{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:50:10Z","timestamp":1777081810561,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["RISE-2401878"],"award-info":[{"award-number":["RISE-2401878"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education on liver function among the U.S. population, utilizing data from the 2017\u20132018 National Health and Nutrition Examination Survey (NHANES). Methods: PFAS concentrations in blood samples were analyzed using online solid-phase extraction combined with liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS), a highly sensitive and specific method for detecting levels of PFAS. Liver function was evaluated using biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin, and the fatty liver index (FLI). Descriptive statistics and multivariable linear regression analyses were employed to assess the associations between exposures and liver outcomes. Bayesian Kernel Machine Regression (BKMR) was utilized to explore the nonlinear and interactive effects of these exposures. To determine the relative influence of each factor on liver health, Posterior Inclusion Probabilities (PIPs) were calculated. Results: Linear regression analyses indicated that income and education were inversely associated with several liver injury biomarkers, while alcohol use and smoking demonstrated stronger and more consistent associations. Bayesian Kernel Machine Regression (BKMR) further highlighted alcohol and smoking as the most influential predictors, particularly for GGT and total bilirubin, with posterior inclusion probabilities (PIPs) close to 1.0. In contrast, PFAS showed weaker associations. Regression coefficients were small and largely non-significant, and PIPs were comparatively lower across most liver outcomes. Notably, education had a higher PIP for ALT and GGT than PFAS, suggesting a more protective role in liver health. People with higher education levels tend to live healthier lifestyles, have better access to healthcare, and are generally more aware of health risks. These factors can all help reduce the risk of liver problems. Overall mixture effects demonstrated nonlinear trends, including U-shaped relationships for ALT and GGT, and inverse associations for AST, FLI, and ALP. Conclusion: These findings underscore the importance of considering both environmental and social\u2013behavioral determinants in liver health. While PFAS exposures remain a long-term concern, modifiable lifestyle and structural factors, particularly alcohol, smoking, income, and education, exert more immediate and pronounced effects on hepatic biomarkers in the general population.<\/jats:p>","DOI":"10.3390\/medsci13030099","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:50:03Z","timestamp":1753714203000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combined Effects of PFAS, Social, and Behavioral Factors on Liver Health"],"prefix":"10.3390","volume":"13","author":[{"given":"Akua","family":"Marfo","sequence":"first","affiliation":[{"name":"Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA"},{"name":"Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3195-706X","authenticated-orcid":false,"given":"Emmanuel","family":"Obeng-Gyasi","sequence":"additional","affiliation":[{"name":"Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA"},{"name":"Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/ieam.258","article-title":"Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins","volume":"7","author":"Buck","year":"2011","journal-title":"Integr. Environ. Assess. Manag."},{"key":"ref_2","unstructured":"National Institute of Health (2024, November 15). Study Links Synthetic Chemicals to Liver Damage, Available online: https:\/\/www.nih.gov\/news-events\/nih-research-matters\/study-links-synthetic-chemicals-liver-damage."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/ajim.23362","article-title":"Historical and current usage of per-and polyfluoroalkyl substances (PFAS): A literature review","volume":"66","author":"Gaines","year":"2023","journal-title":"Am. J. Ind. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127340","DOI":"10.1016\/j.chemosphere.2020.127340","article-title":"What are the effects of PFAS exposure at environmentally relevant concentrations?","volume":"258","author":"Sinclair","year":"2020","journal-title":"Chemosphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1080\/15320383.2019.1592108","article-title":"A review on heavy metals contamination in soil: Effects, sources, and remediation techniques","volume":"28","author":"Li","year":"2019","journal-title":"Soil Sediment Contam. Int. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"046001","DOI":"10.1289\/EHP10092","article-title":"Exposure to per-and polyfluoroalkyl substances and markers of liver injury: A systematic review and meta-analysis","volume":"130","author":"Costello","year":"2022","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jhep.2022.01.016","article-title":"Cigarette smoking and liver diseases","volume":"77","author":"Bataller","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_8","first-page":"617","article-title":"Smoking and liver disease","volume":"16","author":"Rutledge","year":"2020","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0741-8329(01)00176-8","article-title":"Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system","volume":"25","author":"Husain","year":"2001","journal-title":"Alcohol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4161\/oxim.3.3.12288","article-title":"Acetaldehyde adducts in alcoholic liver disease","volume":"3","author":"Setshedi","year":"2010","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","first-page":"147","article-title":"Alcoholic liver disease: Pathogenesis and current management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.jhep.2009.03.007","article-title":"Signalling pathways in alcohol-induced liver inflammation","volume":"50","author":"Mandrekar","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1002\/hep.32743","article-title":"Health Disparities in Chronic Liver Disease","volume":"77","author":"Kardashian","year":"2023","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"265S","DOI":"10.1093\/ajcn\/82.1.265S","article-title":"The economics of obesity: Dietary energy density and energy cost","volume":"82","author":"Drewnowski","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ejim.2023.07.039","article-title":"Relationships between education and non-alcoholic fatty liver disease","volume":"118","author":"Koutny","year":"2023","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","unstructured":"Centers for Disease Control and Prevention (2025, February 20). NHANES 2017-2018 Overview, Available online: https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/search\/datapage.aspx?Component=Demographics&Cycle=2017-2018."