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

摘要

C (CHC) infection remains a leading C global public health burden, affecting an estimated 180 million persons worldwide (1). The natural history of CHC infection is characterized by progressive liver fibro- sis, which may lead to liver cirrhosis, hepatocellular car- cinoma (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 complica- tions such as HCC, liver decompensation, and liver-re- lated mortality has doubled over the past decade and will continue to rise over the next two decades (2, 3). Concur- rent with this epidemiological trend is a continuing rise in the incidence of obesity, diabetes mellitus type 2, meta- bolic 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 patho- genesis of these conditions via its relationship with CHC infection. IR in patients with CHC may be multifactorial in origin, stemming from both coexisting metabolic syn- drome and mechanisms related to viral infection. The lat- ter 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-a and IL-6 and decreased levels of adiponectin (5).