title: Centrilobular necrosis in children after combined liver and small bowel transplantation.
abstract: BACKGROUND
  Centrilobular necrosis is not an uncommon finding after isolated liver transplantation. In this study, we sought to describe hepatic centrilobular necrosis in children after combined liver and small bowel transplantation (LSBT), and to assess the predictive factors, possible causes, and prognosis.
  
  
  METHODS
  Six children aged 4 to 11 years, in whom liver biopsy showed centrilobular necrosis at least once, 3 weeks to 2 years after LSBT, were compared with nine children without this pathology. All six children experienced an acute complication in the few weeks preceding the finding of centrilobular necrosis. In addition, one child had an early arterial thrombosis and one, severe colitis 3 years after LSBT.
  
  
  RESULTS
  Centrilobular necrosis was associated with centrilobular swelling, dropout, endotheliitis, and inflammation. Fibrosis developed early and worsened on follow-up biopsy in three children. Portal symptoms of acute rejection were not constant, and there was no ductopenia. Biologic abnormalities were responsive to increased immunosuppression, including mycophenolate in four cases. However, follow-up biopsies showed persistent lesions in five patients, mildly inflammatory in four. Baseline immunosuppression had to be maintained at high levels. No viral infections, vascular compromise (except in one), and autoimmunity were found. We compared the two groups of children for initial diagnosis, age at transplantation, time receiving parenteral nutrition, ischemic time, presence of an associated transplanted colon, number of reoperations and infections, intestinal rejection, and immunosuppression, and found no differences.
  
  
  CONCLUSIONS
  This severe manifestation of chronic liver rejection occurred despite the heavy immunosuppression needed for LSBT. The previous acute clinical event could have triggered rejection by modifying the effective immunosuppression at the tissue level. Despite high baseline immunosuppression, histologic lesions persisted and significant fibrosis developed in half the children. We speculate that the lack of induction of tolerance in this particular setting of LSBT could be responsible for constant immune stimulation, thus chronic rejection. The optimal protocol of immunosuppression has yet to be defined to avoid this complication.
authors.affiliation: Department of Pediatrics, Necker-Enfants Malades Hospital, 149 rue de Sèvres, 75015 Paris, France. florence.lacaille@nck.ap-hop-paris.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Lacaille
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Fournet
authors.forename: Yann
authors.initials: Y
authors.lastname: Revillon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cezard
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007165:Immunosuppression Therapy; D007421:Intestine, Small / Q000637:transplantation*; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009336:Necrosis