Related Experiment Video
Updated: Jan 13, 2026
06:26
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
682
Inherited Genetic Risk of Liver Fibrosis in Lean Versus Nonlean Metabolic Dysfunction-Associated Steatotic Liver
Kaleb Tesfai1, Luis Antonio Díaz1,2, Juan Pablo Arab2,3
1MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA.
Alimentary Pharmacology & Therapeutics
|October 28, 2025
Summary
Lean metabolic dysfunction-associated steatotic liver disease (MASLD) patients show similar significant fibrosis risk and genetic risk score effects as nonlean MASLD patients. This suggests lean MASLD individuals may face comparable risks to those who are overweight or obese.
Area of Science:
- Hepatology
- Genetics
- Metabolic Disorders
Background:
- Conflicting data exists on liver fibrosis risk in lean metabolic dysfunction-associated steatotic liver disease (MASLD).
- Understanding fibrosis risk in lean MASLD is crucial for accurate patient management.
Purpose of the Study:
- To compare significant fibrosis risk between lean and nonlean MASLD patients.
- To identify factors associated with fibrosis in lean MASLD.
Main Methods:
- Cross-sectional analysis of prospectively enrolled adults with MASLD.
- Age- and sex-matched comparison of lean and nonlean MASLD individuals.
- Fibrosis assessment using transient elastography, MRI elastography, and liver biopsy.
- Calculation of a genetic risk score (GRS) incorporating PNPLA3, TM6SF2, and HSD17B13 genotypes.
- Validation in an external Latin American cohort.
Main Results:
- The prevalence of significant fibrosis was similar in lean (27.3%) and nonlean (31.1%) MASLD patients.
- Individuals with a high genetic risk score (GRS) had a higher prevalence of significant fibrosis (36.5% vs. 25.2%, p=0.043).
- The effect of GRS on fibrosis prevalence was comparable between lean and nonlean MASLD groups.
Conclusions:
- Lean MASLD patients exhibit a similar prevalence of significant fibrosis compared to nonlean MASLD patients.
- Genetic predisposition, as indicated by GRS, significantly influences fibrosis risk in both lean and nonlean MASLD.
- Lean MASLD should not be considered to have a lower risk of significant liver fibrosis.
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