TEXTBOOK OF Hepatology From Basic Science to Clinical Practice doc

TEXTBOOK OF
Hepatology
From Basic Science to Clinical Practice
TTOA01_vol1 3/9/07 10:46 AM Page i
Textbook of Hepatology – Third Edition – Companion CD
A companion CD is included at the back of Volume Two. It contains:
• All chapters in PDF format
• A full text search facility, with search words highlighted in the text.
TTOA01_vol1 3/9/07 10:46 AM Page ii
TEXTBOOK OF
Hepatology
From Basic Science to Clinical Practice
THIRD EDITION
SECTIONS 1–10 AND INDEX
EDITORS
Juan Rodés MD
Director General, Hospital Clinic; Professor of Medicine,
University of Barcelona, Barcelona, Spain
Jean-Pierre Benhamou MD
Professor of Hepatology, Université Denis Diderot Paris 7,
Assistance Publique – Hôpitaux de Paris and Inserm U773,
Service d’Hépatologie, Hôpital Beaujon, Clichy, France
Andres T. Blei MD
Professor of Medicine and Surgery, Northwestern University
Feinberg School of Medicine, Chicago, IL, USA
Jürg Reichen MD
Professor of Medicine, University of Bern; Chief of Hepatology,
University Hospital, Bern, Switzerland
Mario Rizzetto MD
Professor of Gastroenterology, University of Turin, Turin, Italy

ASSOCIATE EDITORS
Jean-François Dufour MD
Professor of Hepatology, University of Bern, Bern, Switzerland
Scott L. Friedman MD
Fishberg Professor of Medicine, Chief, Division of Liver Diseases,
Mount Sinai School of Medicine, New York, NY, USA
Pere Ginès MD
Professor of Medicine, University of Barcelona, Chief, Liver Unit,
Hospital Clinic, Barcelona, Spain
Dominique-Charles Valla MD
Professor of Hepatology, Université Denis Diderot Paris 7,
Assistance Publique – Hôpitaux de Paris and Inserm U773,
Chief, Service d’Hépatologie, Hôpital Beaujon, Clichy, France
Fabien Zoulim MD PhD
Professor of Medicine, Université Lyon 1, Liver Department,
Hospices Civils de Lyon, Head, Inserm U8712, Lyon, France
FOREWORD
Neil McIntyre MD
Emeritus Professor of Medicine, Royal Free and University College
School of Medicine, London, UK
TTOA01_vol1 3/12/07 4:44 PM Page iii
© 2007 by Blackwell Publishing Ltd
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Designs and Patents Act 1988, without the prior permission of the publisher.
First published 1991 by Oxford University Press
Second edition 1999 by Oxford University Press
2007 1
Library of Congress Cataloging-in-Publication Data
Textbook of hepatology : from basic science to clinical practice. — 3rd ed. / edited by
Juan Rodés . . . [et al.].
p. ; cm.
Rev. ed. of: Oxford textbook of clinical hepatology. 2nd ed. 1999.
Includes bibliographical references and indexes.
ISBN: 978-1-4051-2741-7 (alk. paper)
1. Liver—Diseases. I. Rodés, Juan. II. Oxford textbook of clinical hepatology.
III. Title: Hepatology.
[DNLM: 1. Liver Diseases. WI 700 T355 2007]
RC845.O93 2007
616.3′62—dc22
2006101699
ISBN: 978-1-4051-2741-7
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TTOA01_vol1 3/9/07 10:46 AM Page iv
Contents
Volume One
Contributors
Foreword
Preface to the third edition
Preface to the first edition
Section 1 Architecture of the liver, 1
1.1 Macroscopic anatomy of the liver, 3
Jean H.D. Fasel, Holger Bourquain, Heinz-Otto Peitgen and
Pietro E. Majno
1.2 Liver and biliary tract histology, 9
Paulette Bioulac-Sage, Brigitte Le Bail and Charles Balabaud
1.3 Ultrastructure of the hepatocyte, 20
Zahida Khan, James M. Crawford and Donna B. Stolz
1.4 Liver sinusoidal endothelial cells, 29
David Semela and Vijay H. Shah
1.5 Kupffer cells, 36
Hartmut Jaeschke
1.6 The hepatic stellate cell, 43
Massimo Pinzani

1.7 Biliary epithelial cells, 52
Jean-François Dufour
1.8 Hepatic stem cells, 58
Tania Roskams
1.9 Embryology of the liver and intrahepatic biliary tract, 65
Frédéric P. Lemaigre
Section 2 Functions of the liver, 73
2.1 Hepatic circulation, 75
2.1.1 Regulation of hepatic blood flow, 75
Christophe Bureau, Jean-Marie Péron and Jean-Pierre Vinel
2.1.2 Hepatic microcirculation, 79
Yoshiya Ito and Robert S. McCuskey
2.1.3 Hepatic lymph and lymphatics, 84
Glen A. Laine and Charles S. Cox Jr
2.2 Functions of the liver, 89
2.2.1 Functional organization of the liver, 89
Paulo Renato A.V. Correa and Michael H. Nathanson
2.2.2 Cell biology of the hepatocyte, 96
Allan W. Wolkoff and Phyllis M. Novikoff
2.2.3 Molecular biology of the liver cell, 101
Sundararajah Thevananther and Saul J. Karpen
2.2.4 Hepatic transport processes, 109
Ronald P.J. Oude Elferink
2.2.5 Modulation of liver function by hepatic nerves, 114
Gerhard P. Püschel
2.2.6 In vitro techniques: isolated organ perfusion, slices, cells
and subcellular elements, 122
Bruno Stieger
2.3 Metabolism, 129
Intermediate metabolism

2.3.1 Carbohydrates and the liver, 129
Guenther Boden
2.3.2 Lipoprotein metabolism, 133
Erez F. Scapa, Keishi Kanno and David E. Cohen
2.3.3 Protein and amino acid metabolism, 142
Margaret E. Brosnan and John T. Brosnan
2.3.4 Mitochondria and energy formation, 149
Dominique Pessayre
Liver-specific functions
2.3.5 Bilirubin metabolism, 165
Namita Roy-Chowdhury, Yang Lu and
Jayanta Roy-Chowdhury
2.3.6 Metabolism of bile acids, 174
Peter L.M. Jansen and Klaas N. Faber
2.3.7 Ammonia, urea production and pH regulation, 181
Dieter Häussinger
2.3.8 Protein synthesis and degradation in the liver, 192
Armin Akhavan and Vishwanath R. Lingappa
2.3.9 Glutathione, 199
José C. Fernández-Checa and Carmen García-Ruiz
2.3.10 Haem biosynthesis and excretion of porphyrins, 207
Hervé Puy and Jean-Charles Deybach
Metabolism of endo/xenobiotics
2.3.11 Vitamins and the liver (A and D), 214
Masataka Okuno, Rie Matsushima-Nishiwaki and
Soichi Kojima
v
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vi CONTENTS
2.3.12 Normal iron metabolism, 221

Kyle E. Brown
2.3.13 Normal copper metabolism and reducing copper to
subnormal levels for therapeutic purposes, 226
George J. Brewer, Edward D. Harris and
Fred K. Askari
2.3.14 Trace elements and the liver, 233
Brent A. Neuschwander-Tetri
2.3.15 Hepatic metabolism of drugs, 241
Chris Liddle and Catherine A.M. Stedman
2.4 Synthetic function, 250
2.4.1 Albumin and other carrier proteins, 250
Richard A. Weisiger
2.4.2 The liver and coagulation, 255
Maria T. DeSancho and Stephen M. Pastores
2.4.3 Function and metabolism of collagen and other
extracellular matrix proteins, 264
Rebecca G. Wells
2.5 Regulation of the liver cell mass, 274
2.5.1 Control of liver cell proliferation, 274
Nisar P. Malek and K. Lenhard Rudolph
2.5.2 Regeneration of chronically injured liver, 280
Anna Mae Diehl
2.6 Excretion, 290
2.6.1 Physiology of bile formation, 290
Martin Wagner and Michael Trauner
2.6.2 Motility of the biliary tree, 304
Mayank Bhandari and James Toouli
2.7 Immunology of the liver, 312
2.7.1 Cytokines in liver physiology and liver pathology, 312
Tom Luedde and Christian Trautwein

2.7.2 Intrahepatic lymphocytes, 320
Wajahat Z. Mehal
2.7.3 Antibody production and transport in the liver, 325
Alvin B. Imaeda and Wajahat Z. Mehal
Section 3 Basic concepts in pathobiology, 333
3.1 Hepatocyte apoptosis and necrosis, 335
Henning Schulze-Bergkamen, Marcus Schuchmann and
Peter R. Galle
3.2 Ischaemia-reperfusion injury to the liver, 348
Nazia Selzner and Pierre A. Clavien
3.3 Genetics and liver diseases, 356
3.3.1 Genetic polymorphisms in liver disease, 356
Hongjin Huang and Ramsey Cheung
3.3.2 Immunogenetics of liver disease, 364
Peter T. Donaldson
3.3.3 Genetic determinants of complex liver diseases: mouse
models and quantitative trait locus analysis, 371
Frank Lammert
3.4 Cellular cholestasis, 384
Stefano Fiorucci
3.5 Oncogenes and tumour suppressor genes, 391
Dipankar Chattopadhyay and Helen Reeves
3.6 Genomics, gene arrays and proteomics in the study of liver
disease, 398
Geoffrey W. McCaughan, Nicholas A. Shackel, Rohan Williams,
Devanshi Seth, Paul S. Haber and Mark D. Gorrell
Section 4 Pathology, 421
4.1 Histological features, 423
Valeer J. Desmet, Tania Roskams and Miguel Bruguera
4.2 Classifications, scoring systems and morphometry in liver

pathology, 433
Pierre Bedossa and Valerie Paradis
Section 5 Investigation of hepatobiliary
disease, 441
5.1 Signs and symptoms of liver disease, 443
Jürg Reichen
5.2 Biochemical investigations in the management of liver disease,
451
Igino Rigato, J. Donald Ostrow and Claudio Tiribelli
5.3 Hepatic removal kinetics: importance for quantitative
measurements of liver function, 468
Susanne Keiding and Michael Sørensen
5.4 Immunological investigations in liver diseases, 479
Elmar Jaeckel and Michael P. Manns
5.5 Biopsy and laparoscopy, 489
Arthur Zimmermann
5.6 Imaging of the liver, 500
5.6.1 Ultrasonography, 500
Luigi Bolondi, Valeria Camaggi and Fabio Piscaglia
5.6.2 Computerized tomography imaging of the liver, 508
Daniel T. Cohen and Dushyant V. Sahani
5.6.3 Magnetic resonance imaging, 521
Christoforos Stoupis
5.6.4 Angiography, 531
Sanjeeva P. Kalva and Dushyant V. Sahani
5.6.5 Endoscopic retrograde cholangiopancreatography, 540
Alan J. Wigg and James Toouli
5.7 Interventional radiology in hepatobiliary diseases, 549
José Ignacio Bilbao Jaureguízar, Concepció Bru, Joan Falcó Fages
and Lluís Donoso

