title: Insulin resistance, hepatic steatosis and hepatitis C: a complex relationship with relevant clinical implications.
abstract: Insulin resistance (IR) is a common pathophysiological condition where higher-than-normal concentrations of insulin are needed to maintain a normal glycemia and adequate glucose utilization in insulin target tissues. A high proportion (50-80%) of patients chronically infected with the hepatitis C virus (HCV) exhibit evidence of IR. Basic and clinical studies have disclosed a complex bidirectional relationship between IR and HCV infection that has important clinical implications. HCV infection may promote IR through direct viral-dependent mechanisms or due to activation of the inflammatory response resulting in increased production of tumor necrosis factor-a and other cytokine-related molecules. These abnormalities may act synergistically with pre-existing metabolic risk factors and result in the development of hepatic steatosis and type 2 diabetes mellitus (T2DM) which are frequently found in the setting of HCV infection. Moreover, in addition to underlying metabolic abnormalities leading to its development hepatic steatosis also exhibit genotype-specific pathogenic mechanisms. A number of studies have shown that hepatic steatosis is associated to fibrosis progression in patients with HCV and that IR has a negative impact on the response rates to interferon-a-based therapy. Thus, modification of these factors through life-style changes or pharmacological agents may represent an undervalued specific target of therapy aiming to improve sustained virological response rates and reduce HCV related-morbidity and mortality.
authors: School of Medicine, Pontificia Universidad Católica de Chile, Marcoleta #367, Santiago, Chile. marrese@med.puc.cl
authors: Marco
authors: M
authors: Arrese
authors: Arnoldo
authors: A
authors: Riquelme
authors: Alejandro
authors: A
authors: Soza
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D002149:Energy Intake; D005234:Fatty Liver / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D040242:Risk Reduction Behavior; D016896:Treatment Outcome; D019562:Viral Load; D015431:Weight Loss
chemical_list: D000998:Antiviral Agents; D007004:Hypoglycemic Agents