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

James M Paik1, Markos Kalligeros2, Shira Zelber-Sagi3

  • 1The Global NASH/MASH Council, Washington, DC, USA; The Global Center for Liver Outcomes & Policy Research, Georgetown University School of Medicine, Washington, DC, USA.

JHEP Reports : Innovation in Hepatology
|May 7, 2026
PubMed
Summary

Food systems impact liver disease risk differently by country development. Ultra-processed foods and caloric surplus drive Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in lower-income nations, while type 2 diabetes is key in higher-income ones.

Keywords:
Cardiometabolic risk factorsCross-national epidemiologyDietary transitionFood retail environmentHepatic steatosisLiver-related mortality surveillanceNational developmentPath analysis

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Area of Science:

  • Global health
  • Epidemiology
  • Nutritional science

Background:

  • National food systems significantly influence metabolic risk, but pathways to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) vary by development level.
  • Understanding these development-specific pathways is crucial for addressing global liver disease burden.

Purpose of the Study:

  • To examine the food-system pathways associated with MASLD prevalence and liver-related mortality across 204 countries.
  • To identify how these pathways differ based on national development levels, stratified by the Sociodemographic Index (SDI).

Main Methods:

  • A cross-national ecological study utilizing harmonized data from Global Burden of Disease, NCD Risk Factor Collaboration, and FAOSTAT.
  • Structural equation models were employed to analyze associations between food system characteristics, metabolic mediators, and liver outcomes, stratified by low (<0.60) and high (≥0.60) SDI.
  • Data spanned various periods, with exposures anchored to 2005-2011, mediators to 2013-2015, MASLD prevalence to 2019-2021, and mortality to 2023.

Main Results:

  • In low-SDI countries, urbanization linked to ultra-processed food exposure, which correlated with obesity. Caloric surplus was associated with higher MASLD prevalence.
  • In high-SDI countries, ultra-processed food exposure related to higher sugar intake, and type 2 diabetes (T2D) emerged as the dominant correlate of MASLD.
  • Healthcare Access and Quality index positively associated with MASLD prevalence but inversely with MASLD mortality in high-SDI countries.

Conclusions:

  • Structural pathways to MASLD are development-dependent, with ultra-processed food and caloric surplus being key in low-SDI settings, and T2D in high-SDI settings.
  • Findings highlight the need for development-specific interventions targeting food systems and metabolic risk factors to reduce liver disease.
  • Tailored strategies, such as moderating ultra-processed food retail in low-SDI countries and prioritizing T2D management in high-SDI countries, are recommended.