title: Effect of orthotopic liver transplantation on the progression of familial amyloidotic polyneuropathy.
abstract: BACKGROUND
  Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease.
  
  
  METHODS
  Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis.
  
  
  RESULTS
  Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement.
  
  
  CONCLUSIONS
  Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Pomfret
authors.forename: W D
authors.initials: WD
authors.lastname: Lewis
authors.forename: R L
authors.initials: RL
authors.lastname: Jenkins
authors.forename: P
authors.initials: P
authors.lastname: Bergethon
authors.forename: S W
authors.initials: SW
authors.lastname: Dubrey
authors.forename: J
authors.initials: J
authors.lastname: Reisinger
authors.forename: R H
authors.initials: RH
authors.lastname: Falk
authors.forename: M
authors.initials: M
authors.lastname: Skinner
mesh_terms: D000328:Adult; D017772:Amyloid Neuropathies / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D002319:Cardiovascular System / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000503:physiopathology