Abstract:To explore the effect of serum perfluoroalkyl substances (PFAS) on the metabolic-associated fatty liver disease (MAFLD) on the basis of the 2017~2018 US National Health and Nutrition Survey (NHANES) database. The logistic regression model and restricted cubic spline (RCS) were used to evaluate the association and dose-response relationship between PFAS and MAFLD. The main results showed that in a single pollutant model, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorodecanoic acid (PFDA) were negatively associated with the risk of MAFLD, with the ORs of 0.64 (95%CI:0.45~0.91), 0.65 (95%CI:0.46~0.93) and 0.45 (95%CI:0.30~0.67), respectively. In the multi-pollutant model, compared with the lowest quantile (Q1), the risk of MAFLD increased with the increase of perfluoronanoic acid (PFNA) by 62% (OR=1.62, 95%CI:1.10~2.39), 62% (OR=1.62, 95%CI:1.01~2.60) and 172% (OR=2.72, 95%CI: 1.53~4.84) at Q2, Q3, and Q4, respectively. Conversely, there was negative linear dose-response relationship (Poverall<0.001) between PFDA and the risk of MAFLD. The risk of MAFLD were 0.61(95%CI: 0.44~0.85), 0.54(95%CI: 0.34~0.84) and 0.26(95%CI: 0.15~0.45) when the concentration of PFDA reached to Q2, Q3, and Q4 levels. Subgroup analysis showed that serum PFDA had a more significant effect on the risk of MAFLD in 51~65 years old population. Females exposed to serum PFNA were more likely to develop MAFLD. In conclusion, serum PFNA and PFDA were significantly related to the risk of MAFLD, and PFNA exposure played a risky role in the occurrence of MAFLD while PFDA had protective effect. Women, middle-aged and elderly people might be potential susceptible groups.
Lindstrom A B, Strynar M J, Libelo E L. Polyfluorinated compounds: Past, present, and future [J]. Environmental Science & Technology, 2011,45(19):7954-61.
[2]
Kotthoff M, Müller J, Jürling H, et al. Perfluoroalkyl and polyfluoroalkyl substances in consumer products [J]. Environmental Science and Pollution Research, 2015,22(19):14546-59.
[3]
Worley R R, Moore S M, Tierney B C, et al. Per-and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community [J]. Environ. Int., 2017,106:135-43.
[4]
Pérez F, Nadal M, Navarro-Ortega A, et al. Accumulation of perfluoroalkyl substances in human tissues [J]. Environ. Int., 2013,59: 354-62.
[5]
Sunderland E M, Hu X C, Dassuncao C, et al. A review of the pathways of human exposure to poly-and perfluoroalkyl substances (PFASs) and present understanding of health effects [J]. J. Expo. Sci. Environ. Epidemiol., 2019,29(2):131-47.
[6]
Barry V, Winquist A, Steenland K. Perfluorooctanoic Acid (PFOA) exposures and incident cancers among adults living near a chemical plant [J]. Environmental Health Perspectives, 2013,121(11/12): 1313-1318.
[7]
Dzierlenga M W, Allen B C, Clewell H J, III, et al. Pharmacokinetic bias analysis of an association between clinical thyroid disease and two perfluoroalkyl substances [J]. Environ. Int., 2020,141:105784.
[8]
DeWitt J C, Peden-Adams M M, Keller J M, et al. Immunotoxicity of perfluorinated compounds: recent developments [J]. Toxicol. Pathol., 2012,40(2):300-311.
[9]
Christensen K Y, Raymond M, Meiman J. Perfluoroalkyl substances and metabolic syndrome [J]. International Journal of Hygiene and Environmental Health, 2019,222(1):147-153.
[10]
Attanasio R. Association between perfluoroalkyl acids and liver function: Data on sex differences in adolescents [J]. Data in Brief, 2019,27:104618.
[11]
Eslam M, Newsome P N, Sarin S K, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement [J]. Journal of Hepatology, 2020,73(1): 202-209.
[12]
Zheng K I, Fan J G, Shi J P, et al. From NAFLD to MAFLD: a "redefining" moment for fatty liver disease [J]. Chin. Med. J. (Engl), 2020,133(19):2271-2283.
[13]
Zheng K I, Sun D Q, Jin Y, et al. Clinical utility of the MAFLD definition [J]. J Hepatol, 2021,74(4):989-991.
[14]
Chan K E, Koh T J L, Tang A S P, et al. Global prevalence and clinical characteristics of metabolic-associated fatty liver disease: A meta-analysis and systematic review of 10 739 607individuals [J]. The Journal of Clinical Endocrinology & Metabolism, 2022,107(9):2691-2700.
[15]
Zhang Y-T, Zeeshan M, Su F, et al. Associations between both legacy and alternative per-and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8health project in China [J]. Environment International, 2022,158:106913.
[16]
Zeeshan M, Zhang Y-T, Yu S, et al. Exposure to isomers of per-and polyfluoroalkyl substances increases the risk of diabetes and impairs glucose-homeostasis in Chinese adults: Isomers of C8 health project [J]. Chemosphere, 2021,278:130486.
[17]
Han X, Meng L, Zhang G, et al. Exposure to novel and legacy per-and polyfluoroalkyl substances (PFASs) and associations with type 2diabetes: A case-control study in East China [J]. Environment International, 2021,156:106637.
[18]
Duan Y, Sun H, Yao Y, et al. Serum concentrations of per-/ polyfluoroalkyl substances and risk of type 2diabetes: A case-control study [J]. Science of the Total Environment, 2021,787:147476.
