Zakim and Boyer's Hepatology: A Textbook of Liver Disease, 6th Edition

1330 Pages·2011·112.39 MB·English

by  Thomas D. Boyer MD

Zakim and Boyer’s Hepatology

Zakim and Boyer’s
Hepatology
A Textbook of Liver Disease
SIXTH EDITION
T D. B , MD
HOMAS OYER
Chairman of Medicine
Robert and Irene Flinn Professor of Medicine
Director, Liver Research Institute
University of Arizona College of Medicine
Tucson, Arizona
M P. M , MD
ICHAEL ANNS
Professor and Chairman
Department of Gastroenterology, Hepatology, and Endocrinology
Hannover Medical School
Hannover, Germany
A J. S , MBBS, MD
RUN ANYAL
Charles Caravati Professor of Medicine
Chairman, Division of Gastroenterology, Hepatology, and Internal Medicine
Virginia Commonwealth University School of Medicine
Richmond, Virginia
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
ZAKIM AND BOYER’S HEPATOLOGY ISBN: 978-1-4377-0881-3
Copyright © 2012 by Saunders, an imprint of Elsevier Inc.
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Previous editions copyrighted 1982, 1990, 1996, 2003, 2006
Library of Congress Cataloging-in-Publication Data
Zakim and Boyer’s hepatology: a textbook of liver disease / [edited by] Thomas D. Boyer, Michael P. Manns,
Arun J. Sanyal.—6th ed.
p. ; cm.
Hepatology
Includes bibliographical references and index.
ISBN 978-1-4377-0881-3 (hardcover : alk. paper)
1. Liver—Diseases. I. Boyer, Thomas D. II. Manns, Michael P. (Michael Peter) III. Sanyal, Arun
J. IV. Zakim, David. V. Title: Hepatology.
[DNLM: 1. Liver Diseases. WI 700]
RC845.H46 2012
616.3′62—dc23
2011024933
Senior Acquisitions Editor: Kate Dimock
Senior Developmental Editor: Janice M. Gaillard
Editorial Assistant: Kate Crowley
Publishing Services Manager: Anne Altepeter
Senior Project Manager: Cheryl A. Abbott
Design Direction: Steven Stave Working together to grow
Marketing Manager: Abby Swartz
libraries in developing countries
Printed in China www.elsevier.com | www.bookaid.org | www.sabre.org
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Contributors
Paul C. Adams, MD Herbert L. Bonkovsky, MD Henry Lik-Yuen Chan, MD, FRCP
Professor of Medicine Vice President, Research Professor, Division of Gastroenterology
Department of Medicine Director, The Liver, Digestive, and Metabolic and Hepatology
University Hospital Disorders Laboratory Director, Cheng Suen Man Shook Centre
London, Ontario, Canada Department of Medicine for Hepatitis Research
Division of Education and Research Director, Center for Liver Health
Helmut Albrecht, MD Carolinas Medical Center Department of Medicine and Therapeutics
Heyward Gibbes Distinguished Professor Charlotte, North Carolina; The Chinese University of Hong Kong, Shatin
of Medicine and Division Chief Professor, Medicine Hong Kong, China
Division of Infectious Diseases University of Connecticut Health Center
School of Medicine Farmington, Connecticut; Kyong-Mi Chang, MD
University of South Carolina Professor, Biology Associate Professor of Medicine
Columbia, South Carolina University of North Carolina, Charlotte Department of Medicine
Charlotte, North Carolina; Philadelphia Veterans Administration Medical
Jasmohan Bajaj, MBBS, MD, MSc Clinical Professor, Medicine Center and University of Pennsylvania
Associate Professor of Medicine University of North Carolina, Chapel Hill Philadelphia, Pennsylvania
Division of Gastroenterology, Hepatology, Chapel Hill, North Carolina
and Nutrition Alessia Ciancio, MD, PhD
Department of Medicine Jaime Bosch, MD, PhD University of Turin
Virginia Commonwealth University Professor of Medicine AOU San Giovanni Battista di Torino
and McGuire Veterans Administration University of Barcelona Dip Gastro-Hepatology
Medical Center Liver Unit Hospital Clinic Torino, Italy
