{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T09:02:01Z","timestamp":1792314121038,"version":"4.4.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3410,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>The long-term histological outcome after pediatric liver transplantation (OLT) is not yet fully understood.<\/jats:bold>\n                      <jats:bold>De novo<\/jats:bold>\n                      <jats:bold>autoimmune hepatitis, consisting of histological chronic hepatitis associated with autoantibody formation and allograft dysfunction, is increasingly recognized as an important complication of liver transplantation, particularly in the pediatric population. In this study, 158 asymptomatic children with 5-year graft survival underwent protocol liver biopsies (113, 135, and 64 at 1, 5, and 10 years after OLT, respectively). Histological changes were correlated with clinical, biochemical, and serological findings. All patients received cyclosporine A as primary immunosuppression with withdrawal of corticosteroids at 3 months post OLT. Normal or near-normal histology was reported in 77 of 113 (68%), 61 of 135 (45%), and 20 of 64 (31%) at 1, 5, and 10 years, respectively. The commonest histological abnormality was chronic hepatitis (CH), the incidence of which increased with time [25\/113 (22%), 58\/135 (43%), and 41\/64 (64%) at 1, 5, and 10 years, respectively) (<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>&lt; .0001)]. The incidence of fibrosis associated with CH increased with time [13\/25 (52%), 47\/58 (81%), and 37\/41 (91%) at 1, 5, and 10 years, respectively) (<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>&lt; .0001)]. The severity of fibrosis associated with CH also increased with time, such that by 10 years 15% had progressed to cirrhosis. Aspartate aminotransferase (AST) levels were slightly elevated in children with CH (median levels 52 IU\/L, 63 IU\/L, and 48 IU\/L at 1, 5, and 10 years, respectively), but this did not reach statistical significance compared with those with normal histology. On multivariate analysis, the only factor predictive of chronic hepatitis was autoantibody positivity (present in 13% and 10% of children with normal biopsies at 5 and 10 years, respectively, and 72% and 80% of those with CH at 5 and 10 years, respectively) (<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>&lt; .0001). Four children with CH and autoantibodies, who also had raised immunoglobulin G (IgG) levels and AST greater than 1.5\u00d7 normal fulfilled the diagnostic criteria for<\/jats:bold>\n                      <jats:bold>de novo<\/jats:bold>\n                      <jats:bold>autoimmune hepatitis (AIH). Another two were found to be hepatitis C positive. No definite cause for CH could be identified in the other cases.<\/jats:bold>\n                      <jats:bold>In conclusion<\/jats:bold>\n                      <jats:bold>, chronic hepatitis is a common finding in children after liver transplantation and is associated with a high risk of developing progressive fibrosis, leading to cirrhosis. Standard liver biochemical tests cannot be relied on either in the diagnosis or in the monitoring of progress of chronic allograft hepatitis. In contrast, the presence of autoantibodies is strongly associated with the presence of CH. The cause of chronic hepatitis in transplanted allografts is uncertain but may be immune mediated, representing a hepatitic form of chronic rejection. (Hepatology 2006;43:1109\u20131117.)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.21152","type":"journal-article","created":{"date-parts":[[2006,4,20]],"date-time":"2006-04-20T14:51:47Z","timestamp":1145544707000},"page":"1109-1117","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":289,"title":["Progressive histological damage in liver allografts following pediatric liver transplantation"],"prefix":"10.1097","volume":"43","author":[{"given":"Helen M.","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"McKiernan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"H\u00fcbscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-28-20241201","first-page":"214","article-title":"Current results and evolving indications for liver transplantation in children.","volume":"27","author":"Kelly","year":"1998","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R2-28-20241201","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1053\/jlts.2002.34149","article-title":"Longterm survival and late graft loss in pediatric liver transplant recipients: a 15year singlecenter experience.","volume":"8","author":"Wallot","year":"2002","journal-title":"Liver Transpl"},{"key":"R3-28-20241201","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1097\/00000478-199502000-00008","article-title":"Structural integrity and identification of causes of liver allograft dysfunction occurring more than 5 years after transplantation.","volume":"19","author":"Pappo","year":"1995","journal-title":"Am J Surg Pathol"},{"key":"R4-28-20241201","first-page":"195","article-title":"Graft and systemic disease in longterm survivors of liver transplantation.","volume":"25","author":"Slapak","year":"1997","journal-title":"HEPATOLOGY"},{"key":"R5-28-20241201","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1053\/jhep.2003.50231","article-title":"All liver recipients benefit from the protocol 10year liver