Bortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature.

Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is a rare autosomal recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Liver transplantation is the standard treatment for end-stage liver disease in PFIC-2; however, recurrence in the form of autoimmune BSEP disease (AIBD) is a recognized posttransplant complication. AIBD is characterized by cholestasis with normal gamma-glutamyl transpeptidase, severe pruritus, and the presence of anti-BSEP antibodies. We report a case of a PFIC-2 patient who developed recurrent cholestasis and pruritus three years posttransplant. Liver biopsy revealed canalicular cholestasis and giant cell transformation, while BSEP staining on immunohistochemistry was preserved. Serological testing confirmed anti-BSEP antibody positivity. Despite aggressive therapy including plasmapheresis, intravenous immunoglobulin, and rituximab, only partial improvement was achieved, and cholestasis persisted. Given the refractory nature of the disease, bortezomib-a proteasome inhibitor targeting antibody-producing plasma cells-was administered. The patient demonstrated complete clinical and biochemical resolution following bortezomib therapy. This case highlights the diagnostic complexity of AIBD and the potential role of bortezomib in cases unresponsive to conventional immunosuppressive therapies. Early diagnosis and personalized immunomodulation remain key to improving outcomes in this rare but challenging condition.