Hepatitis C virus infection, genotypes and mechanism of insulin resistance


Shiferaw Bekele Woyesa, Andrew W. Taylor-Robinson

Background: Hepatitis C virus (HCV) infection is a major global public health problem that causes profound metabolic abnormalities, primarily in insulin-sensitive target tissues, notably the phenomenon of steatosis or fatty liver. The route of transmission and genetic mutation of HCV, together with the lack of reliable nation-specific epidemiological data on the distribution of genotypes and sub-genotypes of this RNA virus, provide significant challenges to correct diagnosis and effective treatment. Issue: HCV-induced insulin resistance in HCV-infected individuals is independent of the occurrence of metabolic syndrome and diabetes mellitus, primarily type 2 diabetes mellitus that causes insulin resistance. Some but not all HCV genotypes exert a steatotic effect. However, the molecular mechanism(s) by which HCV infection causes insulin resistance in insulin target tissues or hepatic steatosis is not elucidated clearly. Findings: Mechanisms proposed by experimental studies include interference with insulin signaling pathways, upregulation of genes controlling gluconeogenesis, phosphorylation of insulin receptor substrate proteins, and induction and overexpression of inflammatory cytokines that interact closely with host lipid metabolism. Conclusions: We review HCV genotypes and subtypes, the mechanisms by which HCV infection induces insulin resistance, the virus genotypes and subtypes that are implicated in this and those that are steatotic. We conclude by discussing the proposed mechanisms of steatosis and considering HCV laboratory investigation methods from traditional to current techniques.