Vascular Liver Disease
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1 Vascular Liver Disease
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3 Laurie D. DeLeve Guadalupe Garcia-Tsao Editors Vascular Liver Disease Mechanisms and Management
4 Editors Laurie D. DeLeve Division of Gastrointestinal and Liver Diseases University of Southern California Keck School of Medicine Los Angeles, CA 90033, USA Guadalupe Garcia-Tsao Section of Digestive Diseases Yale University School of Medicine New Haven, CT 06520, USA ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
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7 Preface Functions of the liver are highly dependent on its vascular connections to the outside world (the gut and the splanchnic circulation) and the inside world (the heart and the systemic circulation). These connections not only allow the liver to process nutrients and store vitamins that are absorbed from the gut, but also permit removal of bacteria that come from the gut before they reach the systemic circulation. The liver detoxifies and metabolizes endogenous toxins (e.g., ammonia) and, importantly, exogenous substances such as alcohol and most medications that arrive to the liver via the systemic or splanchnic circulations. Additionally, the liver synthesizes substances such as albumin and clotting factors that are secreted into the systemic circulation and produces bile acids that are secreted through the biliary ducts into the gut, facilitating fat absorption. It follows that abnormalities that directly or indirectly affect the hepatic vasculature will lead to significant disease. These abnormalities can be microscopic, at the level of the hepatic sinusoids, or can affect the larger afferent or efferent vessels. This book approaches all of these disease entities and includes the mechanisms and management of intrahepatic vascular disease, including the most common cause of intra- and extrahepatic vascular disease of the liver, cirrhosis, and also reviews the mechanisms and management of less common diseases of the liver vasculature such as sinusoidal obstruction syndrome (previously known as veno-occlusive disease), portal vein thrombosis, the Budd-Chiari syndrome, and congenital vascular malformations. The very fact that these entities are rare increases the challenge to physicians and physician scientists; the low incidence complicates the accrual of patients for clinical research and reduces physician experience in managing patients with these disorders. Although many textbooks have been written on the consequences of cirrhosis on the liver vasculature, this is the only textbook that focuses on the liver vasculature as a separate entity. The authors are authorities in their field, from six different countries one-third of the chapters are from authors outside of the United States (United States, Australia, Italy, Switzerland, Spain, and France). The book is organized in three sections. The first section examines the pathophysiology of circulatory liver diseases. It examines the cellular and biochemical changes of the hepatic microcirculation in aging (Chap. 2), with fibrosis (Chaps. 2 and 4), and toxic injury (Chap. 2) and discusses general and vii
8 viii Preface liver-specific mechanisms involved in hemostasis and thrombosis (Chap. 1). Pathogenic factors underlying circulatory injury in liver transplantation (Chap. 5) and the mechanisms leading to portal hypertension (Chaps. 6 and 7) are also discussed. This section will be of particular interest to basic scientists and clinical investigators interested in the liver circulation, and to gastroenterologists, hepatologists, and hepatobiliary surgeons who would like to read about new developments in the field. Section 2 provides in-depth information on the clinical approach to vascular liver diseases. Chapters 8 and 9 provide descriptions and images of the histology and radiological appearance of vascular liver disease, as well as discussions of the utility of liver biopsy and imaging modalities in diagnosis. The remaining five chapters discuss diagnosis and medical treatment of various vascular liver diseases. Finally, the three chapters in Sect. 3 discuss the interventional radiology and surgical approaches to portal hypertension (Chaps. 15 and 16, respectively) and the indications for liver transplantation in patients with vascular liver disease (Chap. 17). Sections 2 and 3 will be of particular interest to gastroenterologists and hepatologists, to hepatobiliary surgeons and transplant surgeons, and to interventional radiologists with a particular interest in the liver, who will use this as a reference in patient management. Los Angeles, CA Laurie D. DeLeve New Haven, CT Guadalupe Garcia-Tsao
9 Contents Part I Mechanisms 1 Liver Endothelial Cells: Hemostasis, Thrombosis, and Hepatic Vascular Diseases... 3 Simon C. Robson 2 Vascular Liver Disease and the Liver Sinusoidal Endothelial Cell Laurie D. DeLeve 3 Pseudocapillarization and the Aging Liver Dmitri Svistounov, Svetlana N. Zykova, Victoria C. Cogger, Alessandra Warren, Robin Fraser, Bård Smedsrød, Robert S. McCuskey, and David G. Le Couteur 4 Stellate Cells and the Microcirculation Massimo Pinzani 5 Circulatory Injury in Liver Transplantation Ashraf Mohammad El-Badry, Philipp Dutkowski, and Pierre-Alain Clavien 6 Portal Hypertension: Intrahepatic Mechanisms Alexander Zipprich and Roberto J. Groszmann 7 Portal Hypertension: Extrahepatic Mechanisms Jaime Bosch and Juan G. Abraldes Part II Management 8 Histological Diagnosis Dhanpat Jain and A. Brian West 9 Radiological Diagnosis Christopher G. Roth and Donald G. Mitchell ix
