THE LIVER. BIOLOGY AND PATHOBIOLOGY

In its Fifth Edition, this classic book retains its traditional strength of relating molecular physiology to understanding disease pathology and treatment as it explores the current state and future direction of hepatology.

Painstakingly revised, this edition includes 60 new chapters. As in previous editions, a section called Horizons summarizes advances of extraordinary nature in areas expected to have a substantial impact on hepatology. The Fifth Edition’s Horizons section includes emerging topics such as tissue engineering of the liver, liver-directed gene therapy, decoding the liver cancer genome, and imaging cellular proteins and structure.

Contents

List of Contributors

Preface

Acknowledgements

PART ONE INTRODUCTION

• 1 Organizational Principles of the Liver
  Joe W. Grisham
• 2 Embryonic Development of the Liver
  Roque Bort and Kenneth S. Zaret

PART TWO THE CELLS

• 3 Microtubules, Actin Filaments and Motor-mediated Vesicular Transport
  Ronald R. Marchelletta and Sarah F. Hamm-Alvarez
• 4 Molecular Motors
  Peter Satir
• 5 Ion Pumps and Molecular Motors: P-, F-, and V-type ATPases
  Sarah Bond, Daniel J. Cipriano, and Michael Forgac
• 6 Hepatocyte Surface Polarity: Its Dynamic Maintenance and Establishment
  Lelita T. Braiterman and Ann L. Hubbard
• 7 Endocytosis as an Essential Process in Liver Function and Pathology
  Barbara Schroeder and Mark McNiven
• 8 Membrane Transport in Hepatocellular Secretion
  Susan Chi and Mark McNiven
• 9 Mitochondria
  Kastuei Mitra
• 10  Nuclear Pore Complex
  Joseph S. Glavy
• 11 Protein Maturation and Processing at the Endoplasmic Reticulum
  Ramanujan S. Hegde
• 12 Protein Degradation and the Lysosomal System
  Susmita Kaushik and Ana Maria Cuervo
• 13 Peroxisome Assembly, Degradation, and Disease
  Peter K. Kim
• 14 Gap and Tight Junctions in Liver: Composition, Regulation, and Function
  Takashi Kojima, Norimasa Sawada, Hiroshi Yamaguchi, Alfredo G. Fort, and David C. Spray

SECTION A HEPATOCYTE

• 15 Copper Metabolism and the Liver
  Michael L. Schilsky and Dennis J. Thiele
• 16 The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis
  Tracey A. Rouault, Victor Gordeuk, and Gregory Anderson
• 17 Disorders of Bilirubin Metabolism
  Namita Roy Chowdhury and Jayanta Roy Chowdhury
• GH4.21. The porphyrias
  Peter N. Meissner, Richard J. Hift, Ralph E. Kirsch
• 18 Hepatic fatty acid metabolism and dysfunction
  David L. Silver
• 19 Lipoprotein Metabolism and Cholesterol Balance
  David E. Cohen

SECTION B BILE SECRETION

• 20 Bile Acids and the Enterohepatic Circulation
  Alan F. Hofmann
• 21 Hepatocyte Basolateral Membrane Organic Anion Transporters
  Jo. H. Choi, John W. Murray, and Allan W. Wolkoff
• 22 Nuclear Receptors Regulate Bile Acid Synthesis
  Guorong Xu and Gerald Salen
• GH4.27. Hormonal regulation of bile secretion
  Francis R. Simon
• GH4.28. Nucleotide transport and regulation of bile formation
  Richard M. Roman and J. Gregory Fitz
• 23 The Function of the Canalicular Membrane in Bile Formation and Secretion
  Ronald P.J. Oude Elferink and Coen C. Paulusma
• 24 Apical Recycling of Canalicular ABC Transporters
  Yoshiyuki Wakabayashi and Irwin M. Arias
• 25 Cholangiocyte Functions in Health and Disease: The Ciliary Connection
  Anatoliy I. Masyuk, Tatyana V. Masyuk, and Nicholas F. LaRusso