5.8 Positron emission tomography of the liver, 561
Susanne Keiding and Michael Sørensen
5.9 Splanchnic haemodynamic investigations, 567
Didier Lebrec and Richard Moreau
5.10 The Cochrane Hepatobiliary Group, 572
Christian Gluud, on behalf of the Cochrane Hepatobiliary Group
Section 6 Cirrhosis, 581
6.1 The evolution of cirrhosis, 583
John P. Iredale and I. Neil Guha
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CONTENTS vii
6.2 Cellular and molecular pathobiology of liver fibrosis and its
pharmacological intervention, 590
Scott L. Friedman
6.3 Clinical and diagnostic aspects of cirrhosis, 604
I. Neil Guha and John P. Iredale
Section 7 Portal hypertension and its
complications, 621
7.1 Anatomy of the portal venous system in portal
hypertension, 623
J. Michael Henderson
7.2 Pathogenesis of portal hypertension, 630
Roberto J. Groszmann and Juan G. Abraldes
7.3 Clinical manifestions and management of bleeding episodes in
cirrhotics, 640
Jaime Bosch, Juan G. Abraldes and Juan Carlos García-Pagán
7.4 Haemodynamic assessment of portal hypertension, 658
Juan Carlos García-Pagán, Juan Turnes and Jaime Bosch
7.5 Pathogenesis, diagnosis and treatment of ascites in
cirrhosis, 666

Vicente Arroyo, Carlos Terra and Luis Ruiz-del-Arbol
7.6 Hepatorenal syndrome, 711
Pere Ginès and Mónica Guevara
7.7 Pulmonary complications of portal hypertension, 720
Michael J. Krowka
7.8 Hepatic encephalopathy, 728
Dieter Häussinger and Andres T. Blei
7.9 Bacterial infections in portal hypertension, 761
Javier Fernández and Miguel Navasa
7.10 Hypersplenism, 771
P. Aiden McCormick
Section 8 Congenital hepatic fibrosis and
non-parasitic cystic lesions of the liver and bile
ducts, 779
8.1 Congenital conditions, 781
8.1.1 Congenital hepatic fibrosis, 781
Jean-Pierre Benhamou
8.1.2 Simple cyst of the liver, 783
Valérie Vilgrain
8.1.3 Polycystic kidney disease, 789
Valérie Vilgrain
8.1.4 Polycystic liver disease, 795
Valérie Vilgrain
8.1.5 Biliary hamartomas, 797
Valérie Vilgrain
8.1.6 Peribiliary cysts, 802
Valérie Vilgrain
8.1.7 Caroli syndrome, 805
Jean-Pierre Benhamou
8.1.8 Choledochal cyst, 807

Jean-Pierre Benhamou
8.1.9 Ciliated hepatic foregut cyst, 807
Jean-François Cadranel
8.2 Acquired conditions, 810
8.2.1 Inflammatory cystic diseases, 810
Jean-François Cadranel
8.2.2 Neoplasms including cystadenoma, 813
P. Starkel and André P. Geubel
8.2.3 Post-traumatic cystic diseases, 816
Jean-François Cadranel
Section 9 Viral infections of the liver, 819
9.1 Viral hepatitis, 821
9.1.1 Viral hepatitis, 821
Mario Rizzetto and Fabien Zoulim
9.1.2 The viruses of hepatitis, 823
i) Structure, replication and laboratory diagnosis of
hepatitis B virus and hepatitis D virus, 823
Stephan Schaefer and Wolfram H. Gerlich
ii) Structure, replication and laboratory diagnosis of
hepatitis C virus, 849
Ralf Bartenschlager
iii) Hepatitis A, 857
Loriana Di Giammarino and Jules L. Dienstag
iv) Hepatitis B, 865
Geoffrey M. Dusheiko
v) Hepatitis D, 875
Antonella Smedile and Mario Rizzetto
vi) Hepatitis C, 881
Alfredo Alberti and Luisa Benvegnù
vii) Hepatitis E, 893

Rakesh Aggarwal and Krzysztof Krawczynski
9.1.3 Prevention and treatment of viral hepatitis, 899
i) Vaccines against hepatitis A, 899
Pierre Van Damme, Koen Van Herck and
Philippe Beutels
ii) Hepatitis B vaccines and immunization, 907
Daniel Lavanchy
iii) Therapy of acute viral hepatitis, 917
Markus Cornberg, Heiner Wedemeyer and
Michael P. Manns
iv) Antiviral therapy of chronic hepatitis B, 921
Fabien Zoulim and Mario Rizzetto
v) Therapy for chronic hepatitis C, 941
Giorgio Saracco, Fabien Zoulim and
Mario Rizzetto
9.2 Systemic virosis producing hepatitis, 957
Alberto Biglino and Mario Rizzetto
9.3 Human immunodeficiency virus and the liver, 974
Vincent Soriano, Pablo Barreiro, Javier García-Samaniego,
Luz Martín-Carbonero and Marina Nuñez
9.4 Exotic virus infections of the liver, 988
Pierre E. Rollin, Thomas G. Ksiazek, Alberto Queiroz Farias and
Flair José Carrilho
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viii CONTENTS
Section 10 Other infections of the liver, 999
10.1 Bacterial, rickettsial and spirochaetal infections, 1001
José M. Sánchez-Tapias
10.2 Fungal infections affecting the liver, 1011
Roderick J. Hay

10.3 Protozoal infections affecting the liver, 1020
10.3.1 Amoebiasis, giardiasis and cryptosporidiosis, 1020
David Kershenobich, Guillermo Robles Diaz and
Juan Miguel Abdo
10.3.2 Malaria, 1029
Montse Renom and Pedro L. Alonso
10.3.3 Visceral leishmaniasis, 1034
Manuel Corachan
10.4 Helminthiasis, 1040
10.4.1 Blood flukes (schistosomes) and liver flukes, 1040
Flair José Carrilho, Pedro Paulo Chieffi and
Luiz Caetano Da Silva
10.4.2 Echinococcosis of the liver, 1047
S. Bresson-Hadni, G.A. Mantion, J.P. Miguet and
D.A. Vuitton
10.4.3 Ascariasis, visceral larva migrans, strongyloidiasis,
capillariasis and pentastomiasis, 1058
Marcelo Simão Ferreira and Edna Strauss
Index
Colour plate section follows p. 72
Volume Two
Section 11 Immune disorders of the liver,
1069
11.1 Primary biliary cirrhosis, 1071
E. Jenny Heathcote and Piotr Milkiewicz
11.2 Autoimmune hepatitis, 1089
Diego Vergani and Giorgina Mieli-Vergani
11.3 Sclerosing cholangitis, 1103
Konstantinos N. Lazaridis and Nicholas F. LaRusso
11.4 Vanishing bile duct syndrome, 1111

Frank Grünhage and Tilman Sauerbruch
11.5 Overlap syndromes, 1120
Ulrich Beuers
Section 12 Alcoholic liver disease, 1127
12.1 Epidemiological aspects of alcoholic liver disease, 1129
Juan Caballeria
12.2 Ethanol metabolism and pathogenesis of alcoholic liver injury,
1135
Stephen F. Stewart and Christopher P. Day
12.3 Pathology of alcoholic liver disease, 1148
Elie Serge Zafrani
12.4 Alcoholic liver disease: natural history, diagnosis,
clinical features, evaluation, prognosis and
management, 1157
Laurent Spahr and Antoine Hadengue
12.5 Management of the alcoholic patient, including alcoholism and
extrahepatic manifestations, 1179
Georges-Philippe Pageaux and Pascal Perney
Section 13 Hepatic non-alcoholic steatosis,
1193
13 Non-alcoholic fatty liver and non-alcoholic steatohepatitis, 1195
Geoffrey C. Farrell
Section 14 Toxic liver injury, 1209
14.1 Drug-induced liver injury, 1211
Dominique Pessayre and Dominique Larrey
14.2 Toxic liver injury, 1269
Basuki Gunawan and Neil Kaplowitz
14.3 Hepatic injury due to physical agents, 1277
Bernhard H. Lauterburg and Haithem Chtioui
14.4 Hepatic toxicity induced by herbal medicines, 1281

Felix Stickel and Detlef Schuppan
Section 15 Acute liver failure, 1289
15 Acute liver failure and related syndromes, 1291
François Durand and Jacques Bernuau
Section 16 Genetic and metabolic diseases,
1313
16.1 Wilson’s disease, 1315
Michael Schilsky
16.2 Haemochromatosis, 1323
Antonello Pietrangelo
16.3 Alpha 1-antitrypsin deficiency and related disorders, 1330
Jeffrey H. Teckman
16.4 The liver in cystic fibrosis, 1336
Andrew P. Feranchak
16.5 Human hereditary porphyrias, 1343
Elisabeth I. Minder and Xiaoye Schneider-Yin
16.6 Hyperbilirubinaemia, 1352
Peter L.M. Jansen
16.7 The liver in intracellular and extracellular lipidosis, 1360
Dominique P. Germain
16.8 Glycogen storage diseases, 1370
Philippe Labrune
16.9 Mitochondriopathies, 1377
Pierre Rustin
16.10 Genetic cholestatic diseases, 1383
Ronald P.J. Oude Elferink
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CONTENTS ix
Section 17 Vascular diseases, 1389
17.1 Hepatic artery diseases, 1391

