Markers of body fat, the mediating role of alanine aminotransferase, and their association with the risk of metabolic dysfunction-associated steatotic liver disease.
Journal:
European journal of pediatrics
Published Date:
Aug 2, 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity correlates with metabolic dysfunction, yet interactions between anthropometrics, liver enzymes, and risk of MASLD remain unclear. This study included 219 children with obesity (79 with MASLD, 140 without MASLD). Demographic, anthropometric, body composition, and biochemical parameters were analyzed. Multivariable logistic regression, stratified analysis, machine learning (Random Forest, LASSO regression), mediation models, and a nomogram were applied. The results showed that children with MASLD demonstrated elevated adiposity markers (weight, 59.8 vs. 45.5 kg; body mass index [BMI], 28.03 vs. 24.56 kg/m; waist circumference [WC], 82.64 vs. 69.30 cm; waist-to-height ratio [WHtR], 0.54 vs. 0.49), body composition (body fat mass [BFM], 26.06 vs. 18.13 kg; visceral fat area [VFA], 123.89 vs. 85.06 cm), and liver enzymes (alanine aminotransferase [ALT], 40.00 vs. 19.00 U/L; aspartate aminotransferase [AST], 32.00 vs. 26.00 U/L). Multivariable models and machine learning identified weight, WC, BFM, and ALT as top features (AUC = 0.861). ALT mediated 32.9-38.3% of adiposity-MASLD associations, with persistent direct effects. Adiposity-MASLD links were stronger in males and children with obesity duration > 3 years. Conclusion: Weight, WC, BFM, and ALT synergistically drive MASLD risk (AUC = 0.861), with ALT mediating 32.9-38.3% of adiposity-MASLD associations while direct effects persist. The validated nomogram enables personalized risk stratification, supporting early ALT monitoring and adiposity control in high-risk children with obesity duration > 3 years.