Association of metabolic risk factors with the severity of hepatic fibrosis and steatosis in metabolic dysfunction-associated fatty liver disease patients

Abstract Background Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) encompasses diverse hepatic and metabolic dysfunctions. Aim To assess the relationship between cumulative metabolic burden and the severity of hepatic fibrosis and steatosis in MAFLD patients. Methods A cross-sectional study of 357 MAFLD patients classified by metabolic burden (one, two, or three risk factors: obesity, diabetes, and metabolic dysregulation). Fibrosis and steatosis were assessed noninvasively using the Fibrosis-4 (FIB-4) score and Fatty Liver Index (FLI). Results Advanced fibrosis (FIB-4 ≥ 2.67) was infrequent (5.3%) and showed no significant variation across metabolic burden subgroups ( p = 0.907). Instead, multivariate analysis identified age (OR = 1.16, p = 0.008), diabetes (OR = 4.40, p = 0.033), AST (OR = 1.13, p < 0.001), and low platelets (OR = 0.96, p = 0.018) as independent fibrosis predictors. In contrast, advanced steatosis (FLI > 96) increased significantly with metabolic burden (16.4%, 21.9%, and 39.5% across subtypes 1–3; p < 0.001). Steatosis was independently associated with subtype 3 (OR = 7.20, p = 0.036), BMI (OR = 1.64, p < 0.001), GGT (OR = 1.03, p < 0.001), age (OR = 1.06, p = 0.011), and waist/hip ratio (OR = 2.63, p < 0.001). Conclusion In MAFLD, metabolic burden strongly predicts steatosis but not fibrosis. Fibrosis is determined by age, diabetes, and biochemical markers, whereas steatosis reflects cumulative metabolic clustering, particularly obesity. These findings underscore distinct pathogenic pathways and support tailored approaches to risk stratification.