Association of exposure to phenols, pesticides, and phthalates with hepatic steatosis and MASLD in adolescents: the potential role of inflammation and lifestyle factors

Aim: Limited evidence exists on the effects of endocrine-disrupting chemical exposure on metabolic dysfunction-associated steatotic liver disease (MASLD) in adolescents. We aimed to assess the effects of multiple chemicals on the hepatic steatosis index (HSI) and MASLD in adolescents, and to further explore the potential roles of inflammation and lifestyle factors. Methods: Associations between chemical exposures and HSI/MASLD were examined using generalized linear models, restricted cubic spline analysis, weighted quantile sum regression, and Bayesian kernel machine regression. Mediation analysis was conducted to evaluate whether inflammation mediated these relationships. Results: Among 2,163 adolescents (median age 15 years), 490 (22.7%) were diagnosed with MASLD. Bisphenol A, mono-ethyl phthalate, mono-(carboxyoctyl) phthalate, and mono-benzyl phthalate (MBzP) were significantly associated with HSI or MASLD. Both weighted quantile sum and Bayesian kernel machine regression consistently indicated a positive correlation between chemical mixtures and MASLD, with MBzP and bisphenol A identified as key contributors. Mediation analysis showed that white blood cells partially mediated the associations of MBzP with HSI and MASLD, and of mono-(carboxynonyl) phthalate with MASLD. Sedentary behavior and physical activity further modulated the combined effects of chemical mixtures on MASLD. Conclusion: Exposure to phenols, pesticides, and phthalates was significantly associated with HSI or MASLD, with white blood cells acting as a mediator. Reducing sedentary behavior and increasing physical activity may mitigate the adverse impacts of chemical mixtures on MASLD.