1349-P: People with Type 2 Diabetes Have a High Prevalence of Nonalcoholic Steatohepatitis with Significant Fibrosis When Screened by NIS4 or Elastography

Abstract

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Diagnosis remains challenging as a liver biopsy is usually not feasible. NIS4 is a novel plasma diagnostic test combining the measurement of A1c and 3 biomarkers (miR-34a-5p, A2M, YKL-40) linked to NASH disease activity and higher cirrhosis risk. The aim of this study was to assess the prevalence of high-risk NASH (NASH with significant fibrosis [≥F2]) as estimated by NIS4 or elastography in the outpatient setting. A total 400 participants (age: 55±11 years; BMI: 31.6±6.6 kg/m2; T2DM: 32%; obese without T2DM [OB]: 33%), unaware of having NAFLD, were recruited from PCP and endocrine clinics and screened by: a) Elastography (Fibroscan®) for steatosis (controlled attenuation parameter or CAP ≥274 dB/m) and for fibrosis (liver stiffness measurement or LSM ≥7.0 kPa); and b) NIS4 for high-risk NASH (defined as a NIS4 >0.63; low-risk: <0.36). Among patients with T2DM or OB, 68% had steatosis compared to 35% without obesity or T2DM (CON) (p<0.01), while fibrosis (LSM≥7.0 kPa) was present in 14% of patients with T2DM (CON = 1%; p=0.02). High-risk NASH by NIS4 occurred frequently among patients with T2DM, either with (30%) or without (26%) obesity, and rare in those without T2DM (3%; p<0.001). NIS-4 correlated with steatosis (CAP) (r = 0.35) and fibrosis (LSM) (r = 0.32; both p<0.001). Patients with high-risk NASH by NIS4 compared to those with low-risk NASH, more often had steatosis (82% vs 46%), fibrosis (16% vs 4%), AST≥30 IU/L (41% vs. 8%) and ALT≥30 IU/L (36% vs. 15%), hepatic (HOMA-IR: 68% vs. 25%) and adipose tissue (adipo-IR: 80% vs 56%) insulin resistance (all p<0.01). NIS4 correlated with having metabolic syndrome (r=0.41; p<0.01) and was more often increased in people from endocrine vs. PCP clinics (34% vs. 9%; p<0.05). Conclusion: NASH with significant fibrosis is common in T2DM. Patients with elevated NIS4 often have NAFLD with fibrosis and an unfavorable cardiometabolic profile. Disclosure S.Kalavalapalli: None. T.R.Prezant: None. M.A.Connelly: Employee; LabCorp, Stock/Shareholder; LabCorp. D.Barb: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. E.Valdez saenz: None. A.Ortiz rocha: None. J.T.Budd: None. Y.Mohseni: None. K.Y.Chun: None. Funding National Institutes of Health (R01120331-01A1)