High Prevalence of Metabolic Dysfunction-Associated Steatohepatitis With Significant Fibrosis in Primary Care and Endocrinology Clinics.

AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis. NIS2+ is a recently approved serum-based test combining two biomarkers (miR-34a-5p and YKL-40) to identify at-risk MASH (i.e., MASH and significant fibrosis). OBJECTIVE: To assess the prevalence of at-risk MASH by NIS2+ in individuals from primary care or endocrinology clinics. MATERIALS AND METHODS: 798 participants recruited from outpatient clinics were risk-stratified by NIS2+ into low-risk, intermediate-risk or having at-risk MASH (NIS2+ score < 0.46, ≥ 0.46 and < 0.68 or ≥ 0.68, respectively). Presence of steatosis (CAP ≥ 288 dB/m) and clinically significant liver fibrosis (VCTE- ≥ 8.0 kPa) was established by transient elastography (FibroScan). RESULTS: At-risk MASH affected 29% of individuals with both obesity and T2D compared to 3% of those without either condition (p < 0.001). People with at-risk MASH, compared to those at low-risk, more often had steatosis (81% vs. 40%), clinically significant fibrosis (42% vs. 5%), AST or ALT ≥ 40 IU/L, hepatic insulin resistance (by HOMA-IR) and adipose tissue insulin resistance (by adipo-IR) (all p < 0.001). NIS2+ strongly correlated with diagnosis of at-risk MASH by FAST (r = 0.67; p < 0.001), as well as CK-18, ALT and AST and liver fibrosis by VCTE-LSM (all p < 0.001). CONCLUSION: The prevalence of at-risk MASH is high in individuals with obesity and T2D attending outpatient primary care and endocrinology clinics. Their progression to cirrhosis may be prevented with early risk-stratification and timely intervention.