Bo-Göran Ericzon1, Henryk E Wilczek, Marie Larsson, Priyantha Wijayatunga, Arie Stangou, João Rodrigues Pena, Emanuel Furtado, Eduardo Barroso, Jorge Daniel, Didier Samuel, Rene Adam, Vincent Karam, John Poterucha, David Lewis, Ben-Hur Ferraz-Neto, Márcia Waddington Cruz, Miguel Munar-Ques, Juan Fabregat, Shu-Ichi Ikeda, Yukio Ando, Nigel Heaton, Gerd Otto, Ole Suhr. 1. 1 Division of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden. 2 Department of Statistics, Umeå University, Umeå, Sweden. 3 Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. 4 Liver Transplant Unit, Hospital de Curry Cabral, Lisbon, Portugal. 5 Unidade de Transplantação Hepática Pediátrica e de Adultos, Centro Hospitalar e Universitário de Coimbra, Portugal. 6 Liver Transplant Unit, Hospital de Santo António, Porto, Portugal. 7 AP-HP, Hôpital Paul Brousse, Centre Hépatobiliaire, Univ Paris-Sud, Villejuif, France. 8 Liver Transplant/Gastroenterology, Mayo Clinic College of Medicine, Rochester, MN. 9 Hepatobiliary Surgery and Liver Transplantation, Lahey Medical Center, Burlington, MA. 10 Department of Liver Transplantation, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. 11 Department of Neurology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 12 Grupo de Estudio de la PAF, Palma de Mallorca, Spain. 13 Liver Transplant Unit, University Hospital Bellvitge, Spain. 14 Third Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan. 15 Department of Neurology, Graduate School of Medical Science Kumamoto University, Kumamoto, Japan. 16 Liver Unit, King's College Hospital, London, United Kingdom. 17 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, J Gutenberg-Universität, Mainz, Germany. 18 Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden.
Abstract
BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison. METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry. RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease. CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.
BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTRpatients to serve as a base for comparison. METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry. RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease. CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.
Authors: M Ankarcrona; B Winblad; C Monteiro; C Fearns; E T Powers; J Johansson; G T Westermark; J Presto; B-G Ericzon; J W Kelly Journal: J Intern Med Date: 2016-05-10 Impact factor: 8.989
Authors: Eve Piekarski; Renata Chequer; Vincent Algalarrondo; Ludivine Eliahou; Besma Mahida; Jonathan Vigne; David Adams; Michel S Slama; Dominique Le Guludec; Francois Rouzet Journal: Eur J Nucl Med Mol Imaging Date: 2018-03-06 Impact factor: 9.236
Authors: Joseph D Schonhoft; Cecilia Monteiro; Lars Plate; Yvonne S Eisele; John M Kelly; Daniel Boland; Christopher G Parker; Benjamin F Cravatt; Sergio Teruya; Stephen Helmke; Mathew Maurer; John Berk; Yoshiki Sekijima; Marta Novais; Teresa Coelho; Evan T Powers; Jeffery W Kelly Journal: Sci Transl Med Date: 2017-09-13 Impact factor: 17.956