ASSOCIATIONS OF CIRCULATING CERAMIDE LEVELS WITH BODY MASS INDEX AND LIVER FIBROSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE

Background and aims. Non-alcoholic fatty liver disease (NAFLD), now largely encompassed by metabolic dysfunction-associated steatotic liver disease (MASLD), is closely linked to excess adiposity and progressive metabolic injury. Ceramides are bioactive sphingolipids implicated in insulin resistance, lipotoxicity and fibrogenic signaling. We evaluated circulating ceramide levels in relation to body mass index (BMI) and liver fibrosis. Methods. This cross-sectional study included 84 participants: 29 controls without hepatic steatosis or fibrosis and 55 patients with NAFLD (28 with steatosis and 27 with steatohepatitis). BMI was assessed anthropometrically, fasting blood was collected using a standardized protocol, ceramide was measured by a high-sensitivity spectro-chromatographic method, and fibrosis was assessed by transient elastography/FibroScan. Non-parametric comparisons used Mann-Whitney U and Kruskal-Wallis tests; ordered associations were assessed using Spearman correlation. Results. Median BMI was higher in NAFLD than controls (30.68 [IQR 6.21] vs 22.20 [2.50] kg/m2; U=13.000; Z=-7.385; p<0.001). In the NAFLD group, 12.7% had normal weight, 29.1% were overweight and 58.2% had obesity. Ceramide differed across BMI categories (H=38.356; p<0.001): 4.25 [8.54] in normal weight, 59.78 [55.57] in overweight and 59.73 [52.73] in obesity. Ceramide also differed across fibrosis stages (H=45.700; p<0.001), with mean values of 5.28+/-5.41 at F0, 30.74+/-23.74 at F1, 45.37+/-34.97 at F2, 57.80+/-23.11 at F3 and 44.17+/-26.88 at F4. Fibrosis stage correlated positively with ceramide (r=0.654; p<0.001). Conclusions. Excess body mass was accompanied by markedly higher circulating ceramide levels, and ceramide was associated with fibrosis severity. These findings support further study of sphingolipid metabolism as a metabolic marker linking adiposity and liver injury, while the cross-sectional design precludes causal inference.