title: Relapsing features of bile salt export pump deficiency after liver transplantation in two patients with progressive familial intrahepatic cholestasis type 2.
abstract: OBJECTIVE
  PFIC2 is caused by mutations in ABCB11 encoding BSEP. In most cases affected children need liver transplantation that is thought to be curative. We report on two patients who developed recurrent normal GGT cholestasis mimicking primary BSEP disease, after liver transplantation.
  
  
  METHODS
  PFIC2 diagnosis was made in infancy in both patients on absence of canalicular BSEP immunodetection and on ABCB11 mutation identification. Liver transplantation was performed at age 9 (patient 1) and 2.8 (patient 2) years without major complications. Cholestasis with normal GGT developed 17 and 4.8years after liver transplantation, in patient 1 and patient 2, respectively, during an immunosuppression reduction period.
  
  
  RESULTS
  Liver biopsies showed canalicular cholestasis, giant hepatocytes, and slight lobular fibrosis, without evidence of rejection or biliary complications. An increase in immunosuppression resulted in cholestasis resolution in only one patient. Both patients developed atrial fibrillation, and one melanonychia. The newborn of patient 1 developed transient neonatal normal GGT cholestasis. Immunofluorescence staining of normal human liver sections with patient's sera, collected at the time of cholestasis, and using an anti-human IgG antibody to detect serum antibodies, showed reactivity to a canalicular epitope, likely to be BSEP. Indeed, Western blot analysis showed that patient 2 serum recognized rat Bsep.
  
  
  CONCLUSIONS
  Allo-immune mediated BSEP dysfunction may occur after liver transplantation in PFIC2 patients leading to a PFIC2 like phenotype. Extrahepatic features and/or offspring transient neonatal cholestasis of possible immune mediated mechanisms, may be associated. Increasing the immunosuppressive regimen might be an effective therapy.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Hepatology, University Hospital Santa Chiara, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gonzales
authors.forename: Marco
authors.initials: M
authors.lastname: Sciveres
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Redon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Grosse
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.forename: Anne
authors.initials: A
authors.lastname: Davit-Spraul
authors.forename: Monique
authors.initials: M
authors.lastname: Fabre
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics*; D015153:Blotting, Western; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D009154:Mutation; D012008:Recurrence
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters