RESUMO
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.
Assuntos
Anticorpos/imunologia , Colestase Intra-Hepática/cirurgia , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/imunologia , Pré-Escolar , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/imunologia , Doença Hepática Terminal/genética , Doença Hepática Terminal/imunologia , Feminino , Humanos , Lactente , Masculino , Período Pós-Operatório , Recidiva , Transplante de Células-TroncoRESUMO
Progressive familial intrahepatic cholestasis 2 is an autosomal-recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Recurrence of BSEP deficiency after liver transplantation is caused by the development of anti-BSEP antibodies. Antibody-induced BSEP deficiency is typically treated by increasing immunosuppressive therapy. We report, in a child, the first case of allogeneic haematopoietic stem cell transplantation for antibody-induced BSEP deficiency that was refractory to intensive pharmacological immunosuppression and immunoadsorption. After haematopoietic stem cell transplantation, anti-BSEP antibodies were cleared from the patient's serum and later from the canalicular space of the liver graft.