Morikawa Kenichi, Nakamura Akihisa, Shimazaki Tomoe, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan,
Drug Des Devel Ther. 2018 Sep 5;12:2749-2756. doi: 10.2147/DDDT.S133697. eCollection 2018.
Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more efficacious with fewer adverse events, due to the availability of direct-acting antiviral agents, which target specific steps in the HCV life cycle. Recently, a combination regimen consisting of the HCV nonstructural protein 5A inhibitor elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and 4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed-dose combination table or single agent) for 12 or 16 weeks of treatment with or without ribavirin resulted in a high sustained virological response at 12 weeks in treatment-naïve and treatment-experienced patients with HCV Gt 1a, 1b, 4, or 6, including special populations, such as individuals with advanced chronic kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review, we focus on the mode of action, pharmacokinetics, clinical applications, efficacy, and safety profile of EBR/GZR, including special populations who have been considered refractory from the extensive evidence of clinical trials.
由于可获得针对丙型肝炎病毒（HCV）生命周期中特定步骤的直接作用抗病毒药物，HCV治疗取得了巨大进展，疗效更高且不良事件更少。最近，由HCV非结构蛋白5A抑制剂艾尔巴韦（EBR）和HCV NS3/4A蛋白酶抑制剂格卡瑞韦（GZR）组成的联合方案在各国被批准用于治疗慢性HCV 1型和4型基因型（Gts）患者。在III期试验中，EBR/GZR联合用药（固定剂量联合片剂或单药），联合或不联合利巴韦林治疗12周或16周，在初治和经治的HCV Gt 1a、1b、4或6型患者（包括特殊人群，如晚期慢性肾病患者、HCV-HIV合并感染患者和代偿期肝硬化患者）中，12周时均产生了较高的持续病毒学应答。在本综述中，我们重点关注EBR/GZR的作用方式、药代动力学、临床应用、疗效和安全性，包括从大量临床试验证据来看被认为难治的特殊人群。