Richmond, Virginia Barcelona, Spain
Massimo Colombo, MD
Soon Koo Baik, MD Thomas D. Boyer, MD Professor, First Division of Gastroenterology
Department of Medicine Chairman of Medicine Fondazione IRCCS Ca’Granda Ospedale
Yonsei University Wonju College of Medicine Robert and Irene Flinn Professor of Medicine Maggiore Policlinico
Wonju, Korea Director, Liver Research Institute Universita degli Studi di Milano
University of Arizona College of Medicine Milan, Italy
Ulrich Beuers, MD Tucson, Arizona
Hari S. Conjeevaram, MD, MS
Professor of Gastroenterology and Hepatology
Department of Gastroenterology Elizabeth M. Brunt, MD Associate Professor, Department of Internal
and Hepatology Professor, Pathology and Immunology Medicine
Tytgat Institute for Liver and Intestinal Research Washington University School of Medicine Director, GI Fellowship Training Program
Academic Medical Center St. Louis, Missouri University of Michigan
University of Amsterdam Ann Arbor, Michigan
Amsterdam, Netherlands Martin Caselitz, MD
Diane W. Cox, PhD, CCMG, FRSC
Assistant Professor of Medicine (Privatdozent)
Scott W. Biggins, MD, MAS Medical Clinic II, Klinikum Deggendorf Professor, Medical Genetics
Assistant Professor, Section of Hepatology Deggendorf, Germany University of Alberta, Edmonton
and Liver Transplantation Alberta, Canada
Division of Gastroenterology Wolfgang H. Caselmann, MD, PhD
Chris P. Day, FMedSci
Anschutz Medical Campus Professor of Medicine
University of Colorado, Denver Head of Division, Bavarian State Ministry Professor, Institute of Cellular Medicine
Aurora, Colorado of the Environment and Public Health Newcastle University
Munich, Germany Newcastle upon Tyne, United Kingdom
Henri Bismuth, MD
R. Brian Doctor, PhD
Centre Hepato Biliaire Matt Cave, MD
Associate Professor
Paris, France Assistant Professor
Department of Medicine
Department of Medicine
University of Colorado, Denver
Kirsten Muri Boberg, MD, PhD Division of Gastroenterology, Hepatology,
Denver, Colorado
Consulting Physician and Nutrition
Norwegian PSC Research Center Department of Pharmacology and Toxicology
Ronald P.J. Oude Elferink, PhD
Clinic for Specialized Medicine and Surgery University of Louisville
Tytgat Institute for Liver and Intestinal Research
Oslo University Hospital, Rikshospitalet Louisville, Kentucky
Academic Medical Center
Oslo, Norway
University of Amsterdam
Amsterdam, Netherlands
v
vi Contributors
Scott A. Elisofon, MD J.C. García-Pagán, MD, PhD Steve M. Helmke, PhD
Instructor in Pediatrics Senior Consultant in Hepatology Research Instructor
Harvard Medical School; Liver Unit, Hospital Clinic Division of Gastroenterology and Hepatology
Division of Pediatric Gastroenterology Barcelona, Spain; University of Colorado School of Medicine
Children’s Hospital, Boston Senior Research, IDIBAPS and CIBERehd Aurora, Colorado
Boston, Massachusetts Barcelona, Spain
G.M. Hirschfield, MA, MB BChir,
Hashem B. El-Serag, MD, MPH Guadalupe Garcia-Tsao, MD MRCP, PhD
Professor of Medicine Professor of Medicine Staff Hepatologist/Assistant Professor
Chief, Gastroenterology and Hepatology Internal Medicine/Digestive Diseases Liver Centre, Toronto Western Hospital
Michael E. DeBakey Veterans Administration Yale University Department of Medicine
Medical Center and Baylor College of Medicine New Haven, Connecticut; University of Toronto
Houston, Texas Chief, Digestive Diseases Toronto, Ontario, Canada
Veterans Administration Connecticut
Gamal Esmat, MD Healthcare System Douglas Hunt, MD
Professor of Tropical Medicine and Hepatology West Haven, Connecticut Department of Medicine
Department of Tropical Medicine Division of Gastroenterology and Hepatology
Faculty of Medicine Fayez K. Ghishan, MD Scripps Green Hospital
Cairo University Horace W. Steele Endowed Chair La Jolla, California
Cairo, Egypt in Pediatric Research
Professor and Head Massimo Iavarone, MD, PhD
Gregory T. Everson, MD Director, Steele Children’s Research First Division of Gastroenterology
Professor of Medicine Center, Pediatrics Fondazione IRCCS Ca’ Granda
School of Medicine University of Arizona Maggiore Hospital
Director of Hepatology Tucson, Arizona Milan, Italy
Division of Gastroenterology and Hepatology
University of Colorado, Denver Gregory J. Gores, MD Jamal A. Ibdah, MD, PhD, AGAF
Aurora, Colorado Reuben R. Eisenberg Professor of Medicine Professor and Raymond E. and Vaona H. Peck
Division of Gastroenterology and Hepatology Research Chair
Keith Cameron Falkner College of Medicine Director, Digestive Health Center
Senior Research Associate Mayo Clinic Director, University of Missouri Columbia
Department of Medicine Rochester, Minnesota Institute for Clinical and Translational Science
Division of Gastroenterology, Hepatology, Senior Associate Dean for Research
and Nutrition Rainer W. Gruessner, MD, FACS School of Medicine
University of Louisville Professor of Surgery and Immunology University of Missouri, Columbia
Louisville, Kentucky Chairman, Department of Surgery Columbia, Missouri
University of Arizona
Michael B. Fallon, MD Françoise Imbert-Bismut, PhD
Tucson, Arizona
Professor of Medicine APHP UPMC Liver Center
Division Director, Division of Gastroenterology, Sanjeev Gupta, MBBS, MD, FRCP Biochemistry Unit
Hepatology, and Nutrition Paris, France
The Eleazar and Feige Reicher Chair
University of Texas Health Science Center
in Translational Medicine
at Houston Peter L.M. Jansen, MD, PhD
Professor of Medicine (Gastroenterology
Houston, Texas Professor, Gastroenterology and Hepatology
and Liver Diseases) and Pathology
Academic Medical Center
Albert Einstein College of Medicine
Sandy Feng, MD, PhD Amsterdam, Netherlands
Bronx, New York
Associate Professor of Surgery
Director, Abdominal Transplant Surgery Benjamin F. Johnson, MD
Ghassan M. Hammoud, MD, MPH
Fellowship Assistant Physician
Assistant Professor of Clinical Medicine
University of California, San Francisco Department of Medicine
Director, Section of Hepatology
San Francisco, California University of California, San Diego
and Biliary Disease
San Diego, California
Division of Gastroenterology and Hepatology
Hans-Peter Fischer, MD
University of Missouri School of Medicine
Professor, Department of Pathology Maureen M.F. Jonas, MD
Columbia, Missouri
Bonn University Associate Professor, Pediatrics
Bonn, Germany Harvard Medical School;
E.J. Heathcote, MBBS, MD, FRCP,
Senior Associate in Medicine
FRCP(C)
Brett E. Fortune, MD Division of Gastroenterology
The Francis Family Chair
Gastroenterology/Hepatology Fellow Children’s Hospital, Boston
in Hepatology Research
Division of Gastroenterology and Hepatology Boston, Massachusetts
Professor of Medicine
University of Colorado
University of Toronto;
Aurora, Colorado Dean P. Jones, PhD
Head, Patient-Based Clinical Research
Professor of Medicine
Toronto Western Research Institute
Scott L. Friedman, MD Director, Clinical Biomarkers Laboratory
Toronto Western Hospital
Fishberg Professor of Medicine Division of Pulmonary, Allergy, and Critical
Toronto, Ontario, Canada
Division of Liver Diseases Care Medicine
Mount Sinai School of Medicine Emory University
New York, New York Atlanta, Georgia
Contributors vii
Patrick S. Kamath, MD Konstantinos N. Lazaridis, MD Jorge A. Marrero, MD, MS
Professor of Medicine Associate Professor of Medicine Keith S. Henley, MD, Collegiate Professor
