Evidence map›Paper›PMID 38145725›Full record

ArticleClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association2024

Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.

Chaowapong Jarasvaraparn, Eduardo Vilar-Gomez, Katherine P Yates, Laura A Wilson, Brent Neuschwander-Tetri, Rohit Loomba, Oscar Cummings, Miriam Vos, Stavra Xanthakos, Jeffrey Schwimmer and 4 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07731360 (A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity), which is not on this map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% 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.

NCT07731360 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity: Evaluation of a Multiparametric Biomarker Panel and Genetic Risk Score Using LASSO-Regularized Logistic Regression - The PedMASLD-MultiOmics Pilot Study

TypeobservationalSponsorKayseri City HospitalRan2026 to 2027Enrolled180ConditionsMetabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Insulin Resistance SyndromeArmsNon-Invasive Multi-Parameter Diagnostic Panel
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Impact of PNPLA3 I148M on Drug-Induced Hepatocellular Liver Injury: A Systematic Review and Meta-Analysis.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Pooled it
  3. Article
  4. Review
  5. Article
  6. The Phospholipase AJournal of lipid and atherosclerosis · 2026
    Review
  7. Article
  8. Review
  9. JHEP reports : innovation in hepatology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  15. Article
  16. Article
  17. Genetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024
    Review
  18. Article
  19. 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

14 authors at 8 institutions in 1 country.

Chaowapong JarasvaraparnDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, Indiana.
Eduardo Vilar-GomezDivision of Gastroenterology, and Hepatology, Indiana University School of Medicine, Indiana University Health, Indianapolis, Indiana.
Katherine P YatesDepartment of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
Laura A WilsonDepartment of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
Brent Neuschwander-TetriDivision of Gastroenterology, and Hepatology, Saint Louis University, St Louis, Missouri.
Rohit LoombaDivision of Gastroenterology, Hepatology, and Nutrition, University of California, San Diego School of Medicine, La Jolla, California.
Oscar CummingsDivision of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Miriam VosDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Stavra XanthakosDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Jeffrey SchwimmerDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California.
Jean P MollestonDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, Indiana.
Arun SanyalDivision of Gastroenterology, and Hepatology, Virginia Commonwealth University, Richmond, Virginia.
James TonasciaDepartment of Biostatistics and Epidemiology, Johns Hopkins University, Baltimore, Maryland.
Naga ChalasaniDivision of Gastroenterology, and Hepatology, Indiana University School of Medicine, Indiana University Health, Indianapolis, Indiana. Electronic address: nchalasa@iu.edu.
Indiana University School of MedicineJohns Hopkins University · USIndiana University Health · USUniversity of California San Diego · USCincinnati Children's Hospital Medical Center · USEmory University · USSaint Louis University · USVirginia Commonwealth University · US

Funding

Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
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
Nonalcoholic Steatohepatittis Clinical Research Network (NASH CRN)U01DK061731 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI ARUN J SANYAL · 2002 to 2026
$11.2M
Pathogenesis, prognosis, and treatment of NAFLD patientsU01DK061713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ANNA MAE ELIZABETH DIEHL · 2002 to 2026
$10.3M
Collaborative Clinical Research on Non Alcoholic StratohepatitisU01DK061737 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2002 to 2026
$10.2M
Clinical Research Network in Non-Alcoholic SteatohepatitisU01DK061728 · NIDDK · UNIVERSITY OF WASHINGTON · PI KRIS KOWDLEY · 2002 to 2026
$9.0M
Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)U01DK061738 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Norah A. Terrault · 2002 to 2026
$8.9M
Sibling Assessment in Prevention of Pediatric NAFLD in Hispanic ChildrenR01NR019083 · NINR · EMORY UNIVERSITY · PI WELSH, JEAN A. · 2021 to 2025
$3.3M
Biomarker Discovery for Nonalcoholic Fatty Liver Disease in ChildrenR01DK125701 · NIDDK · EMORY UNIVERSITY · PI VOS, MIRIAM B. · 2020 to 2022
$1.0M
NIDDK NIH HHS U01 DK061713NIDDK NIH HHS U01 DK061718NIDDK NIH HHS U01 DK061728NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01 DK061731NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01 DK061737NIDDK NIH HHS U01 DK061738NIDDK NIH HHS U24 DK061730
6 · The paper itself

Abstract

BACKGROUND &

aimsPNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD.

methodsA total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG).

resultsPNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m

conclusionsAge, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.

Indexed as

AcyltransferasesBody Mass IndexDiabetes Mellitus, Type 2LipaseLiver CirrhosisMembrane ProteinsNon-alcoholic Fatty Liver DiseasePhospholipases A2, Calcium-IndependentAdolescentAdultAgedAge FactorsChildFemaleGenetic Predisposition to DiseaseGenotypeAcyltransferasesLipaseMembrane ProteinsPhospholipases A2, Calcium-IndependentPNPLA3 protein, humanAdvanced FibrosisGenotypesModifierPNPLA3

Identifiers

PMID38145725
PMCPMC11045318
OpenAlexW4390147176

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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 OpenQuestion graph.