Peter C. Hayes
17.2 Obstruction of the portal vein, 1395
Juan Carlos García-Pagán, Manuel Hernández-Guerra and
Jaime Bosch
17.3 Disorders of the hepatic veins and hepatic sinusoids, 1403
Dominique-Charles Valla
17.4 Congenital vascular malformations, 1418
Guadalupe García-Tsao
Section 18 Tumours of the liver, 1425
18.1 Benign hepatic tumours, 1427
18.1.1 Liver haemangioma, 1427
Jean-Pierre Benhamou
18.1.2 Benign hepatocellular tumours, 1428
Massimo Colombo and Riccardo Lencioni
18.2 Malignant tumours, 1437
18.2.1 Primary liver cell carcinoma, 1437
Jordi Bruix, Alejandro Forner, María Varela,
Carmen Ayuso and Josep María Llovet
18.2.2 Malignant mesenchymal tumours of the liver, 1457
Miguel Bruguera and Juan Rodés
18.3 Metastatic tumours, 1464
18.3.1 Metastatic liver disease, 1464
Masamichi Kojiro and Antoni Castells
18.3.2 Carcinoid tumours, 1470
Humphrey J.F. Hodgson
Section 19 Biliary tract diseases, 1479
19.1 Intrahepatic cholestasis, 1481
Olivier Chazouillères and Chantal Housset
19.2 Extrahepatic biliary obstruction: systemic effects, diagnosis and
management, 1501

Michelle C. Gallagher and James S. Dooley
19.3 Gallstone disease, 1518
Frank Lammert, Franz-Ludwig Dumoulin and
Tilman Sauerbruch
19.4 Cholangitis and biliary tract infections, 1541
Ulrich Beuers
19.5 Haemobilia, 1550
Antonio Lacy and Nader K. Francis
19.6 Biliary dyskinesia, 1561
C. Ritchie Chalmers and Giles J. Toogood
19.7 Benign biliary tumours, 1573
Miguel Bruguera
19.8 Gallbladder carcinoma, 1575
Thomas A. Aloia, Christopher H. Crane and
Jean-Nicolas Vauthey
19.9 Cholangiocarcinoma, 1583
Steven S. Strasberg and William G. Hawkins
Section 20 The liver in diseases of
other systems, 1607
20.1 The liver in cardiovascular disease, 1609
Susan Tiukinhoy-Laing, Andres T. Blei and Mihai Gheorghiade
20.2 The liver in lung diseases, 1616
Andres T. Blei and Jacob I. Sznajder
20.3 The effect of gastrointestinal diseases on the liver and biliary
tract, 1622
Roger W. Chapman and Peter W. Angus
20.4 Total parenteral nutrition-related liver disease, 1634
Sean W.P. Koppe and Alan L. Buchman
20.5 The effect of skin diseases on the liver, 1642
Daniel Glass and Malcolm Rustin

20.6 The liver in urogenital diseases, 1653
Mónica Guevara, Vicente Arroyo and Juan Rodés
20.7 The effect of haematological and lymphatic diseases on the liver,
1662
Miguel Bruguera and Rosa Miquel
20.8 The liver in graft-vs host disease, 1671
Enric Carreras, Carmen Martínez and Miguel Bruguera
20.9 The effect of endocrine diseases on liver function, 1680
Anthony J. DeSantis and Andres T. Blei
20.10 Musculoskeletal diseases and the liver, 1694
N. Guañabens, J. van den Bogaerde and H.L.C. Beynon
20.11 Amyloidosis, 1702
Philip N. Hawkins
20.12 Hepatic granulomas, 1709
Laura M. Kulik and Andres T. Blei
Section 21 The impact of liver disease on
other systems, 1719
21.1 The effect of liver disease on the cardiovascular system, 1721
Jens H. Henriksen and Søren Møller
21.2 The effect of liver disease on the endocrine system, 1732
Yolanta T. Kruszynska and Pierre M. Bouloux
21.3 Haematological abnormalities in liver disease, 1767
Marco Senzolo and Andrew K. Burroughs
21.4 Haemostasis in liver disease, 1780
Stephen H. Caldwell, Patrick G. Northup and Vinay Sundaram
21.5 The effect of liver disease on the gastrointestinal tract, 1798
Roger W. Chapman and Peter W. Angus
21.6 The effect of liver disease on the skin, 1804
Malcolm Rustin and Daniel Glass
21.7 Effect of liver on the urogenital tract, 1815

Mónica Guevara, Vicente Arroyo and Juan Rodés
21.8 The nervous system in liver disease, 1822
Andres T. Blei
21.9 The effect of liver disease on bone, 1829
Juliet Compston
21.10 The effect of liver disease on nutritional status and energy
metabolism, 1836
Michael R. Charlton
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x CONTENTS
Section 22 The liver in specific settings, 1843
22.1 Paediatric liver diseases, 1845
Marianne Samyn and Giorgina Mieli-Vergani
22.2 Liver diseases in the elderly, 1870
Oliver F.W. James
22.3 Liver diseases and pregnancy, 1879
Andrew K. Burroughs and Evangelos Cholongitas
Section 23 The management of
liver diseases, 1897
23.1 The general management of liver diseases, 1899
Dominique Guyader
23.2 Nutritional aspects of liver and biliary disease, 1905
Bernard Campillo
23.3 Prescribing drugs in liver disease, 1912
Dominique Larrey and Georges-Phillppe Pageaux
23.4 Management of pretransplant patients, 1922
François Durand
Section 24 Surgery, anaesthesia and
the liver, 1931
24.1 General surgical aspects and the risks of liver surgery in patients

with hepatic disease, 1933
Jacques Belghiti and Satoshi Ogata
24.2 Anaesthesia and liver disease, 1938
Kalpana Reddy and Susan V. Mallett
24.3 Postoperative jaundice, 1945
Peter Fickert and Michael Trauner
24.4 Hepatobiliary trauma, 1953
K. Raj Prasad, Patrick A. Couglin and Giles J. Toogood
Section 25 Liver transplantation, 1963
25.1 Surgical techniques, 1965
25.1.1 Liver transplantation, 1965
Peter Neuhaus
25.1.2 Split-liver transplantation, 1970
Ramón Charco, Josep Fuster Obregón, Constantino
Fondevila and Juan Carlos García-Valdecasas
25.1.3 The surgical technique of living donor liver
transplantation using the right hepatic lobe, 1976
Igal Kam, James Trotter and Gregory T. Everson
25.2 Liver transplantation: indications, contraindications and results,
1984
Gregory T. Everson and Fernando E. Membreno
25.3 The perioperative care and complications of liver transplantation,
1996
Mark T. Keegan and David J. Plevak
25.4 Immunosuppression, 2003
James Neuberger
25.5 Recurrent disease and management in liver transplantation, 2010
Xavier Forns and Antoni Rimola
25.6 Post-transplantation management and complications, 2019
Faouzi Saliba and Didier Samuel

25.7 Liver transplantation and quality of life, 2027
Miguel Navasa and Juan Rodés
25.8 Emerging therapies, 2032
25.8.1 Hepatocyte transplantation, 2032
Govardhana Rao Yannam, Jayanta Roy-Chowdhury and
Ira J. Fox
25.8.2 Liver support, 2043
Vanessa Stadlbauer and Rajiv Jalan
Section 26 Mathematics in hepatology, 2053
26.1 Models in clinical hepatology, 2055
W. Ray Kim
26.2 Outcomes research in hepatology, 2065
Raymond S. Koff
26.3 Meta-analysis, 2073
Gioacchino Leandro and Andrew K. Burroughs
26.4 Economic considerations in hepatology, 2080
John B. Wong
26.5 Development of the liver interactome: mapping the regulatory
networks, 2088
Mario Pagano, Susana Neves, Ravi Iyengar and John Cijiang He
Section 27 Appendices, 2097
27.1 Geographic distribution of infections causing liver disease, 2099
Harriet Hughes and Tom Doherty
27.2 Liver injury in man ascribed to non-drug chemicals and natural
toxins, 2105
Regine Kahl and Wim Wätjen
27.3 Rare diseases with hepatic abnormalities, 2122
M. Baraitser and R.M. Winter
Index
Colour plate section follows p. 1268

A companion CD containing all chapters in PDF format with a
full text search is included at the back of Volume Two.
TTOA01_vol1 3/9/07 10:46 AM Page x
Juan Miguel Abdo MD
Chief, Clinical Gastroenterology Unit
Mexico General Hospital
Mexico City, Mexico
Juan G. Abraldes MD
Specialist in Hepatology
Liver Unit, Hospital Clinic
Barcelona, Spain
Rakesh Aggarwal MD DM
Professor, Department of Gastroenterology
All India Institute of Medical Sciences
New Delhi, India
Armin Akhavan MD
California Pacific Medical Center
San Francisco, CA, USA
Alfredo Alberti MD
Professor of Clinical and Experimental Medicine
University of Padua
Padua, Italy
Thomas A. Aloia MD
Assistant Professor of Surgery
Baylor College of Medicine
Houston, TX, USA
Pedro L. Alonso MD
Jefe del Servicio
Centro de Salud Internacional
Hospital Clinic

Barcelona, Spain
Peter W. Angus MB BS MD FRACP
Director of Gastroentrology and Hepatology
Austin Hospital
Melbourne, Vic, Australia
Vicente Arroyo MD
Professor of Medicine
Director of the Institute of Digestive and Metobolic
Diseases
University of Barcelona
Barcelona, Spain
Fred K. Askari MD PhD
Clinical Assistant Professor, Department of Internal
Medicine
University of Michigan Health System
Ann Arbor, MI, USA
Carmen Ayuso MD
Consultant Radiologist
Hospital Clinic
Barcelona, Spain
Charles Balabaud MD
Hepatologist
Hôpital St André
Bordeaux, France
M. Baraitser MD
Consultant in Clinical Genetics
Great Ormond Street Hospital for
Children
London, UK
Pablo Barreiro MD

Department of Infectious Diseases
Hospital Carlos III
Madrid, Spain
Ralf Bartenschlager PhD
Head of Department of Molecular Virology
University of Heidelberg
Heidelberg, Germany
Pierre Bédossa MD
Professor of Pathology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris and Inserm
U773;
Department of Pathology, Hôpital Beaujon
Clichy, France
Jacques Belghiti MD
Hôpital Beaujon
Clichy, France
Jean-Pierre Benhamou MD
Professor of Hepatology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris and Inserm
U773;
Service d’Hépatologie, Hôpital Beaujon
Clichy, France
Luisa Benvegnù MD
Department of Clinical and Experimental
Medicine
University of Padua
Padua, Italy
Jacques Bernuau MD

