Related Experiment Video
Updated: Jun 9, 2026

Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Nonlinear Association Between Metabolic Syndrome Severity and Advanced Fibrosis in Metabolic Dysfunction-Associated
Mohamed I Elsaid1,2,3,4, Yesung Kweon3, Na Li5
1Division of Biostatistics and Population Health, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio.
Background And Aims:
Metabolic dysfunction drives hepatic progression in metabolic dysfunction-associated steatotic liver disease (MASLD), yet conventional binary metabolic syndrome (MetS) definitions may obscure dose-response risk of fibrosis. We evaluated the association between MetS severity and advanced fibrosis probability in a representative US MASLD cohort.
Methods:
Adults aged 20-74 years with ultrasound-defined MASLD in the Third National Health and Nutrition Examination Survey were analyzed. Exposure was the validated MetS severity Z-score (quartiles, percentile categories, and continuous percentile with restricted cubic splines). Outcome was the Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS)-defined advanced fibrosis probability (intermediate-to-high: NFS ≥ -1.455; high: NFS > 0.676). Complex survey logistic regression estimated adjusted odds ratios (aORs).
Results:
Among 3036 participants, 29.6% had intermediate fibrosis probability and 5.2% had high advanced fibrosis probability. High fibrosis probability was most prevalent in non-Hispanic Black adults (8.0%) and least in Mexican Americans (2.6%; P value <.001). Approximately 2.5% of the low MetS severity group had a high probability of advanced fibrosis compared with 11.4% in the very high MetS severity group (P value <.001). Each one-quartile decrease in MetS severity was associated with 21% (aOR = 0.79; 95% confidence interval [CI]: 0.68-0.91) and 32% (aOR = 0.68; 95% CI: 0.48-0.96) lower odds of intermediate-to-high and high probability of advanced fibrosis, respectively. In dose-response analyses, advanced fibrosis risk rose modestly through midrange severities and accelerated beyond the 70th severity percentile, reaching aOR of 3.59 (95% CI: 2.74-4.70) at the 90th vs the 50th percentile.
Conclusion:
MetS severity demonstrates a graded and nonlinear association with advanced fibrosis probability in MASLD. A continuous metabolic-burden measure may enhance upstream triage and risk stratification alongside existing noninvasive pathways.
Related Concept Videos
Ultrasound II: Endoscopic Ultrasound and FibroScan
Endoscopic Ultrasound (EUS):
Cirrhosis II: Pathophysiology
Cirrhosis I: Introduction
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
