Yan Zehui, Wang Yuming
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
Mol Med Rep. 2017 May;15(5):2909-2924. doi: 10.3892/mmr.2017.6351. Epub 2017 Mar 22.
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy. HCV genome heterogeneity and baseline viral load are additionally associated with the treatment response. Multiple host genetic variants localized in genes associated with the immune response have been identified as predictors of spontaneous disease course and therapy outcome in chronic HCV. However, most findings from candidate gene association studies have not been proven universal for all investigated populations and independent studies. Previous findings in independent large genome wide association studies confirmed that interferon‑λ3 gene polymorphisms are associated with spontaneous clearance and treatment responsiveness. A polymorphism of the inosine triphosphatase gene has been identified as a protective factor against ribavirin‑induced anemia and dose reductions. Another genetic variant in the patatin‑like phospholipase domain containing 3 genes is associated with hepatic steatosis and fibrosis in patients with HCV. The present review focused on the identified viral and host factors associated with outcomes of patients with HCV, and assessed the involvement of viral and host genetics in the natural history and treatment outcomes of HCV infection. This will provide novel ideas concerning personalized prevention and individualized clinical management.
丙型肝炎病毒（HCV）感染是全球主要的健康问题。由于宿主遗传学和HCV分子病毒学取得的进展，新出现的数据表明，HCV感染患者的自然病程和治疗反应在很大程度上由复杂的宿主-病毒相互作用决定。HCV基因型是预测聚乙二醇化干扰素-α加利巴韦林治疗反应的最重要病毒因素。HCV基因型1的亚型是预测直接抗病毒治疗疗效的关键病毒因素。HCV基因组异质性和基线病毒载量也与治疗反应相关。多个位于与免疫反应相关基因中的宿主遗传变异已被确定为慢性HCV自发疾病进程和治疗结果的预测因子。然而，候选基因关联研究的大多数发现尚未在所有调查人群和独立研究中得到普遍证实。独立的大型全基因组关联研究先前的发现证实，干扰素-λ3基因多态性与自发清除和治疗反应性相关。肌苷三磷酸酶基因的一种多态性已被确定为对抗利巴韦林诱导的贫血和剂量减少的保护因素。含patatin样磷脂酶结构域3基因中的另一种遗传变异与HCV患者的肝脂肪变性和肝纤维化相关。本综述重点关注已确定的与HCV患者结局相关的病毒和宿主因素，并评估病毒和宿主遗传学在HCV感染自然史和治疗结局中的作用。这将为个性化预防和个体化临床管理提供新的思路。
