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

Abstract

ABSTRACTBackground & AimsIron 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.MethodsA 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.ResultsSignificant decreases in cT1 were observed in responders for all the histological criteria. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. The optimal reduction in cT1 for separating responders from non-responders for MASH resolution was −74ms (64ms-73ms for the other criteria), in close agreement with the previously predefined threshold of −80ms. Those achieving an ≥ 80 ms reduction in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3.ConclusionsThese results demonstrate that a reduction in cT1 of 80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.