Division of Gastroenterology and Hepatology Department of Gastroenterology and Hepatology of Gastroenterology
Mayo Clinic College of Medicine The Mayo Clinic Director, Multidisciplinary Liver Tumor Clinic;
Rochester, Minnesota Rochester, Minnesota Department of Medicine
University of Michigan
Tom H. Karlsen, MD, PhD André Lechel, MD Ann Arbor, Michigan
Department of Organ Transplantation, Institute of Molecular Medicine
Gastroenterology, and Nephrology and Max-Planck-Research Department Craig McClain, MD
Oslo University Hospital Rikshospitalet for Stem Cell Aging Professor, Departments of Medicine
Oslo, Norway Ulm University and Pharmacology and Toxicology
Ulm, Germany Distinguished University Scholar
Deirdre Kelly, FRCPH, FRCP, FRCPI, Associate Vice President
MD, MB, BA Samuel S. Lee, MD, FRCPC for Translational Research
Professor of Paediatric Hepatology Professor of Medicine University of Louisville
The Liver Unit University of Calgary Louisville, Kentucky
Birmingham Children’s Hospital Calgary, Alberta, Canada
Birmingham, West Midlands, United Kingdom Robert McCuskey, AB, PhD
Riccardo Lencioni, MD Professor Emeritus of Cell Biology
J. Kettelle, MD Director, Division of Diagnostic Imaging and Anatomy, Physiology, and Pediatrics
Assistant Professor of Clinical Surgery and Intervention Department of Cell Biology and Anatomy
Surgery Pisa University Hospital; University of Arizona
University of Arizona Associate Professor of Radiology Tucson, Arizona
Tucson, Arizona University of Pisa
Pisa, Italy Barbara H. McGovern, MD
Khalid M. Khan, MB, ChB Associate Professor
Associate Professor Cynthia Levy, MD Tufts University School of Medicine
Surgery Associate Professor of Medicine Boston, Massachusetts
University of Arizona Center for Liver Diseases
John G. McHutchison, MD
Tucson, Arizona Division of Hepatology
University of Miami Miller School of Medicine Senior Vice President
Percy Knolle, MD Miami, Florida Liver Diseases
Gilead Sciences, Inc.
Professor, Institutes of Molecular Medicine
and Experimental Immunology Keith D. Lindor, MD Foster City, California
Friedrich-Wilhelms-Universität Bonn Dean, Mayo Medical School
Darius Moradpour, MD
Bonn, Germany Professor of Medicine
Professor and Chief
Division of Gastroenterology and Hepatology
Division of Gastroenterology and Hepatology
David J. Kramer, MD, FACP Mayo Clinic
Centre Hospitalier Universitaire Vaudois
Professor of Medicine, College of Medicine Rochester, Minnesota
University of Lausanne
Director, Transplant Critical Care Service
Lausanne, Switzerland
Mayo Clinic Stephen Locarnini, MBBS, BSc(Hon),
Jacksonville, Florida PhD, FRC(Path)
Victor J. Navarro, MD
Professor
Professor of Medicine, Pharmacology,
Manoj Kumar, MD, DM Head, Research and Molecular Development
and Experimental Therapeutics
Department of Gastroenterology Victorian Infectious Diseases
Thomas Jefferson University
G.B. Pant Hospital Reference Laboratory
Philadelphia, Pennsylvania
New Delhi, India North Melbourne, Victoria, Australia
James Neuberger, DM, FRCP
Navaneeth C. Kumar, MD, MBBS Anna S.F. Lok, MD
Consultant Physician
Chennai, India Professor, Internal Medicine
Liver Unit
University of Michigan
Queen Elizabeth Hospital
Jennifer C. Lai, MD Ann Arbor, Michigan Birmingham, United Kingdom
Fellow in Gastroenterology
Harmeet Malhi, MBBS
University of California, San Francisco Moises I. Nevah R., MD
San Francisco, California Assistant Professor of Medicine Clinical Fellow
Department of Medicine
Division of Gastroenterology, Hepatology,
Réal Lapointe, MD, FRCSC Division of Gastroenterology and Hepatology and Nutrition
Mayo Clinic
Professor of Surgery Department of Medicine
Rochester, Minnesota
Head of Division of General Surgery University of Texas Health Science
