OBJECTIVETo compare the efficacy and safety of a double therapy containing pegylated interferon and ribavirin to a triple therapy (with addition of a protease inhibitor) for untreated chronic hepatitis C with genotype 1 infection.

METHODSWe searched Pub med, EMBASE, OVID, the Cochrane Library Clinical Trials Registry and included relevant randomized controlled trials for comparing the efficacy and safety of the triple therapy to the double therapy in HCV genotype 1 untreated patient, using terms: protease inhibitor, hepatitis C, genotype 1. The primary endpoints were composed of the rates of SVR, the rates of relapse, the rates of anemia, and the rates of discontinuation due to severe adverse events, respectively.

RESULTSFive trials (involving a total of 3200 patients) were included. Data showed the triple therapy with either telaprevir or boceprevir significantly increased the SVR rate and decreased the relapse rate compared with the double therapy [for SVR rate, 65.4% vs. 40.9%, OR=2.92, 95% CI 2.5 to 3.42, P less than 0.01, and for relapse rate, 11.3% vs. 24.8%, OR=0.42, 95% CI 0.26 to 0.68, P less than 0.01], but the triple therapy associated with higher side effects and intolerability [ higher anemia rate, 44.1 % vs. 26.2%, OR=2.25, 95% CI 1.9 to 2.65, P less than 0.01 and higher discontinuation rate owing to severe adverse events, 12.4% vs. 7.7%, OR=1.66, 95% CI 1.19 to 2.32, P less than 0.01]. Subgroup analysis found that the rates of SVR were still higher and the relapse rates were lower in all triple treatment groups [composed by 24 (or 28) -week groups, 48-week groups, and response-guided therapy groups] than that of the double therapy.

CONCLUSIONA triple therapy with peginterferon-ribavirin plus either boceprevir or telaprevir significantly increased the rate of sustained virologic response among untreated patients infected with hepatitis C genotype 1. Both the incidence of adverse events and the frequency of discontinuation owing to severe adverse events were higher in patients receiving the triple therapy than those receiving the standard double therapy.