Service d’Hépatologie
Hôpital Beaujon
Clichy, France
Ulrich Beuers MD
Professor, Department of Gastroenterology and
Hepatology
Academic Medical Center
Amsterdam, The Netherlands
Philippe Beutels BSc MSc PhD
Lecturer in Health Economics
Faculty of Medicine
University of Antwerp
Antwerp, Belgium
H.L.C. Beynon MD
Consultant Physician and Rheumatologist
Royal Free Hospital
London, UK
Mayank Bhandari MB BS MS
Flinders Medical Centre
Bedford Park, SA, Australia
Alberto Biglino MD
Associate Professor of Infectious Diseases
University of Turin;
Head, Infectious Diseases Unit
Cardinal Massaja Hospital
Asti, Italy
José Ignacio Bilbao Jaureguízar
MD
Department of Radiology
Clínica Universitaria de Navarra

Pamplona, Spain
Paulette Bioulac-Sage MD
Professor of Pathology
Université Bordeaux
Bordeaux, France
Contributors
xi
TTOA01_vol1 3/9/07 10:46 AM Page xi
xii CONTRIBUTORS
Andres T. Blei MD
Professor of Medicine and Surgery
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Guenther Boden MD
Laura H. Carnell Professor of Medicine
Chief, Division of Endocrinology, Diabetes and
Metabolism
Temple University
Philadelphia, PA, USA
J. van den Bogaerde MD
Royal Free Hospital
London, UK
Luigi Bolondi MD
Department of Internal Medicine and
Gastroenterology
University of Bologna
Bologna, Italy
Jaime Bosch MD
Senior Consultant

Liver Unit, Hospital Clinic;
Professor of Medicine
University of Barcelona
Barcelona, Spain
Pierre M. Bouloux MD
Department of Medicine
Royal Free Hospital
London, UK
Holger Bourquain MD
MeVis Research GmbH
Bremen, Germany
S. Bresson-Hadni MD PhD
Professor, Department of Hepatology and Liver
Diseases
Hôpital Jean-Minjoz
Besançon, France
George J. Brewer MD
Active Emeritus Professor of Human Genetics and
Internal Medicine
University of Michigan Medical School
Ann Arbor, MI, USA
John T. Brosnan DPhil DSc
Professor, Department of Biochemistry
Memorial University of Newfoundland
St. John’s, NL, Canada
Margaret E. Brosnan PhD
Professor, Department of Biochemistry
Memorial University of Newfoundland
St. John’s, NL, Canada
Kyle E. Brown MD MSc

Assistant Professor, University of Iowa Carver
College of Medicine;
Staff Physician, Iowa City Veterans Administration
Medical Center
Iowa City, IA, USA
Concepció Bru MD
Senior Consultant Radiologist
Hospital Clinic
Barcelona, Spain
Miguel Bruguera MD
Senior Consultant
Liver Unit, Hospital Clinic
Barcelona, Spain
Jordi Bruix MD
Senior Consultant and BCLC Director
Liver Unit, Hospital Clinic
Barcelona, Spain
Alan L. Buchman MD MSPH FACP
FACG FACN AGAF
Associate Professor
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Christophe Bureau MD
Praticien Hospitalier
CHU Purpan and Inserm U531
Toulouse, France
Andrew K. Burroughs MB ChB
FRCP
Professor of Hepatology

University College School of Medicine;
Consultant Physician
Royal Free Hospital
London, UK
Juan Caballeria MD PhD
Senior Consultant
Liver Unit, Hospital Clinic
Barcelona, Spain
Jean-François Cadranel MD
Associate Professor, Collège Médical des Hôpitaux
de Paris;
Chief, Liver Unit, Hôpital Laennec
Creil, France
Stephen H. Caldwell MD
Director of Hepatology
University of Virginia
Charlottesville, VA, USA
Valeria Camaggi MD
Department of Internal Medicine and
Gastroenterology
University of Bologna
Bologna, Italy
Bernard Campillo MD
Service de Rééducation Digestive
Hôpital Albert Chenevier
Créteil, France
Enric Carreras MD PhD
Senior Consultant
Director of the Stem Cell Transplantation Program
Hospital Clinic

Barcelona, Spain
Flair José Carrilho MD PhD
Full Professor of Gastroenterology
University of São Paulo School of Medicine
São Paulo, Brazil
Antoni Castells MD
Department of Gastroenterology
Hospital Clinic
Barcelona, Spain
C. Ritchie Chalmers MD
MRC Clinical Training Fellow
Hepatobiliary Department
St James’s University Hospital
Leeds, UK
Roger W. Chapman BSc MD MB BS
FRCP
Consultant Hepatologist
John Radcliffe Hospital
Oxford, UK
Ramón Charco MD PhD
Consultant, Liver Transplant Unit
IMDiM, Hospital Clinic
Barcelona, Spain
Michael R. Charlton MD
Professor of Medicine
Director of Hepatology
Mayo Clinic College of Medicine
Rochester, MN, USA
Dipankar Chattopadhyay MB BS
MS MRCS

Clinical Research Associate
Northern Institute of Cancer Research
Newcastle upon Tyne, UK
Oliver Chazouillères MD PhD
Professor of Hepatology
Université Pierre et Marie Curie Paris 6;
Director, Digestive Department, Hôpital
Saint-Antoine
Paris, France
Ramsey Cheung MD
Associate Professor
Stanford University School of Medicine
Stanford, CA, USA
Pedro Paulo Chieffi MD PhD
Associate Professor, Department of
Gastroenterology
University of São Paulo School of
Medicine
São Paulo, Brazil
Evangelos Cholongitas MD
Hepatologist
Royal Free Hospital
London, UK
Haithem Chtioui MD
Department of Clinical Pharmacology
University of Bern
Bern, Switzerland
TTOA01_vol1 3/9/07 10:46 AM Page xii
CONTRIBUTORS xiii
Pierre A. Clavien MD

Multiorgan Transplant Program
Toronto General Hospital
Toronto, ON, Canada
Daniel T. Cohen MD
Radiology Resident, Department of Radiology
Massachusetts General Hospital
Boston, MA, USA
David E. Cohen MD PhD
Director of Hepatology
Brigham and Women’s Hospital;
Associate Professor of Medicine
Harvard Medical School;
Associate Professor of Health Sciences and Technology
Harvard–MIT Division of Health Sciences and
Technology
Boston, MA, USA
Massimo Colombo MD
Professor of Gastroenterology
University of Milan
Milan, Italy
Juliet Compston FRCPath FRCP
Professor of Bone Medicine
University of Cambridge;
Honorary Consultant Physician
Addenbrooke’s Hospital
Cambridge, UK
Manuel Corachan MD
Senior Consultant in Tropical Medicine
Center for International Health
University Hospital

Barcelona, Spain
Markus Cornberg MD
Department of Gastroenterology
Hanover Medical School
Hanover, Germany
Paulo Renato A.V. Correa MD
Resident, Department of Psychiatry
Yale University School of Medicine
New Haven, CT, USA
Patrick A. Couglin MB ChB MRCS
MD
Higher Surgical Trainee,Yorkshire Deanery
Department of Hepatobiliary Surgery
St James’s University Hospital
Leeds, UK
Charles S. Cox Jr MD PhD
Director, Pediatric Trauma Program
Distinguished Professor of Surgery and Pediatrics
University of Texas Medical School
Houston, TX, USA
Christopher H. Crane MD
Associate Professor
Program Director and Section Chief,
Gastrointestinal Section
University of Texas M.D. Anderson Cancer Center
Houston, TX, USA
James M. Crawford MD PhD
Professor and Chair
Department of Pathology, Immunology and
Laboratory Medicine

University of Florida College of Medicine
Gainesville, FL, USA
Luiz Caetano Da Silva MD
Department of Gastroenterology
University of São Paulo School of Medicine
São Paulo, Brazil
Christopher P. Day MD
Centre for Liver Research
University of Newcastle upon Tyne
Newcastle upon Tyne, UK
Maria T. DeSancho MD
Associate Professor of Clinical Medicine
New York Presbyterian Hospital
New York, NY, USA
Anthony J. DeSantis MD
Assistant Professor of Medicine
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Valeer J. Desmet MD
Emeritus Professor of Pathology
Catholic University of Leuven
Leuven, Belgium
Jean-Charles Deybach MD PhD
President of the French Porphyria Center
Professor of Biochemistry and Molecular Biology
Head of Department of Molecular Genetics and
Biochemistry
Hôpital Louis Mourier
Colombes, France

Anna Mae Diehl MD
Florence McAlister Professor
Chief, Division of Gastroenterology
Duke University School of Medicine
Durham, NC, USA
Jules L. Dienstag MD
Carl W. Walter Professor of Medicine
Harvard Medical School;
Physician, Massachusetts General Hospital
Boston, MA, USA
Loriana Di Giammarino MD
Division of Gastroenterology and Hepatology
Center Hospitalier Universitaire Vaudois
University of Lausanne
Lausanne, Switzerland
Tom Doherty MD FRCP DTM&H
Hospital for Tropical Diseases
London, UK
Peter T. Donaldson BSc PhD
Lecturer in Molecular Genetics
University of Newcastle upon Tyne
Newcastle upon Tyne, UK
Lluís Donoso MD
Head, Diagnostic Imaging Centre
Hospital Clinic
Barcelona, Spain
James S. Dooley MD FRCP
Reader and Consultant Hepatologist, Centre for
Hepatology
Royal Free and University College School of

Medicine
London, UK
Jean-François Dufour MD
Professor of Hepatology
University of Bern
Bern, Switzerland
Franz-Ludwig Dumoulin MD
Professor of Medicine
University of Bonn;
Head, Department of Internal Medicine
St Agnes Hospital
Bocholt, Germany
François Durand MD
Professor of Hepatology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris and Inserm
U773;
Service d’Hépatologie, Hôpital Beaujon
Clichy, France
Geoffrey M. Dusheiko MB BCh
FCPSA FRCP FRCP(Ed)
Professor of Medicine, Centre for Hepatology
Royal Free and University College School of
Medicine
London, UK
Gregory T. Everson MD
Professor of Medicine and Director of
Hepatology
University of Colorado Health Sciences Center
Denver, CO, USA

Klaas N. Faber MD
Academic Medical Center
Amsterdam, The Netherlands
Joan Falcó Fages MD
Senior Consultant Radiologist
UDIAT-CD Hospital Parc Taulí
Sabadell, Spain
Geoffrey C. Farrell MD FRACP
Director, Gastroenterology and Hepatology
Unit
The Canberra Hospital;
Professor of Hepatic Medicine
Australian National University
Garran, ACT, Australia
Jean H.D. Fasel MD
Professor and Head of Clinical Anatomy Research
Group, Geneva
Centre Médical Universitaire
Geneva, Switzerland
TTOA01_vol1 3/9/07 10:46 AM Page xiii
xiv CONTRIBUTORS
Andrew P. Feranchak MD
Assistant Professor of Pediatrics
University of Texas Southwestern Medical School
Dallas, TX, USA
Javier Fernández MD
Intensive Care Unit, Hepatology
Hospital Clinic
Barcelona, Spain
José C. Fernández-Checa PhD

