Implications of new obesity definitions in the classification and outcomes of patients with MASLD

Background & Aims: New obesity definitions beyond body mass index (BMI) have recently been proposed. This study aimed to assess the proportion of obesity under these frameworks and their associations with liver-related events (LREs). Approach & Results: We analyzed data from the multinational vibration-controlled transient elastography (VCTE)-Prognosis cohort of 12,583 patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Obesity was defined using three frameworks: BMI alone; the European Association for the Study of Obesity (EASO) criteria (BMI-defined obesity or overweight with waist-to-height ratio [WHtR] ≥0.5 plus comorbidity); and the Lancet Commission criteria (BMI-defined obesity plus ≥1 elevated anthropometric measure, or ≥2 elevated anthropometric measures, or BMI ≥40 kg/m²). LRE incidence per 1,000 person-years was 2.4 (95% CI 1.5-3.7), 3.4 (95% CI 2.6-4.5), and 5.2 (95% CI 4.3-6.3) for BMI-defined normal weight, overweight, and obesity. Overall, 20.4% and 34.1% of patients were not classified as obese by BMI but met obesity criteria under the EASO and Lancet definitions. These newly classified obese groups did not have higher LRE risk compared with their non-obese counterparts (adjusted subdistribution hazard ratio [aSHR] 1.15 [0.64-2.08] for EASO; 0.75 [0.42-1.34] for Lancet ), with incidence rates of 2.9 (95% CI 1.9-4.3) and 2.7 (95% CI 1.8-3.9) per 1,000 person-years. LRE risk increased significantly only when WHtR approached 0.6. Conclusions: New obesity definitions broadened the obesity population but did not improve LRE prediction over BMI alone. Higher waist-based thresholds warrant further evaluation.