The Textbook of Hepatology: From Basic Science to Clinical Practice

Professor Juan Rodés, Professor of Hepatology and Hospital Director, Hospital Clinic, Barcelona, Spain. Currently Editor of the Journal of Hepatology. Professor Jean–Pierre Benhamou, Professor of Hepatology and Gastroenterology, Hôpital Beaujon, Clichy, France, Former Editor of the Journal of Hepatology. Professor Andres Blei, Department of Medicine, Lakeside Veterans Affairs Medical Center, Chicago Professor Jürg Reichen, University of Bern, Switzerland. Former Administrative Secretary of the European Association for the Study of the Liver. Professor Mario Rizzetto, Professor of Gastroenterology, Department of Gastroenterology, San Giovanni Battista Hospital, Turin, Italy. Former Administrative Secretary of the European Association for the Study of the Liver. Professor Jean–François Dufour, Department of Clinical Pharmacology, University of Bern, Switzerland Professor Scott Friedman, Division of Liver Diseases, Mount Sinai School of Medicine, New York Dr Pere Ginès, Consultant Hepatologist, Liver Unit, University of Barcelona, Hospital Clinic, Barcelona Dr Dominique–Charles Valla, Service d′Hépatologie, Fédération Médico–Chirurgicale d′Hépatogastroentérologie, Hôpital Beaujon, Clichy, France Dr Fabien Zoulim, INSERM Unit 271, Lyon

Section 1 Architecture of the liver.
1.1 Macroscopic anatomy of the liver.


Jean H.D. Fasel, Holger Bourquain, Heinz–Otto Peitgen and Pietro E. Majno.


1.2 Liver and biliary tract histology.


Paulette Bioulac–Sage, Brigitte Le Bail and Charles Balabaud.


1.3 Ultrastructure of the hepatocyte.


Zahida Khan, James M. Crawford and Donna B. Stolz.


1.4 Liver sinusoidal endothelial cells.


David Semela and Vijay H. Shah.


1.5 Kupffer cells.


Hartmut Jaeschke.


1.6 The hepatic stellate cell.


Massimo Pinzani.


1.7 Biliary epithelial cells.


Jean–François Dufour.


1.8 Hepatic stem cells.


Tania Roskams.


1.9 Embryology of the liver and intrahepatic biliary tract.


Frédéric P. Lemaigre.


Section 2 Functions of the liver.


2.1 Hepatic circulation.


2.1.1 Regulation of hepatic blood flow.


Christophe Bureau, Jean–Marie Péron and Jean–Pierre Vinel.


2.1.2 Hepatic microcirculation.


Yoshiya Ito and Robert S. McCuskey.


2.1.3 Hepatic lymph and lymphatics.


Glen A. Laine and Charles S. Cox Jr.


2.2 Functions of the liver.


2.2.1 Functional organization of the liver.


Paulo Renato A.V. Correa and Michael H. Nathanson.


2.2.2 Cell biology of the hepatocyte.


Allan W. Wolkoff and Phyllis M. Novikoff.


2.2.3 Molecular biology of the liver cell.


Sundararajah Thevananther and Saul J. Karpen.


2.2.4 Hepatic transport processes.


Ronald P.J. Oude Elferink.


2.2.5 Modulation of liver function by hepatic nerves.


Gerhard P. Püschel.


2.2.6 In vitro techniques: isolated organ perfusion, slices, cells and subcellular elements.


Bruno Stieger.


2.3 Metabolism.


Intermediate metabolism.


2.3.1 Carbohydrates and the liver.


Guenther Boden.


2.3.2 Lipoprotein metabolism.


Erez F. Scapa, Keishi Kanno and David E. Cohen.


2.3.3 Protein and amino acid metabolism.


Margaret E. Brosnan and John T. Brosnan.


2.3.4 Mitochondria and energy formation.


Dominique Pessayre.


Liver–specific functions.


2.3.5 Bilirubin metabolism.


Namita Roy–Chowdhury, Yang Lu and Jayanta Roy–Chowdhury.


2.3.6 Metabolism of bile acids.


Peter L.M. Jansen and Klaas N. Faber.


2.3.7 Ammonia, urea production and pH regulation.


Dieter Häussinger.