Department of Surgery Center, Houston
Michael P. Manns, MD
University of Montreal Houston, Texas
Montreal, Quebec, Canada; Professor and Chairman
Head of Hepato-Pancreato-Biliary and Liver Department of Gastroenterology, Hepatology, Yulia A. Nevzorova, PhD
Transplant Service and Endocrinology Department of Medicine III
Department of Surgery Hannover Medical School University Hospital Aachen
Montreal University Medical Center Hannover, Germany Aachen, Germany
Montreal, Quebec, Canada
viii Contributors
Heather M. Patton, MD Don C. Rockey, MD Leonard B. Seeff, MD
Assistant Clinical Professor of Medicine Dr. Carey G. King, Jr., and Dr. Henry M. Senior Scientific Officer
Division of Gastroenterology Winans, Sr., Chair in Internal Medicine National Institute of Diabetes and Digestive
University of California, San Diego Chief, Division of Digestive and Liver Diseases and Kidney Disease
San Diego, California University of Texas Southwestern National Institutes of Health
Medical Center Bethesda, Maryland
François Penin, PhD Dallas, Texas
Intitut de Biologie et Chimie des Protéines S. Seijo, MD
University of Lyon Jayanta Roy-Chowdhury, MD, MRCP, Hepatic Hemodynamic Laboratory
Lyon, France AGAF Liver Unit
Professor, Department of Medicine Institut de Malalties Digestives I Metaboliques
David Perlmutter, MD Division of Gastroenterology and Liver Diseases IDIBAPS, Clinic Hospital
Vira I. Heinz Professor and Chair, Pediatrics Professor, Department of Genetics Barcelona, Spain
Professor, Cell Biology and Physiology Albert Einstein College of Medicine
University of Pittsburgh School of Medicine; Bronx, New York Vijay H. Shah, MD
Physician-in-Chief and Scientific Director Director, Office of Postdoctoral Affairs
Children’s Hospital of Pittsburgh of UPMC Namita Roy-Chowdhury, PhD Professor of Medicine and Research Chair
Pittsburgh, Pennsylvania Professor, Department of Medicine Division of Gastroenterology and Hepatology
Division of Gastroenterology and Liver Diseases Mayo Clinic
Aurélie Plessier, MD Professor, Department of Genetics Rochester, Minnesota
Hepatology Albert Einstein College of Medicine
Hopital Beaujon Bronx, New York Steven I. Shedlofsky, MD
Clichy, France Professor of Medicine
K. Lenhard Rudolph, MD Internal Medicine
Thierry Poynard, MD, PhD Director, Institute of Molecular Medicine University of Kentucky College of Medicine
Professor of Hepatology and Max-Planck-Research Department Lexington, Kentucky
Department Head on Stem Cell Aging
UPMC APHP Liver Center Ulm University Daniel Shouval, MD
Groupe Hospitalier Pitié Salpêtrière Ulm, Germany Professor of Medicine
Paris, France Director, Liver Unit
Mark W. Russo, MD, MPH Hadassah-Hebrew University Hospital
Puneet Puri, MBBS, MD Medical Director of Liver Transplantation Jerusalem, Israel
Assistant Professor of Medicine Department of Medicine
Division of Gastroenterology, Hepatology, Carolinas Medical Center Claude B. Sirlin, MD
and Nutrition Charlotte, North Carolina Associate Professor
Virginia Commonwealth University University of California, San Diego
School of Medicine Sammy Saab, MD, MPH, AGAF San Diego, California
Richmond, Virginia Associate Professor
Medicine and Surgery Maxwell L. Smith, MD
Charles Rice, PhD Head, Outcomes Research in Hepatology Director of Liver and Transplant Pathology
Maurice R. and Corinne P. Greenberg Professor David Geffen School of Medicine at University Assistant Professor
Head, Laboratory of Virology of California, Los Angeles University of Colorado Anschutz Medical
and Infectious Disease Los Angeles, California Campus
Scientific and Executive Director Aurora, Colorado
Center for the Study of Hepatitis C Arun J. Sanyal, MBBS, MD
