Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation

• Published in: Liver transplantation Vol. 22; no. 5; pp. 656 - 664
• Main Authors: Misumi, Yohei, Narita, Yasuko, Oshima, Toshinori, Ueda, Mitsuharu, Yamashita, Taro, Tasaki, Masayoshi, Obayashi, Konen, Isono, Kaori, Inomata, Yukihiro, Ando, Yukio
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2016
• Subjects: Adult; Aging; Amyloid Neuropathies, Familial - pathology; Amyloidosis - etiology; Creutzfeldt-Jakob disease; Female; Humans; Kaplan-Meier Estimate; Liver; Liver Transplantation - adverse effects; Male; Middle Aged; Mutation; Prealbumin - genetics; Time Factors; Tissue Donors; Transplant Recipients; Transplants & implants
• ISSN: 1527-6465; 1527-6473
• DOI: 10.1002/lt.24371

Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan‐Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow‐up for early amyloidosis detection and new treatments, including TTR stabilizers and gene‐silencing therapies, are required. Liver Transplantation 22 656‐664 2016 AASLD.