title: Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative?
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.
authors: 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.
authors: Bo-Göran
authors: BG
authors: Ericzon
authors: Henryk E
authors: HE
authors: Wilczek
authors: Marie
authors: M
authors: Larsson
authors: Priyantha
authors: P
authors: Wijayatunga
authors: Arie
authors: A
authors: Stangou
authors: João Rodrigues
authors: JR
authors: Pena
authors: Emanuel
authors: E
authors: Furtado
authors: Eduardo
authors: E
authors: Barroso
authors: Jorge
authors: J
authors: Daniel
authors: Didier
authors: D
authors: Samuel
authors: Rene
authors: R
authors: Adam
authors: Vincent
authors: V
authors: Karam
authors: John
authors: J
authors: Poterucha
authors: David
authors: D
authors: Lewis
authors: Ben-Hur
authors: BH
authors: Ferraz-Neto
authors: Márcia Waddington
authors: MW
authors: Cruz
authors: Miguel
authors: M
authors: Munar-Ques
authors: Juan
authors: J
authors: Fabregat
authors: Shu-Ichi
authors: S
authors: Ikeda
authors: Yukio
authors: Y
authors: Ando
authors: Nigel
authors: N
authors: Heaton
authors: Gerd
authors: G
authors: Otto
authors: Ole
authors: O
authors: Suhr
mesh_terms: D000328:Adult; D017668:Age of Onset; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D009202:Cardiomyopathies / Q000235:genetics / Q000401:mortality; D002423:Cause of Death; D058625:End Stage Liver Disease / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D011228:Prealbumin