10 x Contents 10 Hepatic Vascular Pathology After Hematopoietic Cell Transplantation: Sinusoidal Obstruction Syndrome, Focal Nodular Hyperplasia, and Nodular Regenerative Hyperplasia George B. McDonald 11 Management: Cirrhotic Portal Hypertension Joseph K. Lim and Guadalupe Garcia-Tsao 12 Portal Vein Thrombosis Dominique-Charles Valla 13 Budd-Chiari Syndrome Susana Seijo-Ríos, Puneeta Tandon, Jaime Bosch, and Juan Carlos García-Pagán 14 Congenital Hepatic Vascular Malformations Guadalupe Garcia-Tsao Part III Surgery and Interventional Radiology 15 Interventional Radiology in the Treatment of Portal Hypertension Christophe Bureau, Philippe Otal, and Jean-Pierre Vinel 16 Surgical Intervention for Portal Hypertension J. Michael Henderson 17 Liver Transplantation and Vascular Disorders Jan P. Lerut, Eliano Bonaccorsi-Riani, and Pierre Goffette Index
11 Contributors Juan G. Abraldes Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-Idibaps, University of Barcelona and Centro de Investigación Biomédica de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain Eliano Bonaccorsi-Riani Department of Abdominal and Transplantation Surgery, St. Luc Université Catholique de Louvain (UCL), Avenue Hippocrates 10, Brussels, Belgium Jaime Bosch Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-Idibaps, University of Barcelona and Centro de Investigación Biomédica de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain Christophe Bureau Hepato-Gastro-Enterologie, University of Toulouse, CHU Toulouse-Purpan Place du Dr Baylac, Toulouse, 31059, France Pierre-Alain Clavien Department of Surgery, University Hospital of Zurich, Ramistrase 100, CH-8091 Zurich, Switzerland Victoria C. Cogger Centre for Education and Research on Ageing, Sydney Medical School and ANZAC Research Institute, Sydney, NSW, Australia Laurie D. DeLeve Division of Gastrointestinal and Liver Diseases, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue- HMR 603, Los Angeles, CA 90033, USA Philipp Dutkowski Department of Surgery, The Swiss HPB (Hepato-Pancreatico-Biliary) and Transplantation Center, University Hospital of Zurich, Zurich, Switzerland Ashraf Mohammad El-Badry Department of Surgery, The Swiss HPB (Hepato-Pancreatico-Biliary) and Transplantation Center, University Hospital of Zurich, Zurich, Switzerland xi
12 xii Contributors Robin Fraser Department of Pathology, University of Otago, Christchurch, New Zealand Juan Carlos García-Pagán Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona-CIBERehd-IDIBAPS-Institut Clinic de Malalties Digestives 1 Metaboliques, Villarroel 170 street, Barcelona 08036, Spain Guadalupe Garcia-Tsao Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520, USA; Section of Digestive Diseases, VA Connecticut Health Care System, West Haven, CT, USA Pierre Goffette Department of Medical Imaging, St. Luc Université Catholique de Louvain (UCL), Brussels, Belgium Roberto J. Groszmann Department of Medicine-Digestive Diseases, Yale University School of Medicine, PO Box , New Haven, CT , USA J. Michael Henderson Department of General Surgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue/E32, Cleveland, OH , USA Dhanpat Jain Department of Pathology, Yale University School of Medicine, New Haven, CT USA David G. Le Couteur Centre for Education and Research on Ageing, The University of Sydney and Concord R.G. Hospital, Sydney, NSW, Australia Jan P. Lerut Department of Abdominal and Transplantation Surgery, Starzl Abdominal Transplant Unit, St. Luc Université Hospitals Universite catholique de Louvain (UCL), Avenue Hippocrates 10, Brussels, Belgium Joseph K. Lim Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, USA; Section of Gastroenterology, VA Connecticut Health Care System, West Haven, CT, USA Robert S. McCuskey Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA George B. McDonald Gastroenterology/Hepatology Section (D2-190), Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, 1100 Fairview Avenue North, Seattle, WA , USA
13 Contributors xiii Donald G. Mitchell Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA 19102, USA Philippe Otal Radiologie, University of Toulouse, CHU-Toulouse-Rangueil, 1 Ave J Poulhes, Toulouse 31059, France Massimo Pinzani Dipartimento di Medicina Interna, Center for Research, High Education and Transfer DENOThe, Università degli Studi di Firenze, Viale G.B. Morgagni, 85, Firenze, Italy Simon C. Robson Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E/CLS-612, Boston, MA 02215, USA Christopher G. Roth Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA 19102, USA Susana Seijo-Rios Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona-CIBERehd-IDIBAPS-Institut Clinic de Malalties Digestives 1 Metaboliques, Villarroel 170 street, Barcelona 08036, Spain Bård Smedsrød Vascular Biology Research Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway Dmitri Svistounov Vascular Biology Research Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway Puneeta Tandon Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona-CIBERehd-IDIBAPS-Institut Clinic de Malalties Digestives 1 Metaboliques, Villarroel 170 street, Barcelona 08036, Spain Dominique-Charles Valla Hépatologie, Hopital Beaujon, APHP; Université Denis, Diderot-Paris 7; and Inserm U773, 100 Bvd Leclerc, Clichy, France Jean-Pierre Vinel Hepato-Gastro-Enterologie, University of Toulouse, CHU Toulouse-Purpan, Place du Dr Baylac, Toulouse 31059, France Alessandra Warren ANZAC Research Institute and Center for Education and Research on Ageing, The University of Sydney, Sydney, NSW, Australia A. Brian West Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
14 xiv Contributors Alexander Zipprich First Department of Internal Medicine, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany Svetlana N. Zykova Department of Pathology, University Hospital of Northern Norway, Tromsø, Norway; Centre for Education and Research on Ageing, Sydney Medical School and ANZAC Research Institute, Sydney, NSW, Australia
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