The Occurance Of HbsAg Clearance Or Seroconvertion Pegylated Interferon Based Therapy In The Treatment Of Chronic Hepatitis B: A Meta-analysis Of Clinical Controlled Trials

Objective: The antiviral therapy for chronic hepatitis B(CHB) has madegreat progress in recent years. A great many of CHB patients benefit a lotfrom “long-term antiviral therapy". The ultimate goal of antiviral therapy forCHB is to achieve Hepatitis B surface antigen(HBsAg) clearance and/or evenHBsAg seroconversion. It is the closest goal to clinical cure, indicating acompletely immune control of CHB patients, which can realize a safediscontinuation or withdrawal without relapsing[1-5]. Currently, the two kindsof antiviral drugs commonly used in the treatment of CHB patients can onlyachieve a HBsAg clearance rate of3%-11.7%[6,7], and the spontaneousHBsAg clearance rate is only1.2%per year[8]. How to ultilize the availableantiviral drugs to realize individualized treatment, making more patientsachieve the ultimate goal of antiviral therapy is the clinical focus urged to besolved. The clinical first-line anti HBV drugs approved by China Food andDrug Administration including interferon and nucleos(t)ide analogues (NAs),both can be used as single agents or combined with each other. Currently,there is still controversy in the evaluation of combination therapy on itsefficacy and pharmacoeconomics[9,10]. In this study, we compared the efficacyof pegylated interferon (PEG-IFNα) and NAs combination therapy versuspegylated interferon monotherapy and PEG-IFNα based therapy (PEG-IFNαand NAs combination therapy or PEG-IFNα monotherapy) versus NAsmonotherapy in the treatment of chronic hepatitis B on the rates of HBsAgclearance and HBsAg seroconvertion, to investigate the influence of PEG-IFNα based therapy on HBsAg clearance and HBsAg seroconvertionratesin the treatment of chronic hepatitis B.Methods: The electronic database including Pubmed, MEDLINE,EMBASE, OVID database, CNKI, Wanfang database, Cochrane library andsecondary resources were searched. Key words: pegylated interferon orPEG-IFNα, lamivudine or LAM, adefovir or ADV, Entecavir or ETV, chronichepatitis B or CHB, hepatitis B surface antigen or HBsAg. The inclusioncriteria: all included trials were clinical controlled trials, the test objects werepatients with chronic hepatitis B (sera HBsAg positive for≥6months),method were using PEG-IFNα based therapy (PEG-IFNα and NAscombination therapy or PEG-IFNα monotherapy) and PEG-IFNαmonotherapy or NAs monotherapy treating CHB patients. The index ofevaluation the difference of HBsAg clearance rate or HBsAg seroconversionrate between PEG-IFNα and NAs (LAM, ADV) combination therapy versusPEG-IFNα monotherapy and PEG-IFNα based therapy versus NAsmonotherapy were odds ratio (OR) and95%confidence intervals (95%CI).RevMan5.0software was used for statistical analysis. All the included trialswere analysised through fixed-effect model (FEM) and/or random effectsmodel (REM). All the included trials including seven PEG-IFNα and LAMcombination therapy and five PEG-IFNα and ADV combination therapy.Results: Fifteen trials (involving a total of2,717patients) were identifiedfrom all the retrieved literature. The meta-analysis results of different antiviraltherapies were shown as follows:1There were no significant differences on both overall HBsAg clearance andHBsAg seroconversion rates (OR=1.20,95%CI (0.76-1.87), P=0.43andOR=1.35,95%CI (0.77-2.36), P=0.30, respectively) between PEG-IFNαand NAs(LAM/ADV) combination therapy and PEG-IFNα monotherapy(P>0.05). And there were also no significant differences between PEG-IFNαand LAM combination therapy and PEG-IFNα monotherapy on both HBsAgclearance rate (7.0%vs.6.3%) and HBsAg seroconversion rates (3.7%vs.3.5%)(P>0.05). Compared to PEG-IFNα monotherapy, there were also no significant differences on both HBsAg clearance rate (7.3%vs.3.6%) andHBsAg seroconversion rate (8.6%vs.0%)(P>0.05) between PEG-IFNα andADV combination therapy and PEG-IFNα monotherapy;2The HBsAg clearance rate of PEG-IFNα based therapy group (PEG-IFNαand NAs (LAM/ADV) combination therapy or PEG-IFNα monotherapy) ishigher than NAs (LAM/ADV/ETV) monotherapy (5.4%vs.0%), and thedifference between the two groups is of statistic significance (P<0.05); theHBsAg seroconvertion rate is also higher in PEG-IFNα based therapy group(PEG-IFNα and NAs (LAM/ADV) combination therapy or PEG-IFNαmonotherapy) than NAs (LAM/ADV) monotherapy group (2.8%vs.0%), thedifference between the two groups is also of statistic significance (P<0.05).Conclusions:1PEG-IFNα and LAM/ADV combination therapy is not superior PEG-IFNαmonotherapy on overall HBsAg clearance rates and HBsAg seroconvertionrates;2Compared to NAs (LAM/ADV/ETV) monotherapy, PEG-IFNα basedtherapy (PEG-IFNα and NAs (LAM/ADV) combination therapy or PEG-IFNαmonotherapy) is superior to NAs monotherapy on HBsAg clearance rates;PEG-IFNα based therapy (PEG-IFNα and NAs (LAM/ADV) combinationtherapy or PEG-IFNα monotherapy) is also superior to NAs (LAM/ADV)monotherapy on HBsAg seroconvertion rates.