Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease: The Potential Role of Ezetimibe.

Nonalcoholic fatty liver disease (NAFLD) is widely considered to be the hepatic manifestation of the metabolic syndrome and is closely linked to dyslipidemia, obesity, and insulin resistance. Patients with NAFLD have increased mortality when compared to the general population, primarily related to cardiovascular disease or malignancy. The biologic mechanisms that link NAFLD to cardiovascular disease include expansion of visceral adipose tissue, atherogenic dyslipidemia, impaired insulin signaling, systemic inflammation, and endothelial dysfunction. Currently, there are no approved therapies for NAFLD. It has recently been hypothesized that reducing the delivery of dietary cholesterol using the hypolipidemic agent, ezetimibe, could benefit patients with NAFLD. By potently inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) sterol receptor on intestinal enterocytes and within the liver, ezetimibe blocks exogenous cholesterol absorption and has been shown to improve biochemical markers of NAFLD, improve insulin sensitivity and decrease hepatic steatosis. This review summarizes the clinical and epidemiological evidence for the relationship between NAFLD and cardiovascular risk and examines the potential therapeutic role of ezetimibe.