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Acquired transthyretin amyloidosis after domino liver transplant: Phenotypic correlation, implication of liver retransplantation

      Highlights

      • Presentation and recurrence of acquired TTR amyloidosis resembles donor's phenotype.
      • Liver re-transplantation for acquired TTR amyloidosis does not halt amyloid deposit.
      • Amyloid deposits after liver re-transplantation are composed of wtTTR.

      Abstract

      Reports of acquired ATTRm in domino liver transplant (DLT) recipients are infrequent and the approach to management is unknown. We describe two patients, an inherited ATTRm patient who underwent liver transplant and his liver recipient who developed acquired ATTRm 8 years following transplantation. The clinical manifestations of amyloidosis were similar between patients and consisted of peripheral neuropathy, diarrhea and weight loss. Following liver transplantation, the DLT donor went into remission for 4 years, but eventually progressed and died. The DLT recipient was re-transplanted with a healthy liver, but amyloidosis progressed after 5 years, with symptoms resembling the progression of the ATTRm liver donor. Proteomic analysis was utilized to type the amyloid deposits present in the DLT recipient fat aspirate specimen obtained prior to the second transplantation and stomach biopsy obtained at disease progression. The fat amyloid deposits contained almost equal amounts of mutant TTR and wild-type TTR peptides, but the stomach biopsy showed only wild-type TTR. There is a high concordance of disease phenotype between inherited and acquired ATTRm, which may help in early recognition of acquired ATTRm in DLT recipients. Liver re-transplantation for acquired ATTRm may not interrupt the cycle of amyloid deposition since normal hepatically produced TTR may co-deposit with trace amount of pre-existing TTRm amyloid.

      Abbreviations:

      ATTRm (mutated transthyretin amyloidosis), DLT (Domino liver transplant), EF (ejection fraction), GI (Gastrointestinal), IVS (Interventricular septum), LV (left ventricle), MS/MS (tandem mass spectrometry), OLT (Orthotopic liver transplantation), TTR (Transthyretin), TTRm (mutated transthyretin), TTRwt (wild-type transthyretin), TUDCA (Tauroursodeoxycholic acid)

      Keywords

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