Post-transplant alloimmune liver disease in bile salt export pump deficiency: A multicenter study

BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency may develop alloimmune anti-BSEP liver disease (AIBD) after liver transplantation (LT) due to anti-BSEP antibodies, but its frequency and risk factors are not precisely known. METHODS: A multicentre cohort of 35 patients who underwent LT for severe BSEP deficiency was screened retrospectively or prospectively after 2010 for anti-BSEP antibodies. Risk factors, management and outcome of AIBD were analysed. RESULTS: Ten patients (29%) were screened positive for anti-BSEP antibodies and all developed AIBD, in median 5 years (range: 1.5-14) after LT. Clinical remission of AIBD was achieved in nine patients using various immunosuppressive therapies, with decreased or negative anti-BSEP antibody titers in six patients, all having received rituximab or plasmapheresis/immunoadsorption. Relapse occurred in six patients out of nine, although maintenance therapy using rituximab and/or immunoglobulins enabled prolonged relapse-free survival. Because of AIBD, six patients (60%) required liver retransplantation either at initial AIBD episode or at relapse, and three patients (30%) died. Among the 25 patients without AIBD, one died (4%) and another one was retransplanted (4%). While a severe ABCB11 genotype (biallelic truncating variants) was significantly associated with AIBD (80% in patients with AIBD vs 28% in patients without AIBD, p=0.008), negative BSEP immunostaining on native liver, post-LT CMV infection, presence of biliary anastomosis strictures or graft rejection were not. CONCLUSION: In patients with severe BSEP deficiency, AIBD is a frequent post-LT complication that should be screened for, especially in patients with severe ABCB11 genotypes. Early diagnosis and the use of rituximab and plasmapheresis/immunoadsorption may improve patient outcome. IMPACT AND IMPLICATIONS: Alloimmune anti-BSEP liver disease is a frequent and severe complication after liver transplantation in patients with BSEP (Bile Salt Export Pump) deficiency, affecting nearly one-third of recipients in this multicentre cohort study. Patients carrying biallelic protein-truncating ABCB11 variants are at particularly high risk and should undergo systematic post-transplant screening for anti-BSEP antibodies. Early recognition of alloimmune anti-BSEP liver disease and timely treatment with B-cell-depleting and antibody-removal therapies, including rituximab and plasmapheresis/ immunoadsorption, may improve outcomes and reduce graft loss. These findings support the implementation of structured surveillance strategies and risk-adapted management in this rare but life-threatening condition.