The Rockefeller University Charles Caravati Professor of Medicine Emmanuil Smorodinsky, MD
New York, New York; Chairman, Division of Gastroenterology, Liver Imaging Group
New York–Presbyterian Hospital Hepatology, and Internal Medicine Department of Radiology
Weill Medical College of Cornell University Virginia Commonwealth University University of California, San Diego
Ithaca, New York School of Medicine San Diego, California
Richmond, Virginia
Mario Rizzetto, MD Ulrich Spengler, MD
Experimental Department of Gastroenterology S.K. Sarin, MD, DM, FNASc Professor, Department of Internal Medicine 1
San Giovanni Battista Hospital Professor University of Bonn
Turin, Italy Head of Hepatology Bonn, Germany
Director
Eve A. Roberts, MD, MA, FRCPC Institute of Liver and Biliary Sciences (ILBS) Richard K. Sterling, MD, MSc
Adjunct Professor, Paediatrics New Delhi, India Professor of Medicine
Medicine and Pharmacology Associate Chair of Education and Training
University of Toronto Erik Schrumpf, MD, PhD Chief of Hepatology
Toronto, Ontario, Canada; Professor, Head of Section of Gastroenterology Division of Gastroenterology, Hepatology,
Adjunct Scientist and Hepatology and Nutrition
Genetics and Genome Biology Medical Department Medical Director, HIV Liver Disease
Hospital for Sick Children Research Institute Oslo University Hospital–Rikshospitalet Virginia Commonwealth University
Toronto, Ontario, Canada Oslo, Norway School of Medicine
Richmond, Virginia
Contributors ix
Stephen F. Stewart, MD, PhD Jayant A. Talwalkar, MD, MPH Siegfried Wagner, MD, AGAF
Consultant Hepatologist Associate Professor of Medicine Klinikum Deggendorf
Liver Unit Division of Gastroenterology and Hepatology Medizinizche Klinik II
Freeman Hospital Mayo Clinic Deggendorf, Germany;
Newcastle upon Tyne, United Kingdom Rochester, Minnesota Department of Gastroenterology, Hepatology,
and Endocrinology
Doris B. Strader, MD Norah A. Terrault, MD, MPH Medical School of Hannover
Associate Professor of Medicine Professor of Medicine Hannover, Germany
Internal Medicine/Division of Gastroenterology University of California, San Francisco
and Hepatology San Francisco, California Nadia Warner, MD
Fletcher Allen Health Care Molecular Research and Development
Burlington, Vermont Hans L. Tillmann, MD Victorian Infectious Diseases Reference
Assistant Professor Laboratories
Christian P. Strassburg, MD Gastroenterology/Hepatology Research Melbourne, Victoria, Australia
Duke Clinical Research Institute
Professor of Gastroenterology and Hepatology
Durham, North Carolina Vincent Wai-Sun Wong, MD
Department of Gastroenterology, Hepatology,
Associate Professor
and Endocrinology
Christian Trautwein, MD Department of Medicine and Therapeutics
Hannover Medical School
Hannover, Germany Professor of Medicine The Chinese University of Hong Kong
Department of Internal Medicine Hong Kong, China
(Gastroenterology, Hepatology,
R. Todd Stravitz, MD
and Metabolic Diseases) Naglaa Zayed, MD
Professor of Medicine
University Hospital, RWTH Aachen Assistant Professor of Tropical Medicine
Hume-Lee Transplant Center,
Aachen, Germany and Hepatology
Section of Hepatology
Faculty of Medicine, Cairo University
Virginia Commonwealth University
Parsia A. Vagefi, MD Cairo, Egypt
School of Medicine
Clinical Instructor in Surgery
Richmond, Virginia
University of California, San Francisco
San Francisco, California
Priti Sud, MD
Gastroenterology Fellow Dominique Valla, MD
University of Arizona Professor of Hepatology
Tucson, Arizona Universté Denis Diderot and INSERM U773
Paris, France;
Mark S. Sulkowski, MD Head, Liver Unit
Associate Professor of Medicine INSERM U773
The Johns Hopkins University Hôpital Beaujon
Baltimore, Maryland Clichy, France