Global structural determinants of MASLD: Development-stratified pathways linking food systems, metabolic risk, and...

Structural features of national food systems shape metabolic risk, yet their pathways to metabolic dysfunction-associated steatotic liver disease (MASLD) across development levels remain poorly characterized. We examined food-system pathways to MASLD prevalence and liver-related mortality across 204 countries.

A cross-national ecological study harmonized data from the Global Burden of Disease study, NCD Risk Factor Collaboration, and FAOSTAT. Exposures were anchored to 2005-2011, metabolic mediators to 2013-2015, MASLD prevalence to 2019-2021, and liver mortality to 2023. Countries were stratified by Socio-Demographic Index (SDI; low <0.60 vs. high ≥0.60). Structural equation models estimated direct and indirect path associations among food-system characteristics, metabolic mediators, and liver outcomes.

In low-SDI countries (n = 101), urbanization was associated with higher ultra-processed food retail exposure (β = +0.41), which was associated with higher obesity prevalence (β = +0.17). Food price burden was inversely associated with caloric surplus (β = -0.44). Caloric surplus was associated with MASLD prevalence (β = +0.46). Political stability was inversely associated with MASLD prevalence (β = -0.31). In high-SDI countries (n = 103), ultra-processed food exposure was associated with higher sugar kilocalorie share (β = +0.35), which was associated with higher obesity (β = +0.54). Cereal kilocalorie share was independently associated with higher type 2 diabetes (T2D) prevalence (β = +0.17). T2D was the dominant structural correlate of MASLD (β = +0.80). Healthcare Access and Quality index was positively associated with MASLD prevalence (β = +0.28) and inversely associated with MASLD mortality (β = -0.33). Healthcare quality was inversely associated with hepatitis B and hepatitis C mortality in both strata, but not alcohol-related liver disease mortality.

Structural pathways to MASLD differ by development level: ultra-processed food exposure and caloric surplus dominate in low-SDI settings, whereas T2D dominates in high-SDI settings. These findings identify development-specific intervention targets for reducing liver disease burden.

Food-system structural characteristics including ultra-processed food retail exposure, dietary composition, and food price burden are differentially associated with MASLD prevalence through development-stratified pathways, providing a cross-national structural framework that extends beyond individual metabolic risk factors. These findings are relevant to global health researchers, epidemiologists, and policymakers working to understand and reduce rising liver disease burden in diverse economic settings. In low-SDI countries, efforts to monitor and moderate ultra-processed food retail expansion may warrant priority alongside caloric sufficiency programs; in high-SDI countries, structural findings reinforce the centrality of type 2 diabetes detection and management as a liver disease prevention strategy. Because this study is ecological and cross-sectional in design, associations reflect country-level structural patterns and should not be interpreted as individual-level causal effects; prospective and interventional research is needed to evaluate whether modifying these structural antecedents translates to reductions in MASLD burden.