Department of Hepatology, Saint Luc Hospital, CHUM, Montréal, Canada.
J Viral Hepat. 2012 Aug;19(8):525-36. doi: 10.1111/j.1365-2893.2012.01634.x.
Worldwide, 50-70 million subjects are infected with an hepatitis C virus (HCV) genotype 2, 3, 4, 5 or 6. In these patients, the combination of PEG-INF-α and ribavirin remains the currently approved standard-of-care treatment. The identification of different potential therapeutic targets in the HCV life cycle has led to the development of both direct antiviral agents (DAAs) and reagents targeting host functions essential for viral replication. DAAs comprise so far first-generation, second-wave and second-generation NS3/4A protease inhibitors (PIs), nucleos(t)ide (NIs) and non-nucleoside inhibitors of the NS5B RNA polymerase and NS5A complex inhibitors. The main host-protein-directed antiviral agents are cyclophilin inhibitors and silibinin. Whereas the launch of first-generation PIs was a major landmark in the management of genotype 1 (GT-1)-infected patients, these drugs are inactive in most non-GT-1-infected patients. Several of these and other drugs have now reached phase II and even phase III clinical stage development. The purpose of this article is to provide an overview of the clinical results recently reported for the treatment for non-GT-1 HCV infection with a focus on the most promising new compounds and combinations.
在全球范围内，有 5000 万至 7000 万人感染了 HCV 基因型 2、3、4、5 或 6。在这些患者中，PEG-INF-α 和利巴韦林的联合治疗仍然是目前批准的标准治疗方法。对 HCV 生命周期中不同潜在治疗靶点的鉴定，导致了直接抗病毒药物（DAAs）和靶向病毒复制所必需的宿主功能的试剂的发展。DAAs 迄今为止包括第一代、第二代 NS3/4A 蛋白酶抑制剂（PIs）、核苷（NIs）和非核苷 NS5B RNA 聚合酶抑制剂以及 NS5A 复合物抑制剂。主要的宿主蛋白导向抗病毒药物是亲环素抑制剂和水飞蓟素。虽然第一代 PIs 的推出是治疗 GT-1 感染患者的一个重要里程碑，但这些药物在大多数非 GT-1 感染患者中无效。现在，其中一些药物和其他药物已经进入 II 期甚至 III 期临床开发阶段。本文的目的是提供最近关于非 GT-1 HCV 感染治疗的临床结果的概述，重点介绍最有前途的新化合物和组合。
