ArticleNature medicine2019
Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature medicine, 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 254 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
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254citing papers in PubMed, 3 pooled it
30.0field-weighted citation impact, top 1% of its field
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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.
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Who cites it
254 citing papers in PubMed, 3 syntheses or guidelines pooled it, 364 citations in OpenAlex.
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- Regular Aspirin Use Is Associated with a Reduced Risk of Hepatocellular Carcinoma (HCC) in Chronic Liver Disease: a Systematic Review and Meta-analysis.Journal of gastrointestinal cancer · 2023Pooled it
- Aspirin for the prevention of hepatocellular carcinoma: an updated meta-analysis with particular focus on patients with chronic liver disease.European journal of clinical pharmacology · 2022Pooled it
- Trial
- Anti-inflammatory versus metabolic therapy in MASLD: a randomized clinical trial of aspirin and dapagliflozin using fibroscan outcomes.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity.Journal of diabetes investigation · 2026Article
- A Biomimetic cRGDyk-Engineered Platelet Nanoplatform for ACAD11 Delivery to Trigger Pyroptosis in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Steatotic liver disease trajectory: A holistic EASL guidance on the multidisciplinary approach to screening and patient management.JHEP reports : innovation in hepatology · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Intrahepatic Platelets Orchestrate Microenvironmental Remodelling and Cellular Crosstalk in Liver Fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
- Deconformer: efficient cell-type composition profiling of cfRNA across diverse cell types.Briefings in bioinformatics · 2026Article
- Platelet-derived S100A9 contributes to endotheliopathy in alcohol-associated hepatitis.JCI insight · 2026Article
- Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.Cancer metastasis reviews · 2026Review
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Aspirin on the prevention of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Editorial on "Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: Nationwide cohort study with genetic risk analysis".Clinical and molecular hepatology · 2026Article
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- From bench to bedside: Molecular mechanisms, diagnostic tools, and therapeutic strategies in liver fibrosis.Liver research (Beijing, China) · 2026Review
194 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
67 authors at 20 institutions in 8 countries.
Mohsen Malehmir *Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Zurich, Switzerland.
Dominik Pfister *Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Suchira Gallage *Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Marta Szydlowska *Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4660-899X
Donato Inverso *Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0987-3345
Elena KotsilitiDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Valentina LeoneDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Moritz PeiselerCalvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Bas G J SurewaardDepartment of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Dominik RathDepartment of Cardiology and Circulatory Diseases, Internal Medicine Clinic III, Eberhard Karls University Tübingen, Tübingen, Germany.
Adnan AliDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Monika Julia WolfDepartment of Pathology and Molecular Pathology, University and University Hospital Zurich, Zurich, Switzerland.
Hannah DrescherDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Marc E HealyDepartment of Pathology and Molecular Pathology, University and University Hospital Zurich, Zurich, Switzerland.
Daniel DauchDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Daniela KroyDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Oliver KrenkelDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Marlene KohlheppDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Thomas EngleitnerCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, Munich, Germany.
Alexander OlkusDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Tjeerd SijmonsmaDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
Julia VolzInstitute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Carsten DeppermannInstitute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0003-3740-8635
David StegnerInstitute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0003-1059-9865
Patrick HelblingHematology, University Hospital and University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-6488-2805
César Nombela-ArrietaHematology, University Hospital and University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-0415-259X
Anahita RafieiHematology, University Hospital and University of Zurich, Zurich, Switzerland.
Martina HinterleitnerDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0001-7137-0541
Marcel RallDepartment of Cardiology and Circulatory Diseases, Internal Medicine Clinic III, Eberhard Karls University Tübingen, Tübingen, Germany.
Florian BakuDepartment of Cardiology and Circulatory Diseases, Internal Medicine Clinic III, Eberhard Karls University Tübingen, Tübingen, Germany.
Oliver BorstDepartment of Cardiology and Circulatory Diseases, Internal Medicine Clinic III, Eberhard Karls University Tübingen, Tübingen, Germany.
Caroline L WilsonNewcastle Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
Jack LeslieNewcastle Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
Tracy O'ConnorInstitute for Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Christopher J WestonCentre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham, UK.ORCID http://orcid.org/0000-0002-9651-1264
Abhishek ChauhanCentre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham, UK.
David H AdamsCentre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham, UK.
Lozan SheriffInstitute for Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Ana TeijeiroCancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
Marco PrinzInstitute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Ruzhica BogeskaDivision of Experimental Hematology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Natasha AnsteeDivision of Experimental Hematology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Malte N BongersDepartment of Diagnostic and Interventional Radiology, University Hospital of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0003-2852-0270
Mike NotohamiprodjoDepartment of Diagnostic and Interventional Radiology, University Hospital of Tübingen, Tübingen, Germany.
