Exposure to Endocrine-disrupting Chemicals, Iron Metabolism, and Risk of Metabolic Dysfunction-associated Steatotic Liver Disease: A Nationwide Cross-sectional Study in China.

Abstract

Objective: This study aimed to investigate the association between exposure to mixtures of environmental endocrine-disrupting chemicals (EDCs) and metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential mediating role of iron metabolism.

Methods: A total of 6,989 adults from the China Health and Nutrition Survey (2015 cycle) were included. The serum concentrations of 22 EDCs were measured. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were used to evaluate the association between EDC exposure and risk of MASLD. Mediation analyses were performed to assess the mediating role of serum ferritin (SF).

Results: Eight EDCs were positively associated with MASLD. The WQS regression model identified six major contributors, including β-hexachlorocyclohexane, p,p'-DDT, monoethyl phthalate, acenaphthene, perfluorooctanoic acid, and perfluoro-n-pentanoic acid, in mixture effects. The BKMR model demonstrated that higher levels of EDC mixture were associated with an increased risk of MASLD. Subgroup analyses suggested stronger correlations in males and in individuals aged < 65 years. SF was estimated to mediate 11.2%-32.1% of the association between key EDCs and MASLD.

Conclusion: Exposure to EDC mixtures was associated with an increased risk of MASLD, with iron metabolism playing a notable mediating role. Reducing the exposure to key EDCs may help alleviate the burden of MASLD.