ABSTRACT

Background & Aims Iron corrected T1 (cT1) is an MRI derived biomarker of liver disease activity. Emerging data suggest a change in cT1 of ≥ 80 ms reflects histological improvement. We aimed to validate the association between the ≥ 80 ms decline in cT1 and histological improvement, specifically the resolution of MASH.

Methods A retrospective analysis of study participants from three interventional clinical trials with histologically confirmed MASH (n = 150) who underwent multi-parametric MRI to measure cT1 (LiverMultiScan®) and biopsies at baseline and end of study. Histological responders were defined using the four criteria: (1) a decrease in NAFLD Activity score (NAS) ≥ 2 with no worsening in fibrosis, (2) a decrease in fibrosis ≥ 1 stage with no worsening in NAS, (3) both a NAS decrease ≥ 2 and a fibrosis decrease ≥ 1, and (4) MASH resolution with no worsening in fibrosis. Difference in the magnitude of change in cT1 between responders and non-responders was assessed.

Results Significant decreases in cT1 were observed in responders for all the histological criteria. The optimal threshold for separating responders from non-responders was 0.73 for MASH resolution (64ms-73ms for the other criteria), in close agreement with the predefined threshold of 80ms. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. Those achieving an ≥ 80 ms drop in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3.

Conclusions These results demonstrate that a drop in cT1 of ≥ 80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Funded by Perspectum.

Author Declarations

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The central IRB, Advarra Institutional Review Board (00000971) approved the study protocols and all amendments'

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Data Availability

All data produced in the present work are contained in the manuscript

ABBREVIATIONSAUCarea under the curveAUROCarea under the operator characteristic curvecT1iron-corrected T1-mappingFDAfood and drug administrationIQRinterquartile rangeMASHmetabolic dysfunction-associated steatohepatitisMASLDmetabolic dysfunction-associated steatotic liver diseasempMRImulti-parametric magnetic resonance imagingNASNAFLD activity scoreNASH-CRNNASH clinical research networkORodds ratioPDFFproton density fat-fractionROCreceiver operator characteristic curve.