Recurrence of Bile Salt Export Pump Deficiency after Liver Transplantation

Abstract

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.

Familial Intrahepatic Cholestasis

“…Jara et al reported recurrence of cholestasis and pruritus following LT in BSEP patients with no evidence of cellular rejection on liver biopsy in 2009 [36]. In the same year, BSEP antibodies in the serum and at the hepatocyte canalicular membrane of a single patient who underwent two liver transplants were described [37].…”

Histopathological Syndromes of Liver Allograft Rejection and Recurrent Disease

“…Aggressive plasma cellrich interface or perivenular necro-inflammatory activity or inflammatory bile duct damage has not been described [230][231][232].…”

“…Patients in the first group who failed medical or other surgical therapy, if available, are prime candidates for liver transplantation because the cirrhotic liver is replaced by a genetically and structurally normal one that generally cures the disease. Some familial intrahepatic cholestasis syndromes, however, recur after transplantation because of de novo antibodies that develop in response to mutated non-inherited proteins that are introduced with the donor organ (see AIH section) [230][231][232].…”

Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 2

“…7 After liver transplantation a recurrence of PFIC in the allograft because of allo-immunisation of the recipient against BSEP protein of the donor has been reported. 19,20 Management (please describe)…”