Severity of MASH Activity by Iron-Corrected MRI Predicts Insulin Resistance and Cardiometabolic Risk in Type 2 Diabetes.

Abstract

Multiparametric magnetic resonance iron-corrected T1 mapping (cT1) may help identification and risk-stratification of steatohepatitis (MASH). In type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) frequently advances to steatohepatitis with significant fibrosis and increased risk of developing cirrhosis. cT1 allows MASH risk-stratification by measuring liver disease activity (fibro-inflammation) but its association with cardiometabolic risk factors that drive liver disease progression in T2D (insulin resistance, lipotoxicity, metabolic syndrome) remains unclear. We recruited 109 participants with T2D from primary care settings who were classified into four groups according to cT1 and liver fat content (LFC) (LiverMultiScan): a) without steatosis; b) steatosis only without MASH; c) mild-moderate MASH (cT1 ≥800 to ≤875 ms); and d) severe MASH (cT1 >875 ms). We also measured insulin resistance (HOMA-IR), adipose tissue dysfunction (Adipo-IR, plasma adiponectin), and several non-invasive tests of MASH necroinflammation or fibrosis severity (NIS2+®, CK-18, FAST, MRE). Higher MASH disease activity (cT1) was associated with more severe features of the metabolic syndrome as well as increased insulin resistance (HOMA-IR) and adipose tissue dysfunction (higher Adipo-IR and decreased adiponectin levels; all p<0.01). Elevated cT1 correlated with worse hepatic necroinflammation (FAST, NIS2+® and CK-18) and more severe steatosis and fibrosis (all p<0.001). In people with T2D, worse MASH disease activity (measured by cT1) is associated with unfavorable cardiometabolic risk factors that are known to drive liver disease progression. Use of cT1 in this population may help early identification of at-risk individuals who would benefit from earlier aggressive intervention in primary care.