Degasperi Elisabetta, Aghemo Alessio, Colombo Massimo
a Centro A.M. e A. Migliavacca, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università degli Studi di Milano , Via F. Sforza 35, 20122 , Milan , Italy.
Expert Opin Pharmacother. 2015;16(17):2679-88. doi: 10.1517/14656566.2015.1109631. Epub 2015 Nov 7.
Following more than 20 years of Interferon (IFN)-based treatment for hepatitis C virus (HCV), the understanding of viral life cycle led to the development of new antiviral drugs directly targeting HCV replication steps. Daclatasvir (DCV) is a potent inhibitor of non-structural NS5A HCV protein with pangenotypic activity and low-moderate barrier to resistance suitable for IFN-free combination with other direct acting antivirals (DAAs).
The present review summarizes DCV key pharmacokinetic features and results from Phase II and III trials, discussing also NS5A resistance. Main literature articles have been identified through Pubmed and Medline search; moreover, abstracts from recent international meetings on liver disease have been scrutinized.
DCV in combination with other DAAs has provided IFN-free regimens with increased efficacy and tolerability. However, suboptimal barrier to resistance and the rapid development of new second-generation NS5A inhibitors will probably make DCV a relatively short-lived drug.
在基于干扰素（IFN）治疗丙型肝炎病毒（HCV）20多年后，对病毒生命周期的了解促使开发出直接针对HCV复制步骤的新型抗病毒药物。达卡他韦（DCV）是一种有效的非结构NS5A HCV蛋白抑制剂，具有泛基因型活性，对耐药性的屏障较低至中等，适合与其他直接作用抗病毒药物（DAA）进行无IFN联合治疗。
本综述总结了DCV的关键药代动力学特征以及II期和III期试验结果，还讨论了NS5A耐药性。主要文献文章通过PubMed和Medline搜索确定；此外，还仔细研究了近期国际肝病会议的摘要。
DCV与其他DAA联合使用提供了无IFN治疗方案，提高了疗效和耐受性。然而，耐药性屏障欠佳以及新型第二代NS5A抑制剂的快速研发可能会使DCV成为一种寿命相对较短的药物。