Professor, Spanish Research Council
Liver Unit, Hospital Clinic
Barcelona, Spain
Peter Fickert MD
Laboratory of Experimental and Molecular
Hepatology
Medical University of Graz
Graz, Austria
Stefano Fiorucci MD
Associate Professor of Gastroenterology
Universita Degli Studi di Perugia
Perugia, Italy
Constantino Fondevila MD PhD
Transplant Surgeon
Liver Unit, Hospital Clinic;
Digestive Disease Institute, University of Barcelona
Barcelona, Spain
Alejandro Forner MD
Research Fellow
University of Barcelona
Barcelona, Spain
Xavier Forns MD PhD
Senior Specialist
Liver Unit, Hospital Clinic
Barcelona, Spain
Ira J. Fox MD
Charles W. McLaughlin Professor of Surgery
University of Nebraska Medical Center
Omaha, NB, USA
Nader K. Francis MB ChB FRCS PhD

Consultant Surgeon
Yeovil District Hospital
Somerset, UK
Scott L. Friedman MD
Fishberg Professor of Medicine
Chief, Division of Liver Diseases
Mount Sinai School of Medicine
New York, NY, USA
Josep Fuster Obregón MD
Profesor Titular de Cirugía
Universidad de Barcelona;
Jefe de Sección de Círugia Hépatica y Trasplante
Hospital Clinic
Barcelona, Spain
Michelle C. Gallagher BSc MB BS
MRCP
Consultant Gastroenterologist
The Royal Surrey County Hospital
Guildford, UK
Peter R. Galle MD PhD
Professor of Medicine
Johannes Gutenberg University;
Chief Medical Officer
University Hospital of Mainz
Mainz, Germany
Juan Carlos García-Pagán MD
Consultant in Hepatology
Liver Unit, Hospital Clinic
Barcelona, Spain
Carmen García-Ruiz MD

Del Consejo Superior de Investgaciones
Cientificas
Instituto de Investigación Biomedica de
Barcelona
Barcelona, Spain
Javier García-Samaniego MD
Department of Infectious Diseases
Hospital Carlos III
Madrid, Spain
Guadalupe García-Tsao MD
Professor of Medicine
Yale University School of Medicine
New Haven, CT, USA
Juan Carlos García-Valdecasas MD
Jefe de Cirugía
Hospital Clinic;
Catedratic de Cirugía
Universidad de Barcelona
Barcelona, Spain
Wolfram H. Gerlich PhD
Professor of Medical Virology
Justus-Liebig University
Giessen, Germany
André P. Geubel MD
Professor, Department of Gastroenterology
Universitaires Saint-Luc
Université Catholique de Louvain
Brussels, Belgium
Dominique P. Germain MD PhD
Professor of Medical Genetics

Centre de Référence de la Maladie de Fabry et des
Maladies Héréditaires du Tissu Conjonctif;
Assistance Publique – Hôpitaux de Paris
Paris, France
Mihai Gheorghiade MD
Professor of Medicine and Associate Chief of
Cardiology
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Pere Ginès MD
Professor of Medicine, University of Barcelona;
Chief, Liver Unit, Hospital Clinic
Barcelona, Spain
Daniel Glass MB ChB MRCP
Specialist Registrar in Dermatology
West Hertfordshire Hospitals Trust
Hemel Hempstead, UK
Christian Gluud MD DrMedSci
Head of Copenhagen Trial Unit
Centre for Clinical Intervention Research
Copenhagen University Hospital
Copenhagen, Denmark
Mark D. Gorrell MD PhD
Principal Research Fellow, Faculty of Medicine
University of Sydney;
Principal Scientist, Royal Prince Alfred Hospital
Sydney, NSW, Australia
Roberto J. Groszmann MD
Yale University School of Medicine

New Haven, CT, USA
Frank Grünhage MD
Head, Department of Medicine
University of Bonn
Bonn, Germany
Mónica Guevara MD
Associate Invesitgator
IDIBAPS, Hospital Clinic
Barcelona, Spain
I. Neil Guha MB BS MRCP
Specialist Registrar in Hepatology
Southampton General Hospital
Southampton, UK
Basuki Gunawan MD
Fellow, Gastrointestinal and Liver Division
Keck School of Medicine
University of Southern California
Los Angeles, CA, USA
N. Guañabens MD
Department of Rheumatology, Hospital Clinic
Barcelona, Spain
Dominique Guyader MD PhD
Professor of Hepatology
University of Rennes
Rennes, France
Paul S. Haber MD
Centenary Institute of Cancer Medicine and Cell
Biology
Royal Prince Alfred Hospital and The University of
Sydney

Sydney, NSW, Australia
Antoine Hadengue MD
Professeur de Médecine et Chef de Service
Service de Gastroentérologie et Hépatologie
Hôpitaux Universitaires de Genève
Geneva, Switzerland
Edward D. Harris PhD
Professor, Department of Nutrition and Food Science
Texas A&M University
College Station, TX, USA
TTOA01_vol1 3/9/07 10:46 AM Page xiv
CONTRIBUTORS xv
Dieter Häussinger MD
Professor of Internal Medicine
Heinrich Heine University
Dusseldorf, Germany
Philip N. Hawkins MB PhD FRCP
FRCPath FMedSci
Professor of Medicine
University College London;
Consultant, National Amyloidosis Centre
Royal Free Hospital
London, UK
William G. Hawkins MD
Assistant Professor
Washington University in St. Louis
Section of Hepatopancreatobiliary Surgery
Barnes-Jewish Hospital
St. Louis, MO, USA
Roderick J. Hay

Head of School, Medicine and Dentistry
Queen’s University Belfast
Belfast, UK
Peter C. Hayes BMSc MB ChB MD
PhD
Professor of Hepatology
University of Edinburgh;
Consultant, Liver Unit
Royal Infirmary of Edinburgh
Edinburgh, UK
John Cijiang He MD
Department of Pharmacology and Biological
Chemistry
Mount Sinai School of Medicine
New York, NY, USA
E. Jenny Heathcote MB BS MD
FRCP FRCPC
Professor of Medicine
University of Toronto
Toronto, ON, Canada
J. Michael Henderson MD
Department of General Surgery
The Cleveland Clinic Foundation
Cleveland, OH, USA
Jens H. Henriksen MD
Professor of Clinical Physiology
University of Copenhagen and Hvidovre
Hospital
Hvidovre, Denmark
Manuel Hernández-Guerra MD

Liver Unit, Hospital Clinic
Barcelona, Spain
Humphrey J.F. Hodgson FMedSci
Sheila Sherlock Chair of Medicine
Director, The UCL Institute of Hepatology,
Hampstead Campus
Vice Dean and Campus Director
Royal Free and University College School of
Medicine
London, UK
Chantal Housset MD PhD
Professor of Cell Biology
Université Pierre et Marie Curie Paris 6;
Director, Inserm U680, Hôpital Tenon;
Service de Biochimie–Hormonologie, Hôpital
Saint-Antoine
Paris, France
Hongjin Huang PhD
Associate Director, Liver Diseases, Celera
Alameda, CA, USA
Harriet Hughes MD
Hospital for Tropical Diseases
London, UK
Alvin B. Imaeda MD PhD
Yale University School of Medicine
New Haven, CT, USA
John P. Iredale BM DM FRCP
FMedSci
Professor of Medicine
University of Edinburgh

Edinburgh, UK
Yoshiya Ito MD PhD
Research Associate
University of Arizona College of Medicine
Tucson, AZ, USA
Ravi Iyengar MD
Department of Pharmacology and Biological
Chemistry
Mount Sinai School of Medicine
New York, NY, USA
Elmar Jaeckel MD
Department of Gastroenterology, Hepatology and
Endocrinology
Hanover Medical School
Hanover, Germany
Hartmut Jaeschke MD
Department of Pharmacology
University of Arizona
Tucson, AZ, USA
Rajiv Jalan MB BS MD FRCP PhD
Senior Lecturer and Honorary Consultant in
Hepatology
The UCL Institute of Hepatology
London, UK
Oliver F.W. James BM FRCP
Professor, Centre for Liver Research
University of Newcastle upon Tyne
Newcastle upon Tyne, UK
Peter L.M. Jansen MD
Professor of Medicine

Academic Medical Center
Amsterdam, The Netherlands
Regine Kahl MD
Professor and Head of Institute of Toxicology
University of Dusseldorf
Dusseldorf, Germany
Sanjeeva P. Kalva MD DNB
Assistant Radiologist
Massachusetts General Hospital;
Clinical Instructor
Harvard Medical School
Boston, MA, USA
Igal Kam MD
Chief of Transplant Surgery
University of Colorado Health Sciences
Centre
Denver, CO, USA
Keishi Kanno MD PhD
Research Fellow, Division of Gastroenterology
Brigham and Women’s Hospital and Harvard
Medical School
Boston, MA, USA
Neil Kaplowitz MD
Professor of Medicine
Keck School of Medicine
University of Southern California
Los Angeles, CA, USA
Saul J. Karpen MD PhD
Associate Professor of Pediatrics
Director, Texas Children’s Liver Center

Baylor College of Medicine,
Houston, TX, USA
Mark T. Keegan MB BCh BAO BA
MRCPI
Associate Professor of Anesthesia
Consultant in Anesthesia and Critical Care
Mayo Clinic College of Medicine
Rochester, MN, USA
Susanne Keiding MD DSc
Professor, Department of Medicine V
Aarhus University Hospital
Aarhus, Denmark
David Kershenobich MD PhD
Department of Experimental Medicine
National Autonomous University of Mexico
Mexico City, Mexico
Zahida Khan PhD
Department of Pathology
University of Pittsburgh School of Medicine
Pittsburgh, PA, USA
W. Ray Kim MD
Associate Professor of Medicine
Mayo Clinic College of Medicine
Rochester, MN, USA
Raymond S. Koff MD
Clinical Professor of Medicine
University of Connecticut School of
Medicine
Farmington, CT, USA
Soichi Kojima PhD

