ObjectivesTo systematically review the efficacy and safety of pegylated interferon α-2a (Peg-IFNα-2a) combined with entecavir (ETV) versus Peg-IFNα-2a alone in treatment of HBeAg-positive chronic hepatitis B (CHB) patients.MethodsThe Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on Peg-IFNα-2a combined with ETV for HBeAg-positive CHB from inception to March, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 RCTs involving 1 130 patients were included. The results of meta-analysis showed that: compared with Peg-IFNα-2a monotherapy, Peg-IFNα-2a combined with ETV could improve the rate of serum HBV-DNA clearance (RR=2.55, 95%CI 1.83 to 3.55, P<0.000 01), ALT normalization (RR=2.37, 95%CI 1.76 to 3.20, P<0.000 01) and HBeAg seroconversion (RR=2.88, 95%CI 1.18 to 7.03, P=0.02) after 12 weeks of treatment. Additionally, it could improve the rate of serum HBV-DNA clearance (RR=2.10, 95%CI 1.74 to 2.53, P<0.000 01), AST normalization (RR=1.87, 95%CI 1.15 to 3.04, P=0.01), ALT normalization (RR=1.70, 95%CI 1.46 to 1.99, P<0.000 01), serum HBeAg clearance (RR=2.14, 95%CI 1.62 to 2.83, P<0.000 01), HBeAg seroconversion (RR=2.51, 95%CI 1.65 to 3.82, P<0.000 01) and serum HBsAg clearance (RR=2.78, 95%CI 1.06 to 7.31, P=0.04) after 24 weeks of treatment. It could also improve the rate of serum HBV-DNA clearance (RR=1.63, 95%CI 1.32 to 2.02, P<0.000 01), AST normalization (RR=2.75, 95%CI 1.82 to 4.16, P<0.000 01), ALT normalization (RR=1.47, 95%CI 1.33 to 1.63, P<0.000 01), serum HBeAg clearance (RR=1.65, 95%CI 1.42 to 1.91, P<0.000 01), HBeAg seroconversion (RR=1.91, 95%CI 1.51 to 2.41, P<0.000 01) and serum HBsAg clearance (RR=1.57, 95%CI 1.07 to 2.31, P=0.02) after 48 weeks of treatment. There was no statistically significance of adverse reactions in groups.ConclusionsCurrent evidence shows that Peg-IFNα-2a combined with ETV is superior to Peg-IFNα-2a monotherapy in the treatment of HBeAg-positive CHB, and does not increase the incidence of adverse reactions. Due to the limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusion.
ObjectivesTo compare the common application methods of meta-analysis results used in economic evaluations so as to provide reference and suggestions for similar economic evaluations in future.MethodsFour methods were used to calculate the effectiveness deriving from meta-analysis of omeprazole and esomeprazole in the treatment of peptic ulcer, then substituted into the decision tree model to perform cost-effectiveness analysis.ResultsMethod 1 used the risk difference as the incremental effectiveness. The ICER was ￥2 420, and the equal probability point of the cost-effectiveness acceptability curve (CEAC) in the probability sensitivity analysis was approximately ￥2 600. Method 2 used the effective rate of the study group in high-quality literatures as the benchmark, calculated the effective rate of the control group according to the RR. The ICER was ￥2 016, and the equal probability point of the CEAC was approximately￥2 000. Method 3 was based on the effective rate of the control group in high-quality literatures to calculate the effective rate of the study group according to RR. The ICER was ￥2 420 and the equal probability point of the CEAC was approximately￥2 200; Method 4 used literature weights to calculate the effectiveness, the ICER is ￥2 420, and the equal probability point of the CEAC was about ￥2 400.ConclusionsThe results of the four methods share little difference, and the sensitivity analysis results show that the base case analysis results are more robust. However, in the application process, method 1 lacks specific effectiveness of the two groups and underestimate the variation range of the effectiveness difference when one-way sensitivity analysis was performed. Relevant assumptions are further required to limit the possibility of effectiveness calculated greater than 1 in sensitivity analysis among method 2 and 3. Comprehensively, method 4 can be recommended in the economic evaluations for fewer defects of calculating effectiveness.