SECTION C SINUSOIDAL CELLS

• 26 The Hepatic Sinusoidal Endothelial Cell: Morphology, Function, and Pathobiology
  Laurie D. DeLeve
• GH4.30. Endothelial and pit cells
  Filip Braet, Dianzhong Luo, Ilan Spector, David Vermijlen, Eddie Wisse
• 27 Fenestrations in the Liver Sinusoidal Endothelial Cell
  Victoria C. Cogger and David G. Le Couteur
• 28 Hepatic Stellate Cells
  Marcos Rojkind and Karina Reyes-Gordillo
• 29 Hepatic Fibrosis
  Ram´on Bataller and David A. Brenner
• 30 Matrix
  Giuliano Ramadori and Jozsef Dudas

PART THREE INTERRELATED CELL FUNCTIONS

• 31 Insulin Resistance
  Gerald I. Shulman and Varman Samuel
• 32 Ca2+ Signaling in the Liver
  M. Fatima Leite, Mateus T. Guerra, and Michael H. Nathanson
• GH4.35 Synthesis of and signalling through D-3 phosphoinositides
  Rial A Christensen, Isabel De Aos Scherpenseel, Lyuba Varticovski
• GH4.39. Nitric oxide in the liver
  Mark G. Clemens
• 33 Role of Intracellular Iron Movement and Oxidant Stress in Hepatocellular Injury
  John J. Lemasters, Akira Uchiyama, Jae-Sung Kim, Kazuyoshi Kon, and Hartmut Jaeschke
• GH4.18. Hypoxic, Ischemic and reperfusion injury to liver
  John J. Lemasters
• GH4.19. Protective mechanisms against reactive oxygen species
  Masayasu Inoue
• 34 Regulatory Pathways of Liver Gene Expression: The Central Role of Cyclic AMP
  Giuseppe Servillo, Maria Agnese Della Fazia, and Paolo Sassone-Corsi
• 35 AMPK: Central Regulator of Glucose and Lipid Metabolism  
  Maria M. Mihaylova and Reuben J. Shaw
• GH3.16. Energy Metabolism
  Sam Seifter and Sasha Englard
• 36 Liver Regeneration
  Nelson Fausto
• GH4.40. Interleukin-6 signaling during the acute-phase response of the liver
  Johannes G. Bode, Peter C. Heinrich
• GH4.43. Hepatocyte growth factor: its role in hepatic growth and pathobiology
  Reza Zarnegar, Marie C. Defrances, George K. Michalopoulos
• 37 Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the Liver
  Stefano Fumagalli and George Thomas
• GH4.5. Gene regulation and in vivo function of liver transcription factors
  Robert H. Costa, AI-Xuan Le Holternan, Francisco M. Rausa, Guy R. Adami
• 38 Liver Repopulation by Cell Transplantation and the Role of Stem Cells
  David A. Shafritz, Michael Oertel, Mariana D. Dabeva, and Markus Grompe

PART FOUR RELATION TO OTHER ORGANS

• 39 Hepatic Encephalopathy
  Roger F. Butterworth and Javier Vaquero
• 40 The Kidney in Liver Disease
  Moshe Levi
• 41 Critical Role of the Liver in Coagulation
  Robert Fathke, Ze Peng, Basil Golding, and Chava Kimchi-Sarfaty

PART FIVE PATHOBIOLOGICAL ANALYSIS

• 42 Inheritable Cholestatic Disorders
  Paul Gissen and Alex S. Knisely
• GH4.48. Alpha 1-Antitrypsin deficiency
  David H. Perlmutter
• 43 Adaptive Regulation of Hepatocyte Transporters in Cholestasis
  James L. Boyer
• 44 Pathogenesis of Portal Hypertension
  Roberto J. Groszmann and Juan G. Abraldes
• 45 Non-alcoholic Fatty Liver Disease: A Pathophysiological Perspective
  Michael Fuchs and Arun J. Sanyal
• 46 Pathophysiology of Alcoholic Liver Disease
  Natalia Nieto and Marcos Rojkind
• 47 Inflammation and Drug-induced Liver Injury
  Robert A. Roth and Patricia E. Ganey
• 48 Hepatocyte Apoptosis
  Cynthia R.L. Webster
• 49 Back to the Future: A Backward Glance at the Forward Progress of Hepatitis Virus Research
  Harvey J. Alter
• 50 Molecular Biology of Hepatitis Viruses
  Christoph Seeger, Michael M.C. Lai, and William S. Mason
• 51 Immune Mechanisms of Viral Clearance and Disease Pathogenesis During Viral Hepatitis
  Carlo Ferrari and Mario Mondelli
• GH4.41. Innate immune sensing and the toll-like receptors
  Bruce Beutler
• 52 Clinical Implications of the Molecular Biology of Hepatitis B Virus
  Timothy M. Block, Ju-Tao Guo, and Thomas W. London
• 53 Viral Escape Mechanisms in Hepatitis C and the Clinical Consequences of Persistent Infection
  Stanley M. Lemon, Patrizia Farci, and Marc G. Ghany
• 54 Current and Future Therapy for Hepatitis B and C
  Gary L. Davis and Jean-Michel Pawlotsky
• 55 Biological Principles and Clinical Issues Underlying Liver Transplantation for Virus-induced
  End-stage Liver Disease
  James R. Burton Jr, Hugo R. Rosen, and Paul Martin

PART SIX HORIZONS

• 56 Tissue Engineering of the Liver
  Gregory H. Underhill, Salman R. Khetani, Alice A. Chen, and Sangeeta N. Bhatia
• 57 Aging and the Uncertain Roles of Sirtuins
  Fred J. Dice
• 58 The Liver Proteome
  Laura Beretta
• 59 Liver-directed Gene Therapy
  Betsy T. Kren, Clifford J. Steer, Namita Roy Chowdhury, and Jayanta Roy Chowdhury
• GH4.63. Novel strategies for manipulating hepatic gene expression in vivo
  Marxa L. Figueiredo, Eric P. Sandgren
• 60 Decoding the Liver Cancer Genome
  Ju-Seog Lee and Snorri S. Thorgeirsson
• 61 Genome-wide Expression Profiling of Human Hepatocellular Carcinoma
  Anuradha Budhu and Xin Wei Wang
• 62 Cell Cycle Control in the Liver
  Jeffrey H. Albrecht and Lisa K. Mullany
• 63 miRNAs and Liver Biology
  Charles E. Rogler and Leslie E. Rogler
• 64 Imaging Cellular Proteins and Structures: Smaller, Brighter, and Faster
  Erik Snapp
• 65 Zebrafish as a Model System for the Study of Liver Development and Disease
  Randolph P. Matthews
• 66 The Hepatocyte and the Cancer Cell: Dr Jekyll and Mr Hyde
  Jean-Pierre Gillet, Michael M. Gottesman, and Mitsunori Okabe
• 67 The Role of Endocannabinoids and Their Receptors in the Control of Hepatic Functions
  George Kunos, Douglas Osei-Hyiaman, S´andor B´atkai, P´al Pacher, Bin Gao, Won-Il Jeong, Jie Liu, and Gregorz Godlewski
• 68 Telomeres and Aging, Cancer, and Hepatic Fibrosis
  Hans L. Tillmann, Ruben R. Plentz, Yvonne Begus-Nahrmann, Andr´e Lechel, and Lenhard K. Rudolph
• 69 Treatment of Cirrhosis with Vitamin A-coupled Liposomes Carrying siRNA against Heat Shock
  Protein 47
  Yoshiro Niitsu, Yasushi Sato, Kazuyuki Murase, and Junji Kato
• 70 The “Green Liver” and Transcriptional Regulation of Phase II Detoxification Genes
  Christopher Johnson and Jonathan Arias