New Obesity Definitions Reclassify Many MASLD Patients but Do Not Improve Liver Risk Prediction

• New obesity definitions from EASO and the Lancet Commission reclassified 20.4% and 34.1% of MASLD patients as obese who were non-obese by BMI alone.

• These newly classified obese groups did not have a significantly higher risk of liver-related events compared with non-obese patients (adjusted SHR 1.15 and 0.75, respectively).

• Risk of liver-related events increased meaningfully only when waist-to-height ratio approached 0.6, suggesting higher thresholds may be needed.

• BMI alone remains a comparable predictor of liver outcomes in MASLD, and new definitions broaden the obesity population without improving risk stratification.

Study Snapshot

• Design: Multinational cohort study using the VCTE-Prognosis cohort.

• Population: 12,583 patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

• Exposure: Obesity defined by three frameworks: BMI alone, EASO criteria (BMI obesity or overweight with WHtR ≥0.5 plus comorbidity), and Lancet Commission criteria (BMI obesity plus ≥1 elevated anthropometric measure, or ≥2 elevated measures, or BMI ≥40 kg/m²).

• Primary Outcome: Liver-related events (LRE) incidence per 1,000 person-years.

• Key Result: LRE incidence was 2.4 (normal weight), 3.4 (overweight), 5.2 (obese) per 1,000 person-years by BMI. New definitions did not improve LRE prediction (aSHR 1.15 for EASO reclassified; 0.75 for Lancet reclassified).

Why This Study Matters

Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease (MASLD), but body mass index (BMI) has well-known limitations as a measure of adiposity. It does not distinguish fat distribution, muscle mass, or metabolic health. Recently, both the European Association for the Study of Obesity (EASO) and the Lancet Commission have proposed new obesity definitions that incorporate waist circumference, waist-to-height ratio (WHtR), and comorbidity criteria. However, whether these refined definitions improve risk prediction for clinically important outcomes in patients with established MASLD is not known. The present study directly compared the performance of these three obesity frameworks for predicting liver-related events in a large international cohort.

How the Study Was Conducted

Investigators analyzed data from the multinational VCTE-Prognosis cohort, which includes 12,583 patients with MASLD who underwent vibration-controlled transient elastography (VCTE) for liver stiffness measurement. Exclusion criteria were not detailed in the abstract. Obesity was categorized according to three definitions: (1) BMI alone using standard cutoffs; (2) EASO criteria, which define obesity as either BMI ≥30 kg/m², or BMI 25–29.9 kg/m² plus a WHtR ≥0.5 and at least one obesity-related comorbidity (e.g., type 2 diabetes, hypertension, dyslipidemia); and (3) the Lancet Commission criteria, which define obesity as BMI ≥30 kg/m² plus at least one elevated anthropometric measure (waist circumference or WHtR), or at least two elevated anthropometric measures regardless of BMI, or BMI ≥40 kg/m² alone. Patients were followed for incident liver-related events, defined as decompensation (ascites, variceal bleeding, encephalopathy), hepatocellular carcinoma, or liver-related death. Incidence rates were calculated per 1,000 person-years, and adjusted subdistribution hazard ratios (aSHR) were computed accounting for competing risks.

What the Researchers Found

Among the 12,583 patients, the incidence of liver-related events per 1,000 person-years was 2.4 (95% CI 1.5–3.7) for those with normal BMI, 3.4 (95% CI 2.6–4.5) for overweight, and 5.2 (95% CI 4.3–6.3) for obesity by BMI alone. When applying the EASO and Lancet definitions, 20.4% and 34.1% of patients who were not obese by BMI were reclassified as obese. However, these newly classified obese groups did not have a significantly higher risk of liver-related events compared with the non-obese reference group. The adjusted subdistribution hazard ratio was 1.15 (95% CI 0.64–2.08) for the EASO-reclassified group and 0.75 (95% CI 0.42–1.34) for the Lancet-reclassified group. Corresponding incidence rates in these groups were 2.9 (95% CI 1.9–4.3) and 2.7 (95% CI 1.8–3.9) per 1,000 person-years, respectively. Notably, the risk of liver-related events increased significantly only when WHtR approached 0.6, a threshold above the 0.5 cutoff used in the EASO criteria.

What the Findings May Mean

The results suggest that the new obesity definitions, while broadening the classification of obesity among MASLD patients, do not enhance the prediction of liver-related events beyond BMI alone. The lack of association between reclassified obesity and liver outcomes indicates that the simple BMI stratification already captures much of the risk information. However, the observation that higher WHtR thresholds (around 0.6) were associated with increased risk implies that the current cutoff of 0.5 may be too low for identifying patients with highest liver-related risk. This finding aligns with literature suggesting that central adiposity, particularly severe visceral obesity, is a stronger driver of liver disease progression. Importantly, the study does not imply that the new definitions are useless; they may still provide value for other outcomes like cardiovascular disease or metabolic complications, but for liver-specific events in MASLD patients, BMI appears sufficient.

Strengths and Limitations

The study's strengths include its large, multinational cohort, standardized assessment of liver stiffness, and use of competing risk analysis. However, several limitations must be considered. The analysis is observational and cannot establish causation. The cohort is predominantly tertiary care, potentially limiting generalizability to primary care populations. Liver-related events were not adjudicated centrally in all centers. The new obesity definitions themselves are still evolving, and the study did not assess other obesity metrics such as visceral fat imaging or body composition. Furthermore, the EASO and Lancet definitions include comorbidity criteria that may overlap with MASLD itself, potentially introducing confounding. Residual confounding by unmeasured factors (e.g., diet, physical activity, genetic risk) cannot be excluded.

Implications for Practice and Research

For clinicians managing patients with MASLD, this study supports the use of BMI as a simple and adequate risk predictor for liver-related events. The new obesity definitions do not appear to offer added liver-specific risk stratification. However, waist-to-height ratio may become more informative if higher thresholds are adopted. Further prospective studies with centralized event adjudication and longer follow-up are needed to validate these findings and explore whether the new definitions improve prediction of extrahepatic outcomes. Researchers developing obesity classification updates should consider disease-specific outcomes such as liver events in their validation.

References

Cai J, Yip TC, Lin H, et al. Implications of new obesity definitions in the classification and outcomes of patients with MASLD. Hepatology. 2026. PMID: 42507833. URL