Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec and Laval University, 2705 Boulevard Laurier, Quebec, Canada.
Semin Liver Dis. 2011 Nov;31(4):399-409. doi: 10.1055/s-0031-1297928. Epub 2011 Dec 21.
The year 2011 marks the dawn of the new era of direct-acting antivirals for hepatitis C. For the first time since 1998, the U.S. Food and Drug Administration approved two new antiviral drugs for the treatment of chronic hepatitis C virus genotype 1. Dual therapy with pegylated interferon and ribavirin is no longer the standard of care for genotype 1. The new treatment paradigm includes one direct-acting antiviral, a protease inhibitor, in combination with pegylated interferon and ribavirin. This combination nearly doubles the chances of response to treatment, but at the cost of increased toxicity. Many agents with different mechanisms of action and improved safety profiles are in clinical development. The holy grail of HCV treatment is an all oral, interferon-free treatment. The ideal regimen will be potent, well tolerated, with minimal drug-drug interactions and once daily. This article covers new concepts of treatment of hepatitis C with DAAs and gives an overview of the recent highlights in direct-acting antiviral development.
2011 年标志着丙型肝炎直接作用抗病毒药物新时代的到来。自 1998 年以来，美国食品和药物管理局首次批准了两种新的抗病毒药物用于治疗慢性丙型肝炎病毒基因型 1。聚乙二醇干扰素和利巴韦林的双联治疗不再是基因型 1 的标准治疗方法。新的治疗模式包括一种直接作用抗病毒药物，一种蛋白酶抑制剂，与聚乙二醇干扰素和利巴韦林联合使用。这种联合治疗几乎使治疗反应的机会增加了一倍，但代价是毒性增加。许多具有不同作用机制和改善安全性特征的药物正在临床开发中。丙型肝炎治疗的圣杯是一种无干扰素的口服治疗。理想的方案将是有效、耐受性好、药物相互作用最小、每日一次。本文介绍了 DAA 治疗丙型肝炎的新概念，并概述了直接作用抗病毒药物开发的最新亮点。
