Medical University of Bialystok, Department of Infectious Diseases and Hepatology , ul. Żurawia 14, 15-540 Białystok , Poland +48 605203525 ; +48 85 7416921 ;
Expert Opin Emerg Drugs. 2013 Dec;18(4):461-75. doi: 10.1517/14728214.2013.847089. Epub 2013 Oct 8.
About 2.35% of the world population can be infected with hepatitis C virus (HCV) responsible for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently available interferon-based medication is successful in up to 75% of the patients infected with HCV genotypes 1, 2 or 3 and lower efficacy in other genotypes. Unfortunately sustained virologic response (SVR) rate in genotype 1 infected non-responders to previous therapy with advanced hepatic fibrosis even after retreatment with the first generation direct acting antivirals (DAA) is about 40% only.
The second generation DAA, which have recently been submitted for registration (Sofosbuvir and Simeprevir) still need combination with PegIFNα and RBV in patients infected with HCV genotype 1. There is a need for more effective antiviral therapy for difficult to treat patients who are interferon intolerant, developed liver cirrhosis or non-responders to previous therapies. Therefore, IFN-free regimens are step for future therapies consisting of combinations of novel investigational DAA and host targeting agents.
The introduction of novel DAA with a good safety profile and high barrier to resistance can lead to SVR rates exceeding 90% in treatment naïve patients and non-responders to previous therapy infected with different genotypes.
全球约有 2.35%的人口可能感染丙型肝炎病毒（HCV），从而导致慢性肝炎、肝硬化和肝细胞癌。目前可用的基于干扰素的药物在感染 HCV 基因型 1、2 或 3 的患者中成功率高达 75%，而在其他基因型中的疗效较低。不幸的是，即使在第一代直接作用抗病毒药物（DAA）重新治疗后，先前治疗对纤维化程度较高的基因型 1 感染无应答者的持续病毒学应答（SVR）率仍仅约为 40%。
最近提交注册申请的第二代 DAA（索非布韦和西米普雷韦）仍需要与聚乙二醇干扰素α和利巴韦林联合用于感染 HCV 基因型 1 的患者。对于干扰素不耐受、已发展为肝硬化或对先前治疗无应答的难治性患者，需要更有效的抗病毒治疗。因此，无干扰素方案是未来治疗的一个步骤，包括新型研究性 DAA 和宿主靶向药物的联合应用。
具有良好安全性和高耐药屏障的新型 DAA 的引入可使治疗初治患者和先前治疗无应答者的不同基因型感染患者的 SVR 率超过 90%。
