{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:17:59Z","timestamp":1787807879147,"version":"build-2784847793"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n            <jats:title>Background.<\/jats:title>\n            <jats:p>The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods.<\/jats:title>\n            <jats:p>We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results.<\/jats:title>\n            <jats:p>In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.027).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions.<\/jats:title>\n            <jats:p>At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/tp.0000000000004603","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T04:00:25Z","timestamp":1683259225000},"page":"2394-2405","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["Long-term Outcome of Asymptomatic Patients With Graft Fibrosis in Protocol Biopsies After Pediatric Liver Transplantation"],"prefix":"10.1097","volume":"107","author":[{"given":"Steffen","family":"Hartleif","sequence":"first","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hodson","sequence":"additional","affiliation":[{"name":"Department of Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom."},{"name":"Institute of Translational Medicine, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Liver Unit, Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir L.","family":"Cousin","sequence":"additional","affiliation":[{"name":"Swiss Pediatric Liver Centre, Division of Pediatric Specialties, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals Geneva and University of Geneva, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Czubkowski","sequence":"additional","affiliation":[{"name":"Department of Liver Disorders and Transplantation, The Children\u2019s Memorial Health Institute, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"D\u2019Antiga","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation, ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Debray","sequence":"additional","affiliation":[{"name":"Pediatric Liver Unit, National Reference Centre for Rare Pediatric Liver Diseases (Biliary Atresia and Genetic Cholestasis), FILFOIE, Necker-Enfants Malades Hospital, University of Paris, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Demetris","sequence":"additional","affiliation":[{"name":"Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Di Giorgio","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation, ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Starship Child Health, University of Auckland, Auckland, New Zealand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Fischler","sequence":"additional","affiliation":[{"name":"Pediatric Digestive Diseases, Astrid Lindgren Children\u2019s Hospital, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Gonzales","sequence":"additional","affiliation":[{"name":"H\u00e9patologie et Transplantation H\u00e9patique P\u00e9diatriques, Centre de r\u00e9f\u00e9rence de l\u2019atr\u00e9sie des voies biliaires et des cholestases g\u00e9n\u00e9tiques, FSMR FILFOIE, H\u00f4pital Bic\u00eatre, AP-HP, Universit\u00e9 Paris-Saclay, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette S.H.","family":"Gouw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan G.","family":"H\u00fcbscher","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."},{"name":"Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"H\u00e9patologie et Transplantation H\u00e9patique P\u00e9diatriques, Centre de r\u00e9f\u00e9rence de l\u2019atr\u00e9sie des voies biliaires et des cholestases g\u00e9n\u00e9tiques, FSMR FILFOIE, H\u00f4pital Bic\u00eatre, AP-HP, Universit\u00e9 Paris-Saclay, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[{"name":"Pediatric Liver Unit, National Reference Centre for Rare Pediatric Liver Diseases (Biliary Atresia and Genetic Cholestasis), FILFOIE, Necker-Enfants Malades Hospital, University of Paris, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Malenicka","sequence":"additional","affiliation":[{"name":"Pediatric Digestive Diseases, Astrid Lindgren Children\u2019s Hospital, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A.","family":"McLin","sequence":"additional","affiliation":[{"name":"Swiss Pediatric Liver Centre, Division of Pediatric Specialties, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals Geneva and University of Geneva, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Markiewicz-Kijewska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Transplantation, The Children\u2019s Memorial Health Institute, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George V.","family":"Mazariegos","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy K.","family":"Rajanayagam","sequence":"additional","affiliation":[{"name":"Paediatric Gastroenterology, Hepatology and Nutrition, The Royal Children\u2019s Hospital, Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Scheenstra","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Singer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies,\u201d University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Smets","sequence":"additional","affiliation":[{"name":"UClouvain, Clinical and Experimental Research Institute and Cliniques Universitaires Saint Luc, Service de Gastroent\u00e9rologie H\u00e9patologie P\u00e9diatrique, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Sokal","sequence":"additional","affiliation":[{"name":"UClouvain, Clinical and Experimental Research Institute and Cliniques Universitaires Saint Luc, Service de Gastroent\u00e9rologie H\u00e9patologie P\u00e9diatrique, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Squires","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Sturm","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henkjan","family":"Verkade","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Liver Unit, Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham, United Kingdom."