ArticleNature communications2019
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 121 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 3 pooled it
13.8field-weighted citation impact, top 1% of its field
What it found
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Preclinical Analysis of Bone Marrow-Derived Stem Cell Therapy Response and Transcriptomic Overlap Analysis in a Severe Alcoholic Hepatitis Mouse Model.Gut and liver · 2026Pooled it
- Alcohol-Associated Hepatocarcinogenesis: Wnt/β-Catenin in Action.The American journal of pathology · 2026Pooled it
- Pooled it
- Article
- A human single-cell atlas identifies OLR1Nature genetics · 2026Article
- Hepatoprotective effects of resolvin D1 in mice exposed to ethanol and galactosamine.Hepatology communications · 2026Article
- A microbial metabolite reduces alcohol-induced inflammation via dual modulation of NF-κB and Interferon pathway.bioRxiv : the preprint server for biology · 2026Article
- Ligand-dependent reprogramming of HNF4A expression and function suppresses multistep hepatocarcinogenesis.Molecular therapy. Oncology · 2026Article
- Multiplexed targeted mRNA profiling of alcohol-related liver disease reveals stage-specific dysregulation of signaling pathways.Molecular biology reports · 2026Article
- Patient-specific modeling identifies metabolic interventions for reversing glucose use reprogramming in alcohol-associated hepatitis.Communications biology · 2026Article
- Calpain-4 Knockdown Modulates Cholesterol Metabolism and LXRα Nuclear Localization in Experimental Alcohol-Related Liver Disease.Alcohol, clinical & experimental research · 2026Article
- Global changes in gene expression and splicing in alcoholic liver disease.Scientific reports · 2026Article
- Emerging therapeutic regimens as alternatives to glucocorticoids for severe alcohol-associated hepatitis: a comprehensive review.Clinical and molecular hepatology · 2026Review
- Single Cell Analysis Reveals the Presence of Novel Intermediate Cells in Both Mice and Patients With Severe MASLD.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- α-Diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis.JCI insight · 2026Article
- Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis.Scientific reports · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- IL-6 trans-Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
40 authors at 17 institutions in 7 countries.
Josepmaria ArgemiDivision of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, 15261, USA.ORCID http://orcid.org/0000-0003-1696-7753
Maria U LatasaHepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain.ORCID http://orcid.org/0000-0002-0878-1337
Stephen R AtkinsonDivision of Digestive Diseases, Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
Ilya O BlokhinCenter for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Veronica MasseyDivision of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA.
Joel P GueDivision of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, 15261, USA.
Joaquin CabezasDivision of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA.ORCID http://orcid.org/0000-0003-0012-484X
Juan J LozanoCentro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, 28029, Spain.
Derek Van BoovenJohn P. Hussman Institute of Human Genomics. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Aaron BellDepartments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.ORCID http://orcid.org/0000-0001-6648-0834
Sheng CaoDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA.
Lawrence A VernettiUniversity of Pittsburgh Drug Discovery Institute, Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Juan P ArabDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-8561-396X
Meritxell Ventura-CotsDivision of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, 15261, USA.ORCID http://orcid.org/0000-0001-9513-2855
Lia R EdmundsDepartment of Medicine, Division of Endocrinology and Metabolism, Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Constantino FondevilaLiver Transplant Unit, Department of Surgery, Hospital Clinic, University of Barcelona, Barcelona, 08036, Spain.
Peter StärkelService d'Hépato-gastroentérologie, Cliniques Universitaires Saint-Luc and Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, 1200, Belgium.ORCID http://orcid.org/0000-0003-2938-4442
Laurent DubuquoyService des Maladies de l'appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille, Lille, 59000, France.ORCID http://orcid.org/0000-0003-3596-5497
Alexandre LouvetService des Maladies de l'appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille, Lille, 59000, France.
Gemma OdenaDivision of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA.
Juan L GomezDepartments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Tomas AragonDepartment of Gene Therapy and Regulation, Center for Applied Medical Research, University of Navarra, Pamplona, 31008, Spain.
Jose AltamiranoLiver Unit, Department of Internal Medicine, Vall d'Hebron Institut de Recerca. Internal Medicine Department, Hospital Quiron Salud, Barcelona, 08035, Spain.
Juan CaballeriaCentro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, 28029, Spain.
Michael J JurczakDepartment of Medicine, Division of Endocrinology and Metabolism, Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA.ORCID http://orcid.org/0000-0002-6335-6915
D Lansing TaylorUniversity of Pittsburgh Drug Discovery Institute, Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Carmen BerasainHepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain.ORCID http://orcid.org/0000-0001-7075-2476
Claes WahlestedtCenter for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.ORCID http://orcid.org/0000-0003-4471-5916
Satdarshan P MongaDepartments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.ORCID http://orcid.org/0000-0002-8437-3378
Marsha Y MorganUCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, WC1E 6BT, UK.