2.3.8 Protein synthesis and degradation in the liver.


Armin Akhavan and Vishwanath R. Lingappa.


2.3.9 Glutathione.


José C. Fernández–Checa and Carmen García–Ruiz.


2.3.10 Haem biosynthesis and excretion of porphyrins.


Hervé Puy and Jean–Charles Deybach.


Metabolism of endo/xenobiotics.


2.3.11 Vitamins and the liver (A and D).


Masataka Okuno, Rie Matsushima–Nishiwaki and Soichi Kojima.


2.3.12 Normal iron metabolism.


Kyle E. Brown.


2.3.13 Normal copper metabolism and reducing copper to subnormal levels for therapeutic purposes.


George J. Brewer, Edward D. Harris and Fred K. Askari.


2.3.14 Trace elements and the liver.


Brent A. Neuschwander–Tetri.


2.3.15 Hepatic metabolism of drugs.


Chris Liddle and Catherine A.M. Stedman.


2.4 Synthetic function.


2.4.1 Albumin and other carrier proteins.


Richard A. Weisiger.


2.4.2 The liver and coagulation.


Maria T. DeSancho and Stephen M. Pastores.


2.4.3 Function and metabolism of collagen and other extracellular matrix proteins.


Rebecca G. Wells.


2.5 Regulation of the liver cell mass.


2.5.1 Control of liver cell proliferation.


Nisar P. Malek and K. Lenhard Rudolph.


2.5.2 Regeneration of chronically injured liver.


Anna Mae Diehl.


2.6 Excretion.


2.6.1 Physiology of bile formation.


Martin Wagner and Michael Trauner.


2.6.2 Motility of the biliary tree.


Mayank Bhandari and James Toouli.


2.7 Immunology of the liver.


2.7.1 Cytokines in liver physiology and liver pathology.


Tom Luedde and Christian Trautwein.


2.7.2 Intrahepatic lymphocytes.


Wajahat Z. Mehal.


2.7.3 Antibody production and transport in the liver.


Alvin B. Imaeda and Wajahat Z. Mehal.


Section 3 Basic concepts in pathobiology.


3.1 Hepatocyte apoptosis and necrosis.


Henning Schulze–Bergkamen, Marcus Schuchmann and Peter R. Galle.


3.2 Ischaemia–reperfusion injury to the liver.


Nazia Selzner and Pierre A. Clavien.


3.3 Genetics and liver diseases.


3.3.1 Genetic polymorphisms in liver disease.


Hongjin Huang and Ramsey Cheung.


3.3.2 Immunogenetics of liver disease.


Peter T. Donaldson.


3.3.3 Genetic determinants of complex liver diseases: mouse models and quantitative trait locus analysis.


Frank Lammert.


3.4 Cellular cholestasis.


Stefano Fiorucci.


3.5 Oncogenes and tumour suppressor genes.


Dipankar Chattopadhyay and Helen Reeves.


3.6 Genomics, gene arrays and proteomics in the study of liver disease.


Geoffrey W. McCaughan, Nicholas A. Shackel, Rohan Williams, Devanshi Seth, Paul S. Haber and Mark D. Gorrell.


Section 4 Pathology.


4.1 Histological features.


Valeer J. Desmet, Tania Roskams and Miguel Bruguera.


4.2 Classifications, scoring systems and morphometry in liver pathology.


Pierre Bedossa and Valerie Paradis.


Section 5 Investigation of hepatobiliary disease.


5.1 Signs and symptoms of liver disease.


Jürg Reichen.


5.2 Biochemical investigations in the management of liver disease.


Igino Rigato, J. Donald Ostrow and Claudio Tiribelli.


5.3 Hepatic removal kinetics: importance for quantitative measurements of liver function.


Susanne Keiding and Michael Sørensen.


5.4 Immunological investigations in liver diseases.


Elmar Jaeckel and Michael P. Manns.


5.5 Biopsy and laparoscopy.


Arthur Zimmermann.


5.6 Imaging of the liver.


5.6.1 Ultrasonography.


Luigi Bolondi, Valeria Camaggi and Fabio Piscaglia.


5.6.2 Computerized tomography imaging of the liver.


Daniel T. Cohen and Dushyant V. Sahani.


