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Updated: Feb 10, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Clinical Utility of a 50% and 30% Decline in Magnetic Resonance Imaging-Proton Density Fat Fraction in Predicting
Rohit Loomba1, Peter Chen-Yang Nikhil Daniel2, Youxin Wang3
1Division of Gastroenterology and Hepatology, Department of Medicine, MASLD Research Center, University of California at San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, California.
Background & Aims:
Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) response (≥30% relative decline in liver fat content on MRI-PDFF) can help to detect resolution of metabolic dysfunction-associated steatohepatitis (MASH) resolution, but there are limited data on whether it can reliably predict fibrosis improvement. We examined the association between MRI-PDFF super response (≥50% relative decline in liver fat content on MRI-PDFF) and fibrosis regression in a randomized placebo-controlled trial.
Methods:
This is a secondary analysis of a large, multi-center, randomized, placebo-controlled trial that included 163 participants (64% female) with biopsy-confirmed MASH with stage 2 or 3 fibrosis who were treated for 24 weeks with pegozafermin or placebo and underwent contemporaneous laboratory testing, MRI-PDFF, and liver biopsy at 2 time points. The co-primary outcomes were fibrosis improvement without worsening of MASH and MASH resolution with no worsening of fibrosis.
Results:
The median age and body mass index (BMI) of participants were 56.0 years (interquartile range, 48.0-62.0 years) and 36.5 kg/m2 (interquartile range, 32.2-40.2 kg/m2). The proportion of patients who achieved super-response was significantly higher in participants treated with pegozafermin (pooled 15 mg, 30 mg, and 44 mg arms) vs placebo (57.8% vs 11.1%; P < .0001). After multivariable adjustment for age, sex, BMI, race/ethnicity, and type 2 diabetes, MRI-PDFF super-response (adjusted odds ratio, 3.08; 95% confidence interval, 1.32-7.19; P = .009) remained an independent predictor of fibrosis regression without worsening MASH, but not MRI-PDFF response (adjusted odds ratio, 2.10; 95% confidence interval, 0.85-5.16; P = .11). Both MRI-PDFF response (P = .004) and MRI-PDFF super response (P < .001) were significant predictors of MASH resolution without worsening fibrosis.
Conclusions:
MRI-PDFF super response predicts fibrosis regression without worsening MASH, and a greater likelihood of MASH resolution without worsening fibrosis than MRI-PDFF response.
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