Hwang Se-Hyun, Choi Yun-Hee, Huh Da-An, Kim Lita, Park Kangyeon, Lee Jiyoun, Choi Hyeon Jeong, Lim Woohyun, Moon Kyong Whan
Department of Environmental Science, Baylor University, Waco, TX, USA.
Research Institute for Inflammation, Korea University College of Medicine, Seoul, 02841, Republic of Korea; School of Health and Environmental Science, Korea University, Seoul, 02841, Republic of Korea; Department of Safety and Health, Wonkwang University, Iksan, 54538, Republic of Korea.
Environ Pollut. 2025 May 1;372:126085. doi: 10.1016/j.envpol.2025.126085. Epub 2025 Mar 18.
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.
全氟和多氟烷基物质（PFAS）已被报道具有肝毒性作用；然而，它们对非酒精性脂肪性肝病（NAFLD）的影响仍不清楚。本研究旨在调查韩国成年人中PFAS暴露与NAFLD之间的关联，从而有助于推广PFAS的肝毒性作用。利用2018 - 2020年韩国国家环境卫生调查（KoNEHS）的数据，我们分析了2635名韩国成年人。基于五种PFAS的血清浓度估计PFAS暴露水平。使用两个与脂肪变性相关的指标（肝脂肪变性指数[HSI]和脂肪肝指数[FLI]）以及两个与纤维化相关的指标（纤维化-4指数[FIB-4]和天冬氨酸转氨酶与血小板比值指数[APRI]）评估NAFLD。模型将这些指标作为连续变量和二分变量纳入，后者基于先前研究的诊断标准。使用多元线性回归和稳健泊松回归模型检查与PFAS暴露的关联。在PFAS暴露与四个连续指标中的三个（不包括FLI）以及使用这些指标诊断的NAFLD患病率之间观察到正相关。具体而言，HSI仅与全氟壬酸有显著关联，而与纤维化相关的指标（FIB-4和APRI）与所有五种个体PFAS均有显著关联。按性别和肥胖状况分层时，女性和非肥胖组的关联更强。评估PFAS混合物健康影响的贝叶斯核机器回归分析结果表明PFAS混合物与NAFLD之间存在关联，特别是与纤维化相关的指标。此外，与NAFLD指标的显著关联大多在女性和非肥胖组中观察到，支持了个体PFAS暴露分析的结果。我们的研究结果表明PFAS与NAFLD相关，特别是对于纤维化。考虑到韩国人群中血清PFAS浓度较高，有必要进行持续监测和前瞻性队列研究。