5.6.3 Magnetic resonance imaging.


Christoforos Stoupis.


5.6.4 Angiography.


Sanjeeva P. Kalva and Dushyant V. Sahani.


5.6.5 Endoscopic retrograde cholangiopancreatography.


Alan J. Wigg and James Toouli.


5.7 Interventional radiology in hepatobiliary diseases.


José Ignacio Bilbao Jaureguízar, Concepció Bru, Joan Falcó Fages and Lluís Donoso.


5.8 Positron emission tomography of the liver.


Susanne Keiding and Michael Sørensen.


5.9 Splanchnic haemodynamic investigations.


Didier Lebrec and Richard Moreau.


5.10 The Cochrane Hepatobiliary Group.


Christian Gluud, on behalf of the Cochrane Hepatobiliary Group.


Section 6 Cirrhosis.


6.1 The evolution of cirrhosis.


John P. Iredale and I. Neil Guha.


6.2 Cellular and molecular pathobiology of liver fibrosis and its pharmacological intervention.


Scott L. Friedman.


6.3 Clinical and diagnostic aspects of cirrhosis.


I. Neil Guha and John P. Iredale.


Section 7 Portal hypertension and its complications.


7.1 Anatomy of the portal venous system in portal hypertension.


J. Michael Henderson.


7.2 Pathogenesis of portal hypertension.


Roberto J. Groszmann and Juan G. Abraldes.


7.3 Clinical manifestions and management of bleeding episodes in cirrhotics.


Jaime Bosch, Juan G. Abraldes and Juan Carlos García–Pagán.


7.4 Haemodynamic assessment of portal hypertension.


Juan Carlos García–Pagán, Juan Turnes and Jaime Bosch.


7.5 Pathogenesis, diagnosis and treatment of ascites in cirrhosis.


Vicente Arroyo, Carlos Terra and Luis Ruiz–del–Arbol.


7.6 Hepatorenal syndrome.


Pere Ginès and Mónica Guevara.


7.7 Pulmonary complications of portal hypertension.


Michael J. Krowka.


7.8 Hepatic encephalopathy.


Dieter Häussinger and Andres T. Blei.


7.9 Bacterial infections in portal hypertension.


Javier Fernández and Miguel Navasa.


7.10 Hypersplenism.


P. Aiden McCormick.


Section 8 Congenital hepatic fibrosis and non–parasitic cystic lesions of the liver and bile ducts.


8.1 Congenital conditions.


8.1.1 Congenital hepatic fibrosis.


Jean–Pierre Benhamou.


8.1.2 Simple cyst of the liver.


Valérie Vilgrain.


8.1.3 Polycystic kidney disease.


Valérie Vilgrain.


8.1.4 Polycystic liver disease.


Valérie Vilgrain.


8.1.5 Biliary hamartomas.


Valérie Vilgrain.


8.1.6 Peribiliary cysts.


Valérie Vilgrain.


8.1.7 Caroli syndrome.


Jean–Pierre Benhamou.


8.1.8 Choledochal cyst.


Jean–Pierre Benhamou.


8.1.9 Ciliated hepatic foregut cyst.


Jean–François Cadranel.


8.2 Acquired conditions.


8.2.1 Inflammatory cystic diseases.


Jean–François Cadranel.


8.2.2 Neoplasms including cystadenoma.


P. Starkel and André P. Geubel.


8.2.3 Post–traumatic cystic diseases.


Jean–François Cadranel.


Section 9 Viral infections of the liver.


9.1 Viral hepatitis.


9.1.1 Viral hepatitis.


Mario Rizzetto and Fabien Zoulim.


9.1.2 The viruses of hepatitis.


i) Structure, replication and laboratory diagnosis of hepatitis B virus and hepatitis D virus.


Stephan Schaefer and Wolfram H. Gerlich.


ii) Structure, replication and laboratory diagnosis of hepatitis C virus.


Ralf Bartenschlager.


iii) Hepatitis A.


Loriana Di Giammarino and Jules L. Dienstag.


iv) Hepatitis B.


Geoffrey M. Dusheiko.


v) Hepatitis D.


Antonella Smedile and Mario Rizzetto.


vi) Hepatitis C.


Alfredo Alberti and Luisa Benvegnù.


vii) Hepatitis E.


