Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field.
The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more.
Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume:
Relates molecular physiology to understanding disease pathology and treatment
Links the science and pathology of the liver to practical clinical applications
Features 16 new “Horizons” chapters that explore new and emerging science and technology
Includes plentiful full-color illustrations and figures
The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism
Table of contents
Dedication
List of Contributors
Preface
Acknowledgments
Part One: Introduction
1 Organizational Principles of the Liver
Peter Nagy, Snorri S. Thorgeirsson, Joe W. Grisham
2 Embryonic Development of the Liver
Kenneth S. Zaret, Roque Bort, Stephen A. Duncan
Part Two: The Cells
Section A: Cell Biology of the Liver
3 Cytoskeletal Motors: Structure and Function in Hepatocytes
Mukesh Kumar, Arnab Gupta, Roop Mallik
4 Hepatocyte Surface Polarity
Anne Muesch, Irwin Arias
5 Primary Cilia
Carolyn M. Ott
6 Endocytosis in Liver Function and Pathology
Micah B. Schott, Barbara Schroeder, Mark A. McNiven
7 The Hepatocellular Secretory Pathway
Catherine Jackson, Mark A. McNiven
8 Mitochondrial Function, Dynamics, and Quality Control
Marc Liesa, Ilan Benador, Nathanael Miller, Orian S. Shirihai
9 Nuclear Pore Complex
Michelle A. Veronin, Joseph S. Glavy
10 Protein Maturation and Processing at the Endoplasmic Reticulum
Ramanujan S. Hegde
11 Protein Degradation and the Lysosomal System
Susmita Kaushik, Ana Maria Cuervo
12 Peroxisome Assembly, Degradation, and Disease
Rong Hua, Peter K. Kim
13 Organelle–Organelle Contacts: Origins and Functions
Uri Manor
14 Gap and Tight Junctions in Liver: Structure, Function and Pathology
John W. Murray, David C. Spray
15 Ribosome Assembly and its Role in Cell Growth and Proliferation in the Liver
Katherine I. Farley-Barnes, Susan J. Baserga
16 miRNAs and Hepatocellular Carcinoma
Yusuke Yamamoto, Isaku Kohama, Takahiro Ochiya
17 Hepatocyte Apoptosis: Mechanisms and relevance in liver diseases
Gregory J. Gores, Harmeet Malhi
Section B: The Hepatocyte
18 Copper Metabolism and the Liver\
Cynthia Abou Zeid, Ling Yi, Stephen G. Kaler
19 The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis
Tracey A. Rouault, Victor Gordeuk, Gregory J. Anderson
20 Disorders of Bilirubin Metabolism
Namita Roy Chowdhury, Yanfeng Li, Jayanta Roy Chowdhury
21 Hepatic Lipid Droplets in Liver Function and Disease
Douglas G. Mashek, Wenqi Cui, Linshan Shang, Charles P. Najt
22 Lipoprotein Metabolism and Cholesterol Balance
Mariana Acuña-Aravena, David E. Cohen
Section C: Transporters, Bile Acids, and Cholestasis
23 Bile Acids Metabolism in Health and Disease: An update
Tiangang Li, John Y. L. Chiang
24 TGR5 (GPBAR1) in the Liver
Verena Keitel, Christoph G.W. Gertzen, Lina Spomer, Holger Gohlke, Dieter Häussinger
25 Bile Acids as Signaling Molecules
Thierry Claudel, Michael Trauner
26 Hepatic Adenosine Triphosphate-Dependent (ABC) Transporters and Their Role in Physiology
Peter L.M. Jansen
27 Basolateral Plasma Membrane Organic Anion Transporters
M. Sawkat Anwer, Allan W. Wolkoff
28 Hepatic Nuclear Receptors
Raymond E. Soccio
29 Molecular Cholestasis
Paul Gissen, Richard J. Thompson
30 Pathophysiologic Basis for Alternative Therapies for Cholestasis
Claudia D. Fuchs, Emina Halilbasic, Michael Trauner
31 Adaptive Regulation of Hepatocyte Transporters in Cholestasis
James L. Boyer
Section D: Non-Hepatocyte Cells
32 Cholangiocyte Biology and Pathobiology
Massimiliano Cadamuro, Romina Fiorotto, Mario Strazzabosco
33 Polycystic Liver Diseases: Genetics, Mechanisms, and Therapies
Tatyana Masyuk, Anatoliy Masyuk, Nicholas LaRusso
34 The Liver Sinusoidal Endothelial Cell: Basic Biology and Pathobiology
Karen K. Sørensen, Bård Smedsrød
35 Fenestrations in the Liver Sinusoidal Endothelial Cell
Victoria C Cogger, Nicholas J Hunt, David G Le Couteur
36 Stellate Cells and Fibrosis
Youngmin A. Lee, Scott L. Friedman
Part 3: Functions of the Liver
Section A: Metabolic Functions
37 Nonalcoholic Fatty Liver Disease and Insulin Resistance
Max C. Petersen, Varman T. Samuel, Kitt Falk Petersen, Gerald I. Shulman
38 AMPK: Central regulator of glucose and lipid metabolism and target of type 2 diabetes therapeutics
Daniel Garcia, Maria M. Mihaylova, Reuben J. Shaw
39 Insulin-mediated PI3K and AKT Signaling
Jeffrey E. Pessin, Hyokjoon Kwon
40 Ca2+ Signaling in the Liver
Mateus T. Guerra, M. Fatima Leite, Michael H. Nathanson
41 Clinical Genomics of NAFLD
Frank Lammert
Section B: Liver Growth and Regeneration
42 Stem Cell-Fueled Maturational Lineages in Hepatic and Pancreatic Organogenesis
Wencheng Zhang, Amanda Allen, Eliane Wauthier, Xianwen Yi, Homayoun Hani, Praveen Sethupathy, David Gerber, Vincenzo Cardinale, Guido Carpino, Juan Dominguez-Bendala, Giacomo Lanzoni, Domenico Alvaro, Eugenio Gaudio, Lola Reid
43 Developmental Morphogens and Adult Liver Repair
Mariana Machado, Anna Mae Diehl
44 Liver Repopulation by Cell Transplantation and the Role of Stem Cells in Liver Biology
David A. Shafritz, Markus Grompe
45 Liver Regeneration
George K. Michalopoulos
46 β-Catenin Signaling
Satdarshan P. S. Monga
47 Polyploidy in Liver Function, Mitochondrial Metabolism and Cancer
Evan R. Delgado, Elizabeth C. Stahl, Nairita Roy, Patrick D. Wilkinson, Andrew W. Duncan
Part 4: Pathobiology of Liver Disease
48 Hepatic Encephalopathy
Roger F. Butterworth
49 The Kidney in Liver Disease
Moshe Levi, Shogo Takahashi, Xiaoxin X. Wang, Marilyn E. Levi
50 Alpha-1 Antitrypsin Deficiency
David A. Rudnick, David H. Perlmutter
51 Pathophysiology of Portal Hypertension
Roberto J. Groszman, Yasuko Iwakiri
52 Nonalcoholic Fatty Liver Disease: Mechanisms and treatment
Yaron Rotman, Devika Kapuria
53 Alcoholic Liver Disease
Bin Gao, Xiaogang Xiang, Lorenzo Leggio, George F. Koob
54 Drug-induced Liver Injury
Lily Dara, Neil Kaplowitz
55 Oxidative Stress and Inflammation in the Liver
John J. Lemasters, Hartmut Jaeschke
56 The Role of Bile Acid-mediated Inflammation in Cholestatic Liver Injury
Shi-Ying Cai, Man Li, James L. Boyer
57 Toll-like Receptors in Liver Disease
So Yeon Kim, Ekihiro Seki
Part 5: Liver Cancer
58 Experimental Models of Liver Cancer: Genomic assessment of experimental models
Sun Young Yim, Jae-Jun Shim, Bo Hwa Sohn, Ju-Seog Lee
59 Epidemiology of Liver Cancer
Hashem B. El-Serag
60 Mutations and Genomic Alterations in Liver Cancer
Jessica Zucman-Rossi, Jean-Charles Nault
61 Treatment of Liver Cancer
Tim F. Greten
Part 6: Hepatitis
62 Molecular Biology of Hepatitis Viruses
Christoph Seeger, William S. Mason, Michael M.C. Lai
63 Immune Mechanisms of Viral Clearance and Disease Pathogenesis during Viral Hepatitis
Carlo Ferrari, Valeria Barili, Stefania Varchetta, Mario U. Mondelli
64 Clinical Implications of the Molecular Biology of Hepatitis B Virus
Timothy M. Block, Ju-Tao Guo, W. Thomas London
65 Viral Escape Mechanisms in Hepatitis C and the Clinical Consequences of Persistent Infection
Marc G. Ghany, Christopher M. Walker, Patrizia Farci
66 Tracking Hepatitis C Virus Interactions with the Hepatic Lipid Metabolism: A hitchhiker´s guide to solve remaining translational research challenges in hepatitis C
