Triglycerides mediate the relationships of per-and poly-fluoroalkyl substance (PFAS) exposure with nonalcoholic fatty liver disease (NAFLD) risk in US participants
Open accessAbstract
Nonalcoholic fatty liver disease (NAFLD) is recognized as a significant public health problem worldwide. Several clinical studies have investigated the associations between Per- and poly-fluoroalkyl substances (PFAS) compounds with the risk of NAFLD in general adults, but the mediating effect of triglycerides (TG) was remained unexplored. In this study, 6990 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2018) database were enrolled. Firstly, the results of generalized linear models (GLM) and restricted cubic splines (RCS) revealed positive associations of PFAS compounds with NAFLD risk score and liver function, and nearly linear E-R curves indicated no safe threshold. Meanwhile, weighted quantile sum (WQS) regression demonstrated the relationships between PFAS mixtures with NAFLD risk score and liver function, as well as perfluorooctanoic acid (PFOA) was identified as the main contributor to the increased NAFLD risk. Then, mediation analysis was conducted to explore whether serum lipids mediate the relationships. It further highlighted significant mediation effects of TG, with the mediated proportion ranging from 10.4 % to 42.9 %. Finally, sensitivity and stratified analyses were performed, confirming the reliability of these findings. Notably, significant associations were observed in individuals with a BMI ≥ 28, highlighting that these relationships were particularly evident in obese participants. In conclusion, our study suggested that PFAS mixtures exposure may influence NAFLD risk score by mediating TG in human metabolism. This result could provide more comprehensive epidemiological evidence and guide clinical applications.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PFAS exposure is linked to liver dysfunction, NAFLD, and cirrhosis, with moderate risk in adults.
“| Liver Disease | Links to liver dysfunction, NAFLD, cirrhosis. | Moderate | Adults | Long-term liver complications | [232] |”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [232]
Cites
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781 · see citing works
Byrne, C. D., & Targher, G. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.12.012 · Cited by 3,082 · see citing works
Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., & Tiribelli, C. (2006) · BMC Gastroenterology · doi:10.1186/1471-230x-6-33 · Cited by 3,054 · see citing works
Nonalcoholic Fatty Liver Disease
Rinella, M. E. (2015) · JAMA · doi:10.1001/jama.2015.5370 · Cited by 2,289 · see citing works
Per- and polyfluoroalkyl substances in the environment
Evich, M. G., Davis, M. J. B., McCord, J. P., Acrey, B., Awkerman, J. A., Knappe, D. R. U., Lindstrom, A. B., Speth, T. F., Tebes-Stevens, C., Strynar, M. J., et al. (2022) · Science · doi:10.1126/science.abg9065 · Cited by 2,157 · see citing works
Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications
Fabbrini, E., Sullivan, S., & Klein, S. (2010) · Hepatology · doi:10.1002/hep.23280 · Cited by 2,100 · see citing works
Olsen, G. W., Burris, J. M., Ehresman, D. J., Froehlich, J. W., Seacat, A. M., Butenhoff, J. L., & Zobel, L. R. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10009 · Cited by 2,049 · see citing works
Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention
Huang, D. Q., El-Serag, H. B., & Loomba, R. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00381-6 · Cited by 1,855 · see citing works
Polyfluorinated Compounds: Past, Present, and Future
Lindstrom, A. B., Strynar, M. J., & Libelo, E. L. (2011) · Environmental Science & Technology · doi:10.1021/es2011622 · Cited by 1,628 · see citing works
Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease
Ipsen, D. H., Lykkesfeldt, J., & Tveden-Nyborg, P. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2860-6 · Cited by 1,471 · see citing works
Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis
Diehl, A. M., & Day, C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1503519 · Cited by 1,283 · see citing works
Karlas, T., Petroff, D., Sasso, M., Fan, J.-G., Mi, Y.-Q., de Lédinghen, V., Kumar, M., Lupsor-Platon, M., Han, K.-H., Cardoso, A. C., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.022 · Cited by 1,275 · see citing works
Adipose tissue and insulin resistance in obese
Ahmed, B., Sultana, R., & Greene, M. W. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111315 · Cited by 1,059 · see citing works
PFAS Molecules: A Major Concern for the Human Health and the Environment
Panieri, E., Baralic, K., Djukic-Cosic, D., Buha Djordjevic, A., & Saso, L. (2022) · Toxics · doi:10.3390/toxics10020044 · Cited by 651 · see citing works
Li, J., Wang, T., Liu, P., Yang, F., Wang, X., Zheng, W., & Sun, W. (2021) · Food & Function · doi:10.1039/d0fo02736g · Cited by 455 · see citing works
Self-citationCostello, E., Rock, S., Stratakis, N., Eckel, S. P., Walker, D. I., Valvi, D., Cserbik, D., Jenkins, T., Xanthakos, S. A., Kohli, R., et al. (2022) · Environmental Health Perspectives · doi:10.1289/ehp10092 · Cited by 420 · see citing works
A new perspective on NAFLD: Focusing on lipid droplets
Scorletti, E., & Carr, R. M. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.11.009 · Cited by 376 · see citing works
Rickard, B. P., Rizvi, I., & Fenton, S. E. (2022) · Toxicology · doi:10.1016/j.tox.2021.153031 · Cited by 334 · see citing works
Sen, P., Qadri, S. U., Luukkonen, P. K., Ragnarsdóttir, O., McGlinchey, A. J., Jäntti, S. E., Juuti, A., Arola, J. T., Schlezinger, J. J., Webster, T. F., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.09.039 · Cited by 292 · see citing works
Lonardo, A., Byrne, C. D., Caldwell, S. H., Cortez‐Pinto, H., & Targher, G. (2016) · Hepatology · doi:10.1002/hep.28584 · Cited by 243 · see citing works
Moore, M. P., Cunningham, R. P., Meers, G. M.-E., Johnson, S. A., Wheeler, A. A., Ganga, R., Spencer, N., Pitt, J. B., Diaz‐Arias, A. A., Swi, A. I. A., et al. (2022) · Hepatology · doi:10.1002/hep.32324 · Cited by 238 · see citing works
Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease
Mato, J. M., Alonso, C., Noureddin, M., & Lu, S. C.-L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i24.3009 · Cited by 201 · see citing works
Wang, Y., Ling, X., He, S., Cui, H., Yang, Z., An, H., Wang, L., Zou, P., Chen, Q., Liu, J., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.108138 · Cited by 199 · see citing works
Carnero, A. R., Cardama, A. L., Loureiro, P. V., Barbosa‐Pereira, L., de Quirós, A. R. B., & Sendón, R. (2021) · Foods · doi:10.3390/foods10071443 · Cited by 198 · see citing works
Physical activity and telomere length in U.S. men and women: An NHANES investigation
Tucker, L. A. (2017) · Preventive Medicine · doi:10.1016/j.ypmed.2017.04.027 · Cited by 153 · see citing works
Houck, K. A., Patlewicz, G. Y., Richard, A. M., Williams, A. J., Shobair, M., Smeltz, M. G., Clifton, M. S., Wetmore, B. A., Medvedev, A. V., & Makarov, S. S. (2021) · Toxicology · doi:10.1016/j.tox.2021.152789 · Cited by 149 · see citing works
Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention
Lange, N. F., Radu, P., & Dufour, J. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.07.025 · Cited by 137 · see citing works
Liu, B., Zhu, L., Wang, M., & Sun, Q. (2023) · Environmental Health Perspectives · doi:10.1289/ehp11840 · Cited by 120 · see citing works
Zhang, X., Zhao, L., DUCATMAN, A. M., Deng, C., von Stackelberg, K., Danford, C. J., & Zhang, X. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100694 · Cited by 116 · see citing works
Zhang, L., Louie, A., Rigutto, G., Guo, H., Zhao, Y., Ahn, S., Dahlberg, S., Sholinbeck, M., & Smith, M. T. (2022) · Environmental Research · doi:10.1016/j.envres.2022.115188 · Cited by 108 · see citing works
Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues
Dragon, J. A., Hoaglund, M., Badireddy, A. R., Nielsen, G. H., Schlezinger, J. J., & Shukla, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108539 · Cited by 95 · see citing works
Niu, Z., Duan, Z., He, W., Chen, T., Tang, H., Du, S., Sun, J., Chen, H., Hu, Y., Iijima, Y., et al. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.134312 · Cited by 88 · see citing works
Self-citationHo, S. H., Soh, S. X. H., Wang, M. X., Ong, J., Seah, A., Wong, Y., Fang, Z., Sim, S., & Lim, J. T. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.158036 · Cited by 84 · see citing works
Liu, Y., Liu, S., Huang, J., Liu, Y., Wang, Q., Chen, J., Sun, L., & Tu, W. (2023) · Environment International · doi:10.1016/j.envint.2023.107977 · Cited by 84 · see citing works
Fatty Liver Disease: Diagnosis and Stratification
Saiman, Y., Duarte‐Rojo, A., & Rinella, M. E. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-020407 · Cited by 78 · see citing works
Seyyedsalehi, M. S., & Boffetta, P. (2023) · La Medicina del Lavoro · doi:10.23749/mdl.v114i5.15065 · Cited by 77 · see citing works
Mehrabi, F., Ghaedi, M., & Dil, E. A. (2023) · Talanta · doi:10.1016/j.talanta.2023.124581 · Cited by 64 · see citing works
Schlezinger, J. J., Hyötyläinen, T., Sinioja, T., Boston, C. M., Puckett, H. M., Oliver, J., Heiger‐Bernays, W., & Webster, T. F. (2021) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2021.115644 · Cited by 61 · see citing works
Rekik, H., Arab, H., Pichon, L., Khakani, M. A. E., & Drogui, P. (2024) · Chemosphere · doi:10.1016/j.chemosphere.2024.142044 · Cited by 61 · see citing works
Fatty liver index (FLI): more than a marker of hepatic steatosis
Kaneva, A. M., & Bojko, E. R. (2023) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-023-00991-z · Cited by 60 · see citing works
Margolis, R., & Sant, K. E. (2021) · Journal of Xenobiotics · doi:10.3390/jox11030008 · Cited by 59 · see citing works
Mehrabi, F., Ghaedi, M., & Alipanahpour Dil, E. (2024) · Talanta · doi:10.1016/j.talanta.2023.125045 · Cited by 46 · see citing works
Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease
David, N., Antignac, J., Roux, M., Marchand, P., Michalak, S., Oberti, F., Fouchard, I., Lannes, A., Blanchet, O., Calès, P., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.108235 · Cited by 45 · see citing works
Dil, E. A., Asfaram, A., Goudarzi, A., Zabihi, E., & Javadian, H. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.03.132 · Cited by 44 · see citing works
Mehrabi, F., Ghaedi, M., Dil, E. A., & Tayebi, L. (2024) · Talanta · doi:10.1016/j.talanta.2024.125705 · Cited by 44 · see citing works
Wu, Z., Ouyang, T., Liu, H., Cao, L., & Chen, W. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-26941-2 · Cited by 43 · see citing works
‘Micro‐managers’ of hepatic lipid metabolism and NAFLD
Liu, W., Cao, H., Yan, J., Huang, R., & Ying, H. (2015) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1295 · Cited by 33 · see citing works
Ma, X., Fisher, J. A., VoPham, T., Vasiliou, V., & Jones, R. R. (2023) · Environmental Research · doi:10.1016/j.envres.2023.116651 · Cited by 28 · see citing works
Zhang, Z., Xu, S., Song, M., Huang, W., Yan, M., & Li, X. (2024) · Cancer Causes & Control · doi:10.1007/s10552-024-01853-9 · Cited by 15 · see citing works
The Accuracy of Ultrasound Controlled Attenuation Parameter in Diagnosing Hepatic Fat Content
Atzori, S. M., Pasha, Y., Maurice, J. B., Taylor-Robinson, S. D., Campbell, L., & Lim, A. K. P. (2023) · Hepatic Medicine Evidence and Research · doi:10.2147/hmer.s411619 · Cited by 13 · see citing works
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Xenobiotic-induced liver injury: Molecular mechanisms and disease progression
Wang, L., Shao, Z., Wang, X., Lu, W., & Sun, H. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.118854 · Cited by 52 · see citing works