biopsies.","volume":"37","author":"Sebagh","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R6-28-20241201","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/lt.500040603","article-title":"Hepatitis after liver transplantation: the role of the known and unknown viruses.","volume":"4","author":"Pessoa","year":"1998","journal-title":"Liver Transpl Surg"},{"key":"R7-28-20241201","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1053\/jhep.2001.26756","article-title":"Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults.","volume":"34","author":"Heneghan","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R8-28-20241201","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0140-6736(97)06478-7","article-title":"Denovo autoimmune hepatitis after liver transplantation.","volume":"351","author":"Kerkar","year":"1998","journal-title":"Lancet"},{"key":"R9-28-20241201","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/00007890-200107270-00018","article-title":"Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.","volume":"72","author":"Andries","year":"2001","journal-title":"Transplantation"},{"key":"R10-28-20241201","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1097\/00007890-200103150-00016","article-title":"De novo hepatitis with autoimmune antibodies and atypical histology: a rare cause of late graft dysfunction after pediatric liver transplantation.","volume":"71","author":"Gupta","year":"2001","journal-title":"Transplantation"},{"key":"R11-28-20241201","first-page":"131","article-title":"Autoimmune hepatitis as a late complication of liver transplantation.","volume":"32","author":"Hernandez","year":"2001","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R12-28-20241201","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/hep.510300103","article-title":"Development of autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.","volume":"30","author":"Jones","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R13-28-20241201","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1053\/jhep.2002.35339","article-title":"Autoimmunity after liver transplantation.","volume":"36","author":"Vergani","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R14-28-20241201","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1053\/jlts.2001.23792","article-title":"Concurrent de novo autoimmune hepatitis and recurrence of primary biliary cirrhosis postliver transplantation.","volume":"7","author":"Tan","year":"2001","journal-title":"Liver Transpl"},{"key":"R15-28-20241201","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/S0168-8278(01)00070-8","article-title":"Serial liver biopsies: a gateway into understanding the longterm health of the liver allograft.","volume":"34","author":"Lucey","year":"2001","journal-title":"J Hepatol"},{"key":"R16-28-20241201","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/lt.500030601","article-title":"Pathological changes in yearly protocol liver biopsy specimens from healthy pediatric liver recipients.","volume":"3","author":"Rosenthal","year":"1997","journal-title":"Liver Transpl Surg"},{"key":"R17-28-20241201","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/hep.510250435","article-title":"Posttransplantation chronic hepatitis in fulminant hepatic failure.","volume":"25","author":"Mohamed","year":"1997","journal-title":"HEPATOLOGY"},{"key":"R18-28-20241201","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0168-8278(05)80244-2","article-title":"Primary biliary cirrhosis. Histological evidence of disease recurrence after liver transplantation.","volume":"18","author":"Hubscher","year":"1993","journal-title":"J Hepatol"},{"key":"R19-28-20241201","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1097\/00007890-200012150-00008","article-title":"Predictive factors for portal fibrosis in pediatric liver transplant recipients.","volume":"70","author":"Peeters","year":"2000","journal-title":"Transplantation"},{"key":"R20-28-20241201","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1053\/jlts.2003.50165","article-title":"An evaluation of longterm outcomes after liver transplantation for cryptogenic cirrhosis.","volume":"9","author":"Heneghan","year":"2003","journal-title":"Liver Transpl"},{"key":"R21-28-20241201","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jhep.2004.05.013","article-title":"Donor age influences 10year liver graft histology independently of hepatitis C virus infection.","volume":"41","author":"Rifai","year":"2004","journal-title":"J Hepatol"},{"key":"R22-28-20241201","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1053\/jlts.2001.23794","article-title":"Are posttransplantation protocol liver biopsies useful in the long term?","volume":"7","author":"Berenguer","year":"2001","journal-title":"Liver Transpl"},{"key":"R23-28-20241201","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1053\/jlts.2001.23085","article-title":"Recurrent autoimmune hepatitis after liver transplantation: diagnostic criteria, risk factors, and outcome.","volume":"7","author":"Hubscher","year":"2001","journal-title":"Liver Transpl"},{"key":"R24-28-20241201","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.transproceed.2004.12.113","article-title":"Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence.","volume":"37","author":"Nakhleh","year":"2005","journal-title":"Transplant Proc"},{"key":"R25-28-20241201","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/S0168-8278(98)80225-0","article-title":"Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections.","volume":"28","author":"Davison","year":"1998","journal-title":"J