},{"key":"ref_17","first-page":"3","article-title":"CDC National Health Report: Leading causes of morbidity and mortality and associated behavioral risk and protective factors\u2014United States, 2005\u20132013","volume":"63","author":"Johnson","year":"2014","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bashir, T., and Obeng-Gyasi, E. (2023). Combined Effects of Multiple Per-and Polyfluoroalkyl Substances Exposure on Allostatic Load Using Bayesian Kernel Machine Regression. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20105808"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/biostatistics\/kxu058","article-title":"Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures","volume":"16","author":"Bobb","year":"2015","journal-title":"Biostatistics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.2166\/wst.2009.504","article-title":"Contamination, bioaccumulation and toxic effects of perfluorinated chemicals (PFCs) in the water environment: A review paper","volume":"60","author":"Suja","year":"2009","journal-title":"Water Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1111\/apt.18242","article-title":"Trends of chronic liver diseases by income level and socioeconomic factors in the United States: A population-based study","volume":"60","author":"Lee","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bbrc.2011.10.151","article-title":"Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells","volume":"417","author":"Soeda","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejim.2020.01.008","article-title":"The association between education level and chronic liver disease of any etiology","volume":"75","author":"Stroffolini","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/acer.14271","article-title":"Interaction between alcohol use and metabolic risk factors for liver disease: A critical review of epidemiological studies","volume":"44","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Soto-Angona, \u00d3., Anmella, G., Vald\u00e9s-Florido, M.J., De Uribe-Viloria, N., Carvalho, A.F., Penninx, B.W.J.H., and Berk, M. (2020). Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: Common pathways and future approaches. BMC Med., 18.","DOI":"10.1186\/s12916-020-01713-8"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, C.-L., Yao, Z.-Y., Zhang, Y.-F., Cui, X.-T., Sun, A., Cao, J.-Y., and Wang, Z.-S. (2025). Bisphenols exposure and non-alcoholic fatty liver disease: From environmental trigger to molecular pathogenesis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1606654"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3390\/jox14020031","article-title":"Association of Combined PFOA, PFOS, Metals and Allostatic Load on Hepatic Disease Risk","volume":"14","author":"Balogun","year":"2024","journal-title":"J. Xenobiotics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"176717","DOI":"10.1016\/j.scitotenv.2024.176717","article-title":"Effects of per-and polyfluoroalkyl substances on the liver: Human-relevant mechanisms of toxicity","volume":"954","author":"Maerten","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12940-022-00892-6","article-title":"Individual and mixture associations of perfluoroalkyl substances on liver function biomarkers in the Canadian Health Measures Survey","volume":"21","author":"Borghese","year":"2022","journal-title":"Environ. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.aogh.2016.01.005","article-title":"Health consequences of environmental exposures: Changing global patterns of exposure and disease","volume":"82","author":"Landrigan","year":"2016","journal-title":"Ann. Glob. Health"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Valacchi, G., and Daiber, A. (2023). Environmental Stressors and Oxinflammatory Tissues Responses, CRC Press.","DOI":"10.1201\/9781003328100"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/713611043","article-title":"Ethanol and hormesis","volume":"33","author":"Calabrese","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1258\/acb.2010.009303","article-title":"Cigarette smoking and serum liver enzymes: The role of alcohol and inflammation","volume":"47","author":"Wannamethee","year":"2010","journal-title":"Ann. Clin. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Park, E.Y., Lim, M.K., Oh, J.-K., Cho, H., Bae, M.J., Yun, E.H., Kim, D.-I., and Shin, H.-R. (2013). Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063439"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1177\/000456329603300607","article-title":"The effects of cigarette smoking and alcohol consumption on serum liver enzyme activities: A dose-related study in men","volume":"33","author":"Whitehead","year":"1996","journal-title":"Ann. Clin. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.dld.2015.07.154","article-title":"Education level and chronic liver disease by aetiology: A proportional mortality study","volume":"47","author":"Fedeli","year":"2015","journal-title":"Dig. Liver Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1590\/S1679-45082015AO2878","article-title":"Physical activity as a protective factor for development of non-alcoholic fatty liver in men","volume":"13","author":"Pinto","year":"2015","journal-title":"Einstein"},{"key":"ref_38","first-page":"939","article-title":"The Multifaceted Role of Bilirubin in Liver Disease: A Literature Review","volume":"12","author":"Pal","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.2174\/1381612043384655","article-title":"The antioxidants and pro-antioxidants network: An overview","volume":"10","author":"Vertuani","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1559325818798282","DOI":"10.1177\/1559325818798282","article-title":"Nonmonotonic dose\u2013response curves occur in dose ranges that are relevant to regulatory decision-making","volume":"16","author":"Hill","year":"2018","journal-title":"Dose-Response"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:15Z","timestamp":1760033835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["medsci13030099"],"URL":"https:\/\/doi.org\/10.3390\/medsci13030099","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]}}}