Retransplantation After Acquired Transthyretin Amyloidosis Following Domino Liver Transplantation: Outcomes and Challenges

BACKGROUND: Acquired transthyretin (ATTR) amyloidosis is a rare iatrogenic complication of domino liver transplantation (DLT), in which mutant transthyretin (TTR) continues to be produced by the graft, leading to systemic amyloid deposition in recipients. Liver retransplantation has been proposed as a potential therapeutic strategy, but its clinical benefit remains uncertain. This case series aims to describe the clinical evolution of three patients with acquired ATTR amyloidosis who underwent liver retransplantation and assess the impact of the procedure on disease progression. METHODS: We retrospectively reviewed three male patients diagnosed with acquired ATTR amyloidosis after DLT and followed at a national referral center. Clinical data were extracted from medical records, including neurological findings, autonomic and systemic involvement, timing of symptom onset, and outcomes after retransplantation. All patients underwent electrodiagnostic studies and tissue biopsy confirming ATTR amyloidosis. RESULTS: All three patients developed neuropathic symptoms approximately nine years after DLT. Two had advanced disease at the time of retransplantation, with marked autonomic and cardiac involvement. These two patients showed continued neurological and systemic deterioration after retransplantation. The third patient, who underwent earlier retransplantation and had a milder phenotype, demonstrated clinical stabilization over two years of follow-up. INTERPRETATION: Liver retransplantation appears to offer limited benefit in halting disease progression in acquired ATTR amyloidosis, particularly when performed at advanced stages. Earlier intervention, before the establishment of significant systemic involvement, may improve outcomes. These findings highlight the need for timely diagnosis and individualized management in this underrecognized condition.