Pau Sancho-BruCentro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, 28029, Spain.ORCID http://orcid.org/0000-0001-5569-9259
Philippe MathurinService des Maladies de l'appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille, Lille, 59000, France.
Shinji FuruyaDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77845, USA.
Carolin LacknerMedical University of Graz, Institute of Pathology, Graz, 8036, Austria.
Ivan RusynDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77845, USA.
Vijay H ShahDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA.
Mark R ThurszDivision of Digestive Diseases, Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
Jelena MannNewcastle Fibrosis Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Matias A AvilaHepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain.
Ramon BatallerDivision of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, 15261, USA. bataller@pitt.edu.ORCID http://orcid.org/0000-0001-6570-3557
University of Pittsburgh · USCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESUniversity of North Carolina at Chapel Hill · USInserm · FRUniversity of Miami · USUniversity of Pittsburgh Medical Center · USImperial College London · GBMayo Clinic in Arizona · USTexas A&M University · USUniversidad de Navarra · ESCliniques Universitaires Saint-Luc · BEMedical University of Graz · ATNewcastle University · GBPontificia Universidad Católica de Chile · CLThe Royal Free Hospital · GBUniversitat de Barcelona · ESVall d'Hebron Institut de Recerca · ES
Funding
Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9MRole of Wnt/Beta-Catenin Signaling in Liver DevelopmentR01DK062277 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Satdarshan Singh Monga · 2004 to 2026
$9.0MT32 Research Training in Diabetes and EndocrinologyT32DK007052 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROBERT M O'DOHERTY · 1986 to 2026
$6.3MMeasuring the Temporal-Spatial Responses of Dormancy and Drug Resistance in a Human Breast Cancer Metastatic Niche within a Liver-on-a-Chip Microphysiological PlatformUH3TR000503 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2014 to 2016
$6.2MMolecular Subtypes for Targeted Therapies in Alcoholic HepatitisU01AA021908 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATALLER, RAMON · 2013 to 2017
$6.0MElucidating the role of the FXR-PTEN-PI3K-AKT-mTOR axis in liver progenitor cell-driven liver regenerationR01DK101426 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIN, DONGHUN · 2014 to 2023
$3.8MEpigenetic Regulation of Alcoholic Liver FibrosisU01AA018663 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KISSELEVA, TATIANA, MANN, DEREK · 2010 to 2019
$3.7MMolecular Mechanisms of Liver Fibrosis (Diversity Supplement)R37AA021171 · NIAAA · MAYO CLINIC ROCHESTER · PI VIJAY H. SHAH · 2019 to 2026
$3.0MMolecular Mechanisms of Liver FibrosisR01AA021171 · NIAAA · MAYO CLINIC ROCHESTER · PI SHAH, VIJAY H. · 2012 to 2018
$2.5MMapping Disease Pathways for Biliary AtresiaR01DK109365 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIN, DONGHUN, SINDHI, RAKESH K. · 2017 to 2020
$2.4MDelineating Molecular Mechanisms Underlying Liver Progenitor Cell-Driven Liver RegenerationR01DK116993 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MONGA, SATDARSHAN SINGH, SHIN, DONGHUN · 2018 to 2021
$2.2MEpigenetic Signaling Pathways Contributing to Alcohol DependenceR01AA023781 · NIAAA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HEILIG, MARKUS ALEXANDER, WAHLESTEDT, CLAES ROBERT · 2015 to 2019
$2.1MMedical Research Council MR/K001949/1Medical Research Council MR/M003132/1Medical Research Council MR/R014019/1Medical Research Council MR/R023026/1NCATS NIH HHS UH3 TR000503NIAAA NIH HHS R01 AA021171NIAAA NIH HHS R01 AA023781NIAAA NIH HHS R37 AA021171NIAAA NIH HHS U01 AA018663NIAAA NIH HHS U01 AA021908NIAAA NIH HHS U01 AA026972NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK062277NIDDK NIH HHS R01 DK101426NIDDK NIH HHS R01 DK109365NIDDK NIH HHS R01 DK114012NIDDK NIH HHS R01 DK116993NIDDK NIH HHS T32 DK007052
Abstract
Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
Indexed as
AdultAgedAnimalsBiopsyChromatin Assembly and DisassemblyDisease ProgressionDNA MethylationEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression RegulationHepatitis, AlcoholicHepatocyte Nuclear Factor 4HepatocytesHumansLiverHepatocyte Nuclear Factor 4NR2A3 protein, humanTGFB1 protein, humanTransforming Growth Factor beta1
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