Abstract 16988: Fatty Liver Index is Reduced With Ezetimibe in an Analysis of 15,095 Patients Randomized to Ezetimibe vs Placebo in the Improve-it Trial

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the US, and is associated with early atherogenesis and increased risk of cardiovascular (CV) death. Although no pharmacologic therapy has proven benefit in NAFLD, recent clinical studies suggest that ezetimibe may reduce histologic evidence of liver inflammation and improve serum markers of NAFLD. In this post hoc analysis of the IMPROVE-IT trial, we assessed the impact of ezetimibe in patients with presumed NAFLD, using the Fatty Liver Index (FLI), a validated prediction score for hepatic steatosis. Methods: Of the 18,144 IMPROVE-IT patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), 15,095 had both baseline ALT 2x ULN and sufficient data with which to calculate FLI, a calculated score composed of triglycerides (TG), gamma-glutamyltransferase (GGT), body mass index (BMI), and waist circumference. FLI ≥ 60 has been strongly correlated with NAFLD, while values <30 indicate low probability of NAFLD. Differences in FLI between treatment arms over time were tested with non-parametric Wilcoxon rank-sum tests. Results: Baseline FLI was ≥ 60 in 6798 (45%) patients and <30 in 3438 (23%). E/S reduced median absolute FLI from 55.0 to 51.2 over 72 months, a reduction of 6.9%, which was significantly greater than that observed in P/S group (all p<0.001 at each time-point, Fig). Of those with initial FLI ≥ 60 treated with E/S, 26.3% had 48-month FLI score < 60 (compared to 21.6% in P/S group, p<0.001). E/S significantly reduced both TG and GGT compared to P/S (both p<0.001 at 72 months). E/S significantly reduced FLI regardless of baseline ALT (normal vs. 1-2x ULN) ( p =0.002; interaction p =0.53). Conclusion: Ezetimibe significantly reduced surrogate markers of NAFLD, suggesting that it may offer protection against progression of non-alcoholic fatty liver disease, metabolic syndrome, and atherogenic risk.