Role of ezetimibe in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis, advanced fibrosis and inflammatory changes. Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol. Ezetimibe exerts beneficial effects on several metabolic variables. Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers. The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients. Our group investigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers. These results are promising for patients with NAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment. However, it should be mentioned that most results are from animal studies and, although modest elevation of liver function tests may raise the suspicion of NAFLD, none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.