Buti M, Calleja J L, Lens S, Diago M, Ortega E, Crespo J, Planas R, Romero-Gómez M, Rodríguez F G, Pascasio J M, Fevery B, Kurland D, Corbett C, Kalmeijer R, Jessner W
Hospital Vall d'Hebron and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
University Hospital Puerta de Hierro Majadahonda, Madrid, Spain.
Aliment Pharmacol Ther. 2017 Feb;45(3):468-475. doi: 10.1111/apt.13883. Epub 2016 Nov 29.
Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis.
To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis.
Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed.
Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients.
Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].
丙型肝炎病毒（HCV）感染是肝硬化及后续肝细胞癌的主要病因。HCV基因4型在中东、埃及和非洲广泛存在，也已传播至欧洲。关于在感染HCV基因4型的肝硬化患者中使用直接抗病毒药物的数据有限。
在III期、开放标签、单臂PLUTO研究中，评估12周simeprevir（HCV NS3/4A蛋白酶抑制剂）联合sofosbuvir（HCV核苷酸类似物NS5B聚合酶抑制剂）治疗初治以及曾接受（聚乙二醇化）干扰素±利巴韦林治疗的HCV基因4型感染患者（无论有无代偿期肝硬化）的疗效和安全性。
成年慢性HCV基因4型感染患者接受simeprevir 150 mg每日一次及sofosbuvir 400 mg每日一次，疗程12周。主要疗效终点为治疗结束后12周持续病毒学应答（SVR12）。同时评估安全性。
40例患者接受治疗；大多数为男性（73%）且曾接受治疗（68%）。总体而言，7/40（18%）例患者有代偿期肝硬化。所有患者均达到SVR12[100%（Clopper-Pearson 95%置信区间：91-100%）]。20/40（50%）例患者报告了不良事件，均为1级或2级。未报告严重不良事件，无患者停止研究治疗。2/40（5%）例患者出现3级治疗中出现的实验室异常。
simeprevir联合sofosbuvir治疗12周，在初治以及曾接受治疗的HCV基因4型感染患者（无论有无代偿期肝硬化）中SVR12率达100%，且耐受性良好。[NCT02250807]
