Open AccessHepatitis C virus induced insulin resistance impairs response to anti viral therapy
Author(s) -
Abdel-Rahman El-Zayadi,
Mahmoud Anis
Publication year - 2012
Publication title -
world journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.427
H-Index - 155
eISSN - 2219-2840
pISSN - 1007-9327
DOI - 10.3748/wjg.v18.i3.212
Subject(s) - insulin resistance , steatosis , cirrhosis , hepatitis c virus , steatohepatitis , interferon , adipokine , hepatocellular carcinoma , cancer research , hepatitis b virus , fatty liver , hepatitis c , immunology , biology , medicine , insulin , virus , disease
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.