Long-term outcome of acquired transthyretin amyloidosis.

BACKGROUND

Acquired transthyretin (ATTR) amyloidosis is increasingly reported among domino liver transplantation (DLT) recipients who receive livers from patients with hereditary variant TTR (ATTRv) amyloidosis. However, its long-term outcomes and the effects of disease-modifying drugs remain unclear.

METHODS

We retrospectively analyzed 30 DLT recipients who received liver grafts from ATTRv amyloidosis patients. Longitudinal evaluations included clinical scores, nerve conduction studies (NCS),123I-metaiodobenzylguanidine scintigraphy, echocardiography, electrocardiography,99mTc-pyrophosphate scintigraphy, and serum biomarkers.

RESULTS

Overall survival at 1, 3, and 10 years after DLT was 86.7%, 76.7%, and 57.7%, respectively. Amyloid deposition occurred in 17 recipients, with a median time from DLT to deposition of 7.7 years (range, 3.1-9.0 years). Among the 12 patients followed for >3 years after amyloid detection, tafamidis clinically stabilized neuropathy in most cases, however, NCSs revealed progressive subclinical axonal degeneration. Two patients experienced clinically significant neuropathy progression during tafamidis treatment, which was stabilized after switching to siRNA therapy. Clinically significant cardiac amyloidosis developed in only one patient.

CONCLUSIONS

Acquired ATTR amyloidosis frequently develops in long-term DLT recipients. Although tafamidis stabilizes clinical manifestations in most patients, it may not completely prevent disease progression in some cases. Further long-term evaluation is needed to determine optimal treatment strategies, including siRNA therapy.