Hepatol"},{"key":"RU26-28-20241201","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0168-8278(00)80175-0","article-title":"Autoantibodies associated with acute rejection after liver transplantation for type2 autoimmune hepatitis.","volume":"33","author":"DuclosVallee","year":"2000","journal-title":"J Hepatol"},{"key":"RU27-28-20241201","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0168-8278(99)80175-5","article-title":"Development of cytochrome P450 2D6specific LKMautoantibodies following liver transplantation for Wilsons disease: possible association with a steroidresistant transplant rejection episode.","volume":"31","author":"Lohse","year":"1999","journal-title":"J Hepatol"},{"key":"R28-28-20241201","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00007890-200201150-00015","article-title":"Late cellular rejection in paediatric liver transplantation: aetiology and outcome.","volume":"73","author":"DAntiga","year":"2002","journal-title":"Transplantation"},{"key":"R29-28-20241201","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/01.TP.0000132328.33460.43","article-title":"Outcome and risk factors of de novo autoimmune hepatitis in livingdonor liver transplantation.","volume":"78","author":"MiyagawaHayashino","year":"2004","journal-title":"Transplantation"},{"key":"R30-28-20241201","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/00007890-199501150-00008","article-title":"Importance of concomitant viral infection during late acute liver allograft rejection.","volume":"59","author":"Cakaloglu","year":"1995","journal-title":"Transplantation"},{"key":"R31-28-20241201","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/336176a0","article-title":"Abnormal differentiation of thymocytes in mice treated with cyclosporin A.","volume":"336","author":"Gao","year":"1988","journal-title":"Nature"},{"key":"R32-28-20241201","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1053\/jlts.2002.33485","article-title":"Autoimmune hepatitis after liver transplantation and other lessons of selftolerance.","volume":"8","author":"Czaja","year":"2002","journal-title":"Liver Transpl"},{"key":"R33-28-20241201","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/lt.20123","article-title":"Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation.","volume":"10","author":"Neuberger","year":"2004","journal-title":"Liver Transpl"},{"key":"R34-28-20241201","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1136\/adc.75.6.502","article-title":"Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy.","volume":"75","author":"Murphy","year":"1996","journal-title":"Arch Dis Child"},{"key":"R35-28-20241201","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1097\/01.TP.0000062570.83203.A3","article-title":"Pediatric liver transplantation for biliary atresia: results of primary grafts in 328 recipients.","volume":"75","author":"Diem","year":"2003","journal-title":"Transplantation"},{"key":"R36-28-20241201","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/lt.20358","article-title":"Longterm outcome of pediatric liver transplantation for biliary atresia: a 10year followup in a single center.","volume":"11","author":"Fouquet","year":"2005","journal-title":"Liver Transpl"},{"key":"R37-28-20241201","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1097\/01.TP.0000160758.13505.D2","article-title":"Pediatric transplantation: the Hamburg experience.","volume":"79","author":"Kim","year":"2005","journal-title":"Transplantation"},{"key":"R38-28-20241201","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/01.TP.0000131663.87106.1A","article-title":"Health status ten years after pediatric liver transplantation-looking beyond the graft.","volume":"78","author":"Avitzur","year":"2004","journal-title":"Transplantation"},{"key":"R39-28-20241201","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1097\/00007890-200008270-00015","article-title":"Comparative longterm evaluation of tacrolimus and cyclosporine in pediatric liver transplantation.","volume":"70","author":"Jain","year":"2000","journal-title":"Transplantation"},{"key":"R40-28-20241201","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/00007890-199560120-00013","article-title":"A randomized prospective trial of steroid withdrawal after liver transplantation.","volume":"60","author":"McDiarmid","year":"1995","journal-title":"Transplantation"},{"key":"R41-28-20241201","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1097\/01.TP.0000063938.49112.C2","article-title":"Steroid withdrawal after pediatric liver transplantation: a longterm followup study in 109 recipients.","volume":"75","author":"Diem","year":"2003","journal-title":"Transplantation"},{"key":"R42-28-20241201","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/lt.500050505","article-title":"Outcome of liver retransplantation in children.","volume":"5","author":"Achilleos","year":"1999","journal-title":"Liver Transpl Surg"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.21152","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200605000-00028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T08:02:47Z","timestamp":1733040167000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200605000-00028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.21152","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2006,5]]}}}