Clinically Inferred Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Association with Atrial...

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to atrial fibrillation (AF); however, its relationship with specific AF subtypes remains unclear. This prospective, single-center, observational case-control study investigated whether MASLD is independently associated with AF presence and its subtypes. Materials: A total of 327 participants were analyzed, including 119 controls and 208 patients with AF. Comprehensive clinical history, anthropometric measures, laboratory testing, 24 h Holter ECG, and echocardiography were performed. Clinically inferred MASLD was defined according to the current EASL-EASD-EASO guidelines using clinical and non-invasive indices (Hepatic Steatosis Index, Fatty Liver Index, Fibrosis-4 Index). No liver biopsy or imaging confirmation of steatosis or fibrosis was performed, and therefore, the diagnosis represents a clinically inferred ("probable") MASLD. To minimize systematic bias and improve baseline comparability between groups, propensity score matching and complementary regression analyses were applied. Results: Overall probable MASLD prevalence did not differ between AF and controls (42% vs. 44%, p = 0.742). A clear phenotypic gradient emerged across subtypes: lowest in permanent AF (PermAF, 27.1%) versus paroxysmal (47.1%) and persistent AF (51.4%) (p = 0.021). PermAF exhibited the most advanced comorbidity-highest CHF (78.6%), CKD (71.4%), HFpEF (48.6%), FIB-4 (median 2.67), the lowest TG/HDL-cholesterol ratio (1.93 vs. 3.32; p < 0.001), and progressive renal impairment. Statin therapy reached 80% in clinically inferred MASLD-positive PermAF. The elevated FIB-4 observed in PermAF must be interpreted with explicit caution: this group was substantially older (median 79.5 years) and carried the highest burden of chronic heart failure and chronic kidney disease; therefore, in this subgroup, FIB-4 most plausibly reflects age and cardio-renal comorbidity rather than histologically confirmed hepatic fibrosis. After matching, MASLD was not an independent predictor of AF presence (OR = 0.96; 95% CI: 0.59-1.46) or its clinical severity. Conclusions: Probable MASLD, defined by clinical and non-invasive indices, was not independently associated with AF in this cohort, but AF subtypes exhibited a clear phenotypic gradient-from a metabolically driven profile in early AF to a cardio-renal and fibrotic pattern in advanced, elderly AF. Elevated FIB-4 values in PermAF most plausibly reflect age and cardio-renal comorbidity rather than true histologically confirmed hepatic fibrosis. These findings support a phenotype- and population-dependent MASLD-AF relationship and underscore the need for imaging- and histology-verified longitudinal studies.