University of Groningen Studies on bile duct Injury and the protective role of oxygenated machine perfusion in liver transplantation Karimian, Negin IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2017 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Karimian, N. (2017). Studies on bile duct Injury and the protective role of oxygenated machine perfusion in liver transplantation. [Groningen]: University of Groningen. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 07-04-2019
Studies on Bile Duct Injury and the Protective Role of Oxygenated Machine Perfusion in Liver Transplantation Negin Karimian
Different parts of this thesis were funded by the Groningen University Institute for Drug Exploration (GUIDE), Groningen Institute for Organ Transplantation (GIOT), grants from the Jan Kornelis de Cock Foundation, the Tekke Huizinga Foundation and Innovative Actieprogramma Groningen (IAG-3). For the printing of this thesis, financial support of the following institutions and companies is gratefully acknowledged: The University of Groningen (RUG) University Medical Center Groningen (UMCG) Groningen University Institute for Drug Exploration (GUIDE) Organ Assist HbO2Therapeutics Negin Karimian Studies on Bile Duct Injury and the Protective Role of Oxygenated Machine Perfusion in Liver Transplantation Dissertation University of Groningen, The Netherlands ISBN: 978-94-034-0092-1 (Printed book) ISBN: 978-94-034-0091-4 (Ebook) Copyright 2017 Negin Karimian, The Netherlands All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without the written permission of the author. Cover photo Cover and Layout Printed by Negin Karimian Dopolavoro.org, Naples, Italy Gildeprint drukkerijen, Enschede, The Netherlands
Studies on Bile Duct Injury and the Protective Role of Oxygenated Machine Perfusion in Liver Transplantation PhD thesis to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus Prof. E. Sterken and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 4 Dec 2017 at 12.45 by Negin Karimian born on 19 July 1986 in Shiraz, Iran
Promoters: Evaluation Committee: Prof. R.J. Porte Prof. J.A. Lisman Prof. A.J. Moshage Prof. J.N.M. IJzermans Prof. A. Masclee
Paranimfen: Dr. Golnar Karimian Dr. Freeha Arshad
To Mom, Dad, Golnar and Negar, whom I owe to all I am today
Table of Contents 1 General Introduction and Aims of This Thesis..................... 1 Part A Bile Duct Injury in Liver Transplantation 2 Biliary Complications after Orthotopic Liver Transplantation.............. 13 3 The Origin of Biliary Strictures after Liver Transplantation: Is it the Amount of Epithelial Injury or Insufficient Regeneration that Counts?.................. 29 4 Preservation Injury of the Distal Extrahepatic Bile Duct of Donor Livers Is Representative for Injury of the Intrahepatic Bile Ducts...................... 37 5 CCR5 Deficiency Results in Decreased Hepatic Recruitment of Regulatory T Cells after Obstructive Biliary Injury in Mice.......................... 47 Part B Oxygenated Machine Perfusion: A Potential Strategy to Improve Organ Quality prior to Transplantation 6 Normothermic Machine Perfusion Reduces Bile Duct Injury and Improves Biliary Epithelial Function in Rat Donor Livers........................... 65 7 Ex-situ Normothermic Machine Perfusion of Donor Livers............... 85 8 Criteria for Viability Assessment of Discarded Human Donor Livers during Ex-vivo Normothermic Machine Perfusion............................ 103 9 Oxygenated Hypothermic Machine Perfusion after Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers............... 123 10 Dual Hypothermic Oxygenated Machine Perfusion in Liver Transplantation with Donation after Circulatory Death Grafts.......................... 145 Part C Addendum 11 Summary and General Discussion........................... 163 Nederlandse Samenvatting............................... i Acknowledgements.................................... Biography......................................... vii xiii