Evidence map›Paper›PMID 31744629›Full record

ArticleEnvironment international2020

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach.

Ran Jin, Rob McConnell, Cioffi Catherine, Shujing Xu, Douglas I Walker, Nikos Stratakis, Dean P Jones, Gary W Miller, Cheng Peng, David V Conti and 2 more

Open access · goldAbstract read
In one paragraph

Article in Environment international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 5 pooled it
9.7field-weighted citation impact, top 1% of its field
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

101 citing papers in PubMed, 5 syntheses or guidelines pooled it, 217 citations in OpenAlex.

  1. Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026
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41 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Ran JinDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: jinr@usc.edu.
Rob McConnellDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: rmcconne@usc.edu.
Cioffi CatherineNutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA, USA. Electronic address: catherine.cioffi@emory.edu.
Shujing XuDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: shujingx@usc.edu.
Douglas I WalkerClinical Biomarkers Laboratory, Division of Pulmonary Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA; Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address: douglas.walker@mssm.edu.
Nikos StratakisDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: nstratak@usc.edu.
Dean P JonesClinical Biomarkers Laboratory, Division of Pulmonary Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA. Electronic address: dpjones@emory.edu.
Gary W MillerRollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address: gary.miller@columbia.edu.
Cheng PengDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: chengpen@usc.edu.
David V ContiDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: dconti@med.usc.edu.
Miriam B VosNutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: mvos@emory.edu.
Leda ChatziDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: chatzi@usc.edu.
University of Southern California · USEmory University · USChildren's Healthcare of Atlanta · US

Funding

Translational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROB S MCCONNELL · 1996 to 2026
$46.4M
Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI William JAMES GAUDERMAN, KIMBERLY D SIEGMUND · 2016 to 2026
$25.5M
Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI William Michael Caudle · 2013 to 2026
$22.6M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OOKHTENS, MURAD · 1995 to 2020
$21.8M
Graduate and Postdoctoral Training in ToxicologyT32ES012870 · NIEHS · EMORY UNIVERSITY · PI Carmen Joseph Marsit · 2004 to 2026
$9.1M
National Exposure Assessment Laboratory at EmoryU2CES026560 · NIEHS · EMORY UNIVERSITY · PI WALLER, LANCE A · 2015 to 2015
$8.3M
Southern California Children's Environmental Health Center (SC-CEHC)P01ES022845 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MCCONNELL, ROB S · 2013 to 2018
$4.0M
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
An environment-wide association study in autism spectrum disorders using novel bioinformatics methods and metabolomics via mass spectrometryR01MH107205 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI KONG, SEK WON · 2015 to 2019
$2.1M
Incorporating intermediate biomarkers of folate with colorectal cancerR01CA140561 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, DAVID V, SCHUMACHER, FREDRICK RAY · 2011 to 2015
$1.9M
Orbitrap Elite/H-ESI BundleS10OD018006 · OD · EMORY UNIVERSITY · PI JONES, DEAN PAUL · 2014 to 2014
$600k
The adipose exposome effects on the plasma metabolome, body composition and metabolic outcomes after bariatric surgeryR21ES028903 · NIEHS · EMORY UNIVERSITY · PI CHATZI, VAIA LIDA, ZIEGLER, THOMAS R · 2018 to 2019
$455k
NCI NIH HHS P01 CA196569NCI NIH HHS R01 CA140561NIEHS NIH HHS F32 ES029828NIEHS NIH HHS P01 ES022845NIEHS NIH HHS P30 ES007048NIEHS NIH HHS P30 ES019776NIEHS NIH HHS R01 ES029944NIEHS NIH HHS R21 ES028903NIEHS NIH HHS R21 ES029681NIEHS NIH HHS T32 ES012870NIEHS NIH HHS U2C ES026560NIH HHS S10 OD018006NIMH NIH HHS R01 MH107205
6 · The paper itself

Abstract

backgroundToxicant-associated steatohepatitis has been described in adults but less is known regarding the role of toxicants in liver disease of children. Perfluoroalkyl substances (PFAS) cause hepatic steatosis in rodents, but few previous studies have examined PFAS effects on severity of liver injury in children.

objectivesWe aimed to examine the relationship of PFAS to histologic severity of nonalcoholic fatty liver disease (NAFLD) in children.

methodsSeventy-four children with physician-diagnosed NAFLD were recruited from Children's Healthcare of Atlanta between 2007 and 2015. Biopsy-based liver histological features were scored for steatosis, lobular and portal inflammation, ballooning, and fibrosis. Plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS), and untargeted plasma metabolomic profiling, were determined using liquid chromatography with high-resolution mass spectrometry. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with PFAS. A structural integrated analysis was applied to identify latent clusters of children with more severe form of NAFLD based on their PFAS levels and metabolite pattern.

resultsPatients were 7-19 years old, mostly boys (71%), Hispanic (51%), and obese (85%). The odds of having nonalcoholic steatohepatitis (NASH), compared to children with steatosis alone, was significantly increased with each interquartile range (IQR) increase of PFOS (OR: 3.32, 95% CI: 1.40-7.87) and PFHxS (OR: 4.18, 95% CI: 1.64-10.7). Each IQR increase of PFHxS was associated with increased odds for liver fibrosis (OR: 4.44, 95% CI: 1.34-14.8), lobular inflammation (OR: 2.87, 95% CI: 1.12-7.31), and higher NAFLD activity score (β coefficient 0.46; 95% CI: 0.03, 0.89). A novel integrative analysis identified a cluster of children with NASH, characterized by increased PFAS levels and altered metabolite patterns including higher plasma levels of phosphoethanolamine, tyrosine, phenylalanine, aspartate and creatine, and decreased plasma levels of betaine.

conclusionsΗigher PFAS exposure was associated with more severe disease in children with NAFLD. PFAS may be an important toxicant contributing to NAFLD progression; however larger, longitudinal studies are warranted to confirm these findings.

Indexed as

Non-alcoholic Fatty Liver DiseaseAdolescentChildFluorocarbonsHumansMaleMetabolomicsSulfonic AcidsYoung AdultFluorocarbonsSulfonic Acids

Identifiers

PMID31744629
PMCPMC6944061
OpenAlexW2985102732

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Registered trials

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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 OpenQuestion graph.