Per- and polyfluoroalkyl substances exposures are associated with non-alcoholic fatty liver disease, particularly fibrosis

Abstract

Per- and polyfluoroalkyl substances (PFAS) have been reported to exert hepatotoxic effects; however, their impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to investigate the association between PFAS exposure and NAFLD in Korean adults, thereby contributing to the generalization of PFAS's hepatotoxic effects. Using data from the 2018–2020 Korean National Environmental Health Survey (KoNEHS), we analyzed 2635 Korean adults. PFAS exposure levels were estimated based on the serum concentrations of five PFAS. NAFLD was assessed using two steatosis-related indices (hepatic steatosis index [HSI] and fatty liver index [FLI]) and two fibrosis-related indices (fibrosis-4 index [FIB-4] and aspartate aminotransferase to platelet ratio index [APRI]). The models included these indices as continuous and dichotomous variables, the latter based on diagnostic criteria from previous studies. Associations with PFAS exposure were examined using multiple linear regression and robust Poisson regression models. Positive associations were observed between PFAS exposure and three of the four continuous indices, excluding the FLI, as well as the prevalence of NAFLD diagnosed using these indices. Specifically, the HSI showed a significant association only with perfluorononanoic acid, whereas fibrosis-related indices (FIB-4 and APRI) were significantly associated with all five individual PFAS. The associations were stronger in female and non-obese groups when stratified by sex and obesity status. The results of the Bayesian kernel machine regression analysis evaluating the health effects of PFAS mixtures indicated an association between PFAS mixtures and NAFLD, particularly fibrosis-related indices. Additionally, significant associations with NAFLD indices were mostly observed in females and non-obese groups, supporting the findings from the individual PFAS exposure analyses. Our findings suggest that PFAS are associated with NAFLD, particularly for fibrosis. Considering the high serum PFAS concentrations in the Korean population, continuous monitoring and prospective cohort studies are warranted.