Global burden of nonalcoholic fatty liver disease from 1990 to 2046: A global population-based observational trend analysis using GBD 2021 data.

Nonalcoholic fatty liver disease (NAFLD; now often termed metabolic dysfunction-associated steatotic liver disease), driven by obesity and lifestyle changes, affects approximately 25% of the world's population and imposes growing public-health, economic, and healthcare burdens with widening disparities. We analyzed incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for NAFLD using data from the Global Burden of Disease 2021 study across 5 socio-demographic index (SDI) quintiles, 21 Global Burden of Disease regions, and 204 countries and territories. We quantified temporal trends (1990-2021), geographic patterns, and SDI correlations; performed age-period-cohort modeling, decomposition and health-inequality analyses; and generated projections to 2046, including frontier analyses. From 1990 to 2021, the global NAFLD burden increased substantially. Incidence increased 1.95-fold over this period, corresponding to an absolute rise of ~23.5 million cases (≈23,497,114), driven chiefly by population growth (~74%) and epidemiologic change (~34%), with additional contributions from population aging. Prevalence, mortality, and DALYs also rose worldwide, with the heaviest burdens observed in intermediate-SDI countries and high-burden regions in North Africa, the Middle East, and Latin America. Inequality analyses indicated widening disparities for prevalence, mortality, and DALYs. Projections suggest continued growth through 2046, with persistent sex differences in prevalence. NAFLD remains a pervasive global health challenge marked by pronounced geographic and sociodemographic disparities. Targeted prevention and intervention strategies are needed, particularly for intermediate-SDI settings and identified high-burden regions.