Digestive Disease Institute, Virginia Mason Medical Center, 1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101, USA.
Expert Opin Investig Drugs. 2013 Sep;22(9):1107-21. doi: 10.1517/13543784.2013.806482. Epub 2013 Jun 4.
Rapid breakthroughs in the treatment of hepatitis C virus (HCV) infection have dramatically altered the treatment landscape for this chronic disease. In 2011, the protease inhibitors (PIs) boceprevir and telaprevir in combination with peginterferon (peg-IFN) and ribavirin (RBV) were the first direct-acting antivirals (DAAs) approved in the United States for treatment of genotype (GT) 1 HCV. Several DAAs currently in late-stage clinical trials, including NS3/NS4A serine PIs, NS5A inhibitors, NS5B polymerase inhibitors (both nucleoside and non-nucleoside) and cyclophilin inhibitors, both with and without peg-IFN and RBV, are promising for the treatment of HCV. DAA regimens offer several advantages including that they specifically target HCV viral replication and thus appear to be less dependent on host characteristics, very high SVR rates accompanied by fewer side effects (SE) and lower pill burdens. A review on the treatment of HCV is important and timely as the development on DAAs is progressing rapidly and the health-care providers need to be aware about this as these regimens are anticipated to become clinically available soon.
The literature was searched and reviewed using PubMed as well as data gathered from those presented at the international liver meetings, AASLD and EASL as well as CROI.
With the potential of eliminating IFN and RBV, several DAAs under clinical development appear to be promising using novel approaches with good antiviral effects, shorter duration and lower SE profile.
丙型肝炎病毒 (HCV) 感染治疗的快速突破极大地改变了这种慢性疾病的治疗格局。2011 年,蛋白酶抑制剂 (PI) boceprevir 和 telaprevir 与聚乙二醇干扰素 (peg-IFN) 和利巴韦林 (RBV) 联合用于治疗基因型 (GT) 1 HCV,成为美国批准的首个直接作用抗病毒药物 (DAA)。目前有几种 DAA 处于后期临床试验阶段,包括 NS3/NS4A 丝氨酸 PI、NS5A 抑制剂、NS5B 聚合酶抑制剂(核苷和非核苷)和亲环素抑制剂,无论是否与 peg-IFN 和 RBV 联合使用,都有望用于治疗 HCV。DAA 方案具有几个优势,包括它们特异性针对 HCV 病毒复制,因此似乎不太依赖宿主特征、很高的 SVR 率,副作用 (SE) 较少,且用药负担较轻。鉴于 DAA 的快速发展,对 HCV 治疗进行综述非常重要且及时,医疗保健提供者需要了解这些方案,因为预计它们很快就会在临床上应用。
使用 PubMed 搜索和综述文献,并收集来自国际肝脏会议、AASLD 和 EASL 以及 CROI 的数据。
几种处于临床开发阶段的 DAA 有可能消除 IFN 和 RBV,它们采用新颖的方法,具有良好的抗病毒效果、较短的疗程和较低的 SE 特征,因此前景广阔。