Impact of Insulin-Sensitizing Agents on Risk for Liver Cancer and Liver-Related Death in Diabetic Patients with Compensated Hepatitis C Cirrhosis

Extract

Chronic hepatitis C (CHC) infection remains a leading global public health burden, affecting an estimated 180 million persons worldwide (1). The natural history of CHC infection is characterized by progressive liver fibrosis, which may lead to liver cirrhosis, hepatocellular carcinoma (HCC), decompensated liver disease, and liver-related death. Substantial epidemiological data suggest that due to an aging cohort of prevalent CHC infection in the United States, the burden of CHC-related complications such as HCC, liver decompensation, and liver-related mortality has doubled over the past decade and will continue to rise over the next two decades (2, 3). Concurrent with this epidemiological trend is a continuing rise in the incidence of obesity, diabetes mellitus type 2, metabolic syndrome, and nonalcoholic fatty liver disease, all of which are highly prevalent in patients with CHC infection. Insulin resistance (IR) plays a central role in the pathogenesis of these conditions via its relationship with CHC infection. IR in patients with CHC may be multifactorial in origin, stemming from both coexisting metabolic syndrome and mechanisms related to viral infection. The latter include increased hepatic free fatty acid accumulation, direct viral effects on insulin signaling through interaction with the signaling molecules insulin receptor substrates 1 and 2 (4), and chronic inflammatory processes in hepatic and adipose tissue that contribute to increased levels of proinflammatory cytokines such as TNF-α and IL-6 and decreased levels of adiponectin (5).