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: Bo-Göran Ericzon, 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
• Journal: Transplantation (Transplantation) Vol. 99 Issue 9 Pg. 1847-54 (Sep 2015) ISSN: 1534-6080 [Electronic] United States
• PMID: 26308415 (Publication Type: Journal Article)

Chemical References

• Prealbumin

Topics

• Adult
• Age of Onset
• Amyloid Neuropathies, Familial (diagnosis, genetics, mortality, surgery)
• Cardiomyopathies (genetics, mortality)
• Cause of Death
• End Stage Liver Disease (diagnosis, genetics, mortality, surgery)
• Female
• Genetic Predisposition to Disease
• Humans
• Kaplan-Meier Estimate
• Liver Transplantation (adverse effects, mortality)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Mutation
• Odds Ratio
• Phenotype
• Prealbumin (genetics)
• Proportional Hazards Models
• Registries
• Retrospective Studies
• Risk Factors
• Time Factors
• Time-to-Treatment
• Treatment Outcome