Hepatitis C Virus Diversity and Hepatic Steatosis

P. Roingeard


J Viral Hepat. 2013;20(2):77-84. 

In This Article

HCV and Insulin Resistance

Like metabolic syndrome, chronic HCV infection is associated with insulin resistance.[34] Glucose metabolism is modified to a significantly greater extent in the early stages of chronic HCV infection than in chronic hepatitis B virus (HBV) infection. HCV infection thus causes insulin resistance, which can progress to type 2 diabetes mellitus in susceptible individuals.[35] Various mechanisms have been put forward to account for the induction of insulin resistance by HCV. Direct effects in hepatocytes have been attributed to viral interference with the insulin signal transduction pathway mediated by HCV core protein and to the ER stress induced by viral replication (reviewed in[36]). However, insulin resistance has also been shown to occur in uninfected cells, such as striated muscle cells, by unknown mechanisms.[3] Interestingly, the adipose tissue did not appear to be involved in the pathogenesis of viral insulin resistance, as free fatty acid efflux from adipose tissue responds to insulin in normal persons and in patients with chronic hepatitis C.[3] Liver tissues contain large numbers of insulin receptors. The liver controls hepatic glucose production, the replenishment of glycogen stores, increases in triglyceride biosynthesis and decreases in VLDL and apoB production and secretion. In conditions of insulin resistance, hepatic steatosis has been shown to occur principally due to an increase in the influx of fatty acids into the liver, as a result of higher levels of peripheral lipolysis and hepatic lipogenesis.[37] Decreases in fatty acid oxidation and fat export further contribute to hepatic steatosis.[38] Furthermore, hyperinsulinaemia leads to the direct activation of SREBP-1c, causing lipogenesis.[38] Patients with chronic HCV infection have significantly higher fasting serum insulin concentrations and homoeostatic model assessments (HOMAR-IR, a marker for insulin resistance) than healthy volunteers.[39,40] Moreover, patients infected with a genotype 3 virus have significantly lower HOMA-IR values than patients infected with other genotypes, providing support for the widely held view that hepatic steatosis is virally induced in genotype 3 infections but metabolically induced in infections with other genotypes.[39,40]