Thomas Pietschmann, Gabrielle Vieyres
67 Nucleoside Antiviral Agents for HCV: What’s left to do?
Franck Amblard, Seema Mengshetti, Junxing Shi, Sijia Tao, Leda Bassit, Raymond F. Schinazi
68 Hepatitis E Virus: An emerging zoonotic virus causing acute and chronic liver disease
Xiang-Jin Meng
69 Biological Principles and Clinical Issues Underlying Liver Transplantation for Viral-Induced End-stage Liver Disease in the Era of Highly Effective Direct-Acting Antiviral Agents
Michael S. Kriss, James R. Burton, Jr., Hugo R. Rosen
70 Time for the Elimination of Hepatitis C Virus as a Global Health Threat
John W. Ward, Alan R. Hinman, Harvey J. Alter
Part 7: Horizons
H1 Genome Editing by Targeted Nucleases and the CRISPR/Cas Revolution
Shawn M. Burgess
H2 Imaging Cellular Proteins and Structures: Smaller, Brighter, and Faster
Aubrey V. Weigel, Erik Lee Snapp
H3 Liver-directed Gene Therapy
Patrik Asp, Chandan Guha, Namita Roy Chowdhury, Jayanta Roy Chowdhury
H4 Telomeres and Telomerase in Liver Generation and Cirrhosis
Sonja C. Schätzlein, K. Lenhard Rudolph
H5 Toxins and Biliary Atresia
Michael Pack, Rebecca G. Wells
H6 The Dual Role of ABC Transporters in Drug Metabolism and Resistance to Chemotherapy
Jean-Pierre Gillet, Marielle Boonen, Michel Jadot, Michael M. Gottesman
H7 Stem-cell-derived Liver Cells: From model system to therapy
Helmuth Gehart, Hans Clevers
H8 Extracellular Vesicles and Exosomes: Biology and pathobiology
Gyongyi Szabo, Fatemeh Momen-Heravi
H9 Integrated Technologies for Liver Tissue Engineering
Tiffany N. Vo, Amanda X. Chen, Quinton B. Smith, Arnav Chhabra, Sangeeta N. Bhatia
H10 Stem Cells, IPS Cells, Reprogramming: Therapy promise
Stephen A. Duncan
H11 Chromatin Regulation and Transcription Factor Cooperation in Liver Cells
Ido Goldstein
H12 Drug Interactions in the Liver
Guruprasad P. Aithal, Gerd A. Kullak-Ublick
H13 Metabolic Regulation of Hepatic Growth
Wolfram Goessling
H14 The Gut Microbiome and Liver Disease
Lexing Yu, Jasmohan S. Baja, Robert F. Schwabe
H15 Lineage Tracing: Efficient tools to determine the fate of hepatic cells in health and disease
Frédéric Lemaigre
H16 The Hepatocyte as a Household for Plasmodium Parasites
Vanessa Zuzarte-Luis, Maria M. Mota
Index
IRWIN M. ARIAS, MD, National Institutes of Health, Bethesda, Maryland, USA.
HARVEY J. ALTER, MD, National Institutes of Health, Bethesda, Maryland, USA.
JAMES L. BOYER, MD, Yale University School of Medicine, New Haven, Connecticut, USA.
DAVID E. COHEN, MD, Weill Cornell Medical College, New York, USA.
DAVID A. SHAFRITZ, MD, Albert Einstein College of Medicine, New York, USA.
SNORRI S. THORGEIRSSON, MD, National Institutes of Health, Bethesda, Maryland, USA.
ALLAN W. WOLKOFF, MD, Albert Einstein College of Medicine, New York, USA.
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