Secondary Logo

Institutional members access full text with Ovid®

Alloimmunity and Cholestasis After Liver Transplantation in Children With Progressive Familial Intrahepatic Cholestasis

Krebs-Schmitt, Dorothee*; Briem-Richter, Andrea*; Brinkert, Florian*; Keitel, Verena; Pukite, Ieva; Lenhartz, Henning*; Fischer, Lutz§; Grabhorn, Enke*

Journal of Pediatric Gastroenterology and Nutrition: February 2019 - Volume 68 - Issue 2 - p 169–174
doi: 10.1097/MPG.0000000000002200
Original Articles: Hepatology

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 3 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 3 patients. In 1 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.

Conclusions: The underlying mutation may 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.

*University Children's Hospital, Pediatric Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg

Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

Department of Pediatric Gastroenterology, University Hospital, Riga, Latvia

§Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Address correspondence and reprint requests to Dorothee Krebs-Schmitt, MD, Pediatric Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (e-mail:

Received 23 May, 2018

Accepted 8 October, 2018

Drs Krebs-Schmitt and Briem-Richter contributed equally to the study.

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,