title: Heterozygous α1-antitrypsin Z allele mutation in presumed healthy donor livers used for transplantation.
abstract: OBJECTIVE
  The Z allele (Glu342Lys) in α1-antitrypsin (AAT) deficiency is a combined deficiency and dysfunctional allele. Carrying one Z allele induces a risk of a more aggressive evolution in patients with a chronic liver disease. As most of the carriers of Z allele do not have overt liver disease, it is likely that Z allele-containing livers have been used previously for liver transplantation. We analyzed the incidence, epidemiology, and clinical features of AAT accumulation in the hepatocytes after liver transplantation.
  
  
  METHODS
  Follow-up biopsies of liver transplant recipients were analyzed with periodic acid Schiff staining until 2006 (n=486); from 2006 on (n=303), all biopsies were stained with a specific monoclonal antibody against mutated AATZ protein. Genotyping of both recipient and donor was performed in the case of positive staining.
  
  
  RESULTS
  Of 789 liver transplantation patients, six patients (0.8%) showed mutated AATZ accumulation in the transplanted liver. Mutation analysis confirmed the presence of the Z allele in all donor organs including one transplanted organ with the SZ phenotype. There was a clear concordance between the isoelectrical focusing of the recipient AAT after transplantation and the genotype of the donor.
  
  
  CONCLUSIONS
  Presumed healthy donor organs containing the Z allele were used for transplantation in 0.8% of cases in our series. As the presence of a Z allele is an independent risk factor of aggravation of chronic liver disease, AATZ accumulation in biopsies after liver transplantation should be actively looked for.
authors: aDepartment of Gastroenterology, OLV Hospital, Aalst Departments of bHepatology cPathology dHuman Genetics eAbdominal Transplantation Surgery, University Hospitals Leuven, Leuven fHistocompatibility and Immunogenetics Lab, Mechelen, Belgium.
authors: Philip
authors: P
authors: Roelandt
authors: Pieter
authors: P
authors: Dobbels
authors: Mina
authors: M
authors: Komuta
authors: Anniek
authors: A
authors: Corveleyn
authors: Marie-Paule
authors: MP
authors: Emonds
authors: Tania
authors: T
authors: Roskams
authors: Raymond
authors: R
authors: Aerts
authors: Diethard
authors: D
authors: Monbaliu
authors: Louis
authors: L
authors: Libbrecht
authors: Wim
authors: W
authors: Laleman
authors: Chris
authors: C
authors: Verslype
authors: Werner
authors: W
authors: Van Steenbergen
authors: Schalk
authors: S
authors: van der Merwe
authors: Jacques
authors: J
authors: Pirenne
authors: Frederik
authors: F
authors: Nevens
authors: David
authors: D
authors: Cassiman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics
chemical_list: D000515:alpha 1-Antitrypsin