ISSN 1849-9031 (Online)

ISSN 1849-8922    (Print)

Could platelet derived growth factor α mediate hepatitis C induced insulin resistance and hepatic fibrosis?
Kristina Blaslov, Davorka Dušek, Anna Mrzljak.

Abstract


Hepatitis C virus (HCV) infection represents an important risk factor for Type 2 diabetes mellitus (T2DM) development. Although the HCV diabetogenic potential depends on its genotype, it is probably due to dysglycemia and dyslipidemia promotion, visceral obesity, and genetic predisposition. Hepatic steatosis represents a common feature of chronic HCV infection as well as T2DM. Thus, we hypothesize that these two conditions might share a common mechanism in hepatic steatosis pathogenesis. Lipid accumulation in the hepatocytes represents the “first hit” that increases the liver vulnerability to many factors that constitute the “second hit” and promote hepatic injury, inflammation, and fibrosis. Many inflammatory cytokines and growth factors are released during liver injury, including platelet-derived growth factors (PDGFs). It was recently demonstrated that elevated hepatic PDGF-A gene expression and increased secretion of PDGF-A are associated with hepatic steatosis and fibrosis in patients with T2DM. Since HCV infection is often accompanied with systemic insulin resistance, we hypothesize that chronic hyperinsulinemia might lead to increased secretion of PDGF-α and thus mediate the HCV-related hepatic steatosis and fibrosis.