Part of the book: Drug Discovery and Development
Diabetes type 2 mellitus (T2DM) is the most common extrahepatic association of hepatitis C virus (HCV) infection. Substantial research has suggested that insulin resistance (IR) has crucial importance in development of type 2 diabetes in HCV-infected patients. Several pathophysiological mechanisms are proposed, such as direct effect of HCV proteins on inhibition of the insulin-signaling pathway inducing central insulin resistance (IR), while overproduction of inflammatory cytokines and increased lipolysis promote peripheral IR. IR in HCV-infected patients is associated with impaired sustained virologic response (SVR) and higher incidence of hepatocellular carcinoma (HCC). Some, but not all, studies have shown improvements in achieving SVR in patients with interferon/ribavirin (RBV) therapy co-treated with metformin or pioglitazone as well as beneficiary effect on the incidence of hepatocellular carcinoma. Recent studies indicate that response to the new direct-acting antiviral (DAA) treatments is unaffected by insulin resistance thus diminishing importance of IR in the new era of DAA. Additionally, viral eradication by DAAs has been shown to ameliorate insulin resistance, attenuating the risk of new-onset diabetes type 2. However, those metabolic improvements are sustainable long after the treatment remains unclear.
Part of the book: Update on Hepatitis C