Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Pharmacol Ther. 2011 Oct;132(1):30-8. doi: 10.1016/j.pharmthera.2011.05.005. Epub 2011 May 18.
Hepatitis C virus (HCV) is presently the leading indication for liver transplantation in Western countries. Treatment for HCV infection includes a combination of pegylated interferon and ribavirin, which produces highly variable response rates. This reflects the lack of information regarding the roles of host and viral components during viral pathogenesis. Vital processes regulated by the liver, including metabolism, lipid homeostasis, cellular proliferation, and the immune response, are known to be systematically dysregulated as a result of persistent HCV infection. Nuclear receptors and their ligands are recognized as indispensable regulators of liver homeostasis. Pathways mediated by the nuclear receptor superfamily have been shown to be profoundly disrupted during HCV infection, leading to an increased importance in elucidating the exact nature of this complex relationship. Expanded understanding of the role of nuclear receptors in HCV infection may therefore be an essential step in the search for a more universally effective treatment.
丙型肝炎病毒(HCV)目前是西方国家进行肝移植的主要指征。HCV 感染的治疗包括聚乙二醇干扰素和利巴韦林联合治疗,但应答率差异很大。这反映了在病毒发病机制过程中,人们对宿主和病毒成分作用的认识还很缺乏。肝脏调节的重要过程,包括代谢、脂质稳态、细胞增殖和免疫反应,已知会因持续的 HCV 感染而被系统性地扰乱。核受体及其配体被认为是肝脏稳态不可或缺的调节剂。核受体超家族介导的途径在 HCV 感染过程中被证明受到严重破坏,因此阐明这种复杂关系的确切性质变得更加重要。因此,扩大对核受体在 HCV 感染中作用的认识,可能是寻找更普遍有效的治疗方法的重要步骤。