Efficacy And Safety Of Interferon-alpha Combined With Thymosin Alpha 1 For Chronic Hepatitis B:A Meta-analysis

Object: To systematically evaluate the efficacy of interferon-alpha(IFN-?)combined with thymosin-alpha1(T?1)in the treatment of HBe Ag-positive chronic hepatitis B(CHB),at the same time to evaluate the safety of drug combination,providing the evidence-based medical evidence for clinical use of drugs.Methods: Such databases as Pub Med,The Cochrane Library,Embase,CBM(China Biology Medicine disc),CNKI(China National Knowledge Infrastructure),Wan Fang Data and VIP database were searched for the randomized controlled trials(RCT)about IFN-? combined with T?1 for CHB from inception to June 2017.Two reviewers according to the inclusion and exclusion criteria independently screened literature,extracted data,and assessed the methodological quality from the literature included.The enumeration data uses odds ratio(OR)represent for the outcome indicator,The difference between P<0.05 is statistically significant.Meta-analysis was then conducted using Rev Man 5.3 sofware which provided by the Cochrane Cooperative Network,quality evaluation based on the improved Jadad scoring standard,evaluation of publication bias using inverted funnel graphs.Results: A total of 15 studies were included,involving 1282 patients with 648 in the experimental group and 634 in the control group.The result of the meta-analysis of IFN-? combined with T?1 for CHB showed that: 1.After 3 months of treatment,For the serum ALT normalization rate and HBe Ag seroconversion rate,there was no significant difference between the combination therapy group and the IFN-? monotherapy group(P>0.05);but for the serum HBV DNA negative rate,the combination therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05).2.After 6 months of treatment,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag seroconversion rate,HBs Ag negative conversion rate,the combination therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05);3.Follow up for 6 months,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag loss rate,HBe Ag seroconversion rate,the combination therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05).4.At the end of the treatment,subgroup analysis based on half-life of IFN-?.(1)At normal IFN-? group,for the serum ALT normalization rate,HBV DNA negative rate,the HBe Ag negative conversion rate,the combined therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05);but for the serum HBs Ag negative conversion rate,there was no significant difference between the normal IFN-? combined therapy group and the the normal IFN-?monotherapy group(P>0.05).(2)At Peg IFN-? group,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag loss rate,HBe Ag seroconversion rate,HBs Ag negative conversion rate,the combination therapy group was higher than the Peg IFN-? monotherapy group,the difference is statistically significant(P<0.05);(3)Two subgroups merger analysis,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag loss rate,HBe Ag seroconversion rate,HBs Ag negative conversion rate,the combination therapy group was higher than the Peg IFN-? monotherapy group,the difference is statistically significant(P<0.05).5.At the end of follow-up,subgroup analysis based on half-life of IFN-?,(1)At normal IFN-? group,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag loss rate,HBe Ag seroconversion rate,HBs Ag negative conversion rate,the combination therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05).(2)At Peg IFN-?group,for the serum HBe Ag loss rate,HBe Ag seroconversion rate,the combination therapy group was higher than the IFN-? monotherapy group,the difference is statistically significant(P<0.05);but for the serum ALT normalization rate,HBV DNA negative rate and HBs Ag negative conversion rate,because lack of research and greater heterogeneity among studies,it is unable to combine quantitative analysis.(3)Two subgroups merger analysis,for the serum ALT normalization rate,HBV DNA negative rate,HBe Ag loss rate,HBe Ag seroconversion rate and HBs Ag negative conversion rate,the combination therapy group was higher than the Peg IFN-? monotherapy group,the difference is statistically significant(P<0.05).6.At the adverse reactions(influenza like symptoms,granulocytopenia)incidenc easpect,there was no significant difference between the normal IFN-? combined therapy group and the the normal IFN-? monotherapy group(P>0.05).Conclusion: The efficacy of IFN-? combined with T?1 in the treatment of CHB is better than that of IFN-?monotherapy;Furthermore,at the end of the treatment,the efficacy of Peg IFN-? combined with T?1 is better than that of common interferon IFN-? combined with T?1 in the treatment of CHB.The regimen of IFN-? combined with T?1 in the treatment of CHB with good safety,which is worthy of clinical application.Due to the quantity and quality limitation of the included studies,the evidence of the conclusion still need to be further verified by more high quality researchs.