},{"name":"University of Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Graft Injury Group (GIG)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,10,21]]},"reference":[{"key":"R1-20250604","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/hep.32223","article-title":"European Liver Transplant Registry: donor and transplant surgery aspects of 16,641 liver transplantations in children.","volume":"75","author":"de Ville de Goyet","year":"2022","journal-title":"Hepatology"},{"key":"R2-20250604","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1097\/TP.0b013e3182129215","article-title":"One thousand consecutive primary liver transplants under tacrolimus immunosuppression: a 17- to 20-year longitudinal follow-up.","volume":"91","author":"Jain","year":"2011","journal-title":"Transplantation"},{"key":"R3-20250604","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/ajt.14489","article-title":"Living donor liver transplantation for biliary atresia: an analysis of 2085 cases in the registry of the Japanese Liver Transplantation Society.","volume":"18","author":"Kasahara","year":"2018","journal-title":"Am J Transplant"},{"key":"R4-20250604","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1111\/ajt.14626","article-title":"Long-term outcome of liver transplantation in childhood: a study of 20-year survivors.","volume":"18","author":"Martinelli","year":"2018","journal-title":"Am J Transplant"},{"key":"R5-20250604","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jamcollsurg.2017.12.042","article-title":"One thousand pediatric liver transplants during thirty years: lessons learned.","volume":"226","author":"Venick","year":"2018","journal-title":"J Am Coll Surg"},{"key":"R6-20250604","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/lt.24696","article-title":"Health-related quality of life after pediatric liver transplantation: a systematic review.","volume":"23","author":"Parmar","year":"2017","journal-title":"Liver Transpl"},{"key":"R7-20250604","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/petr.12119","article-title":"Liver allograft pathology in healthy pediatric liver transplant recipients.","volume":"17","author":"Briem-Richter","year":"2013","journal-title":"Pediatr Transplant"},{"key":"R8-20250604","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.clinre.2013.10.009","article-title":"Clinical and histological outcomes following living-related liver transplantation in children.","volume":"38","author":"Dattani","year":"2014","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"R9-20250604","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/lt.21549","article-title":"Graft histology characteristics in long-term survivors of pediatric liver transplantation.","volume":"14","author":"Ekong","year":"2008","journal-title":"Liver Transpl"},{"key":"R10-20250604","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/hep.21152","article-title":"Progressive histological damage in liver allografts following pediatric liver transplantation.","volume":"43","author":"Evans","year":"2006","journal-title":"Hepatology"},{"key":"R11-20250604","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/lt.20358","article-title":"Long-term outcome of pediatric liver transplantation for biliary atresia: a 10-year follow-up in a single center.","volume":"11","author":"Fouquet","year":"2005","journal-title":"Liver Transpl"},{"key":"R12-20250604","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/lt.23565","article-title":"Low-dose steroids associated with milder histological changes after pediatric liver transplantation.","volume":"19","author":"Kosola","year":"2013","journal-title":"Liver Transpl"},{"key":"R13-20250604","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/lt.23534","article-title":"Progressive graft fibrosis and donor-specific human leukocyte antigen antibodies in pediatric late liver allografts.","volume":"18","author":"Miyagawa-Hayashino","year":"2012","journal-title":"Liver Transpl"},{"key":"R14-20250604","doi-asserted-by":"crossref","first-page":"6638","DOI":"10.3748\/wjg.v20.i21.6638","article-title":"Protocol liver biopsy is the only examination that can detect mid-term graft fibrosis after pediatric liver transplantation.","volume":"20","author":"Sanada","year":"2014","journal-title":"World J Gastroenterol"},{"key":"R15-20250604","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1002\/hep.22686","article-title":"Graft fibrosis after pediatric liver transplantation: ten years of follow-up.","volume":"49","author":"Scheenstra","year":"2009","journal-title":"Hepatology"},{"key":"R16-20250604","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/lt.23708","article-title":"Acoustic radiation force impulse imaging for assessing graft fibrosis after pediatric living donor liver transplantation: a pilot study.","volume":"19","author":"Tomita","year":"2013","journal-title":"Liver Transpl"},{"key":"R17-20250604","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1399-3046.2011.01483.x","article-title":"Graft fibrosis in patients with biliary atresia after pediatric living-related liver transplantation.","volume":"15","author":"Ueno","year":"2011","journal-title":"Pediatr Transplant"},{"key":"R18-20250604","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1111\/j.1600-6143.2012.04210.x","article-title":"Novel histologic scoring system for long-term allograft fibrosis after liver transplantation in children.","volume":"12","author":"Venturi","year":"2012","journal-title":"Am J Transplant"},{"key":"R19-20250604","doi-asserted-by":"crossref","first-page":"e13212","DOI":"10.1111\/petr.13212","article-title":"Histological findings in protocol biopsies following pediatric liver transplant: low incidence of abnormalities at 5 years.","volume":"22","author":"Sheikh","year":"2018","journal-title":"Pediatr Transplant"},{"key":"R20-20250604","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ebiom.2016.05.040","article-title":"Progressive fibrosis is driven by genetic predisposition, allo-immunity, and inflammation in pediatric liver transplant recipients.","volume":"9","author":"Varma","year":"2016","journal-title":"EBioMedicine"},{"key":"R21-20250604","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/ajt.16270","article-title":"Subclinical biliary strictures as a cause of long-term allograft dysfunction in children who underwent liver 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Hepatol"},{"key":"R25-20250604","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/lt.24616","article-title":"Late graft hepatitis and fibrosis in pediatric liver allograft recipients: current concepts and future developments.","volume":"22","author":"Kelly","year":"2016","journal-title":"Liver Transpl"},{"key":"R26-20250604","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1097\/TP.0000000000003099","article-title":"Peripheral donor-specific antibodies are associated with histology and cellular subtypes in protocol liver biopsies of pediatric recipients.","volume":"104","author":"Cousin","year":"2020","journal-title":"Transplantation"},{"key":"R27-20250604","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1097\/TP.0000000000000638","article-title":"Long-term clinical relevance of de novo donor-specific antibodies after pediatric liver 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biopsies.","volume":"28","author":"Perito","year":"2022","journal-title":"Liver Transpl"},{"key":"R31-20250604","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11894-020-00802-1","article-title":"Transition of pediatric liver transplant patients to adult care: a review.","volume":"23","author":"Stevens","year":"2021","journal-title":"Curr Gastroenterol Rep"},{"key":"R32-20250604","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1002\/lt.26482","article-title":"Standardizing the histological assessment of late posttransplantation biopsies from pediatric liver allograft recipients.","volume":"28","author":"Hubscher","year":"2022","journal-title":"Liver 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