The activation of HIF-1α was confirmed in liver biopsy specimens from patients with chronic hepatitis C. In Huh7.5 cells, the ectopic expression of HCV NS5A has the potential to induce insulin resistance by the phosphorylation of insulin receptor substrate (IRS)-1 at serine residue (Ser307) followed by decreased phosphorylation of Akt, forkhead box O1 (FoxO1) and glycogen synthase kinase 3 beta (GSK3β), the downstream players of insulin signaling pathway (85). Here, FOXO1 is linked to Insulin resistance.