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) as a result of anti-BSEP antibodies, but its frequency and risk factors are not precisely known.

Methods

A multicenter 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 analyzed.

Results

Ten patients (29%) were screened positive for anti-BSEP antibodies and all developed AIBD, in median 5 years (range: 1.5-14 years) 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 of nine patients, 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%). Although a severe ABCB11 genotype (biallelic protein-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.

Conclusions

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 LT in patients with BSEP deficiency, affecting nearly one-third of recipients in this multicenter 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.