Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor. Methods: C57BL/6J mice were divided into five treatment groups as follows: basal diet (1113), high-fat diet (HFD) only, HFD with EZ (5 mg/kg/day), HFD with AC (100 mg/kg/day), and HFD with both EZ and AC for 24 weeks. Results: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha 1 (PPAR-alpha 1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model. Conclusions: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.