Molecular Cellular Pathology Research Unit
RIKEN
Wako, Japan
TTOA01_vol1 3/9/07 10:46 AM Page xv
xvi CONTRIBUTORS
Nicholas F. LaRusso MD
Chair, Department of Internal Medicine
Professor of Medicine and Biochemistry/Molecular
Biology
Mayo Clinic College of Medicine
Rochester, MN, USA
Bernhard H. Lauterburg MD
Department of Clinical Pharmacology
University of Bern
Bern, Switzerland
Daniel Lavanchy MD MHEM
Department of Epidemic and Pandemic Alert and
Response
World Health Organization
Geneva, Switzerland
Konstantinos N. Lazaridis MD
Assistant Professor of Medicine
Mayo Clinic College of Medicine
Rochester, MN, USA
Brigitte Le Bail MD
Professor of Pathology
Université Bordeaux
Bordeaux, France
Gioacchino Leandro MD
Consultant Gastroenterologist

IRCCS De Bellis
Castellana Grotte, Italy
Didier Lebrec MD
Service d’Hépatologie
Hôpital Beaujon
Clichy, France
Frédéric P. Lemaigre MD PhD
Professor, Christian de Duve Institute of Cellular
Pathology
Université Catholique de Louvain
Brussels, Belgium
Riccardo Lencioni MD
Associate Professor of Radiology
University of Pisa
Pisa, Italy
Chris Liddle BSc (Med) MB BS PhD
FRACP
Associate Dean, Information Technology
Professor of Clinical Pharmacology and Hepatology
University of Sydney
Sydney, NSW, Australia
Vishwanath R. Lingappa MD
California Pacific Medical Center
San Francisco, CA, USA
Josep María Llovet MD
Professor of Research – ICREA
Liver Unit, Hospital Clinic
Barcelona, Spain
Yang Lu MD
Department of Medicine

Albert Einstein College of Medicine
Bronx, NY, USA
Masamichi Kojiro MD
Department of Pathology
Kurume University School of Medicine
Kurume, Japan
Sean W.P. Koppe MD
Fellow in Gastroenterology and Hepatology
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Krzysztof Krawczynski MD PhD
Distinguished Consultant, Division of Viral Hepatitis
Centers for Disease Control and Prevention
Atlanta, GA, USA
Michael J. Krowka MD
Professor of Medicine
Mayo Clinic College of Medicine
Rochester, MN, USA
Yolanta T. Kruszynska MD
Associate Professor of Medicine
University of California at San Diego
La Jolla, CA, USA
Thomas G. Ksiazek DVM PhD
Branch Chief, Special Pathogens Branch
Centers for Disease Control and Prevention
Atlanta, GA, USA
Laura M. Kulik MD
Transplant Hepatologist
Northwestern Memorial Hospital

Chicago, IL, USA
Philippe Labrune MD PhD
Professor and Head of Department of Paediatric and
Medical Genetics
Hôpital Antoine Béclère
Clamart, France
Antonio Lacy MD
Jefe de Sección, Cirugía Gastrointestinal
Institut Clínic de Malaties Digestives i Metaboliques
Hospital Clinic
Barcelona, Spain
Glen A. Laine MD PhD
Wiseman-Lewie-Worth Chair in Cardiology
Director, Michael E. DeBakey Institute
Texas A&M University
College Station, TX, USA
Frank Lammert MD
Professor of Medicine
University of Bonn;
Department of Internal Medicine I
University Hospital Bonn
Bonn, Germany
Dominique Larrey MD PhD
Professor of Hepatology
Montpellier School of Medicine;
Head, Department of Hepatogastroenterology and
Transplantation
CHU Saint-Eloi
Montpellier, France
Tom Luedde MD PhD

Institute of Genetics
University of Cologne
Cologne, Germany
Geoffrey W. McCaughan MB BS
PhD FRACP
A.W. Morrow Professor of Medicine
(Gastroenterology and Hepatology)
The University of Sydney and Royal Prince Alfred
Hospital Centenary Research Institute
Sydney, NSW, Australia
P. Aiden McCormick MD
Newman Clinical Research Professor
University College Dublin;
Consultant Hepatologist, Liver Unit
St Vincent’s Hospital
Dublin, Ireland
Robert S. McCuskey PhD
Professor of Cell Biology, Pediatrics and
Physiology
University of Arizona
Tucson, AZ, USA
Pietro E. Majno MD FRCS
Transplantation Unit
Hôpitaux Universitaires de Genève
Geneva, Switzerland
Nisar P. Malek MD
Consultant in Internal Medicine and
Gastroenterology
Hanover Medical School
Hanover, Germany

Susan V. Mallett MB BS FRCA
Consultant Anaesthetist
The Royal Free Hospital
London, UK
Michael P. Manns MD
Department of Gastroenterology
Hanover Medical School
Hanover, Germany
G.A. Mantion MD
Department of Hepatology and Liver
Diseases
Hôpital Jean-Minjoz
Besançon, France
Luz Martín-Carbonero MD
Department of Infectious Diseases
Hospital Carlos III
Madrid, Spain
Carmen Martínez MD
Hematology Department
Hospital Clinic
Barcelona, Spain
Rie Matsushima-Nishiwaki MD
First Department of Internal Medicine
Gifu University School of Medicine
Gifu, Japan
TTOA01_vol1 3/9/07 10:46 AM Page xvi
CONTRIBUTORS xvii
Wajahat Z. Mehal MD DPhil
Yale University School of Medicine
New Haven, CT, USA

Fernando E. Membreno
MD MSc
Director of Hepatology and Liver Transplantation
Methodist Specialty and Transplant Hospital
San Antonio, TX, USA
Giorgina Mieli-Vergani MD PhD
FRCP FRCPCH
Alex Mowat Professor of Paediatric Hepatology
King’s College London School of Medicine
London, UK
J.P. Miguet MD
Department of Hepatology and Liver Diseases
Hôpital Jean-Minjoz
Besançon, France
Piotr Milkiewicz MD PhD MRCP
Associate Professor and Reader in Hepatology
Pomeranian Medical School
Szczecin, Poland
Elisabeth Irene Minder
ProfDrMed
Chefärztin, Zentrallabor
Stadtspital Triemli
Zurich, Switzerland
Rosa Miquel MD
Servicio de Anatomia Patologica
Hospital Clinic
Barcelona, Spain
Søren Møller MD DMSc
Chief Physician and Associate Professor
Department Clinical Physiology

Hvidovre Hospital
Hvidovre, Denmark
Richard Moreau MD
Service d’Hépatologie
Hôpital Beaujon
Clichy, France
Michael H. Nathanson MD
PhD
Professor of Medicine and Cell Biology
Chief, Section of Digestive Diseases
Yale University School of Medicine
New Haven, CT, USA
Miguel Navasa MD
Liver Unit, Hospital Clinic
Barcelona, Spain
James Neuberger DM FRCP
Consultant Physician
Queen Elizabeth Hospital
Birmingham, UK
Peter Neuhaus MD
Professor of Surgery
Charite Campus Virchow Clinic
Berlin, Germany
Brent A. Neuschwander-Tetri MD
FACP
Professor of Internal Medicine
Saint Louis University School of Medicine
St. Louis, MO, USA
Susana Neves MD
Department of Pharmacology and Biological

Chemistry
Mount Sinai School of Medicine
New York, NY, USA
Patrick G. Northup MD MHES
Assistant Professor, Gastroenterology and
Hepatology
University of Virginia
Charlottesville, VA, USA
Phyllis M. Novikoff PhD
Associate Professor
Albert Einstein College of Medicine
Bronx, NY, USA
Marina Nuñez MD
Department of Infectious Diseases
Hospital Carlos III
Madrid, Spain
Satoshi Ogata MD
Hôpital Beaujon
Clichy, France
Masataka Okuno MD
First Department of Internal Medicine
Gifu University School of Medicine
Gifu, Japan
J. Donald Ostrow MD
Affiliated Professor of Medicine
Gastrointestinal and Hepatology Division
University of Washington School of
Medicine
Seattle, WA, USA
Ronald P.J. Oude Elferink

Professor of Experimental Hepatology
AMC Liver Center
Amsterdam, The Netherlands
Mario Pagano MD
Department of Pharmacology and Biological
Chemistry
Mount Sinai School of Medicine
New York, NY, USA
Georges-Philippe Pageaux
MD PhD
Professor of Hepatology
CHU Saint-Eloi
Montpellier, France
Valérie Paradis MD PhD
Professor of Pathology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris and Inserm
U773;
Department of Pathology, Hôpital Beaujon
Clichy, France
Stephen M. Pastores MD
Associate Attending Physician
Memorial Sloan-Kettering Cancer Center
New York, NY, USA
Heinz-Otto Peitgen PhD
Professor and President of MeVis Research
MeVis Research GmbH
Bremen, Germany
Pascal Perney MD
Professor of Internal Medicine

CHU Saint-Eloi
Montpellier, France
Jean-Marie Péron MD PhD
Professor of Hepatogastroenterology
Service d’Hépatogastroenterologie
Toulouse, France
Dominique Pessayre MD
Director of Research
Université Paris 7
Paris, France
Antonello Pietrangelo MD PhD
Professor of Medicine
Center for Hemochromatosis
University of Modena and Reggio Emilia
Modena, Italy
Massimo Pinzani MD PhD
Professor of Medicine
Dipartmento di Medicina Interna
Università delgi Studi di Firenze
Florence, Italy
Fabio Piscaglia MD
Department of Internal Medicine and Gastroenterology
University of Bologna
Bologna, Italy
David J. Plevak MD
Professor of Anesthesiology
Mayo Clinic College of Medicine
Rochester, MN, USA
K. Raj Prasad MS MCh FRCS
Consultant Surgeon

St James’s University Hospital
Leeds, UK
Gerhard P. Püschel MD
Full Professor and Head, Department of
Biochemistry of Nutrition
Institute of Nutrition Science
University of Potsdam
Potsdam, Germany
Hervé Puy MD PhD
Professor of Biochemistry and Molecular Biology
Vice President of the French Porphyria Center
Hôpital Louis Mourier
Colombes, France
Alberto Queiroz Farias MD PhD
Department of Gastroenterology
University of São Paulo School of Medicine
São Paulo, Brazil
TTOA01_vol1 3/9/07 10:46 AM Page xvii
xviii CONTRIBUTORS
Montse Renom MD
Centro de Salud Internacional
Hospital Clinic
Barcelona, Spain
Kalpana Reddy MB BS FRCA
Specialist Registrar in Anaesthesia and Intensive Care
Medicine
Royal London Hospital
London, UK
Helen L. Reeves BM BS BMedSci
MRCP FRCP(Ed) PhD

