Long-Term Management of Recurrent Antibody-Induced Bile Salt Export Pump Deficiency After Liver Transplantation Using...

Progressive Familial Intrahepatic Cholestasis type 2 (PFIC-2) is a rare autosomal recessive liver disorder caused by ABCB11 mutations impairing the bile salt export pump (BSEP). Liver transplantation is typically considered curative; however, a subset of patients develop antibody-induced BSEP deficiency (AIBD), a rare post-transplant complication driven by recipient IgG antibodies against graft BSEP. Patients often present with recurrent cholestasis and graft dysfunction. Therapeutic plasma exchange (TPE) is increasingly used to remove circulating antibodies, often alongside immunomodulatory therapies. We describe a patient with PFIC-2 who developed four distinct AIBD relapses over a 24-year period, beginning 12 years after transplantation. Each relapse was treated with a coordinated regimen including TPE, intravenous immunoglobulin (IVIg), rituximab, and optimized maintenance immunosuppression. TPE procedures were performed using the Spectra Optia system with one plasma volume exchange using citrate anticoagulation. Across all relapses, TPE was associated with rapid reductions in cholestatic markers, with the greatest improvements noted after apheresis initiation. TPE procedure intensity evolved over time, with earlier initiation and a gradual increase in the total number of exchanges per relapse. Biopsies demonstrated progressive cholestatic injury, yet graft function remained preserved and re-transplantation was avoided. Adverse events were infrequent and managed conservatively. This case highlights the potential role of early and sustained use of TPE as part of a multimodal strategy for managing recurrent AIBD. Consistent clinical and biochemical improvement across relapses supports incorporating TPE with immunosuppression and B-cell targeted therapy in similar presentations. Further studies are needed to clarify optimal timing, frequency, and treatment combinations.