Clinical Utility of a 50% and 30% Decline in Magnetic Resonance Imaging-Proton Density Fat Fraction in Predicting Fibrosis Improvement in Metabolic Dysfunction-Associated Steatohepatitis.

In 30 seconds

This secondary analysis of a multicentre, randomised, placebo-controlled trial assessed whether MRI-PDFF declines predict histological improvement in 163 participants with biopsy-confirmed MASH and stage 2 or 3 fibrosis treated with pegozafermin or placebo for 24 weeks. A ≥50% relative decline in liver fat was independently associated with fibrosis improvement without worsening MASH (adjusted odds ratio, 3.08; 95% confidence interval, 1.32-7.19; P = .009), whereas a ≥30% decline was not. Both thresholds predicted MASH resolution without worsening fibrosis.

Key findings

• MRI-PDFF super-response (≥50% decline) independently predicted fibrosis improvement without worsening MASH (adjusted odds ratio, 3.08; 95% confidence interval, 1.32-7.19; P = .009).
• A ≥30% MRI-PDFF decline did not independently predict fibrosis improvement (adjusted odds ratio, 2.10; 95% confidence interval, 0.85-5.16; P = .11).
• Both MRI-PDFF response and super-response predicted MASH resolution without worsening fibrosis (P = .004 and P < .001, respectively).
• Super-response occurred more often with pooled pegozafermin doses than placebo (57.8% vs 11.1%; P < .0001).

Why it matters

The findings suggest that the magnitude of liver-fat reduction matters when using MRI-PDFF to assess fibrosis improvement in MASH. A ≥50% decline was more informative for fibrosis regression than the commonly used ≥30% response threshold, while both thresholds were associated with MASH resolution. This distinction may help interpret imaging response as a marker of histological outcomes, although it does not establish MRI-PDFF as a substitute for biopsy.

What to keep in mind

This was a secondary analysis of a 24-week trial in participants with stage 2 or 3 fibrosis; the findings may not apply to other populations or longer-term outcomes.