Center for Hepatitis C, Atlanta Medical Center, Atlanta, GA 30309, USA.
Lancet Infect Dis. 2012 Sep;12(9):717-28. doi: 10.1016/S1473-3099(12)70060-9. Epub 2012 May 29.
For the past decade, the standard treatment for chronic hepatitis C infection has been pegylated-interferon plus ribavirin. With US Food and Drug Administration approval of boceprevir and telaprevir--two protease inhibitors--the standard-of-care treatment for genotype-1 infection, the main genotype worldwide, is now peginterferon plus ribavirin and a protease inhibitor. Rates of sustained virological response or cure with triple combination treatment have improved substantially, both in patients who have had previous treatment and in those who have not. Improvements have been most substantial in populations regarded as difficult to treat, such as individuals with cirrhosis. However, despite improved response rates, protease inhibitors have incremental toxic effects, high costs, increased pill burden, and many drug interactions. Moreover, because new antiviral drugs directly inhibit hepatitis C virus, viral resistance has become an important issue, essentially precluding use of protease inhibitor monotherapy, and potentially restricting future treatment options for patients who consequently do not achieve sustained virological response. Protease inhibitors are the first of many antiviral medications that will probably be combined in future interferon-free regimens.
在过去的十年中，慢性丙型肝炎感染的标准治疗方法一直是聚乙二醇干扰素加利巴韦林。在美国食品和药物管理局批准博赛泼维（boceprevir）和特拉泼维（telaprevir）——两种蛋白酶抑制剂——用于基因型 1 感染（全球主要基因型）的标准治疗后，现在的标准治疗方案是聚乙二醇干扰素加利巴韦林和一种蛋白酶抑制剂。对于既往接受过治疗和未接受过治疗的患者，三联疗法的持续病毒学应答或治愈率都有了显著提高。在被认为难以治疗的人群中，如肝硬化患者，改善最为显著。然而，尽管应答率有所提高，但蛋白酶抑制剂具有附加的毒性作用、高昂的成本、增加的药物负担和许多药物相互作用。此外，由于新的抗病毒药物直接抑制丙型肝炎病毒，病毒耐药性已成为一个重要问题，基本上排除了蛋白酶抑制剂单药治疗的可能，并可能限制随后未能达到持续病毒学应答的患者的未来治疗选择。蛋白酶抑制剂是未来无干扰素治疗方案中可能联合使用的众多抗病毒药物中的第一种。
