Liver transplantation for lethal genetic syndromes: a novel model of personalized genomic medicine. J Am Coll Surg 2013 Apr;216(4):534-43; discussion 543-4
Date
03/26/2013Pubmed ID
23521929DOI
10.1016/j.jamcollsurg.2012.12.050Scopus ID
2-s2.0-84875297717 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
BACKGROUND: Our aim was to analyze our single-center experience with orthotopic liver transplantation for metabolic lethal genetic syndromes in children and adults.
STUDY DESIGN: From 1984 to 2012, all pediatric (younger than 18 years) and adult (18 years and older) patients who underwent orthotopic liver transplantation for lethal genetic disorders were identified. Data on diagnostic pathways and specific outcomes were analyzed for both groups. Outcomes measures included recurrence rate as well as graft and patient survival.
RESULTS: Metabolic lethal genetic syndrome was the primary indication for orthotopic liver transplantation in 152 of 4,564 patients (3.3%) at University of California, Los Angeles during the study period (74 pediatric patients and 78 adults). Genetic testing was performed in only 12% of the 152 patients and in 39% of patients after 2006. Two patients (1.3%) experienced a recurrence of the genetic disease. Overall 5- and 20-year survival rates were 89% and 77% for children and 73% and 50% for adults. Survival of pediatric patients was superior to adults (log-rank p < 0.009). Multivariate analysis identified age (hazard ratio = 2.18), preoperative life support (hazard ratio = 2.68), and earlier transplantation (hazard ratio = 3.41) as independent predictors of reduced survival.
CONCLUSIONS: Orthotopic liver transplantation achieved excellent long-term survival in pediatric and adult patients with lethal genetic syndromes and represents a model of personalized genomic medicine by providing gene therapy through solid organ transplantation.
Author List
Petrowsky H, Brunicardi FC, Leow VM, Venick RS, Agopian V, Kaldas FM, Zarrinpar A, Markovic D, McDiarmid SV, Hong JC, Farmer DG, Hiatt JR, Busuttil RWMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Child
Child, Preschool
Female
Genetic Diseases, Inborn
Genetic Therapy
Genomics
Humans
Infant
Liver Diseases
Liver Transplantation
Male
Middle Aged
Models, Theoretical
Precision Medicine
Retrospective Studies
Severity of Illness Index
Syndrome
Young Adult