Host-targeting therapies for hepatitis C virus infection: current developments and future applications.
Host-targeting therapies for hepatitis C virus infection: current developments and future applications.
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DOI：
10.1177/1756284818759483
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发表时间：
2018
影响因子：
4.2
通讯作者：
Baumert TF
中科院分区：
文献类型：
--
作者：
Crouchet E;Wrensch F;Schuster C;Zeisel MB;Baumert TF
慢性丙型肝炎病毒（HCV）感染是全世界慢性肝病和肝细胞癌（HCC）的主要原因。在过去的几年中，随着多种直接作用抗病毒药物 (DAA) 的批准，抗 HCV 疗法经历了一场革命，这些药物能够实现无干扰素治疗，并显着改善患者的持续病毒学应答。如今，DAA 已成为 HCV 治疗的标准治疗方法。然而，仍然存在一些局限性，包括获得治疗的机会、部分患者治疗失败以及晚期纤维化患者治愈后持续发生 HCC 的风险。通过靶向参与 HCV 生命周期的保守宿主蛋白，宿主靶向剂 (HTA) 为具有高耐药性屏障的泛基因型抗病毒方法提供了机会。此外，当与 DAA 联合应用时，HTAs 可以通过互补的作用机制改善对难治患者的治疗。在这篇综述中，我们总结了在临床前和临床开发中评估的不同 HTA，并讨论了它们在抗 HCV 治疗中的潜在作用。
Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) worldwide. In the past few years, anti-HCV therapies have undergone a revolution with the approval of multiple direct-acting antivirals (DAAs), which enable interferon-free treatments with considerable improvement of sustained virologic response in patients. Today, DAAs have become the standard of care for HCV therapy. However, several limitations remain, which include access to therapy, treatment failure in a subset of patients and persistent risk of HCC development following cure in patients with advanced fibrosis. By targeting conserved host proteins involved in the HCV life cycle, host-targeting agents (HTAs) offer opportunities for pan-genotypic antiviral approaches with a high barrier to drug resistance. Moreover, when applied in combination with DAAs, HTAs could improve the management of difficult-to-treat patients by acting through a complementary mechanism of action. In this review, we summarize the different HTAs evaluated in preclinical and clinical development and discuss their potential role for anti-HCV therapies.
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