Tobias GeislerDepartment of Cardiovascular Medicine, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.
Dominic J WithersMetabolic Signalling Group, MRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0002-8009-7521
Jerry WareDepartment of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.ORCID http://orcid.org/0000-0001-8860-6338
Derek A MannNewcastle Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
Hellmut G AugustinDivision of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany.
Alexandros VegiopoulosDKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael D MilsomDivision of Experimental Hematology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Adam J RoseNutrient Metabolism and Signalling Lab, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, and Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.ORCID http://orcid.org/0000-0001-9132-8244
Patricia F LalorCentre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham, UK.
Josep M LlovetMount Sinai Liver Cancer Program (Divisions of Liver Diseases, Department of Medicine, Department of Pathology, Recanati Miller Transplantation Institute), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-0547-2667
Roser PinyolLiver Cancer Translational Research Laboratory, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain.
Frank TackeDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Roland RadCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, Munich, Germany.
Matthias MatterInstitute of Pathology, University Hospital of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2005-5266
Nabil DjouderCancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
Paul KubesCalvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.ORCID http://orcid.org/0000-0002-2835-4244
Percy A KnolleInstitute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0003-2983-0414
Kristian UngerResearch Unit of Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
Lars ZenderDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Bernhard NieswandtInstitute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Meinrad GawazDepartment of Cardiology and Circulatory Diseases, Internal Medicine Clinic III, Eberhard Karls University Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0003-1124-9592
Achim WeberDepartment of Pathology and Molecular Pathology, University and University Hospital Zurich, Zurich, Switzerland. achim.weber@usz.ch.ORCID http://orcid.org/0000-0003-0073-3637
Mathias HeikenwalderDivision of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany. heikenwaelder@helmholtz-muenchen.de.ORCID http://orcid.org/0000-0002-3135-2274
German Cancer Research Center · DEUniversity of Tübingen · DERWTH Aachen University · DEUniversity Hospital of Zurich · CHUniversity of Würzburg · DENational Institute for Health Research · GBNewcastle University · GBUniversity of Calgary · CAUniversity of Zurich · CHHelmholtz Zentrum München · DESpanish National Cancer Research Centre · ESUniversity Children's Hospital Tübingen · DEConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESInstitució Catalana de Recerca i Estudis Avançats · ESMonash University · AUMRC London Institute of Medical Sciences · GBTechnical University of Munich · DEUniversity Hospital of Basel · CHUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity of Arkansas for Medical Sciences · US
Funding
THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deanna L Benson · 2015 to 2026
$35.4MCancer Research UK 23390Cancer Research UK 26813Medical Research Council G0300101Medical Research Council G0300102Medical Research Council G0400496Medical Research Council G0700301Medical Research Council G0802577Medical Research Council MC_PC_14123Medical Research Council MC_U120097114Medical Research Council MR/K001949/1Medical Research Council MR/M009157/1NCI NIH HHS P30 CA196521Wellcome Trust
Abstract
Non-alcoholic fatty liver disease ranges from steatosis to non-alcoholic steatohepatitis (NASH), potentially progressing to cirrhosis and hepatocellular carcinoma (HCC). Here, we show that platelet number, platelet activation and platelet aggregation are increased in NASH but not in steatosis or insulin resistance. Antiplatelet therapy (APT; aspirin/clopidogrel, ticagrelor) but not nonsteroidal anti-inflammatory drug (NSAID) treatment with sulindac prevented NASH and subsequent HCC development. Intravital microscopy showed that liver colonization by platelets depended primarily on Kupffer cells at early and late stages of NASH, involving hyaluronan-CD44 binding. APT reduced intrahepatic platelet accumulation and the frequency of platelet-immune cell interaction, thereby limiting hepatic immune cell trafficking. Consequently, intrahepatic cytokine and chemokine release, macrovesicular steatosis and liver damage were attenuated. Platelet cargo, platelet adhesion and platelet activation but not platelet aggregation were identified as pivotal for NASH and subsequent hepatocarcinogenesis. In particular, platelet-derived GPIbα proved critical for development of NASH and subsequent HCC, independent of its reported cognate ligands vWF, P-selectin or Mac-1, offering a potential target against NASH.
Indexed as
AnimalsBlood PlateletsBody WeightCytokinesCytoplasmic GranulesEndotheliumHepatocytesHumansHyaluronan ReceptorsHyaluronic AcidKupffer CellsLiverLiver NeoplasmsMice, TransgenicNon-alcoholic Fatty Liver DiseasePlatelet Aggregationadhesion receptorCytokinesHyaluronan ReceptorsHyaluronic AcidPlatelet Aggregation InhibitorsPlatelet Glycoprotein GPIb-IX Complex
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