Evidence map›Paper›PMID 39282813›Full record

ArticleJournal of pediatric gastroenterology and nutrition2024

Environmental toxicants modulate disease severity in pediatric metabolic dysfunction-associated steatohepatitis.

Ajay K Jain, Stefanie A Busgang, Chris Gennings, Katherine P Yates, Jeffrey B Schwimmer, Philip Rosenthal, Karen F Murray, Jean P Molleston, Ann Scheimann, Stavra A Xanthakos and 6 more

Abstract readMulticenter Study
In one paragraph

Article in Journal of pediatric gastroenterology and nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
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

16 authors.

Ajay K JainDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Saint Louis University, St. Louis, Missouri, USA.ORCID 0000-0002-9420-5722
Stefanie A BusgangHHEAR Data Center, Icahn School of Medicine at Mount Sinai, Statistical Services and Methods Development Resource, New York, New York, USA.
Chris GenningsHHEAR Data Center, Icahn School of Medicine at Mount Sinai, Statistical Services and Methods Development Resource, New York, New York, USA.
Katherine P YatesDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Jeffrey B SchwimmerDepartment of Pediatrics, Division of Gastroenterology, UC San Diego, La Jolla, California, USA.
Philip RosenthalDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, San Francisco Benioff Children's Hospital, University of California, San Francisco, California, USA.
Karen F MurrayPediatrics Institute, Cleveland Clinic and Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
Jean P MollestonDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, Indiana, USA.
Ann ScheimannDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Stavra A XanthakosDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Cynthia A BehlingDepartment of Pediatrics, Division of Gastroenterology, UC San Diego, La Jolla, California, USA.
Danielle CarpenterDepartment of Pathology, Saint Louis University, St. Louis, Missouri, USA.
Mark FishbeinDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Brent A Neuschwander-TetriDivision of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri, USA.
James TonasiaDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Miriam B VosDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.

Funding

Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Statistical Services and Methods Development ResourceU2CES026555 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GENNINGS, CHRIS · 2015 to 2025
$26.4M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
The Saint Louis University Component of the NASH CRNU01DK061718 · NIDDK · SAINT LOUIS UNIVERSITY · PI BRENT A NEUSCHWANDER-TETRI · 2002 to 2026
$12.0M
VEDS Year2-Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Data Coordinating CenterU24DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI JEANNE M CLARK, David M Shade · 2019 to 2026
$11.3M
Role of bile acid receptors FXR and TGR5 in preventing injury in short bowel syndromeR01DK131136 · NIDDK · SAINT LOUIS UNIVERSITY · PI JAIN, AJAY K. · 2021 to 2025
$1.9M
Role of intestinal microbiota in driving injury mechanisms in short bowel syndromeR21AI169487 · NIAID · SAINT LOUIS UNIVERSITY · PI JAIN, AJAY K. · 2022 to 2023
$428k
Human Health Exposure Analysis ResourceNational Center for Advancing Translational Sciences (NCATS) UL1TR000448National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK061718National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK061730National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U24DK061730NCATS NIH HHS UL1 TR000448NIAID NIH HHS R21 AI169487NIDDK NIH HHS R01 DK131136NIDDK NIH HHS U01 DK061718NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U24 DK061730NIEHS NIH HHS U2C ES026555NIH HHS NIH-1R01DK131136-01NIH HHS NIH-R21AI169487-01Saint Louis University Liver Center
6 · The paper itself

Abstract

objectivesMetabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH.

methodsEnvironmental chemicals, common in household items, perfluoroalkyl substances (PFAS), polybrominated flame retardants (polybrominated diphenyl ethers [PBDEs]), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2. Mixture models, using repeated holdout weighted quantile sum regression (WQS

resultsFour hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Mean (standard deviation) for Nonalcoholic Steatohepatitis Score (NAS) and alanine aminotransferase (ALT) for MASLD were 3.1 (1.0), 67.9 (43.4), and for MASH 4.2 (1.4), 144 (121). There was an inverse association between PFAS/PBDE mixture and MASH versus MASLD, lobular inflammation (p = 0.026), NAS (p = 0.009, FDR p = 0.04), and log-transformed ALT (p = 0.005, FDR p = 0.025) driven by perfluorohexane sulfonate (PFHXS). Metabolites from positive hydrophilic interaction liquid chromatography mode, biliverdin (p = 0.002) and 1-methylhistidine (associated with meat ingestion, p = 0.02) and reverse phase negative mode, hippuric acid (solvent exposure, p = 0.022) significantly associated with MASH.

conclusionsSignificant negative PFAS/PBDE mixture effect and odds of MASH were dominated by PHFXS. Several metabolites are significantly associated with MASH which inform mechanistic pathways and could drive key therapeutic and diagnostic strategies in children.

Indexed as

Environmental PollutantsSeverity of Illness IndexAdolescentChildChild, PreschoolDisease ProgressionEnvironmental ExposureFemaleHalogenated Diphenyl EthersHumansMaleNon-alcoholic Fatty Liver DiseaseEnvironmental PollutantsHalogenated Diphenyl EtherschildrenMASHMASLDmetabolitesPHFXS

Identifiers

PMID39282813
PMCPMC11955998

What OpenQuestion holds

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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 OpenQuestion graph.