Colpitts Che C, Baumert Thomas F
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 3 Rue Koeberlé, 67000, Strasbourg, France.
Université de Strasbourg, 67000, Strasbourg, France.
Hepatol Int. 2016 Sep;10(5):741-8. doi: 10.1007/s12072-016-9724-7. Epub 2016 Apr 5.
Hepatitis C virus (HCV) infection remains a major global health problem, with 130-170 million chronically infected individuals at risk to develop severe liver disease, including hepatocellular carcinoma. Although the development of direct-acting antivirals offers cure for a large majority of patients, there are still a number of clinical challenges. These include DAA failure in a significant subset of patients, difficult-to-treat genotypes and limited access to therapy due to high costs. Moreover, recent data indicate that the risk for liver cancer persists in patients with advanced fibrosis. These challenges highlight the need for continued efforts towards novel therapeutic strategies for HCV. Over the past two decades, advances in HCV model systems have enabled a detailed understanding of HCV entry and its clinical impact. Many of the virus-host interactions involved in HCV entry have now been identified and explored as antiviral targets. Furthermore, viral entry is recognized as an important factor for graft reinfection and establishment of persistent infection. HCV entry inhibitors, therefore, offer promising opportunities to address the limitations of DAAs. Here, we summarize recent advances in the field of HCV entry and discuss perspectives towards the prevention and cure of HCV infection and virus-induced liver disease.
丙型肝炎病毒（HCV）感染仍然是一个重大的全球健康问题，有1.3亿至1.7亿慢性感染者面临发展为严重肝脏疾病（包括肝细胞癌）的风险。尽管直接作用抗病毒药物的出现为大多数患者带来了治愈的希望，但仍存在一些临床挑战。这些挑战包括相当一部分患者中直接作用抗病毒药物治疗失败、难以治疗的基因型以及由于成本高昂导致治疗可及性有限。此外，最近的数据表明，晚期纤维化患者患肝癌的风险仍然存在。这些挑战凸显了继续努力探索HCV新型治疗策略的必要性。在过去二十年中，HCV模型系统的进展使人们能够详细了解HCV的进入过程及其临床影响。现在已经确定了许多参与HCV进入的病毒-宿主相互作用，并将其作为抗病毒靶点进行了探索。此外，病毒进入被认为是移植物再感染和持续性感染建立的一个重要因素。因此，HCV进入抑制剂为解决直接作用抗病毒药物的局限性提供了有前景的机会。在这里，我们总结了HCV进入领域的最新进展，并讨论了预防和治愈HCV感染及病毒诱导的肝脏疾病的前景。
