Association and Mechanism of Coexposure to Perfluoroalkyl and Polyfluoroalkyl Substances and Blood Heavy Metals in Metabolic Dysfunction-Associated Steatotic Liver Disease

INTRODUCTION: Heavy metals can increase perfluoroalkyl and polyfluoroalkyl substances (PFAS) adsorption. However, no research has examined the relationship of coexposure to PFAS and heavy metals in metabolic dysfunction-associated steatotic liver disease (MAFLD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey database (2017–2018 cycle). The influence of PFAS and heavy metals on MAFLD or controlled attenuation parameter (CAP) was analyzed using logistic or linear regression, weighted quantile sum regression, and Bayesian kernel machine regression. A network of gene-gene interactions for the overlapping genes related to PFAS, heavy metals, and MAFLD was generated by GeneMANIA. The biological function of the overlapping genes was explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. RESULTS: The study analyzed 1,270 participants, with 36.378% of participants suffering from MAFLD. Perfluoromethylheptane sulfonic acid isomers (Sm-PFOS), Cd, and Se were identified as MAFLD risk factors (all P < 0.05). Positive associations were observed between perfluorononanoic acid, n-perfluorooctane sulfonic acid, Sm-PFOS, selenium, manganese, and CAP (all P < 0.05). Se, Pb, Sm-PFOS, and Mn played a significant role in the combined effect on both MAFLD and CAP. Bayesian kernel machine regression revealed a positive relationship of coexposure to PFAS and heavy metals on MAFLD or CAP. The top gene interaction type of 51 overlapping genes was coexpression (59.55%). Kyoto Encyclopedia of Genes and Genome results involved environmental information processing, human diseases, metabolism, and organismal systems. DISCUSSION: Perfluorononanoic acid, Sm-PFOS, Pb, Se, Mn, and Cd were associated with MAFLD or CAP. Reducing exposure to PFAS and heavy metals may help prevent MAFLD development or CAP increase.