Senior Lecturer and Honorary Consultant
Gastroenterologist
University of Newcastle upon Tyne
Newcastle upon Tyne, UK
Jürg Reichen MD
Professor of Medicine
University of Bern;
Chief of Hepatology
University Hospital
Bern, Switzerland
Igino Rigato MD
Liver Research Center
University of Trieste
Trieste, Italy
Antoni Rimola MD PhD
Senior Consultant
Liver Unit, Hospital Clinic
Barcelona, Spain
Mario Rizzetto MD
Professor of Gastroenterology
University of Turin
Turin, Italy
Guillermo Robles-Diaz MD
Department of Experimental Medicine
National Autonomous University of Mexico
Mexico City, Mexico
Juan Rodés MD
Director General
Hospital Clinic;
Professor of Medicine

University of Barcelona
Barcelona, Spain
Pierre E. Rollin MD
Team Leader, Disease Assessment Section
Centers for Disease Control and Prevention
Atlanta, GA, USA
Tania Roskams MD
Professor of Pathology
University of Leuven
Leuven, Belgium
Jayanta Roy-Chowdhury MD
MRCP
Professor, Departments of Medicine and Molecular
Genetics
Albert Einstein College of Medicine
Bronx, NY, USA
Namita Roy-Chowdhury MD PhD
Professor, Departments of Medicine and Molecular
Genetics
Albert Einstein College of Medicine
Bronx, NY, USA
Antoni Rimola MD PhD
Senior Consultant
Liver Unit, Hospital Clinic
Barcelona, Spain
K. Lenhard Rudolph MD
Heisenberg Professor for Regenerative Medicine and
Ageing
Hanover Medical School
Hanover, Germany

Luis Ruiz-del-Arbol MD
Associate Professor
Universidad de Alcala and Hospital Ramón y Cajal
Madrid, Spain
Malcolm Rustin BSc MD FRCP
Consultant Dermatologist
The Royal Free Hospital
London, UK
Pierre Rustin PhD
CNRS Research Director
Hôpital Robert Debré
Paris, France
Dushyant V. Sahani MD
Department of Radiology
Massachusetts General Hospital
Boston, MA, USA
Faouzi Saliba MD
Associate Professor
Hôpital Paul Brousse
Villejuif, France
Didier Samuel MD PhD
Professor
Hôpital Paul Brousse
Villejuif, France
Marianne Samyn MD FRCPCH
Consultant Paediatric Hepatologist
King’s College London School of Medicine
London, UK
José M. Sánchez-Tapias MD PhD
Senior Consultant

Liver Unit, Hospital Clinic
Barcelona, Spain
Giorgio Saracco MD
Associate Professor of Gastroenterology
University of Turin
Turin, Italy
Tilman Sauerbruch MD
Professor of Medicine
University of Bonn;
Head, Department of Medicine
University Hospital Bonn
Bonn, Germany
Erez F. Scapa MD
Research Fellow, Division of Gastroenterology
Harvard Medical School
Boston, MA, USA
Stephan Schaefer PD DrMed
Provisional Head, Institut für Medizinische
Mikrobiologie, Virologie und Hygiene
Universität Rostock
Rostock, Germany
Michael Schilsky MD
Associate Professor of Clinical Medicine
Weill Medical College of Cornell University;
Medical Director, Center for Liver Disease and
Transplantation
Weill Cornell Medical Center
New York, NY, USA
Xiaoye Schneider-Yin PhD
Biochemikerin, Zentrallabor

Stadtspital Triemli
Zurich, Switzerland
Henning Schulze-Bergkamen MD
1st Medical Department
University of Mainz
Mainz, Germany
Marcus Schuchmann MD
1st Medical Department
University of Mainz
Mainz, Germany
Detlef Schuppan MD PhD
Professor of Medicine
Harvard Medical School;
Consultant Hepatologist
Beth Israel Deaconess Medical Center
Boston, MA, USA
Nazia Selzner MD PhD
Transplant Hepatology Fellow
Multiorgan Transplant Program
Toronto General Hospital
Toronto, ON, Canada
David Semela MD
Instructor in Medicine
Mayo Clinic College of Medicine
Rochester, MN, USA
Marco Senzolo MD PhD
Consultant Physician in Gastroenterology
University Hospital of Padua
Padua, Italy
Devanshi Seth BSc MSc PhD

Senior Scientist, Royal Prince Alfred Hospital
Sydney, NSW, Australia
Nicholas A. Shackel MD
Centenary Institute of Cancer Medicine and Cell
Biology
Royal Prince Alfred Hospital and The University of
Sydney
Sydney, NSW, Australia
TTOA01_vol1 3/9/07 10:46 AM Page xviii
CONTRIBUTORS xix
Vijay H. Shah MD
Associate Professor of Medicine, Physiology and
Cancer Cell Biology
Mayo Clinic College of Medicine
Rochester, MN, USA
Marcelo Simão Ferreira MD
University of São Paulo School of Medicine
São Paulo, Brazil
Antonella Smedile MD
Department of Gastroenterology
Molinette Hospital
Turin, Italy
Michael Sørensen MD
Department of Medicine V
Aarhus University Hospital
Aarhus, Denmark
Vincent Soriano MD PhD
Section Chief, Department of Infectious Diseases
Hospital Carlos III
Madrid, Spain

Laurent Spahr MD
Médecin Adjoint Agrégé et Chargé de Cours
Service de Gastroentérologie et Hépatologie
Hôpitaux Universitaires de Genève
Geneva, Switzerland
Vanessa Stadlbauer MD
Clinical Research Fellow
The UCL Institute of Hepatology
London, UK
Peter Starkel MD PhD
Professor, Department of Gastroenterology
Universitaires Saint-Luc
Université Catholique de Louvain
Brussels, Belgium
Catherine A.M. Stedman MB ChB
FRACP PhD
Consultant Gastroenterologist and Clinical
Pharmacologist
Christchurch Hospital
Christchurch, New Zealand
Stephen F. Stewart MB ChB PhD
Consultant Hepatologist
Freeman Hospital
Newcastle upon Tyne, UK
Felix Stickel MD
Assistant Professor and Consultant Hepatologist
Institute of Clinical Pharmacology
University of Bern
Bern, Switzerland
Bruno Stieger PhD

Department of Medicine
University Hospital
Zurich, Switzerland
Donna B. Stolz PhD
Assistant Director, Center for Biologic Imaging
University of Pittsburgh
Pittsburgh, MA, USA
Christoforos Stoupis MD
Radiologist, Kreisspital
Maennedorf, Switzerland
Steven M. Strasberg MD FRCSC
FACS FRCS(Ed)
Pruett Professor of Surgery
Washington University in St. Louis;
Head of Hepatopancreatobiliary Surgery
Barnes-Jewish Hospital
St. Louis, MO, USA
Edna Strauss MD PhD
Professor, School of Medicine
University of São Paulo School of Medicine
São Paulo, Brazil
Vinay Sundaram MD
Senior Resident, Department of Internal
Medicine
University of Virginia
Charlottesville, VA, USA
Jacob I. Sznajder MD PhD
Professor of Medicine
Chief, Division of Pulmonary and Critical
Medicine

Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Jeffrey H. Teckman MD
Associate Professor of Pediatrics and Biochemistry
Saint Louis University School of Medicine
St. Louis, MO, USA
Carlos Terra MD
Department of Medicine, Hospital Clinic
Barcelona, Spain
Sundararajah Thevananther
PhD
Assistant Professor
Texas Children’s Liver Center
Baylor College of Medicine
Houston, TX, USA
Claudio Tiribelli MD PhD
Professor of Medicine
Director, Liver Research Center
University of Trieste
Trieste, Italy
Susan Tiukinhoy-Laing MD
Division of Cardiology
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Giles J. Toogood MD
Consultant in Hepatobiliary Transplantation
St. James’s University Hospital
Leeds, UK

James Toouli MB BS FRACS PhD
Professor of Surgery
Flinders University
Adelaide, SA, Australia
Michael Trauner MD
Professor of Medicine
Medical University Graz
Graz, Austria
Christian Trautwein MD
Professor, Medizinische Klinik III
University Hospital
Aachen, Germany
James Trotter MD
Associate Professor, Division of Gastroenterology
and Hepatology
University of Colorado Health Sciences Center
Denver, CO, USA
Juan Turnes MD
Research Associate
Liver Unit, Hospital Clinic
Barcelona, Spain
Dominique-Charles Valla MD
Professor of Hepatology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris and Inserm
U773;
Chief, Service d’Hépatologie, Hôpital Beaujon
Clichy, France
Pierre Van Damme MD PhD
Professor, Faculty of Medicine

University of Antwerp;
Director, WHO Collaborating Centre for the Control
and Prevention of Viral Hepatitis
Antwerp, Belgium
Koen Van Herck MD
Research Assistant, Department of Epidemiology
and Social Medicine
University of Antwerp
Wilrijk, Belgium
María Varela MD
Research Fellow
Liver Unit, Hospital Clinic
Barcelona, Spain
Jean-Nicolas Vauthey MD FACS
Professor of Surgery and Chief of Liver Service
University of Texas M.D. Anderson Cancer
Center
Houston, TX, USA
Diego Vergani MD PhD FRCP
FRCPath
Professor and Director of the Alex Mowat
Immunopathology Laboratory
King’s College London School of Medicine
London, UK
Valérie Vilgrain MD
Professor of Radiology, Université Denis Diderot
Paris 7;
Assistance Publique – Hôpitaux de Paris;
Chief, Department of Radiology, Hôpital
Beaujon

Clichy, France
TTOA01_vol1 3/9/07 10:46 AM Page xix
xx CONTRIBUTORS
Jean-Pierre Vinel MD
Professor of Hepatogastroenterology
Service d’Hépatogastroenterologie
Toulouse, France
D.A. Vuitton MD PhD
Emeritus Professor of Clinical Immunology
Université de Franch-Comté
Besançon, France
Martin Wagner MD
Fellow, Medical University Graz
Graz, Austria
Wim Wätjen PhD
Institute of Toxicology
University of Dusseldorf
Dusseldorf, Germany
Heiner Wedemeyer MD
Department of Gastroenterology
Hanover Medical School
Hanover, Germany
Richard A. Weisiger MD PhD
Professor of Medicine
University of California
San Francisco, CA, USA
Rebecca G. Wells MD
Assistant Professor of Medicine and of Pathology and
Laboratory Medicine
The University of Pennsylvania School of