Self-citationHealth Risk Assessment of Dietary Chemical Exposures: A Comprehensive Review
Pekmezci, H., Sipahi, S., & Başaran, B. (2025) · Foods · doi:10.3390/foods14234133 · Cited by 32 · see citing works
Goswami, L., Dikshit, P. K., Prakash, A., Vidanage, P. W., Verma, J. P., & Oh, S. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.138743 · Cited by 28 · see citing works
Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS
Hasan, M., Habib, A., Alam, M., Islam, S., & Halim, E. (2025) · Pollutants · doi:10.3390/pollutants5040043 · Cited by 21 · see citing works
Yun, J., & Min, Y. (2025) · American Journal of Industrial Medicine · doi:10.1002/ajim.23732 · Cited by 8 · see citing works
Li, W., Qian, Y., Cai, X., He, Y., Meng, X., & Zhang, L. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.118125 · Cited by 6 · see citing works
Hari, A., Balik-Meisner, M. R., Mav, D., Phadke, D. P., Scholl, E. H., Shah, R., Casey, W., Auerbach, S. S., Wallqvist, A., & Pannala, V. R. (2025) · Toxics · doi:10.3390/toxics13080684 · Cited by 5 · see citing works
Nielsen, G. H., Reed, E. R., Lara, B., Sherr, D. H., Heiger‐Bernays, W., Hyötyläinen, T., Webster, T. F., & Schlezinger, J. J. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117658 · Cited by 4 · see citing works
Li, F., Wang, J., Liu, Y., Sun, T., Ji, C., & Wu, H. (2026) · Environment & Health · doi:10.1021/envhealth.5c00503 · Cited by 1 · see citing works
Perfluoroalkyl and polyfluoroalkyl substances exposure and liver disease: A review
Peng, J., Gong, R., Li, R., Li, L., Yu, H., & Wen, Q. (2026) · Toxicology · doi:10.1016/j.tox.2026.154509 · Cited by 1 · see citing works
Lipid metabolism links seminal PFAS exposure to IVF outcomes
Huang, G., Fang, J., Chen, Y., Zhong, S., Li, J., Tan, X., Wang, X.-Y., Wu, Y., Liang, R., Yang, L., et al. (2026) · Environment International · doi:10.1016/j.envint.2026.110292
Self-citationSun, M., Chu, C., Zhao, K., Qian, Z. M., Schootman, M., McMillin, S. E., Dong, J., Bao, W., Amjad, M., Moryani, H. T., et al. (2026) · Toxics · doi:10.3390/toxics14060478
Hu, X., Sheng, N., Chen, Y., Shi, W., Ji, S., Wu, B., Qu, Y., (26302), Z. L., Yu, L., Meng, X., et al. (2026) · Journal of Environmental Exposure Assessment · doi:10.20517/jeea.2025.82
Fu, J., Qiao, G., Ma, K., Jia, J., Li, H., Bai, Z., Xiong, L., Zhang, Y., Geng, X., Duan, H., et al. (2026) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2026.142869
Li, S.-S., Yang, Z.-S., Tian, X., Wu, Y.-D., Song, J.-K., Wang, W.-L., Tang, Z.-L., & Wang, J.-B. (2026) · Cardiovascular Toxicology · doi:10.1007/s12012-026-10157-0
Liu, A., Ran, M., Tian, Y., Li, X., Wang, M., Wang, J., 吴宇峰, Liu, D., & Zhang, Y. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.120977
- Authors
- Qiao, W., Li, J., Luo, L., Peng, W., Wang, X., Jin, R., & Li, J.
- Affiliations
- Capital Medical University (CN)
- Corresponding author
- Li, Jiashuo
- Wang, Xi
- Jin, Ronghua
- Li, Junnan
- Venue
- Ecotoxicology and Environmental Safety
- Publisher
- Elsevier BV
- Published
- 2025-01
- Volume
- 289
- Pages
- 117436
- ISSN
- 0147-6513 (ISSN-L)
- OpenAlex
- W4405013968
- Cited by
- 16
- References
- 52
- Citations by year
- 2026: 8 · 2025: 8
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Ecotoxicology and Environmental Safety (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Capital Medical University (DTQL202403)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Keywords
- per- and polyfluoroalkyl substances, PFAS exposure, non-alcoholic fatty liver disease, triglycerides, mediation analysis, perfluorooctanoic acid, PFAS mixtures, liver function, obesity, dose-response relationship, serum lipids
- MeSH terms
- Adult, Caprylates, Environmental Exposure, Environmental Pollutants, Female, Fluorocarbons, Humans, Male, Middle Aged, Nutrition Surveys, Triglycerides, United States, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
