Efficacy And Safety Of Triple Therapy With A Protease Inhibitor In Patients With Untreated Chronic Hepatitis C: A Meta Analysis

Background: For the past decade, the standard treatment of genotype1hepatitis C virus is pegylated interferon combined with ribavirin for48weeks. The rate of sustained virologic response (SVR) has been less than50%in patients with HCV genotype1infection, which has not met ourexpectation for curing patients with HCV in the clinic. So the triple therapyprotocol (peginterferon–ribavirin plus a protease inhibitor, Telaprevir orboceprevir) is proposed. It is still unclear whether the triple therapy could beas effective and safe as that of the standard double therapy. We reviewedrelevant recent literatures and compared the efficacy and safety of a doubletherapy containing pegylated interferon and ribavirin to a triple therapy(with addition of a protease inhibitor).Methods: We searched Pub med, EMBASE, OVID, the CochraneLibrary Clinical Trials Registry, and included relevant randomizedcontrolled trials for comparing the efficacy and safety of the triple therapy tothe double therapy in HCV genotype1untreated patient, using terms: protease inhibitor, hepatitis C, genotype1. The primary endpoints werecomposed of the rates of SVR, the rates of relapse, the rates of anemia, andthe rates of discontinuation due to severe adverse events, respectively。Results: Five trials (involving a total of3200patients) were included.Data showed the triple therapy with either telaprevir or boceprevirsignificantly increased the SVR rate and decreased the relapse rate comparedwith the double therapy [for SVR rate,65.4%vs.40.9%, OR=2.92,95%CI(2.5,3.42), P <0.00001, and for relapse rate,11.3%vs.24.8%, OR=0.42,95%CI (0.26,0.68), P=0.0005], but the triple therapy associated withhigher side effects and intolerability [for anemia rate,44.1%vs.26.2%,OR=2.25,95%CI (1.9,2.65), P<0.00001, and for discontinuation rateowing to severe adverse events,12.4%vs.7.7%, OR=1.66,95%CI (1.19,2.32), P=0.003]. Subgroup analysis found that the rates of SVR were stillhigher and the relapse rates were lower in all triple treatment groups[composed by24(or28)-week groups,48-week groups, andresponse-guided therapy groups] than that of the double therapy.Conclusions: A triple therapy with peginterferon–ribavirin plus eitherboceprevir or telaprevir significantly increased the rate of sustainedvirologic response among untreated patients infected with hepatitis Cgenotype1. Both the incidence of adverse events and the frequency ofdiscontinuation owing to severe adverse events were higher in patientsreceiving the triple therapy than those receiving the standard double therapy.