Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with “at-risk” MASH (steatohepatitis with significant fibrosis stage ≥F2) and cirrhosis. Magnetic resonance (MR) iron-corrected T1 mapping (cT1) allows for improved MASH risk stratification, but whether it may help define their metabolic profile needs further validation.Methods: We measured AST, ALT, HbA1c, insulin, FFA, liver MR-PDFF and cT1 in 100 participants, classified based upon presence of liver steatosis (MR-PDFF >5%) and liver disease (MASH) activity by cT1 into 4 groups: a) non-obese controls (C; n=8); b) no-MASLD with T2D or obesity (n=19); both groups without steatosis; c) mild-moderate MASH (mMASH; cT1 >800-875 ms; n=13) and severe MASH (sMASH; cT1 >875 ms; n=50).Results: Mean age was 56±1 and 80% had T2D. The severity of MASH was associated with higher ALT, AST, worse steatosis (mMASH: 11±1% vs. sMASH: 20±1%; p <0.001) and fibrosis (mMASH: 2.2±0.1 vs. sMASH: 2.9 ±0.1 kPa; p <0.001). More active MASH (cT1) correlated with degree of steatosis (r=0.78; p<0.001) and fibrosis (r=0.24, p<0.01). CK-18 (hepatocyte apoptosis and fibrosis marker) increased with MASH severity (mMASH: 143±25 vs. sMASH: 360±34 U/L; p<0.01). Insulin resistance (IR) by HOMA-IR worsened with disease progression (no-MASLD: 2.8±0.5, mMASH: 4.8±1.0 vs. sMASH: 6.7±0.7; p<0.01), as well as adipose tissue dysfunction based on lower adiponectin (C: 10.4±2.2, no-MASLD: 5.7±1.0, mMASH: 4.5±0.7, sMASH: 4.2±0.4 µg/mL; p<0.01) and adipose tissue-IR (2.6±0.9, 4.0±0.8, 7.3±1.9, 7.9±0.6; respectively, p=0.01). Worse cT1 was associated with higher BMI and TG; as well as lower HDL-C (all p<0.001).Conclusion: Worse steatohepatitis by cT1 is associated with IR, BMI and atherogenic dyslipidemia. Measurement of cT1 in clinical practice may define a subset of people with “at-risk” MASH and an unfavorable metabolic profile in need of more aggressive management.
A. Ortiz Rocha: None. S. Kalavalapalli: None. E. Godinez Leiva: None. D. Barb: Other Relationship; Inventiva Pharma, Boehringer-Ingelheim. S.A. Marangi: None. N. Cuervo-Pardo: None. H.B. Thomaides-Brears: Employee; Perspectum Ltd. Stock/Shareholder; Perspectum Ltd. J.T. Rosenberg: None. P.Y. Broqua: None. M.P. Cooreman: Employee; Inventiva Pharma. R. Lomonaco: None. E. Valdez Saenz: None. A. Sharma: None. K. Cusi: Research Support; Boehringer-Ingelheim, Echosens, Inventiva, Perspectum Ltd, LabCorp. Consultant; Arrowhead Pharmaceuticals, Inc, AstraZeneca, TERNS Pharmaceuticals, 89bio, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sagimet Biosciences.
NIH/NIDDK (R01DK120331)
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