title: Early activation of interferon-stimulated genes in human liver allografts: relationship with acute rejection and histological outcome.
abstract: BACKGROUND
  Innate immunity mechanisms have been shown to play a paramount role in organ transplantation. Our aim was to investigate the hypothesis that activation of the interferon system may affect clinically relevant outcomes, such as acute rejection and/or early fibrosis progression, after liver transplantation.
  
  
  METHODS
  We studied 71 consecutive recipients (57 males; 25 with hepatitis C) who underwent two per protocol graft biopsies: the first, within 60 days after the transplant operation (median 24) and the second, after 1 year. The mRNA expression for five interferon-stimulated genes (Mx1, OAS2, PKR, IRF7A, IFI16) was measured on the first biopsy specimens. The main outcome measures were acute rejection during the first post-transplant year and fibrosis progression at the second biopsy.
  
  
  RESULTS
  On multivariate analysis, the independent predictors of gene expression were hepatitis C (Mx1, OAS2, PKR and IFI16), donor age (IFI16) and recipient gender (IRF7A) (P < .05 for all). During the first post-transplant year, 19/71 patients (27%) had acute cellular rejection. At multivariate analysis, acute cellular rejection was independently predicted by high IRF7A mRNA expression. At the end of follow-up, 25 patients had some degree of fibrosis (F2 or higher in seven cases). On multivariate analysis, hepatitis C etiology, recipient age, and OAS2 overexpression were independent predictors of early fibrosis progression.
  
  
  CONCLUSIONS
  In the early postoperative period of liver transplantation, interferon-stimulated gene activation is dependent on hepatitis C recurrence (the main factor responsible for early fibrosis progression) and donor age, and is related to the risk of acute cellular rejection.
authors.affiliation: Department of Clinical and Experimental Medicine, Università del Piemonte Orientale A. Avogadro, Via G. Solaroli 17, 28100 Novara, Italy. rosalba.minisini@med.unipmn.it
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minisini
authors.forename: Paola
authors.initials: P
authors.lastname: Giarda
authors.forename: Glenda
authors.initials: G
authors.lastname: Grossi
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Claudio
authors.initials: C
authors.lastname: Avellini
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Occhino
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000367:Age Factors; D001706:Biopsy; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D006084:Graft Rejection / Q000175:diagnosis / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics* / Q000601:surgery; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D007372:Interferons / Q000502:physiology*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011183:Postoperative Complications / Q000209:etiology / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012008:Recurrence; D015533:Transcriptional Activation / Q000235:genetics*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins; C470837:PROKR1 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C076700:IFI16 protein, human; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins