Introduction & Objective: MASH is associated with metabolic syndrome; insulin resistance is a key driver of the disease. Advanced fibrosis (F3/F4) is the strongest predictor of major liver-related outcomes. We aimed to evaluate whether the level of fasting insulin (FI) predicts the histological severity of MASH.
Methods: Using the EMMINENCE trial (NCT02784444), we examined patients with liver histology and FI data. 393 patients with available data were divided into 3 groups according to the FI tertiles: lower, ≤ 15.11 mIU/L; middle, 15.16 - 24.23 mIU/L; upper ≥ 24.25 mIU/L. Logistic regressions were performed to predict histological severity.
Results: The upper tertile of FI was associated with a higher histological severity (fibrosis and hepatocyte ballooning, table). This was consistent with more severe patient characteristics such as higher liver enzymes, triglycerides, fibrosis biomarkers, HbA1c, and liver stiffness measurement (Table). The upper tertile was predictive of advanced fibrosis and ballooning in univariate analysis (p<0.0001). After adjustment on HbA1c level and diabetes status, the upper tertile remains highly predictive of advanced fibrosis (p=0.001).
Conclusions: FI predicts severity of ballooning and fibrosis, independent of HbA1c level and diabetes status. Further research is warranted to assess FI as a noninvasive test to monitor MASH.
S.A. Harrison: Other Relationship; Akero Therapeutics, Inc. Consultant; 89bio, Inc., Agilos Therapeutics. Other Relationship; Altimmune Inc. Advisory Panel; Arrowhead Pharmaceuticals, Inc. Consultant; Asteroid Therapeutics, Bluejay Therapeutics. Research Support; Bristol-Myers Squibb Company. Consultant; BOEHRINGER INGELHEIM PHARMA, INC, Boxer Capital. Advisory Panel; Chronwell Inc. Consultant; Corcept Therapeutics, ECCOGENE, INC, DEXCOM, INC. Advisory Panel; ECHOSENS NORTH AMERICA, INC. Consultant; Enyo Pharma. Other Relationship; GALECTIN THERAPEUTICS, INC. Consultant; GALECTO, INC, HEPAGENE THERAPEUTICS. Other Relationship; HEPION PHARMACEUTICALS, INC, Gilead Sciences, Inc. Consultant; GlaxoSmithKline plc. Other Relationship; Hepta Bio. Consultant; HISTOINDEX PTE. LTD. Advisory Panel; Humana. Other Relationship; Madrigal Pharmaceuticals, Inc., Intercept Pharmaceuticals, Inc. Advisory Panel; Inventiva Pharma. Other Relationship; Ionis Pharmaceuticals, Medpace. Stock/Shareholder; MGGM THERAPEUTICS LLC. Consultant; NEUROBO PHARMACEUTICALS INC. Other Relationship; NGM BIOPHARMACEUTICALS, INC, NORTHSEA THERAPEUTICS B.V., Novo Nordisk. Research Support; Pfizer Inc. Consultant; PIPER SANDLER & CO. Other Relationship; POXEL. Consultant; Regeneron Pharmaceuticals Inc. Other Relationship; Sagimet Biosciences, Sonic Incytes. Consultant; Takeda Canada. Other Relationship; Terns Pharmaceuticals. Consultant; TRAMONTANE THERAPEUTICS INC (Kriya). Other Relationship; Viking Therapeutics. Consultant; CALIMETRIX, LLC. J. Dubourg: Stock/Shareholder; Poxel SA. S. Jeannin: None. J.R. Colca: Stock/Shareholder; Cirius Therapeutics, Inc. V. Ratziu: None.
