Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment Frontiers of Gastrointestinal Research Vol. 28 Series Editor Markus M. Lerch Greifswald Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment Volume Editor Alexander L. Gerbes Munich 23 figures and 31 tables, 2011 Basel · Freiburg · Paris · London · New York · Bangalore · Bangkok · Shanghai · Singapore · Tokyo · Sydney Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents®. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. 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No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. © Copyright 2011 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN 0302–0665 ISBN 978–3–8055–9591–9 e-ISBN 978–3–8055–9592–6 Frontiers of Gastrointestinal Research Founded 1975 by L. van der Reis, San Francisco, Calif. Alexander L. Gerbes Klinikum München-Grosshadern Liver Center Munich Ludwig Maximilian University of Munich Munich, Germany Library of Congress Cataloging-in-Publication Data Ascites, hyponatremia, and hepatorenal syndrome : progress in treatment / volume editor, Alexander L. Gerbes Munich. p. ; cm. -- (Frontiers of gastrointestinal research, ISSN 0302-0665 ; v. 28) Includes bibliographical references and indexes. ISBN 978-3-8055-9591-9 (hard cover : alk. paper) -- ISBN 978-3-8055-9592-6 (e-ISBN) 1. Liver--Cirrhosis--Complications--Treatment. I. Gerbes, A. L. (Alexander L.) II. Series: Frontiers of gastrointestinal research ; v. 28. 0302-0665 [DNLM: 1. Liver Cirrhosis--complications. 2. Liver Cirrhosis--therapy. 3. Ascites--therapy. 4. Hepatorenal Syndrome--therapy. 5. Hyponatremia--therapy. W1 FR946E v.28 2011 / WI 725] RC848.C5A83 2011 616.3'624--dc22 2010032384 Section Title Contents VII Preface Gerbes, A.L. (Munich) 1 Differential Diagnosis of Ascites Appenrodt, B. (Bonn) 11 Current Treatment Strategies: Diuretics Bernardi, M. (Bologna) 23 Paracentesis Sanyal, A.J.; Bajaj, J.S.; Shaw, J. (Richmond, Va.) 32 Large-Volume Paracentesis: Which Plasma Expander? Terg, R.A. (Buenos Aires) 40 Albumin: Not Just a Plasma Expander Davies, N.A.; Garcia, R.; Proven, A.; Jalan, R. (London) 52 Transjugular Intrahepatic Portosystemic Shunt for Ascites: Which Patients Will Benefit? Salerno, F.; Cazzaniga, M. (San Donato Milanese) 65 Spontaneous Bacterial Peritonitis – Prophylaxis and Treatment Wiest, R. (Regensburg); Garcia-Tsao, G. (New Haven, Conn./West Haven, Conn.) 83 Clinical Implications of Hyponatremia in Cirrhosis Heuman, D.M. (Richmond, Va.) 91 Vaptans for Ascites – Chances and Risks Wong, F. (Toronto, Ont.) 102 Cardiorenal Syndrome – A New Entity? Møller, S.; Krag, A. (Hvidovre) 112 Renal Failure in Cirrhosis Gustot, T. (Brussels/Clichy/Paris); Moreau, R. (Clichy/Paris) 122 Novel Definition of Hepatorenal Syndrome: Clinical Consequences Fernandez, J.; Arroyo, V. (Barcelona) 130 Role of Infections in Hepatorenal Syndrome Wiest, R. (Regensburg) 142 TIPS for HRS Sauerbruch, T.; Appenrodt, B. (Bonn) 149 Vasoconstrictor Therapy for Hepatorenal Syndrome Yeo, C.-M. (New Haven, Conn.); Garcia-Tsao, G. (New Haven, Conn./West Haven, Conn.) V VI Contents 163 Terlipressin for Hepatorenal Syndrome: The US Experience Musana, A.K.; Sanyal, A.J. (Richmond, Va.) 172 Terlipressin for Hepatorenal Syndrome: Predictors of Response Cárdenas, A.; Ginès, P. (Barcelona) 178 Safety of Terlipressin for Hepatorenal Syndrome Krag, A.; Møller, S. (Hvidovre) 189 Terlipressin for Hepatorenal Syndrome: Novel Strategies and Future Perspectives Angeli, P. (Padova) 198 Hepatorenal Syndrome and Liver Transplantation Gonwa, T.A. (Jacksonville, Fla.) 208 Author Index 209 Subject Index Section Title Preface In patients with cirrhosis of the liver treatment focuses on the therapy of complications. Ascites is the most frequent and hepatorenal syndrome the most lethal complica- tion of liver cirrhosis. Fortunately, major progress has been made in recent years in providing effective treatment and thus reducing mortality in these patients. Therefore, the topics of ascites, hyponatremia and hepatorenal syndrome are very well suited to be presented as a book in the Frontiers in Gastrointestinal Research series. Consequently, this project highlights and critically appraises recent achievements and novel advances. It also provides the background needed to grasp the novel con- cepts, but is not intended to represent an encyclopedic