Molecular mechanisms of insulin resistance in chronic hepatitis C

Abstract

It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

Serum vaspin may be a good indicator of fibrosis in chronic hepatitis C and is not altered by antiviral therapy

“…Some studies indicated that successful antiviral treatment improves insulin sensitivity in CHC patients [8,11] however, information on behavior of certain adipokines is very scarce. In our study there was no difference in serum vaspin between the pretreatment level and, at the level measured at weeks 12 and 48 (end of the therapy).…”

“…Insulin sensitivity in CHC is affected not only by inflammation but also by a direct viral influence [5,11,20]. Some studies suggested that induction of vaspin mRNA expression in human adipose tissue could be a compensatory mechanism associated with obesity and insulin resistance [13,19,21].…”

“…The main metabolic disturbance en-compasses insulin resistance (IR) [3,4], which contributes to a high prevalence of hepatic steatosis [5], increased incidence of impaired glucose tolerance or type 2 diabetes mellitus [6] and hyperlipidemia [7]. Of great clinical relevance is the fact that IR accelerates the progression of liver injury and fibrosis and decreases the rate of sustained virological response elevating the risk of hepatocellular carcinoma development [8][9][10][11].…”

Insulin resistance in patients with cirrhosis and portal hypertension

“…IR has been described in several liver disorders (9,14,32,39), where it may have important clinical consequences. Thus it has been suggested that IR has a negative impact on the response rates to interferon-based therapy in chronic hepatitis C virus infection (19) and that IR could be a predictor of the presence of PH in patients with nonalcoholic fatty liver disease (16).…”

Pathomechanism of insulin resistance in chronic hepatitis C

“…Ponadto HOMA-IR był niezależ-nym czynnikiem progresji włóknienia w PZWC [13]. Stopień insulinooporności ściśle wiąże się z zasięgiem włóknienia i jego progresją [14][15][16]. Insulinooporność występowała głównie u pacjentów zakażonych genotypem 1 lub 4 i z wyższą wiremią [10,17,18].…”