PEG-interferon Monotherapy Versus Peg-interferon And Nucleos(t)ide Analogues For Hepatitis B Patients:a Meta-analysis Of Randomized Controlled Trails

Background:Peg-interferon and Nucleos(t)ide analogues（NA）is currently approvedfor adult patients with chronic HBV infection, but a single-drug therapy isoften unsatisfactory than combined therapeutics. In this study, we comparedthe efficacy and safety of peg-interferon combined with NA and peg-interferon monotherapy.Methods:The relevant randomized controlled trials with peg-interferoncombined with NA and peg-interferon monotherapy were searchedthroughout PubMed, OVID, EMBASE, the Chinese Medical Database(WanFang、CNKI, VIP database) since Janurary1990. Twelve reports fitinto our inclusion criteria for analysis and were included in this study usingRevMan5.0through fixed-effect model and random model. Among thesestudies, eight were associated with peg-interferon add-on LAM combination therapy, four with peg-interferon add-on ADV combinationtherapy.Results：According to the results of meta-analysis, the patients receiving acombination therapy had higher biochemical response rate at the end oftreatment than monotherapy groups (50.3%vs.39.3%, OR=1.63,95%CI=1.33-2.01, P<0.00001). Regardless of the peg-interferon add-onLAM combination therapy or peg-interferon plus ADV combinationtherapy, subgroup analysis showed the patients receiving a combinationtherapy had higher biochemical response rate than monotherapy groups. Thepatients receiving a combination therapy had higher virologic response ratethe end of treatment than monotherapy whether the peg-interferon add-onLAM combination therapy (65.9%vs.34.9%, OR=3.57,95%CI=1.83-6.95,P=0.0002) or peg-interferon add-on ADV combination therapy (74.6%vs.46.2%, OR=3.66,95%CI=2.13-6.30, P<0.00001). The patients receiving acombination therapy had higher sustained biochemical response rate at theend of follow up than monotherapy groups (47.6%vs.42.1%, OR=1.28,95%CI=1.05-1.55, P=0.01). Subgroup analysis showed the patientsreceiving a peg-interferon add-on LAM combination therapy had higherbiochemical response rate than peg-interferon monotherapy, but nosignificant difference was obtained in the group of peg-interferon add-onADV combination therapy. At the end of follow up, the patients receiving peg-interferon add-on ADV combination therapy had higher HBeAg lossrate than peg-interferon monotherapy. But no significant difference wasobtained in the group of peg-interferon add-on LAM combination therapy.No statistically significant difference in HBeAg seroconversion rate, HBsAgloss or seroconversion rate, histological response rate, and the occurrence ofsevere adverse events between patients receiving a combination therapy andpeg-interferon monotherapy.Conclusion:At the end of follow up, peg-interferon add-on NA combinationtherapy might have higher biochemical response rate compared with thepeg-interferon monotherapy for CHB. The patients receiving peg-interferonadd-on ADV combination therapy had higher HBeAg loss rate at the followup than peg-interferon monotherapy.