caa a22 4500 445889292 CHVBK 20180317145610.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00535-011-0440-8 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0440-8 Early activation of interferon-stimulated genes in human liver allografts: relationship with acute rejection and histological outcome [Elektronische Daten] [Rosalba Minisini, Paola Giarda, Glenda Grossi, Davide Bitetto, Pierluigi Toniutto, Edmondo Falleti, Claudio Avellini, Giuseppa Occhino, Carlo Fabris, Mario Pirisi] 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 60days after the transplant operation (median 24) and the second, after 1year. 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. Springer, 2011 Type I interferon nationallicence Tolerance nationallicence Interferon regulatory factor-7A nationallicence Ischemia-reperfusion injury nationallicence Fibrosis nationallicence Minisini Rosalba Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut Giarda Paola Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut Grossi Glenda Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut Bitetto Davide DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut Toniutto Pierluigi DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut Falleti Edmondo DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut Avellini Claudio Department of Medical and Morphological Research, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut Occhino Giuseppa Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut Fabris Carlo DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut Pirisi Mario Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut Journal of Gastroenterology Springer Japan 46/11(2011-11-01), 1307-1315 0944-1174 46:11<1307 2011 46 535 https://doi.org/10.1007/s00535-011-0440-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0440-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Minisini Rosalba Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Giarda Paola Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Grossi Glenda Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Bitetto Davide DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut NATIONALLICENCE 700 1- Toniutto Pierluigi DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut NATIONALLICENCE 700 1- Falleti Edmondo DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut NATIONALLICENCE 700 1- Avellini Claudio Department of Medical and Morphological Research, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut NATIONALLICENCE 700 1- Occhino Giuseppa Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Fabris Carlo DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy aut NATIONALLICENCE 700 1- Pirisi Mario Department of Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/11(2011-11-01), 1307-1315 0944-1174 46:11<1307 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer