Abstract 9341: Hepatic Steatosis Index and Fibrosis-4 Scores in Patients With Type 2 Diabetes - Post Hoc Analyses from VERTIS CV

Abstract

Introduction: Given the potential link between non-alcoholic fatty liver disease and increased cardiovascular (CV) risk, the associations between markers of hepatic steatosis/fibrosis with CV and kidney outcomes were explored. Methods: These post hoc analyses were conducted on data from the VERTIS CV trial that randomized patients with type 2 diabetes (T2D) and atherosclerotic CV disease (ASCVD) to ertugliflozin 5 or 15 mg or placebo, with all randomized groups pooled for the present analyses. The presence of hepatic steatosis was estimated by hepatic steatosis index (HSI; 8 х ALT/AST + BMI + 2 if T2D + 2 if female); and for hepatic fibrosis, fibrosis-4 score (FIB-4; [age х AST]/[platelets count х √ALT]). Patients were divided into quartiles (Q1 to Q4) according to baseline for each score. CV and kidney outcomes (CV death/myocardial infarction/stroke [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and sustained ≥40% decrease in eGFR from baseline/dialysis or transplantation/kidney death) were stratified by baseline HSI and FIB-4 quartiles. Results: Among 8246 patients, the mean age was 64.4 years, mean BMI 32.0 kg/m 2 , mean HSI 44.0, and mean FIB-4 score 1.34. Event rates of MACE, HHF/CV death, CV death, and HHF increased with FIB-4 quartile ( Fig A ). The hazard ratios (HR, 95% CI) of events by FIB-4 quartile (Q4 vs Q1) were 1.48 (1.25, 1.76), 2.0 (1.63, 2.51), 1.85 (1.45, 2.36), and 2.94 (1.98, 4.37) for MACE, HHF/CV death, CV death, and HHF, respectively. The kidney composite did not differ across FIB-4 quartiles. CV and kidney outcomes did not differ across HSI quartiles, except for higher incidence of HHF in the upper HSI quartile (HR [95% CI], Q4 vs Q1: 1.52 [1.07, 2.17]) ( Fig B ). Conclusion: In VERTIS CV, baseline fibrosis scores were associated with incident CV events in patients with T2D and ASCVD, despite the upper cutoff excluding advanced fibrosis. Steatosis only correlated with HHF, and neither measure was associated with the composite kidney outcome.