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

Abstract

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.

• Authors: Dorothee Krebs-Schmitt, Andrea Briem-Richter, Florian Brinkert, Verena Keitel, Ieva Pukite, Henning Lenhartz, Lutz Fischer, Enke Grabhorn
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 68 Issue 2 Pg. 169-174 (Feb 2019) ISSN: 1536-4801 [Electronic] United States
• PMID: 30664572 (Publication Type: Case Reports, Journal Article)

Chemical References

• ABCB11 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 11
• Antibodies

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 11 (deficiency, immunology)
• Antibodies (immunology)
• Child, Preschool
• Cholestasis, Intrahepatic (genetics, immunology, surgery)
• End Stage Liver Disease (genetics, immunology, surgery)
• Female
• Humans
• Infant
• Liver Transplantation (adverse effects)
• Male
• Postoperative Period
• Recurrence
• Stem Cell Transplantation