textbook. Contributions are provided by the most renowned experts at the forefront of clinical research. Their state of the art contributions provide up-to-date references and conclude with a bullet point summary. Just to pick some of the hot topics that are elaborated in this book. The Transjugular Intrahepatic Portosystemic Shunt (TIPS) and paracentesis, respectively have been introduced into clinical routine, but several pitfalls need to be observed. Chapters deal with the most relevant issues of complications of paracentesis, the right choice of plasma expanders, and selection of patients who will experience survival benefit from TIPS. Beneficial effects of albumin infusion independent of its properties as a plasma expander are discussed. There is a broad spectrum of acute kidney injury in cirrhosis. Hepatorenal syn- drome was considered as a terminal renal failure in cirrhosis until recently. Now, drug treatment can improve renal function and prolong survival – a clinical breakthrough. However, important issues for clinical outcome are still under debate, such as predic- tors of response and ways to reduce the incidence of side effects of vasoconstrictor therapy. The role of combined kidney-liver transplantation versus conventional liver- only transplantation is considered. Finally, hyponatremia, an indicator of poor prognosis in cirrhosis can now be addressed with vaptans, new pharmaceutical compounds. The role of vaptans for treating patients with ascites is still a matter of controversy. Section Title VII VIII Preface I gladly accepted the invitation by Markus Lerch, the series editor, to design and organize this volume, and am very grateful that a highly selected group of interna- tional experts has contributed to this book. I do appreciate that despite their extremely busy agenda they took the time to share their knowledge and expertise. They come from the Americas and from Europe and thus provide a truly universal perspective. It is my hope that this book provides practical advice for practitioners and cli- nicians who care for patients with cirrhosis. Furthermore, clinicians and scientists working in the field should find the latest data and inspiration for future research. Alexander L. Gerbes Munich, Germany Gerbes AL (ed): Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment. Front Gastrointest Res. Basel, Karger, 2011, vol 28, pp 1–10 Differential Diagnosis of Ascites B. Appenrodt Department for Internal Medicine I, University of Bonn, Bonn, Germany Abstract Approximately 80– 85% of causes of ascites are related to portal hypertension; however, malignancy- related ascites, cardiac failure and tuberculosis and other less common causes should always be con- sidered. If ascites is suspected the patient should be carefully evaluated, including clinical history and physical examination. Diagnostic paracentesis should be performed routinely to determine the cause of ascites and spontaneous bacterial peritonitis. Basic tests include a cell count with differen- tial and total protein concentration in ascitic fluid. Culture and other optional tests like the serum ascites albumin gradient can be performed based on clinical suspicion. New tests have been devel- oped especially for the diagnosis of spontaneous bacterial peritonitis such as measurement of lacto- ferrin concentration in ascitic fluid or detection of bacterial DNA. These tests still need to be evaluated further. Copyright © 2011 S. Karger AG, Basel Ascites is defined as accumulation of fluid in the peritoneal cavity. It is a common complication of cirrhosis, indicating portal hypertension which occurs in 80– 85% of patients with ascites [1]. Nearly 60% of patients with compensated liver cirrhosis develop ascites within 10 years after onset of the liver disease. Once patients have developed ascites their prognosis is poor; nearly half of them die within 2– 3 years [2]. However, other less common causes of ascites should be evaluated in the differential diagnosis of ascites. Other causes of ascites are, for example, malignancy (10%), car- diac failure (5%) and abdominal tuberculosis (2%) (table 1) [3]. Clinical Work- Up and Problems In patients where cirrhosis is not the cause of ascites, a clinical work- up should be elicited for other causes of ascites. Furthermore, in approximately 5– 10% of patients there is more than one cause of ascites [1].