Steatosis and insulin resistance in hepatitis C: A way out for the virus?

作     者：José A Del Campo Manuel Romero-Gómez 

作者机构：Unit for The Clinical Management of Digestive Diseases and CIBERehdHospital Universitario de Valme 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2009年第15卷第40期

页      面：5014-5019页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by A Grant  PAI-CTS-532  from Junta de Andalucía  Andalucía  Spain. CIBEREHD was Funded by Instituto de Salud Carlos Ⅲ 

主　　题：Steatosis Insulin resistance Hepatitis Cvirus 

摘      要：The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.