S2863 Predictors of Incident Metabolic Associated Steatohepatitis: The All of Us Research Program

Introduction: Metabolic-Associated Steatohepatitis (MASH) is a progressive, underdiagnosed liver disease linked to metabolic dysfunction. Despite its growing burden, prospective predictors remain poorly understood. Methods: We analyzed data from 627,584 adults in the NIH All of Us Research Program (2018–present). After excluding those without EHR consent, with baseline MASH, or missing covariates, we evaluated associations between demographic, socioeconomic, and lifestyle factors and incident MASH. Our minimally adjusted model included age, sex, race, Hispanic ethnicity, household income, educational attainment, area deprivation index and smoking history. The fully adjusted model added cardio metabolic risk factors: hypertension, diabetes and body mass index. Results: Our final sample included 203,910 adults. Over a mean follow-up of 42 ± 23 months, 5,107 developed MASH. After adjusting for covariates, risk was higher in individuals aged 40–59 vs < 40 [adjusted Hazard Ratio (HR): 1.41, 95% CI: 1.30–1.53]; Asians [HR: 1.22, 1.04–1.42], Middle Eastern/North Africans [HR: 1.35, 1.00–1.83] vs Whites, Hispanics [HR: 1.51, 1.31–1.74] vs non-Hispanics; and among those with former HR [1.10, 1.03–1.18] and current cigarette use HR [1.11, 1.03–1.20], vs never use. Blacks had lower risk HR [0.46, 0.42–0.50] compared to Whites. Higher household income had an inverse dose-response association with incident MASH (2% lower risk per $10,000 higher income). No such associations were seen with educational attainment or area deprivation index. Conclusion: Demographic, socioeconomic, and lifestyle factors independently predict incident MASH. Targeted interventions should consider these risk profiles.