Artificial intelligence predicts recurrent autoimmune hepatitis after liver transplantation in a multicenter cohort study
Hepatology Communications, vol. 10
Abstract
BACKGROUND: Autoimmune hepatitis (AIH) is an important indication for liver transplantation (LT), but recurrence affects over 30% of recipients, threatening long-term survival. Current strategies to prevent recurrence and progressive graft fibrosis remain suboptimal, with limited evidence to guide selection of immunosuppressive regimens. We aimed to develop a dynamic, individualized, artificial intelligence-powered model for post-transplant recurrent AIH. METHODS: We conducted a multicenter, retrospective cohort study of 706 patients who underwent LT for AIH between January 1987 and June 2020 at 33 centers in North America, South America, Europe, and Asia. We trained 4 predictive machine learning models-Logistic Regression, Random Forest, XGBoost, and Gradient Boost-to predict recurrent AIH (rAIH) using 62 clinical and laboratory variables, including demographic, biochemical features, and immunosuppressive drugs up to 1-year post-transplant. Feature importance was assessed using SHapley Additive exPlanations (SHAP) to enable interpretability at both individual and population levels.Results:AIH recurred in 16.5% of patients after LT. SHAP analysis identified younger age at LT, higher necroinflammatory activity in the explanted liver, and elevated MELD score at LT as key predictors of rAIH in the overall population. Tacrolimus-based therapy was associated with a lower risk of recurrence, while cyclosporine use conferred a higher risk. The addition of long-term prednisone to a regimen of tacrolimus and mycophenolate mofetil did not provide additional protective effect against rAIH. CONCLUSIONS: Our AI-powered clinical decision model provides personalized prediction of post-transplant rAIH. While it offers insight into modifiable and non-modifiable predictors, prospective validation is required before informing immunosuppressive decisions.
Authors 74
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University Health Network · University of Toronto · Toronto General Hospital Research Institute
Affiliation as printed
Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
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Affiliation as printed
Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
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Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
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Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
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University Hospitals Birmingham NHS Foundation Trust · NIHR Birmingham Liver Biomedical Research Unit · NIHR Birmingham Biomedical Research Centre · University of Birmingham
Affiliation as printed
Center for Liver Research and NIHR Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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University Health Network · University of Toronto · Erasmus MC
Affiliation as printed
Erasmus MC University Medical Center, Rotterdam, The Netherlands
Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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University Health Network · University of Toronto
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Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Baylor University Medical Center
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Baylor University Medical Center, Dallas, Texas, USA
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Baylor University Medical Center
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Baylor University Medical Center, Dallas, Texas, USA
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Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
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Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
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Sahlgrenska University Hospital
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Sahlgrenska University Hospital, Gothenburg, Sweden
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Sahlgrenska University Hospital
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Sahlgrenska University Hospital, Gothenburg, Sweden
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Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey
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Department of Gastroenterology, Adiyaman University School of Medicine, Adiyaman, Turkey
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Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey
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Affiliation as printed
Clinic of Gastroenterology and Liver Transplantation, Guven Hospital Ankara, Turkey
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Affiliation as printed
Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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University Health Network · University of Toronto
Affiliation as printed
Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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University Health Network · University of Toronto
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Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Beth Israel Deaconess Medical Center · Harvard University
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Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Hospital Clínic de Barcelona · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · Universitat de Barcelona
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Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
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Hospital Clínic de Barcelona · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · Universitat de Barcelona
Affiliation as printed
Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
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Affiliation as printed
Koç University School of Medicine, Department of Gastroenterology and Liver Transplantation Center, Istanbul, Turkey
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Koç University · Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi
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Division of Pediatric Gastroenterology and Hepatology, Organ Transplantation Center, Koc University School of Medicine, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
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Medizinische Hochschule Hannover
Affiliation as printed
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Medizinische Hochschule Hannover
Affiliation as printed
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Medizinische Hochschule Hannover
Affiliation as printed
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, New York, USA
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Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, New York, USA
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Children's Memorial Health Institute
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Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
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Children's Memorial Health Institute
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Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
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Children's Memorial Health Institute
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Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
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The University of Tokyo, Tokyo, Japan
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Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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University of Miami Miller School of Medicine, Miami, Florida, USA
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University of Miami Miller School of Medicine, Miami, Florida, USA
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Stanford Medicine · Stanford University
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Stanford University School of Medicine, Stanford, California, USA
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Stanford Medicine · Stanford University
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Stanford University School of Medicine, Stanford, California, USA
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Children's Memorial Health Institute
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The Children’s Memorial Health Institute, Warsaw, Poland
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Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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University Medical Center Hamburg-Eppendorf
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University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
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University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
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University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
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University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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Liver Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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University Medical Center Hamburg-Eppendorf
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University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · Instituto de Investigación Biomédica de Málaga · Universidad de Málaga
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Gastroenterology Service—IBIMA, University Hospital and CIBERehd, University of Málaga, Málaga, Spain
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Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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Bart van Hoek Aachen
Leiden University Medical Center
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Leiden University Medical Center, Leiden, The Netherlands
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Maaike Biewenga Aachen
Leiden University Medical Center
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Leiden University Medical Center, Leiden, The Netherlands
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Friedrich-Alexander-Universität Erlangen-Nürnberg · University of Zurich · Universitätsklinikum Erlangen · University Hospital Zurich
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Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
Department of Medicine, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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University of Utah, Salt Lake City, Utah, USA
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The University of Texas Southwestern Medical Center
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University of Texas Southwestern Medical Center, Dallas, Texas, USA
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The University of Texas Southwestern Medical Center
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University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
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Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
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University of Padova, Padova, Italy
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Epatocentro Ticino · Università della Svizzera italiana
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Epatocentro Ticino, Università della Svizzera Italiana, Lugano, Switzerland
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UPMC Pediatric Liver Center, Palermo, Italy
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Bambino Gesù Children's Hospital · Istituti di Ricovero e Cura a Carattere Scientifico
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Hepatogastroenterology, Nutrition and Liver Transplant Unit, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy
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Henry Ford Health System, Detroit, Michigan, USA
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Hôpital Necker-Enfants Malades · Université Paris Cité
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Pediatric Liver Unit, French National Reference Center for Rare Diseases Biliary Atresia and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France
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Hôpital Necker-Enfants Malades · Université Paris Cité
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Pediatric Liver Unit, French National Reference Center for Rare Diseases Biliary Atresia and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France
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Hôpital Necker-Enfants Malades
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Gastroenterology–Hepatology–Nutrition Unit, Hôpital Necker–Enfants Malades, Paris, France
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
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Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Humanitas University · IRCCS Humanitas Research Hospital
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Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS, Humanitas Research Hospital, Rozzano, Milan, Italy
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Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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King's College Hospital NHS Foundation Trust
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King’s College Hospital NHS Foundation Trust, London, UK
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University Hospitals Birmingham NHS Foundation Trust · NIHR Birmingham Biomedical Research Centre · University of Birmingham
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Center for Liver and Gastrointestinal Research and National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham; Centre for Rare Disease and ERN Rare Liver Centre, Liver Transplant and Hepatobiliary Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
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Affiliation as printed
Division of Preventive Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Affiliation as printed
Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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