Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

Abstract

Background and aim: Cholesterol absorption inhibitor ezetimibe is being used to treat nonalcoholic fatty liver disease (NAFLD) and related metabolic comorbidities. However, its specific efficacy remains unclear. Hence, a meta-analysis was undertaken to clarify the effects of ezetimibe on NAFLD and related metabolic comorbidities. Methods: Electronic databases were searched for clinical trials that investigated the effects of ezetimibe on NAFLD and related metabolic comorbidities. The primary outcome of interest was the effect of ezetimibe on liver enzymes and histology. The secondary outcome of interest was the effect of ezetimibe on lipid metabolism and hepatic insulin resistance. Results: The end-of-treatment (vs. baseline) hepatic steatosis grade and NAFLD activity score (NAS) were significantly improved (steatosis grade: weighted mean difference [WMD]: −0.62, 95% CI: −0.96 to −0.27, P = 0.0005; NAS: WMD: −1.00, 95%CI: −1.46 to −0.55, P < 0.0001) without significant improvement in hepatic lobular inflammation, ballooning, or fibrosis. In Asian participants, the end-of-treatment alanine aminotransferase was significantly decreased (WMD: −12.11 IU/L, 95%CI: −23.81 to −0.41 IU/L, P = 0.04). Treatment with ezetimibe significantly reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (TC: WMD: −37.96 mg/dL, 95%CI: −59.52 to −16.40 mg/dL, P = 0.0006; LDL-C: WMD: −35.55 mg/dL, 95%CI: −57.02 to −14.07 mg/dL, P = 0.001) without a significant effect on triglycerides, high-density lipoprotein cholesterol, glycosylated haemoglobin or the homeostasis model of assessment for insulin resistance index. Conclusions: Results of the meta-analysis confirm beneficial effects of ezetimibe on hepatic steatosis and cholesterol metabolism in patients with NAFLD.