title: Hepatitis C virus induced insulin resistance impairs response to anti viral therapy.
abstract: Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.
authors.affiliation: Tropical Medicine Department, Faculty of Medicine, Ain-Shams University and Cairo liver center, Dokki, Giza 12311, Egypt. clcz@tedata.net.eg
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: El-Zayadi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Anis
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology
chemical_list: D054392:Adipokines; D000998:Antiviral Agents