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Portal Hypertension in the 21st Century Portal Hypertension in the 21st Century Edited by R. J. Groszmann J. Bosch Yale University School of Medicine Hepatic Hemodynamic Laboratory New Haven, CT, USA Liver Unit, Hospital Clinic University of Barcelona, Spain The proceedings of a symposium sponsored by Axcan Pharma Inc. and NicOx S.A., held in Montreal, Canada, April 2-4, 2004 AXCAN PHARMA SPRINGER-SCIENCE+BUSINESS MEDIA, B.V. Library of Congress Cataloging-in-Publication Data is available. ISBN 978-94-010-3774-7 ISBN 978-94-007-1042-9 (eBook) DOI 10.1007/978-94-007-1042-9 Printed on acid-free paper All Rights Reserved © 2004 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers and Axcan Pharma Inc. in 2004 Softcover reprint of the hardcover 1st edition 2004 No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic, mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owners. Contents List of principal contributors ix Preface J Rodes xv Section I: Introductory lectures 1 Portal hypertensive syndrome: its importance and complications AT Blei 3 2 The vascular endothelium and nitric oxide JL Wallace 13 3 Endothelial-derived nitric oxide as a marker for healthy endothelium we Sessa 19 Section II: Mechanisms of disease progression 4 Mechanisms of hepatic fibrogenesis SL Friedman 27 5 The role of hepatic stellate cells/myofibroblasts M Pinzani 37 6 Structural changes in the liver leading to cirrhosis and portal hypertension IR Wanless 47 Section III: Pathophysiology: increased resistance and increased blood flow 7 The paradox: vasoconstriction and vasodilation Y Iwakira, RJ Groszmann 57 v CONTENTS 8 Nitric-oxide-mediated vasodilation and portal hypertension R Wiest 69 9 Impaired vasodilation in cirrhotic livers MR Loureiro-Silva, RJ Groszmann 81 10 Enhanced release of vasoconstrictors JC Garcia-Pagan 89 11 Endogenous cannabinoids and circulatory dysfunction in cirrhosis W W~~~J~ Section IV: Mini-symposium: Possibilities of manipulating NO biosynthesis in the treatment of portal hypertension 12 NCX-1105: a liver-specific NO donor S Fiorucci, E Antonelli, A Morelli 10 5 13 Possibilities of manipulating NO biosynthesis in the treatment of portal hypertension: statins JG Abraldes, C Zafra, J Bosch 111 14 Pathophysiological role of Akt and endothelial nitric oxide synthase in cirrhosis M Morales-Ruiz 121 15 Nitric oxide synthase gene transfer JS Lee, V Shah 127 16 Inhibition of nitric-oxide-mediated vasodilation (including K+ channels) R Moreau 133 Section V: Introduction to variceal bleeding 17 Esophageal varices: from appearance to rupture; natural history and prognostic indicators G D'Amico 147 18 Pathophysiology of variceal bleeding A Escorsell, J Bosch 155 19 Approaches to the management of pediatric portal hypertension: results of an informal survey BL Shneider 167 Section VI: Therapeutic tools 20 Therapeutic tools in portal hypertension: drugs A Albillos 175 vi CONTENTS 21 Endoscopy in the management of portal hypertension GJ Monkewich, NE Marcon 185 22 Transjugular intrahepatic portosystemic shunt (TIPS): current indications Z Hassoun, G Pomier-Layrargues 209 Section VII: Present therapy 23 Prevention of first variceal bleeding: drugs o Lebrec 221 24 Prevention of first variceal bleeding: endoscopy M Schepke, T Sauerbruch 227 25 Treatment of acute variceal bleeding: general management and prevention of infections G Garcia-Tsao 233 26 Hemostatic treatments R de Franchis 241 27 Prevention of recurrent portal hypertensive bleeding NO Grace 251 28 Cost -effectiveness of primary prophylaxis for esophageal variceal bleeding JA Talwalkar 261 Section VIII: Problems in treatment 29 The cirrhotic patient with no varices and with small varices C Merkel, M Bolognesi, A Gatta 271 30 Gastric varices SK Sarin 277 31 The patient who cannot receive beta-blockers TO Boyer 301 32 Hepatic venous pressure gradient: the facts JO Vorobioff, JG