부산대학교 도서관

Background and Aims:Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients.Over 80％ of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phase Ⅲ clinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients (age ≥18 years)were enrolled for this single-arm,multicenter,phase Ⅲ MANASA study (NCT03020082).Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight ＜75/≥75 kg) for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them (97.9％,123/141) had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2％,123/141).Overall,140 patients completed the 12-week treatment,and 97.1％ (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group,95％ confidence interval:92.9-99.2％).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1％ after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.