Evidence map›Paper›PMID 40914107›Full record

ArticleEnvironment international2025

Assessing the impact of perfluoroalkyl substances on liver health: a comprehensive study using multi-donor human liver spheroids.

Lucy Golden-Mason, Matthew P Salomon, Chikako Matsuba, Yufen Wang, Veronica Wendy Setiawan, Lida Chatzi, Ana C Maretti-Mira

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Lucy Golden-MasonDivision of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Matthew P SalomonDepartment of Cancer Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Chikako MatsubaDivision of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Yufen WangDivision of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Veronica Wendy SetiawanDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Lida ChatziDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Ana C Maretti-MiraDivision of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: marettim@usc.edu.

Funding

Translational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROB S MCCONNELL · 1996 to 2026
$46.4M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOLDEN, LUCY MARY · 1995 to 2020
$21.8M
Southern California Superfund Research and Training Program for PFAS Assessment, Remediation, and Prevention (ShARP)P42ES036506 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAIA LIDA CHATZI · 2025 to 2026
$8.2M
Effects of DDE exposure on adipose tissue function, weight loss and metabolic improvement after bariatric surgery: A new paradigm for study of lipophilic chemicalsR01ES030364 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHATZI, VAIA LIDA · 2020 to 2024
$3.2M
Environmental Chemical Exposures and Longitudinal Changes of Glucose Metabolism, Insulin Sensitivity and B Cell Function in YouthR01ES029944 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHATZI, VAIA LIDA · 2019 to 2023
$3.1M
Longitudinal integration of environmental exposures, omics, and childhood NAFLD (LEON) StudyU01HG013288 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AUNG, TUN (MAX) M, CHATZI, VAIA LIDA · 2023 to 2025
$2.4M
Hepatotoxic effects of perfluoroalkyl substances: a new epidemiological approach for studying environmental fatty liver diseaseR01ES030691 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHATZI, VAIA LIDA · 2020 to 2022
$1.9M
Innate Immunity, Cholesterol, and NASH PathogenesisR01DK117004 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOLDEN, LUCY MARY · 2020 to 2023
$1.5M
NHGRI NIH HHS U01 HG013288NIDDK NIH HHS P30 DK048522NIDDK NIH HHS R01 DK117004NIEHS NIH HHS P30 ES007048NIEHS NIH HHS P42 ES036506NIEHS NIH HHS R01 ES029944NIEHS NIH HHS R01 ES030364NIEHS NIH HHS R01 ES030691
6 · The paper itself

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.

Indexed as

Environmental PollutantsFluorocarbonsLiverAlkanesulfonic AcidsFemaleHepatocytesHumansMaleSpheroids, CellularAlkanesulfonic AcidsEnvironmental PollutantsFluorocarbonsCancerCellChatLipid MetabolismLiver SpheroidsPFAS (Per- and Polyfluoroalkyl Substances)scRNA-seq

Identifiers

PMID40914107
PMCPMC12459911

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.