Influence of HCV infection on insulin-like growth factor 1 and proinflammatory cytokines: association with risk for growth hormone resistance development.

Communications between the endocrine, immune systems and the liver have been postulated. The liver is the central organ in growth hormone/insulin-like growth factor (GH-IGF) axis. Infection with hepatitis C virus (HCV) can lead to liver problems. Although proinflammatory cytokines are an integral part of inflammation in chronic liver diseases, their involvement in mediating hepatic GH resistance during HCV infection remains to be elucidated. To address this issue, our study aimed at evaluating the influence of HCV infection on serum profile of IGF-1, TNF-alpha and IL-6 to assess their possible relation to hepatic dysfunction and GH resistance development. Twenty-five chronic HCV patients were studied together with 15 healthy control subjects. Serum concentration of IGF-1, TNF-alpha and IL-6 was determined by ELISA. HCV viral load was assessed by Real-time polymerase chain reaction using TaqMan probe technology. Basal serum GH levels were determined by a chemiluminescence assay and serum aminotransferases' activities were also measured. TNF-alpha and IL-6 demonstrated higher serum levels, while IGF-1 levels were significantly lower in HCV patients compared to healthy controls. A statistically significant positive correlation was observed between GH and IL-6 levels (P<0.05), a similar trend was found between GH levels, GH/IGF-1 ratio and AST/ALT ratio (P<0.01, P<0.01, respectively). A significant negative correlation was observed between HCV viral load and GH levels (P<0.05). The progressive increase in HCV viral load matches the decrease in circulating IGF-1 levels but without reaching statistical significance. We conclude that the GH insensitivity could be induced by HCV infection and mediated by proinflammatory cytokines through their possible role in blunting the hepatic response to GH. This crosstalk between proinflammatory cytokines and GH-IGF-1 axis could be responsible for triggering impaired glucose metabolism and diabetes later on in chronic HCV infection.