Decreases in liver cT1 accurately reflect histological improvement induced by therapies in MASH: a multi-centre pooled cohort analysis

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 I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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' I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript * AUC : area under the curve AUROC : area under the operator characteristic curve cT1 : iron-corrected T1-mapping FDA : food and drug administration IQR : interquartile range MASH : metabolic dysfunction-associated steatohepatitis MASLD : metabolic dysfunction-associated steatotic liver disease mpMRI : multi-parametric magnetic resonance imaging NAS : NAFLD activity score NASH-CRN : NASH clinical research network OR : odds ratio PDFF : proton density fat-fraction ROC : receiver operator characteristic curve.