Rakesh Aggarwal and Krzysztof Krawczynski.


9.1.3 Prevention and treatment of viral hepatitis.


i) Vaccines against hepatitis A.


Pierre Van Damme, Koen Van Herck and Philippe Beutels.


ii) Hepatitis B vaccines and immunization.


Daniel Lavanchy.


iii) Therapy of acute viral hepatitis.


Markus Cornberg, Heiner Wedemeyer and Michael P. Manns.


iv) Antiviral therapy of chronic hepatitis B.


Fabien Zoulim and Mario Rizzetto.


v) Therapy for chronic hepatitis C.


Giorgio Saracco, Fabien Zoulim and Mario Rizzetto.


9.2 Systemic virosis producing hepatitis.


Alberto Biglino and Mario Rizzetto.


9.3 Human immunodeficiency virus and the liver.


Vincent Soriano, Pablo Barreiro, Javier García–Samaniego, Luz Martín–Carbonero and Marina Nuñez.


9.4 Exotic virus infections of the liver.


Pierre E. Rollin, Thomas G. Ksiazek, Alberto Queiroz Farias and Flair José Carrilho.


Section 10 Other infections of the liver.


10.1 Bacterial, rickettsial and spirochaetal infections.


José M. Sánchez–Tapias.


10.2 Fungal infections affecting the liver.


Roderick J. Hay.


10.3 Protozoal infections affecting the liver.


10.3.1 Amoebiasis, giardiasis and cryptosporidiosis.


David Kershenobich, Guillermo Robles Diaz and Juan Miguel Abdo.


10.3.2 Malaria.


Montse Renom and Pedro L. Alonso.


10.3.3 Visceral leishmaniasis.


Manuel Corachan.


10.4 Helminthiasis.


10.4.1 Blood flukes (schistosomes) and liver flukes.


Flair José Carrilho, Pedro Paulo Chieffi and Luiz Caetano Da Silva.


10.4.2 Echinococcosis of the liver.


S. Bresson–Hadni, G.A. Mantion, J.P. Miguet and D.A. Vuitton.


10.4.3 Ascariasis, visceral larva migrans, strongyloidiasis, capillariasis and pentastomiasis.


Marcelo Simão Ferreira and Edna Strauss.


Section 11 Immune disorders of the liver.


11.1 Primary biliary cirrhosis.


E. Jenny Heathcote and Piotr Milkiewicz.


11.2 Autoimmune hepatitis.


Diego Vergani and Giorgina Mieli–Vergani.


11.3 Sclerosing cholangitis.


Konstantinos N. Lazaridis and Nicholas F. LaRusso.


11.4 Vanishing bile duct syndrome.


Frank Grünhage and Tilman Sauerbruch.


11.5 Overlap syndromes.


Ulrich Beuers.


Section 12 Alcoholic liver disease.


12.1 Epidemiological aspects of alcoholic liver disease.


Juan Caballeria.


12.2 Ethanol metabolism and pathogenesis of alcoholic liver injury.


Stephen F. Stewart and Christopher P. Day.


12.3 Pathology of alcoholic liver disease.


Elie Serge Zafrani.


12.4 Alcoholic liver disease: natural history, diagnosis, clinical features, evaluation, prognosis and management.


Laurent Spahr and Antoine Hadengue.


12.5 Management of the alcoholic patient, including alcoholism and extrahepatic manifestations.


Georges–Philippe Pageaux and Pascal Perney.


Section 13 Hepatic non–alcoholic steatosis.


13 Non–alcoholic fatty liver and non–alcoholic steatohepatitis.


Geoffrey C. Farrell.


Section 14 Toxic liver injury.


14.1 Drug–induced liver injury.


Dominique Pessayre and Dominique Larrey.


14.2 Toxic liver injury.


Basuki Gunawan and Neil Kaplowitz.


14.3 Hepatic injury due to physical agents.


Bernhard H. Lauterburg and Haithem Chtioui.


14.4 Hepatic toxicity induced by herbal medicines.


Felix Stickel and Detlef Schuppan.


Section 15 Acute liver failure.


15 Acute liver failure and related syndromes.


François Durand and Jacques Bernuau.


Section 16 Genetic and metabolic diseases.


