Effects Of IFN Combined With Nas Therapy In HBeAg-positive Chronic Hepatitis B:A Meta-analysys

Background and Aims:Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen(HBeAg)as a valuable endpoint in treating HBeAg-positive chronic hepatitis B(CHB)patients.In theory,combination therapy with IFN and NAs seems to be a logical alternative approach to enhance the therapeutic efficacy.However,there is no evidence of the superiority of this combined therapy.To evaluate the effect of combination therapy[interferon(IFN)plus nucleos(t)ide analogues(NAs)]versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients.Methods:Two researchers independently performed literature retrieval by electronic searches of PubMed/Medline,Web of Science and Embase,which published from Jan 2000 to Sep 2018,with CHB receiving IFN and NA combination therapy or IFN monotherapy.By screening the title,abstract and full text,the relevant articles are screened and the article quality is evaluated.Extract data of combination therapy and interferon monotherapy on HBeAg seroconversion or seroclearance.Risk ratio(RR)and their 95%confidence intervals(CIs)was estimated with a fixed-effects model when I~2<50%for the test for heterogeneity.P value<0.05 was deemed significant.Results:Twelve studies were included.Our meta-analysis demonstrated that IFN and NAs combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment(EOT)(RR=1.190,p=0.031;RR=1.239,p=0.005).Sub-analysis showed IFN plus adefovir dipivoxi(ADV)therapy had a better HBeAg seroconversion or seroclearance rate at EOT(RR=1.469,p=0.008;RR=1.462,p=0.010)or at the end of follow-up(EOF)(RR=1.549,p=0.012;RR=1.533,p=0.014).Conclusion:Compared with IFN monotherapy,the combined therapy had a higher e-antigen serological response at EOT,but failed to improve the sustained response at EOF.Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients.The effect of other combination therapies is not superior to IFN monotherapy.