Medicine
Philadelphia, PA, USA
Alan J. Wigg MB BS FRACP PhD
Consultant Gastroenterology and Hepatologist
Flinders Medical Centre
Adelaide, SA, Australia
Rohan B.H. Williams PhD
School of Biotechnology and Biomolecular
Sciences
University of New South Wales
Sydney, NSW, Australia
R.M. Winter MD
Professor of Dysmorphlogy and Clinical
Genetics
Institute of Child Health
London, UK
Allan W. Wolkoff MD
Professor, Department of Medicine
Albert Einstein College of Medicine
Bronx, NY, USA
John B. Wong MD
Chief, Division of Clinical Decision Making
Tufts-New England Medical Center;
Professor of Medicine
Tufts University School of Medicine
Boston, MA, USA
Govardhana Rao Yannam MD
MRCS
Postdoctoral Research Associate
University of Nebraska Medical Center

Omaha, NE, USA
Elie Serge Zafrani MD
Professor of Pathology
Hôpital Henri Mondor
Creteil, France
Arthur Zimmermann MD
Professor of Pathology
University of Bern
Bern, Switzerland
Fabien Zoulim MD PhD
Professor of Medicine, Université Lyon 1;
Liver Department, Hospices Civils de Lyon;
Head, Inserm U8712
Lyon, France
TTOA01_vol1 3/9/07 10:46 AM Page xx
Juan Rodés and I conceived the idea of this book at his
summer house in Montferri in the late 1980s, envisaging it as a
predominantly European text. We had both been active in the
organization of the European Association for the Study of the
Liver (EASL) so, not surprisingly, we chose as fellow editors
our friends Jean-Pierre Benhamou (France), Johannes Bircher
(Switzerland) and Mario Rizzetto (Italy), all past secretaries of
EASL. The five of us met several times in different cities to plan
the book.
In the preface to the first edition, which appeared in 1991, we
noted our wish to produce a comprehensive account of clinical
hepatology, covering not only common liver problems but also
the rare conditions seen from time to time by gastroenterologists,
and general physicians and surgeons, as well as by hepatologists.
We felt it important to cover the effects of liver disease on other

parts of the body, and to describe how diseases of other systems
affected the liver, interactions which often cause confusing
clinical pictures. We added some appendices: one listed non-
drug chemicals and toxins causing liver damage, another gave
the geographical distribution of infectious diseases, and a third
listed some rare diseases in which the liver may be involved,
particularly in children. These appendices have been retained.
As we noted in the preface to the second edition, the first
enjoyed considerable success and achieved much critical
acclaim. I certainly found it useful in my own practice. In the
second edition the focus on clinical medicine was strengthened,
as it has been in this edition, and the emphasis in the basic
science sections was placed on new concepts and techniques. As
a result of these changes some material has had to be left out so,
as is the case with some other reference books, the hungry reader
of this edition may well find pearls by returning to some of the
chapters in the second edition.
The present edition, which I am delighted to see is accom-
panied by a CD, has retained the general format of the two
earlier editions, but several topics have been greatly expanded.
Clinicians will welcome the increased number of subsections
on liver transplantation, imaging and the complex area of con-
genital and acquired non-infectious conditions which cause
fibrosis or cystic change in the liver or biliary tract. In the basic
science sections there are more contributions dealing with
molecular and cell biology, genetic aspects of liver disease and
immunology. One interesting innovation is the introduction of
a section on mathematics in hepatology, which I suspect will
lead to some interesting developments in future editions.
The number of individual contributions has risen from 146 in

the first edition to 209 in this one; the number in the basic
science sections has doubled – from 25 to 51. The first edition
involved 193 authors; 333 have contributed to this one. Based on
past experience, the editors’ problems in getting manuscripts in
on time must have been formidable. Although the book still has
a distinctly European flavour there are contributions from many
other countries. The proportion coming from the USA has risen
from 9% in the first edition to 24% in this one; the American
influence is particularly evident in the coverage of molecular and
cell biology.
Johannes Bircher and I stepped down as editors for this edi-
tion. That our former editorial colleagues enrolled seven others
to join them, two of them based in the USA, reflects the increas-
ing complexity of our knowledge of the liver and its diseases.
This book is an attempt to clarify the field for others. I wish Juan,
Jean-Pierre and Mario and their new colleagues, and their new
publisher, Blackwell Publishing Ltd, every success with this
splendid third edition.
Neil McIntyre
Foreword
xxi
TTOA01_vol1 3/9/07 10:46 AM Page xxi
This is now the third edition of a textbook the first edition of
which was conceived and published back in 1992. In this edition,
important changes have been introduced to bring the style of
the book more up to date under the guidance of Blackwell
Publishing Ltd. Their professionalism, management skills and
hard work has helped us to produce this new and exciting edi-
tion. The editors, Juan Rodés, Jean-Pierre Benhamou, Andres
Blei, Jürg Reichen, Mario Rizzetto, and associate editors, Jean-

François Dufour, Scott Friedman, Pere Ginès, Dominique-
Charles Valla and Fabien Zoulim, would like to express their
deepest gratitude, especially to Alison Brown (Publisher) and
Rebecca Huxley (Senior Development Editor).
When this book was first published, there were five editors:
Neil McIntyre, Johannes Bircher, Jean-Pierre Benhamou, Mario
Rizzetto and Juan Rodés. In this edition, two of the former
editors have retired but we are honoured that one has con-
tinued his involvement by writing the foreword to the book.
Their collaboration on the first two editions deserves our
grateful recognition as it set the Textbook of Hepatology in pro-
cess. This third edition has brought about significant changes to
the editorial team, which now includes friends and colleagues
from the other side of the Atlantic, Andres Blei and Scott
Friedman. This has achieved our objective of making the
Textbook more international.
At the first meeting of the editors and associate editors, it
was quickly agreed that the Textbook should present the substan-
tial scientific progress that has taken place over the last few
years: concepts such as genomics, proteomics, gene arrays,
metabolomics, bioinformatics, stem cells, molecular and cell
biology, and genetics are now extensively covered throughout
the book.
The most significant changes can probably be seen in the sec-
tions on functions of the liver, basic concepts of pathobiology,
assessment of hepatobiliary disease, portal hypertension and
its complications, congenital hepatic fibrosis and non-parasitic
cystic diseases of the liver, hepatic non-alcoholic steatosis,
tumours of the liver, liver transplantation, and mathematics in
hepatology. We have encouraged the use of tables and figures to

aid interpretation and understanding. The scientific informa-
tion is current and exhaustive and is essential for clinical deci-
sion making whether diagnostic or therapeutic. We also believe
that this book fulfils the requisites necessary for it to be highly
useful for translational research.
On this occasion the book has over 200 chapters, contributed
by authors from five continents. Our objective of delivering an
excellent book has been achieved with the help of everyone who
has participated in the book. We fully understand the pressures
of time on everyone and for this reason we are very grateful to
all of them. Our thanks in particular go to Nicki van Berckel, who
also found time to have her second baby, Dylan, and the Senior
Development Editor at Blackwell Publishing Ltd, Rebecca
Huxley, whose experience has been invaluable. Sincerest thanks
to all involved in taking this project to completion.
Juan Rodés
Jean-Pierre Benhamou
Andres T. Blei
Jürg Reichen
Mario Rizzetto
Jean-François Dufour
Scott L. Friedman
Pere Ginès
Dominique-Charles Valla
Fabien Zoulim
Preface to the third edition
xxii
TTOA01_vol1 3/9/07 10:46 AM Page xxii
We all met several times, in different cities, to plan this book. We
wanted to produce a comprehensive account of clinical hepatol-

ogy, covering not only the common hepatological problems but
also the rare conditions which are seen from time to time by
hepatologists, gastroenterologists, and general physicians. We
thought it important to consider how the liver may be affected in
diseases of other systems, and to describe the effects of diseases
of the liver on other parts of the body, as these interactions
often create a confusing clinical picture; these topics occupy two
large sections of the book which should be of particular value to
general physicians and specialists in other diseases. We felt a
need for a fuller than usual account of the effect of infections on
the liver; patients with bacterial, fungal and parasitic infections,
and those with viral infections other than the classical viral hep-
atitides, often have abnormal liver function tests, or symptoms
or signs suggesting liver disease.
There are chapters on other topics which have received little
attention in other texts, such as symptoms and signs, diagnostic
strategy, general management, and prescribing and anaesthesia
in liver disease. There are chapters on liver disease in children, in
the elderly, and in drug addicts and homosexual men, and one
on the history of liver disease.
We also thought it would be helpful to have some appendices:
listing non-drug chemicals and toxins causing liver damage, the
geographical distribution of infectious diseases, and the rare
diseases in which the liver may be involved (particularly in
children). Another appendix contains the excellent handouts
produced for patients by the American Liver Foundation.
Colleagues often remark that it is irritating, when reading
chapters with many references, to have to search at the end of the
chapter to find the original sources. We therefore decided to use
mainly short ‘text references’ to enable readers to decide quickly

if they are already familiar with the source and, if not, to allow
them to jot the reference down with the minimum of effort. We
consider this experiment to have been worthwhile, but we hope
that readers will tell us if they prefer the conventional approach.
More than 200 authors have contributed to this book; nearly
all are acknowledged internationally as experts in their field(s) of
interest. We are grateful to all of them. We believe that their
expertise is reflected in their contributions, many of which we
consider to be quite outstanding.
Our major purpose was to provide a book for practising
clinicians. We hope this text will prove useful not only to hepa-
tologists, gastroenterologists, and general physicians, but also to
specialists in other fields. It was for this reason that we chose the
title ‘clinical hepatology’. We believe that this book will provide
solutions to many of the hepatological problems which arise in
clinical practice, but only our readers can tell whether our belief
is justified. If, when using this book, you fail to find the informa-
tion you are seeking, we would be grateful if you could draw
these omissions to our attention (using the cards enclosed), so
that they can be corrected in the next edition.
Our book is being brought out in English, French, and
Spanish. We would like to thank the staff of the Oxford
University Press, Flammarion, and Salvat, not only for their
willingness to publish it but for their help and enthusiasm
during the long gestation period. We are particularly grateful
to the executive editor for the book, Irene Butcher, who dealt
initially with all the manuscripts, and later with the galleys and
page proofs of this English edition.
Neil McIntyre
Jean-Pierre Benhamou

Johannes Bircher
Mario Rizetto
Juan Rodés
Preface to the first edition
xxiii
TTOA01_vol1 3/9/07 10:46 AM Page xxiii
1 Architecture of the liver
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