16.1 Wilson’s disease.


Michael Schilsky.


16.2 Haemochromatosis.


Antonello Pietrangelo.


16.3 Alpha 1–antitrypsin deficiency and related disorders.


Jeffrey H. Teckman.


16.4 The liver in cystic fibrosis.


Andrew P. Feranchak.


16.5 Human hereditary porphyrias.


Elisabeth I. Minder and Xiaoye Schneider–Yin.


16.6 Hyperbilirubinaemia.


Peter L.M. Jansen.


16.7 The liver in intracellular and extracellular lipidosis.


Dominique P. Germain.


16.8 Glycogen storage diseases.


Philippe Labrune.


16.9 Mitochondriopathies.


Pierre Rustin.


16.10 Genetic cholestatic diseases.


Ronald P.J. Oude Elferink.


Section 17 Vascular diseases.


17.1 Hepatic artery diseases.


Peter C. Hayes.


17.2 Obstruction of the portal vein.


Juan Carlos García–Pagán, Manuel Hernández–Guerra and Jaime Bosch.


17.3 Disorders of the hepatic veins and hepatic sinusoids.


Dominique–Charles Valla.


17.4 Congenital vascular malformations.


Guadalupe García–Tsao.


Section 18 Tumours of the liver.


18.1 Benign hepatic tumours.


18.1.1 Liver haemangioma.


Jean–Pierre Benhamou.


18.1.2 Benign hepatocellular tumours.


Massimo Colombo and Riccardo Lencioni.


18.2 Malignant tumours.


18.2.1 Primary liver cell carcinoma.


Jordi Bruix, Alejandro Forner, María Varela, Carmen Ayuso and Josep María Llovet.


18.2.2 Malignant mesenchymal tumours of the liver.


Miguel Bruguera and Juan Rodés.


18.3 Metastatic tumours.


18.3.1 Metastatic liver disease.


Masamichi Kojiro and Antoni Castells.


18.3.2 Carcinoid tumours.


Humphrey J.F. Hodgson.


Section 19 Biliary tract diseases.


19.1 Intrahepatic cholestasis.


Olivier Chazouillères and Chantal Housset.


19.2 Extrahepatic biliary obstruction: systemic effects, diagnosis and management.


Michelle C. Gallagher and James S. Dooley.


19.3 Gallstone disease.


Frank Lammert, Franz–Ludwig Dumoulin and Tilman Sauerbruch.


19.4 Cholangitis and biliary tract infections.


Ulrich Beuers.


19.5 Haemobilia.


Antonio Lacy and Nader K. Francis.


19.6 Biliary dyskinesia.


C. Ritchie Chalmers and Giles J. Toogood.


19.7 Benign biliary tumours.


Miguel Bruguera.


19.8 Gallbladder carcinoma.


Thomas A. Aloia, Christopher H. Crane and Jean–Nicolas Vauthey.


19.9 Cholangiocarcinoma.


Steven S. Strasberg and William G. Hawkins.


Section 20 The liver in diseases of other systems.


20.1 The liver in cardiovascular disease.


Susan Tiukinhoy–Laing, Andres T. Blei and Mihai Gheorghiade.


20.2 The liver in lung diseases.


Andres T. Blei and Jacob I. Sznajder.


20.3 The effect of gastrointestinal diseases on the liver and biliary tract.


Roger W. Chapman and Peter W. Angus.


20.4 Total parenteral nutrition–related liver disease.


Sean W.P. Koppe and Alan L. Buchman.


20.5 The effect of skin diseases on the liver.


Daniel Glass and Malcolm Rustin.


20.6 The liver in urogenital diseases.


Mónica Guevara, Vicente Arroyo and Juan Rodés.


20.7 The effect of haematological and lymphatic diseases on the liver.


Miguel Bruguera and Rosa Miquel.


20.8 The liver in graft–vs.–host disease.


Enric Carreras, Carmen Martínez and Miguel Bruguera.


20.9 The effect of endocrine diseases on liver function.


Anthony J. DeSantis and Andres T. Blei.


20.10 Musculoskeletal diseases and the liver.


N. Guañabens, J. van den Bogaerde and H.L.C. Beynon.


20.11 Amyloidosis.


Philip N. Hawkins.


