Introduction and Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis. NIS2+™is a novel blood-based diagnostic test developed to identify “at-risk” MASH (steatohepatitis with significant fibrosis stage ≥F2) that combines miR-34a-5p (microRNA linked to altered lipid metabolism) and YKL-40 (biomarker of fibrosis). Our aim was to assess the prevalence of “at-risk” MASH by NIS2+™ in unselected people from primary care or endocrine outpatient university clinics.Methods: We recruited 687 participants and assessed for “at-risk” MASH by NIS2+™ (defined as NIS2+™ ≥0.68). We measured by transient elastography (Fibroscan®) steatosis (CAP≥274 dB/m) and fibrosis (Liver Stiffness Measurement [VCTE-LSM]≥7.0 kPa). A subset underwent magnetic resonance (MR) iron-corrected T1 mapping for MASH disease activity (cT1) and MR-elastography (MRE) for fibrosis (n=51).Results: Overall, 44% had T2D (28% with obesity); 25% obesity alone, without T2D; and 31% neither. “At-risk” MASH by NIS2+™ was observed in up to 20% individuals with obesity and T2D, 13% with obesity only and 3% in those without obesity or T2DM (all p<0.001 vs. obesity and/or T2D). People with “at-risk” MASH vs. low-risk MASH by NIS2+™ had more often steatosis (80% vs 46%), fibrosis (30% vs 5%), AST≥40 IU/L (39% vs. 1%), ALT≥40 IU/L (46% vs. 4%), hepatic IR (HOMA-IR≥3.0: 66% vs. 32%) and adipose tissue IR (adipo-IR≥2.0: 80% vs 62%) (all p<0.01). NIS2+™ correlated with CK-18, a marker of hepatocyte apoptosis (r=0.49, p<0.001), with cT1 (r=0.44, p=0.002) and liver fibrosis by VCTE-LSM (r=0.29, p<0.001) or MRE (r=0.28, p=0.049).Conclusion: “At-risk” MASH with severe steatohepatitis and significant fibrosis (stage ≥F2) is common in unselected patients with obesity and/or T2D (~20%) in outpatient primary care and endocrinology clinics. More awareness and early risk-stratification will help identify people in need of early intervention and intensive multidisciplinary care.
S. Kalavalapalli: None. E. Godinez Leiva: None. A. Ortiz Rocha: None. N. Cuervo-Pardo: None. K.Y. Chun: Employee; LabCorp. T.R. Prezant: None. M.A. Connelly: Employee; LabCorp. Stock/Shareholder; LabCorp. A. Sharma: None. D. Barb: Other Relationship; Inventiva Pharma, Boehringer-Ingelheim. 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); PI: Kenneth Cusi.
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