant differencesbetween the two groups（RR0.06,95%CI0.01,0.23, P <0.0001）. Adverse drugreactions didn’t be meta-analysis. Two deaths occurred during the on-treatment period,both in the lamivudine group.Conclusions: In patients with HBeAg-positive chronic hepatitis B, entecavir is ableto inhibit the replication of HBV DNA faster and more efficiently than lamivudine. In addition to this, entecavir led to greater liver function improvement than lamivudine.Entecavir and lamivudine is similar to HBeAg loss and HBeAg seroconversion, Thedrug resistance of Lamivudine is higher than that of entecavir，entecavir is as safe andtolerance as lamivudine.