20.12 Hepatic granulomas.


Laura M. Kulik and Andres T. Blei.


Section 21 The impact of liver disease on other systems.


21.1 The effect of liver disease on the cardiovascular system.


Jens H. Henriksen and Søren Møller.


21.2 The effect of liver disease on the endocrine system.


Yolanta T. Kruszynska and Pierre M. Bouloux.


21.3 Haematological abnormalities in liver disease.


Marco Senzolo and Andrew K. Burroughs.


21.4 Haemostasis in liver disease.


Stephen H. Caldwell, Patrick G. Northup and Vinay Sundaram.


21.5 The effect of liver disease on the gastrointestinal tract.


Roger W. Chapman and Peter W. Angus.


21.6 The effect of liver disease on the skin.


Malcolm Rustin and Daniel Glass.


21.7 Effect of liver on the urogenital tract.


Mónica Guevara, Vicente Arroyo and Juan Rodés.


21.8 The nervous system in liver disease.


Andres T. Blei.


21.9 The effect of liver disease on bone.


Juliet Compston.


21.10 The effect of liver disease on nutritional status and energy metabolism.


Michael R. Charlton.


Section 22 The liver in specific settings.


22.1 Paediatric liver diseases.


Marianne Samyn and Giorgina Mieli–Vergani.


22.2 Liver diseases in the elderly.


Oliver F.W. James.


22.3 Liver diseases and pregnancy.


Andrew K. Burroughs and Evangelos Cholongitas.


Section 23 The management of liver diseases.


23.1 The general management of liver diseases.


Dominique Guyader.


23.2 Nutritional aspects of liver and biliary disease.


Bernard Campillo.


23.3 Prescribing drugs in liver disease.


Dominique Larrey and Georges–Phillppe Pageaux.


23.4 Management of pretransplant patients.


François Durand.


Section 24 Surgery, anaesthesia and the liver.


24.1 General surgical aspects and the risks of liver surgery in patients with hepatic disease.


Jacques Belghiti and Satoshi Ogata.


24.2 Anaesthesia and liver disease.


Kalpana Reddy and Susan V. Mallett.


24.3 Postoperative jaundice.


Peter Fickert and Michael Trauner.


24.4 Hepatobiliary trauma.


K. Raj Prasad, Patrick A. Couglin and Giles J. Toogood.


Section 25 Liver transplantation.


25.1 Surgical techniques.


25.1.1 Liver transplantation.


Peter Neuhaus.


25.1.2 Split–liver transplantation.


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.


Igal Kam, James Trotter and Gregory T. Everson.


25.2 Liver transplantation: indications, contraindications and results.


Gregory T. Everson and Fernando E. Membreno.


25.3 The perioperative care and complications of liver transplantation.


Mark T. Keegan and David J. Plevak.


25.4 Immunosuppression.


James Neuberger.


25.5 Recurrent disease and management in liver transplantation.


Xavier Forns and Antoni Rimola.


25.6 Post–transplantation management and complications.


Faouzi Saliba and Didier Samuel.


25.7 Liver transplantation and quality of life.


Miguel Navasa and Juan Rodés.


25.8 Emerging therapies.


25.8.1 Hepatocyte transplantation.


Govardhana Rao Yannam, Jayanta Roy–Chowdhury and Ira J. Fox.


25.8.2 Liver support.


Vanessa Stadlbauer and Rajiv Jalan.


Section 26 Mathematics in hepatology.


26.1 Models in clinical hepatology.


W. Ray Kim.


26.2 Outcomes research in hepatology.


Raymond S. Koff.


26.3 Meta–analysis.


Gioacchino Leandro and Andrew K. Burroughs.


26.4 Economic considerations in hepatology.


John B. Wong.


26.5 Development of the liver interactome: mapping the regulatory networks.


Mario Pagano, Susana Neves, Ravi Iyengar and John Cijiang He.


Section 27 Appendices.


27.1 Geographic distribution of infections causing liver disease.


Harriet Hughes and Tom Doherty.


27.2 Liver injury in man ascribed to non–drug chemicals and natural toxins.


Regine Kahl and Wim Wätjen.


27.3 Rare diseases with hepatic abnormalities.


M. Baraitser and R.M. Winter