title: Recurrence of Progressive Familial Intrahepatic Cholestasis Type 2 Phenotype After Living-donor Liver Transplantation: A Case Report.
abstract: BACKGROUND
  Progressive familial intrahepatic cholestasis 2 (PFIC2) is the result of mutations in the ABCB11, which encodes for bile salt export pump (BSEP). An absence of BSEP in the canalicular membrane causes cholestasis and leads to the development of end-stage liver disease in the first decade of life. Liver transplantation (LT) has been considered curative for BSEP disease. However, patients with PFIC2 having undergone LT have recently been reported to develop recurrence of cholestasis together with the clinical and histological features of primary BSEP disease.
  
  
  METHODS
  We herein present a rare case of a patient with PFIC2 who developed post-transplantation recurrence of progressive intrahepatic cholestasis due to antibodies against BSEP after living-donor LT, which mimicked primary BSEP disease. The patient had mutations in the ABCB11 gene, resulting in the complete absence of BSEP in the native liver, explaining the lack of tolerance. Immunofluorescence staining of normal human liver sections with the patient's serum and using an anti-human immunoglobulin G antibody to detect serum antibodies showed reactivity to the BSEP epitope in the canalicular membrane. We suggest that the patients having undergone LT had been associated with a risk of autoantibody formation against the BSEP protein. The absence of primary tolerance for the BSEP epitopes may explain the formation of the anti-BSEP antibodies after LDLT.
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan; Department of Pediatric Surgery, National Hospital Organization Fukuyama Medical Center, Okinogamicho, Fukuyama-city, Hiroshima, Japan. Electronic address: masahata@pedsurg.med.osaka-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Masahata
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uehara
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ibuka
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakahata
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Nara Hospital Kinki University Faculty of Medicine, Otoda-cho, Ikoma-shi, Nara, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kondou
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kubitz
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ueno
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002780:Cholestasis, Intrahepatic / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D019520:Living Donors; D009154:Mutation; D010641:Phenotype; D012008:Recurrence
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001323:Autoantibodies