Abraldes, RJ Groszmann 309 33 HemodynamiC monitoring: implications for randomized controlled trials and clinical practice U Thalheimer, 0 Samonakis, C Triantos, 0 Patch, AK Burroughs 323 34 What to do with non-responders C Villanueva, C Aracil, J Balanz6 337 35 What else we need J Turnes, JC Garcia-Pagan, J Bosch 349 Index 361 vii List of principal contributors J.G. ABRALOES VA Healthcare System Hepatic Hemodynamic Laboratory/111 J 950 Campbell Avenue West Haven, CT 06516 USA A. ALBILLOS Department of Gastroenterology Hospital Universitario Ram6n y Cajal University of Alcala Ctra. de Colmenar, km. 9,100 28034 Madrid Spain A.T. BLEI Northwestern University Feinberg School of Medicine 303 E Chicago Seale 10-573 Chicago, IL 60611 USA J.BOSCH Hepatic Hemodynamic Laboratory, Liver Unit Hospital Clinic Villaroel 170 08036 Barcelona Spain T.O. BOYER Liver Research Institute University of Arizona AHSC 245136, Rm 6309 1501 N Campbell Avenue Tucson, AZ 85724 USA ix PORTAL HYPERTENSION IN THE 21ST CENTURY A.BURROUGHS Liver Transplantation Hepato-Biliary Medicine Royal Free Hospital Pond Street Hampstead, London NW32QG UK G. D'AMICO Department of Gastroenterology Ospedale V Cervello Via Trabucco 180 90146 Palmero Italy R. DE FRANCHIS University of Milan IRCCS Ospedale Maggiore Department of Internal Medicine Gastroenterology and Gastrointestinal Endoscopy Service Via Pace 9 20122 Milan Italy S. FlO RUCCI Department of Gastroenterology University of Peru9ia Via E dal POllO 06122 Perugia Italy S.L. FRIEDMAN Mount Sinai School of Medicine Box 1123, Room 1170 F 1425 Madison Avenue New York, NY 10029 USA J.C. GARCiA-PAGAN Hepatic Hemodynamic Laboratory Liver Unit Hospital Clinic Villaroel 170 08036 Barcelona Spain x LIST OF PRINCIPAL CONTRIBUTORS G. GARCIA-TSAO Yale University School of Medicine VA Connecticut Healthcare System 333 Cedar Street, 1080 LMP New Haven, CT 06516 USA N.D. GRACE Tufts University Medical School Division of Gastroenterology Brigham and Womens Hospital Harvard University 75 Francis Street Boston, MA 02115 USA R.J. GROSZMANN VA Connecticut Healthcare System Hepatic Hemodynamic Laboratory/111 J 950 Campbell Avenue West Haven, CT 06516 USA W. JIMENEZ Laboratorio Hormonal Hospital Clinic Universitari Villaroel 170 08036 Barcelona Spain D. LEBREC INSERM U-481 and Service d'Hepatologie Hopital Beaujon 100 Bd du General Leclerc 92110 Clichy France M.R. LOUREIRO-SILVA Yale University School of Medicine Hemodynamic Hepatic Laboratory VA Connecticut Healthcare System 111 H - 950 Campbell Avenue West Haven, CT 06516 USA xi PORTAL HYPERTENSION IN THE 21 ST CENTURY N.E. MARCON The Center for Therapeutic Endoscopy and Endoscopic Oncology St Michaels Hospital 30 Bond Street Toronto, Ontario M5B 1W 8 CANADA C.MERKEL Department of Clinical and Experimental Medicine University of Padua Via Giustiniani, 2 35128 Pad ova Italy M. MORALES-RUIZ Hormonal Laboratory Hospital Clinic, IDIBAPS University of Barcelona Villaroel 170 08036 Barcelona Spain R. MOREAU Service hepato-gastroenterologie INSERM U-481 Hopital Beaujon 92118 Clichy France M. PINZANI Dipartimento di Medicina Interna Universita degli Studi di Firenze Viale G.B. Morgagni, 85 1-50134 Firenze Italy G. POMIER-LAYRARGUES Liver Unit, H6pital Saint-Luc Centre Hospitalier de l'Universite de Montreal 264 East Rene-Levesque Blvd Montreal, Quebec H2X 1 P1 Canada xii

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Portal hypertension is the most important complication of a great variety of both acute and chronic liver diseases. Nevertheless, hepatic cirrhosis is the most frequent cause of portal hypertension. Gastrointestinal bleeding due to rupture of oesophageal varices is, without doubt, the most severe co

Portal Hypertension in the 21st Century: The proceedings of a symposium sponsored by Axcan Pharma Inc. and NicOx S.A., held in Montrél, Canada, April 2–4, 2004 PDF

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