2606-P: Metabolic Heterogeneity of Obesity and the Risk of Liver Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease

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Introduction and Objective: Obesity is a major risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), yet it is metabolically heterogeneous. The impact of distinct metabolic states on MASLD risk across varying degrees of obesity remains unclear. We aimed to evaluate the associations between metabolic obesity phenotypes and liver fibrosis in MASLD.Methods: Two cross-sectional cohorts were included: a liver biopsy cohort (n=558) and a vibration-controlled transient elastography (VCTE) cohort (n=6,113). Advanced fibrosis was defined as F3-F4, determined by liver stiffness ≥10 kPa in the VCTE cohort or histologic F3-F4 in the biopsy cohort. Metabolic heterogeneity of obesity was defined using four metabolic obesity phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy overweight/obesity (MUOO). Logistic regression was used to evaluate the associations between metabolic obesity phenotypes and advanced fibrosis risk in MASLD, adjusted for age and sex.Results: The prevalences of advanced fibrosis were 12.4% in the biopsy cohort and 11.3% in the VCTE cohort. Across the two cohorts, individuals with MUOO had the highest risk of advanced fibrosis. Compared with MHNW, MUOO (adjusted-OR=1.69, 95% CI 1.29-2.21), MUNW (adjusted-OR=1.34, 95% CI 0.98-1.83), and MHOO (adjusted-OR=1.24, 95% CI 0.89-1.72) were associated with increased advanced fibrosis risk (P<0.001). Subgroup and sensitivity analyses supported these findings.Conclusion: MUOO confers the greatest risk of advanced fibrosis in MASLD, underscoring the importance of metabolic phenotype-based risk stratification beyond BMI alone.

Disclosure

Y. Chen: None.

Funding

China Association of Chinese Medicine Launches 2025 Joint Research Initiative on Priority Diseases (Grant No. NCIM25-4), the Key Research and Development Program of Jiangsu Province (BE2023767), the Health Research Program of Anhui (AHWJ2023A30169), and the Natural Science Foundation of Anhui Province (2508085QH314)



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