Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Best Pract Res Clin Gastroenterol. 2012 Aug;26(4):413-27. doi: 10.1016/j.bpg.2012.09.004.
Understanding of the natural history and treatment responsiveness of chronic hepatitis C virus (HCV) infection has evolved rapidly in recent years. Advances in HCV molecular virology and host genetics can now better predict spontaneous clearance and treatment outcomes. HCV genotype is the most important viral factor predicting interferon-α treatment responsiveness; HCV-1 subtype is emerging as a key determinant of the efficacy of direct acting antiviral therapy. Genome-wide association studies have recently identified several clinically important host determinants of the outcomes of peginterferon-α and ribavirin treatment outcome: IL28B polymorphism is associated with spontaneous clearance and treatment responsiveness; ITPA polymorphism protects against ribavirin-induced anaemia and dose reductions; genetic determinants of liver fibrosis progression rate have been proposed. In this review, we evaluate the role of viral and host genetics in the natural history and treatment outcomes of chronic HCV infection, and consider how this knowledge might help individualize clinical management in the era of DAA therapy.
近年来，人们对慢性丙型肝炎病毒（HCV）感染的自然史和治疗反应的理解迅速发展。HCV 分子病毒学和宿主遗传学的进步现在可以更好地预测自发清除和治疗结果。HCV 基因型是预测干扰素-α治疗反应性的最重要的病毒因素；HCV-1 亚型是直接作用抗病毒治疗疗效的关键决定因素。全基因组关联研究最近确定了几个与 peginterferon-α 和利巴韦林治疗结果相关的临床重要宿主决定因素：IL28B 多态性与自发清除和治疗反应性相关；ITPA 多态性可预防利巴韦林引起的贫血和剂量减少；已提出了肝纤维化进展速度的遗传决定因素。在这篇综述中，我们评估了病毒和宿主遗传学在慢性 HCV 感染的自然史和治疗结果中的作用，并考虑了如何在 DAA 治疗时代帮助个体化临床管理。
