Department of Medicine, Center for Liver Diseases and Transplantation, Carolinas Medical Center, Charlotte, NC 28203, USA.
Department of Medicine, Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Trends Mol Med. 2014 Jun;20(6):315-21. doi: 10.1016/j.molmed.2014.02.002. Epub 2014 Mar 11.
An exciting paradigm shift is occurring in the treatment of hepatitis C virus (HCV). We now have the capacity to specifically target therapy to HCV proteins, and thereby directly interrupt the viral life cycle. The first direct-acting antivirals (DAAs), the NS3-4A serine protease inhibitors boceprevir and telaprevir, improved the rate of sustained virologic response (SVR), but their toxicities combined with PEG-IFN and RBV limited their overall efficacy. Sofosbuvir, a nucleotide HCV polymerase inhibitor, is now available and offers better tolerability and efficacy across all HCV genotypes. The next phase of therapy will be combining several classes of DAAs without IFN in order to make sustained clearance of hepatitis C deliverable to a much larger number of infected individuals.
在丙型肝炎病毒 (HCV) 的治疗中，正在发生令人兴奋的范式转变。我们现在有能力将治疗专门针对 HCV 蛋白，从而直接阻断病毒的生命周期。第一批直接作用抗病毒药物（DAA），即 NS3-4A 丝氨酸蛋白酶抑制剂博赛泼维与特拉泼维，提高了持续病毒学应答 (SVR) 的比率，但由于它们与 PEG-IFN 和 RBV 的联合应用的毒性限制了它们的总体疗效。现在已经有核苷酸 HCV 聚合酶抑制剂索非布韦上市，它在所有 HCV 基因型中具有更好的耐受性和疗效。下一阶段的治疗将是联合几种 DAA 类药物而无需 IFN，以便使更多的感染个体能够实现 HCV 的持续清除。