[19]
Yang Q, Guo X, Sun P, et al. Association of serum levels of perfluoroalkyl substances (PFASs) with the metabolic syndrome (MetS) in Chinese male adults: A cross-sectional study [J]. Science of the Total Environment, 2018,621:1542-1549.
[20]
Jeddi M Z, Dalla Zuanna T, Barbieri G, et al. Associations of perfluoroalkyl substances with prevalence of metabolic syndrome in highly exposed young adult community residents-A cross-sectional study in Veneto Region, Italy [J]. International Journal of Environmental Research and Public Health, 2021,18(3):1194.
[21]
Liu H-S, Wen L-L, Chu P-L, et al. Association among total serum isomers of perfluorinated chemicals, glucose homeostasis, lipid profiles, serum protein and metabolic syndrome in adults: NHANES, 2013~2014 [J]. Environmental Pollution, 2018,232:73-79.
[22]
Su T-C, Kuo C-C, Hwang J-J, et al. Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults [J]. Environment International, 2016,88:15-22.
[23]
Conway B, Innes K E, Long D. Perfluoroalkyl substances and beta cell deficient diabetes [J]. Journal of Diabetes and Its Complications, 2016,30(6):993-998.
[24]
Jain R B, Ducatman A. Selective associations of recent low concentrations of perfluoroalkyl substances with liver function biomarkers: NHANES 2011to 2014 data on US adults aged ³20years [J]. J Occup Environ Med, 2019,61(4):293-302.
[25]
Attanasio R. Sex differences in the association between perfluoroalkyl acids and liver function in US adolescents: Analyses of NHANES 2013~2016 [J]. Environmental Pollution, 2019,254(PtB):113061.
[26]
Chen Y-l, Li H, Li S, et al. Prevalence of and risk factors for metabolic associated fatty liver disease in an urban population in China: a cross-sectional comparative study [J]. BMC Gastroenterology, 2021,21(1):212.
[27]
Das K P, Wood C R, Lin M T, et al. Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis [J]. Toxicology, 2017,378:37-52.
[28]
Zhang L, Ren X M, Guo L H. Structure-based investigation on the interaction of perfluorinated compounds with human liver fatty acid binding protein [J]. Environ Sci Technol, 2013,47(19):11293-11301.
[29]
Foreman J E, Chang S-C, Ehresman D J, et al. Differential hepatic effects of perfluorobutyrate mediated by mouse and human PPAR-alpha [J]. Toxicological Sciences, 2009,110(1):204-211.
[30]
Eddowes P J, Sasso M, Allison M, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease [J]. Gastroenterology, 2019,156(6):1717-1730.
[31]
Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021 [J]. Diabetes Care, 2021,44(Suppl 1):S15-S33.
[32]
Guo B, Guo Y, Nima Q, et al. Exposure to air pollution is associated with an increased risk of metabolic dysfunction-associated fatty liver disease [J]. Journal of Hepatology, 2022,76(3):518-525.
[33]
Gleason J A, Post G B, Fagliano J A. Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007~2010 [J]. Environmental Research, 2015,136:8-14.
[34]
John, Bassler, Alan, et al. Environmental perfluoroalkyl acid exposures are associated with liver disease characterized by apoptosis and altered serum adipocytokines [J]. Environmental pollution (Barking, Essex: 1987), 2019:247:1055-1063.
[35]
Lin T-W, Chen M-K, Lin C-C, et al. Association between exposure to perfluoroalkyl substances and metabolic syndrome and related outcomes among older residents living near a Science Park in Taiwan [J]. International Journal of Hygiene and Environmental Health, 2020,230:113607.
[36]
Spratlen M J, Perera F P, Lederman S A, et al. The association between perfluoroalkyl substances and lipids in cord blood [J]. Journal of Clinical Endocrinology & Metabolism, 2020,105(1):43-54.
[37]
Jain R B, Ducatman A. Roles of gender and obesity in defining correlations between perfluoroalkyl substances and lipid/lipoproteins [J]. Science of the Total Environment, 2019,653:74-81.
[38]
Christensen K Y, Raymond M, Meiman J. Perfluoroalkyl substances and metabolic syndrome [J]. Int. J. Hyg. Environ. Health, 2019,222(1): 147-153.
[39]
Kim C H, Younossi Z M. Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome [J]. Cleve Clin J Med, 2008, 75(10):721-728.
[40]
Lau C, Anitole K, Hodes C, et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings [J]. Toxicol. Sci., 2007,99(2): 366-394.
[41]
Wan H T, Zhao Y G, Wei X, et al. PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport [J]. Biochim. Biophys. Acta, 2012,1820(7):1092-101.
[42]
Khansari M R, Yousefsani B S, Kobarfard F, et al. In vitro toxicity of perfluorooctane sulfonate on rat liver hepatocytes: probability of distructive binding to CYP 2E1and involvement of cellular proteolysis [J]. Environ. Sci. Pollut. Res. Int., 2017,24(29):23382-8.
[43]
Feige J N, Gelman L, Michalik L, et al. From molecular action to physiological outputs: Peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions [J]. Progress in Lipid Research, 2006,45(2):120-59.
[44]
Luo M, Tan Z, Dai M, et al. Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity [J]. Archive für Toxikologie, 2016,91(2):1-11.
[45]
Sen P, Qadri S, Luukkonen P K, et al. Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease [J]. Journal of Hepatology, 2022, 76(2):283-293.
[46]
Harada K, Inoue K, Morikawa A, et al. Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion [J]. Environ. Res., 2005,99(2):253-261.