Das Debasis, Pandya Mayank
Department of Chemistry, School of Science, RK University, Rajkot-360020, Gujarat, India.
Mini Rev Med Chem. 2018;18(7):584-596. doi: 10.2174/1389557517666170913111930.
Hepatitis C virus (HCV) infection is a major health problem worldwide. Approximately, 170-200 million individuals are chronically infected worldwide and a quarter of these patients are at increased risk of developing liver cirrhosis, hepatocellular carcinoma and even liver failure. A complete eradication of the virus is one of the most important treatment goals for antiviral research. In 2011, the first-generation protease inhibitors boceprevir (BOC) telaprevir (TVR) were approved by FDA as the direct-acting antiviral agents. A number of promising new direct-acting antiviral agents (DAAs) have been developed in the past few years. Due to their increased efficacy, safety, and tolerability, interferon-free oral therapies with DAAs are in use for patients with chronic HCV and cirrhosis patients. In this review, we will discuss the results of clinical trials of several DAAs and the approved combinations, including NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors. A number of drugs, including Sovaldi®, Harvoni® Viekira Pak®, Epclusa®, Zepatier® have been approved by FDA in the past two-three years. The latest advancement of DAA therapy and related side effects due to the therapy are also discussed.
丙型肝炎病毒（HCV）感染是一个全球性的重大健康问题。全球约有1.7亿至2亿人受到慢性感染，其中四分之一的患者发展为肝硬化、肝细胞癌甚至肝衰竭的风险增加。彻底清除病毒是抗病毒研究最重要的治疗目标之一。2011年，第一代蛋白酶抑制剂博赛匹韦（BOC）和特拉匹韦（TVR）被美国食品药品监督管理局（FDA）批准为直接作用抗病毒药物。在过去几年中，已经开发出了许多有前景的新型直接作用抗病毒药物（DAA）。由于其疗效、安全性和耐受性的提高，含DAA的无干扰素口服疗法正在用于慢性HCV患者和肝硬化患者。在本综述中，我们将讨论几种DAA以及已批准的联合用药的临床试验结果，包括NS3/4A蛋白酶抑制剂、NS5A抑制剂和NS5B抑制剂。过去两到三年，包括索华迪（Sovaldi®）、哈维尼（Harvoni®）、维建乐（Viekira Pak®）、丙通沙（Epclusa®）、夏帆宁（Zepatier®）在内的多种药物已获FDA批准。本文还讨论了DAA治疗的最新进展以及该治疗引起的相关副作用。
