Independent Associations of Food Insecurity and Neighborhood Deprivation: Independent Associations with Incident Metabolic Dysfunction-Associated Steatotic Liver Disease in a Diverse U.S. Cohort.

Background/Objectives: Social determinants of health are implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), yet longitudinal evidence on incident disease is scarce, and whether individual- and community-level determinants act independently remains unclear. The objective of this study was to examine whether individual food insecurity and neighborhood deprivation are independently associated with incident MASLD. Methods: In this retrospective cohort of 40,693 U.S. adults without baseline MASLD in the diverse NIH All of Us Research Program, food insecurity (two-item Hunger Vital Sign) and neighborhood deprivation (validated five-domain composite) were co-primary exposures, with incident MASLD ascertained from validated diagnostic codes. Proportional hazards models were adjusted for demographic, socioeconomic, and metabolic factors, including obesity. Results: Over 116,220 person-years, 1240 (3.0%) participants developed MASLD. Both associations remained significant after adjustment for demographic, socioeconomic, and major metabolic risk factors, including obesity (food insecurity adjusted hazard ratio [aHR] 1.32, 95% CI 1.13-1.53; neighborhood deprivation aHR 1.20, 95% CI 1.05-1.37). Unadjusted cumulative incidence was highest among participants with both exposures and lowest among those with neither. Findings were consistent across sensitivity analyses; the food-insecurity association remained when neighborhood disadvantage was specified with a census-based index. Conclusions: Food insecurity and neighborhood deprivation were independently associated with higher incidence of MASLD. Nutrition-focused, equity-oriented interventions warrant evaluation to reduce MASLD burden and advance health equity.