Viral and host factors associated with outcomes of hepatitis C virus infection
Viral and host factors associated with outcomes of hepatitis C virus infection
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与丙型肝炎病毒感染结果相关的病毒和宿主因素
DOI：
10.3892/mmr.2017.6351
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发表时间：
2017-05-01
影响因子：
3.4
通讯作者：
Wang, Yuming
中科院分区：
文献类型：
--
作者：
Yan, Zehui;Wang, Yuming
丙型肝炎病毒（HCV）感染是全球主要的健康问题。由于在宿主遗传学和HCV分子病毒学方面取得的进展，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取决于复杂的宿主-病毒相互作用。HCV基因型是预测聚乙二醇干扰素-a加利巴韦林治疗反应的最重要的病毒因素。HCV基因型1的亚型是预测直接作用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。位于与免疫应答相关的基因中的多种宿主遗传变异已被确定为慢性HCV自发性病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结果尚未被证明对所有调查人群和独立研究具有普遍性。先前在独立的大型全基因组关联研究中的发现证实，干扰素λ 3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多态性已被确定为对利巴韦林诱导的贫血和剂量减少的保护因素。另一种在马铃薯糖蛋白样磷脂酶结构域中含有3个基因的遗传变异与HCV患者的肝脂肪变性和纤维化相关。目前的审查集中在确定的病毒和宿主因素与丙型肝炎患者的结果，并评估参与病毒和宿主遗传学的自然历史和治疗结果的丙型肝炎病毒感染。这将为个体化预防和个体化临床管理提供新的思路。
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-a 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-lambda 3 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.