ArticleEnvironment international2025
Assessing the impact of perfluoroalkyl substances on liver health: a comprehensive study using multi-donor human liver spheroids.
Article in Environment international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Enhanced Environmental PFAS Characterization Using a Virtual High-Resolution Mass Spectral Library Generated by Transfer Learning-Based Neural Network.Environmental science & technology · 2026Article
- Effects of gestational perfluorohexanesulfonic acid exposure at human realistic dose on social communication deficit in mouse offspring.EBioMedicine · 2026Article
- PFOS and PFOA exposure induces liver injury and sex-dependent immune effects in C57BL/6 mice.iScience · 2026Article
- Artificial intelligence driven exposome and multi omics integration for biomarker discovery in liver cancer: a literature review.Frontiers in immunology · 2026Review
- A systems-level integration of liver-kidney transcriptomics and genome-scale metabolic models reveals organ-specific injury mechanisms.Frontiers in toxicology · 2026Article
- From environment to organs: individual and combined effects of MPs and PFAS on urinary system health.Frontiers in physiology · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundAlthough per- and polyfluoroalkyl substances (PFAS) have been linked to chronic liver diseases, the specific cellular and molecular mechanisms by which different PFAS contribute to human liver dysfunction remain unclear. This study aims to elucidate those mechanisms.
methodsWe exposed a multi-donor human liver spheroid model composed of multiple cell types to 20 µM of PFHxS, PFOA, PFOS, or PFNA for seven days, followed by single-cell RNA sequencing and lipid staining.
resultsPFAS impacted liver spheroids in a compound- and sex-specific manner. PFOA and PFHxS increased lipid accumulation, while PFOS and PFNA triggered multiple cancer-related pathways. PFOA upregulated de novo lipogenesis, particularly in female-derived hepatocytes, whereas PFHxS downregulated lipid transportation and efflux pathways across all hepatocytes. PFNA upregulated pathways involved in cell cycle progression, oxidative stress, DNA repair, and inflammation in hepatocytes from both sexes. Notably, 61.3% of the PFNA-exposed cells expressed a transcriptomic cancer signature. PFOS predominantly affected male-derived hepatocytes, showing a mild effect. All compounds impaired immune-related pathways in T/NK and Kupffer cells. Furthermore, PFAS exposure reduced cell-cell communication and elicited cellular interactions involved in angiogenesis, apoptosis, cell proliferation and adhesion, lipid metabolism, and inflammation.
conclusionsOur findings suggest that PFAS disrupt liver metabolism and may promote pro-oncogenic signaling through compound- and sex-specific mechanisms. These insights enhance our understanding of PFAS hepatotoxicity and underscore the importance of considering sex as a biological variable in future toxicological and public health assessments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.