title: Long-term outcome of human leukocyte antigen mismatching in liver transplantation: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
abstract: A perfect or nearly perfect human leukocyte antigen (HLA) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with 1 or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with 1 or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HLA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9).
  
  
  CONCLUSIONS
  Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively.
authors.affiliation: Department of Transplantation Medicine, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Vijayan
authors.initials: V
authors.lastname: Balan
authors.forename: Kris
authors.initials: K
authors.lastname: Ruppert
authors.forename: A Jake
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ledneva
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Duquesnoy
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Detre
authors.forename: Yuling L
authors.initials: YL
authors.lastname: Wei
authors.forename: Jorge
authors.initials: J
authors.lastname: Rakela
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schafer
authors.forename: John P
authors.initials: JP
authors.lastname: Roberts
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
authors.forename: Russell H
authors.initials: RH
authors.lastname: Wiesner