title: Hepatitis C, insulin resistance and diabetes: clinical and pathogenic data.
abstract: Epidemiological data indicate a strong risk for development of insulin resistance (IR), and, ultimately, overt diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection. Steatosis, or fatty liver, is closely linked with IR in persons without HCV, such as those with metabolic syndrome, primarily due to increased visceral fat leading to altered adipokine production and increased free fatty acid (FFA) release. Moreover, there is evidence that liver fat can have an impact on the development of hepatic IR independently of changes in adipose tissue. Multiple mechanisms can account for the development of IR in patients with chronic HCV. In particular, there is evidence for a triangular interaction between steatosis, inflammatory processes and IR. In patients infected by the genotype 1 virus, steatosis is strongly related to IR, leading to a metabolic steatosis, while, in genotype 3 patients, steatosis is related to viral load in the context of a viral steatosis. Chronic inflammatory processes in the liver may be mediated by persistently activated macrophages and other immune cells, with concomitant overproduction of pro-inflammatory cytokines such as tumour necrosis factor-alpha. Activation of inflammatory pathways, together with increased levels of FFAs, can disrupt hepatocyte intracellular pathways and inhibit insulin signalling, leading to IR. Molecular studies have also shown that the HCV core protein can directly inhibit the insulin signalling pathway and increase reactive oxygen species production, both of which can further exacerbate IR. The available data provide an understanding of chronic HCV whereby chronic inflammatory processes, steatosis and IR contribute to each other, leading to an increased risk of DM, and its associated poor outcomes, in persons with chronic HCV.
authors.affiliation: UPMC University Paris 06, F-75005, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D024821:Metabolic Syndrome / Q000150:complications*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species