title: Graft fibrosis after pediatric liver transplantation: ten years of follow-up.
abstract: Previously we reported the presence of portal fibrosis in 31% (n = 84) of the grafts in protocol biopsies 1 year after pediatric liver transplantation (LTx). To assess the natural history of graft fibrosis after pediatric liver transplantation, we extended the analysis of graft histology in follow-up protocol biopsy specimens obtained 5 and 10 years after transplantation. We correlated histological results with clinical parameters at the time of LTx and during follow-up, to allow identification of risk factors for the development of fibrosis. From 1 year to 5 years after LTx, the prevalence of fibrosis increased from 31% to 65% (n = 66) but remained stable thereafter (at 10 years, 69%, n = 55). At 10 years after LTx, however, the percentage of patients with severe fibrosis had increased from 10% (at 5 years) to 29%. Of the 69% of children without fibrosis at 1 year post-transplantation, 64% (n = 39) had developed some degree of fibrosis at 10 years. Fibrosis was strongly related to transplant-related factors such as prolonged cold ischemia time, young age at the time of transplantation, high donor/recipient age ratio, and the use of partial grafts (P < 0.05). Fibrosis was not significantly related to rejection, chronic hepatitis, or the nature of the immunosuppressive therapy.
  
  
  CONCLUSIONS
  Biopsies after pediatric LTx show that most grafts developed fibrosis within 5 years. At 10 years after LTx, the graft fibrosis had progressed to severe fibrosis in at least 25% of the patients. Development of fibrosis, starting either before or after the first year post-LTx, was strongly related to transplant-related factors, indicating the importance of these factors to long-term graft prognosis.
authors.affiliation: Department of Pediatric Gastroenterology, Beatrix Children's Hospital, The Netherlands. r.scheenstra@bkk.umcg.nl
authors.forename: Rene
authors.initials: R
authors.lastname: Scheenstra
authors.forename: Paul M G J
authors.initials: PM
authors.lastname: Peeters
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D050377:Cold Ischemia; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D023001:Transplantation Tolerance / Q000276:immunology
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase