Optimal screening criteria for metabolic dysfunction-associated steatotic liver disease with fibrosis

Early detection of metabolic dysfunction-associated steatotic liver disease (MASLD) with fibrosis may facilitate interventions that can prevent disease progression and may justify screening. However, the optimal combination and threshold of cardiometabolic risk factors (CMRFs) for identifying MASLD with fibrosis remains unclear. We aimed to evaluate the diagnostic performance of various CMRFs-based screening criteria. We analyzed data from 75,124 individuals who underwent comprehensive health screening, including liver ultrasonography and CMRFs assessment. Liver fibrosis risk was assessed using the fibrosis-4 (FIB-4) index, with age-specific thresholds (≥2.0 for age >65 years, ≥1.3 for age ≤65 years). We evaluated multiple screening approaches based on different combinations and thresholds of CMRFs. MASLD with fibrosis was present in 5.8% of participants. The ≥2 CMRFs criterion achieved the highest sensitivity (86.0%) but moderate specificity (50.2%), while ≥3 CMRFs provided balanced performance (62.9% sensitivity, 72.3% specificity). Diabetes mellitus (DM)-based criteria showed high specificity but limited sensitivity. The comprehensive DM OR obesity OR ≥2 CMRFs criterion achieved high sensitivity (81.7%) and moderate specificity (55.8%). CMRFs-based screening criteria showed varying performance for identifying MASLD with fibrosis. The ≥2 CMRFs criterion maximizes case detection, while ≥3 CMRFs provides balanced performance. The comprehensive DM OR obesity OR ≥2 CMRFs approach achieves high sensitivity while maintaining reasonable specificity, offering practical utility for routine clinical screening.