Alloimmunity and Cholestasis after Liver Transplantation in Children with Progressive Familial Intrahepatic Cholestasis

Objectives: Bile salt export pump (BSEP) deficiency is an important reason for chronic cholestasis leading to liver transplantation (LT) in early childhood. The underlying pathology is a dysfunction of BSEP due to various mutations in the ABCB11 gene. Cases of clinical recurrence after LT due to alloantibodies directed against BSEP (antibody-induced BSEP deficiency; AIBD) have been reported. Most of these patients could be controlled by intensified immunosuppression. Methods: We here report on three children with BSEP-deficiency and end-stage liver disease, which developed AIBD after LT refractory to extensive immunosuppressive and immunomodulatory treatments; retransplantation was necessary in all three patients. In one patient, a stem cell transplantation was performed successfully. Results: AIBD seems to be induced by triggering factors such as initial impaired graft function or infections after LT. Conclusion: The underlying mutation might play a role in this process. Intensifying immunosuppression may be able to control AIBD, but some cases seem to be refractory to treatment and require retransplantation. Stem cell transplantation may provide a new therapeutic option for cases refractory to conservative treatment. Address correspondence and reprint requests to D. Krebs-Schmitt, MD; Pediatric Gastroenterology and Hepatology; University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (. e-mail: d.schmitt@uke.de). Received 23 May, 2018 Accepted 8 October, 2018 There are no conflicts of interest. There are no sources of funding. D. Krebs-Schmitt and A. Briem-Richter: Authors contributed equally. Conflicts of interest and Source of Funding: © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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