The Liver

List of Contributors x Preface xx Acknowledgments xxi Part One: Introduction 1 1 Organizational Principles of the Liver 3 Peter Nagy, Snorri S. Thorgeirsson, and Joe W. Grisham 2 Embryonic Development of the Liver 14 Kenneth S. Zaret, Roque Bort, and Stephen A. Duncan Part Two: The Cells 23 Section A: Cell Biology of the Liver 25 3 Cytoskeletal Motors: Structure and Function in Hepatocytes 27 Mukesh Kumar, Arnab Gupta, and Roop Mallik 4 Hepatocyte Surface Polarity 36 Anne Müsch and Irwin M. Arias 5 Primary Cilia 50 Carolyn M. Ott 6 Endocytosis in Liver Function and Pathology 62 Micah B. Schott, Barbara Schroeder, and Mark A. McNiven 7 The Hepatocellular Secretory Pathway 75 Catherine L. Jackson and Mark A. McNiven 8 Mitochondrial Function, Dynamics, and Quality Control 86 Marc Liesa, Ilan Benador, Nathanael Miller, and Orian S. Shirihai 9 Nuclear Pore Complex 94 Michelle A. Veronin and Joseph S. Glavy 10 Protein Maturation and Processing at the Endoplasmic Reticulum 108 Ramanujan S. Hegde 11 Protein Degradation and the Lysosomal System 122 Susmita Kaushik and Ana Maria Cuervo 12 Peroxisome Assembly, Degradation, and Disease 137 Rong Hua and Peter K. Kim 13 Organelle-Organelle Contacts: Origins and Functions 151 Uri Manor 14 Gap and Tight Junctions in Liver: Structure, Function, and Pathology 160 John W. Murray and David C. Spray 15 Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the Liver 174 Katherine I. Farley-Barnes and Susan J. Baserga 16 miRNAs and Hepatocellular Carcinoma 183 Yusuke Yamamoto, Isaku Kohama, and Takahiro Ochiya 17 Hepatocyte Apoptosis: Mechanisms and Relevance in Liver Diseases 195 Harmeet Malhi and Gregory J. Gores Section B: The Hepatocyte 207 18 Copper Metabolism and the Liver 209 Cynthia Abou Zeid, Ling Yi, and Stephen G. Kaler 19 The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis 215 Tracey A. Rouault, Victor R. Gordeuk, and Gregory J. Anderson 20 Disorders of Bilirubin Metabolism 229 Namita Roy Chowdhury, Yanfeng Li, and Jayanta Roy Chowdhury 21 Hepatic Lipid Droplets in Liver Function and Disease 245 Douglas G. Mashek, Wenqi Cui, Linshan Shang, and Charles P. Najt 22 Lipoprotein Metabolism and Cholesterol Balance 255 Mariana Acuña-Aravena and David E. Cohen Section C: Transporters, Bile Acids, and Cholestasis 269 23 Bile Acid Metabolism in Health and Disease: An Update 271 Tiangang Li and John Y.L. Chiang 24 TGR5 (GPBAR1) in the Liver 286 Verena Keitel, Christoph G.W. Gertzen, Lina Spomer, Holger Gohlke, and Dieter Häussinger 25 Bile Acids as Signaling Molecules 299 Thierry Claudel and Michael Trauner 26 Hepatic Adenosine Triphosphate-Binding Cassette Transport Proteins and Their Role in Physiology 313 Peter L.M. Jansen 27 Basolateral Plasma Membrane Organic Anion Transporters 327 M. Sawkat Anwer and Allan W. Wolkoff 28 Hepatic Nuclear Receptors 337 Raymond E. Soccio 29 Molecular Cholestasis 351 Paul Gissen and Richard J. Thompson 30 Pathophysiologic Basis for Alternative Therapies for Cholestasis 364 Claudia D. Fuchs, Emina Halilbasic, and Michael Trauner 31 Adaptive Regulation of Hepatocyte Transporters in Cholestasis 378 James L. Boyer Section D: Non-Hepatocyte Cells 391 32 Cholangiocyte Biology and Pathobiology 393 Massimiliano Cadamuro, Romina Fiorotto, and Mario Strazzabosco 33 Polycystic Liver Diseases: Genetics, Mechanisms, and Therapies 408 Tatyana Masyuk, Anatoliy Masyuk, and Nicholas LaRusso 34 The Liver Sinusoidal Endothelial Cell: Basic Biology and Pathobiology 422 Karen K. Sørensen and Bård Smedsrød 35 Fenestrations in the Liver Sinusoidal Endothelial Cell 435 Victoria C. Cogger, Nicholas J. Hunt, and David G. Le Couteur 36 Stellate Cells and Fibrosis 444 Youngmin A. Lee and Scott L. Friedman Part Three: Functions of The Liver 455 Section A: Metabolic Functions 457 37 Non-alcoholic Fatty Liver Disease and Insulin Resistance 459 Max C. Petersen, Varman T. Samuel, Kitt Falk Petersen, and Gerald I. Shulman 38 AMPK: Central Regulator of Glucose and Lipid Metabolism and Target of Type 2 Diabetes Therapeutics 472 Daniel Garcia, Maria M. Mihaylova, and Reuben J. Shaw 39 Insulin-Mediated PI3K and AKT Signaling 485 Hyokjoon Kwon and Jeffrey E. Pessin 40 Ca¯2+ Signaling in the Liver 496 Mateus T. Guerra, M. Fatima Leite, and Michael H. Nathanson 41 Clinical Genomics of NAFLD 509 Frank Lammert Section B: Liver Growth and Regeneration 521 42 Stem Cell-Fueled Maturational Lineages in Hepatic and Pancreatic Organogenesis 523 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, and Lola Reid 43 Developmental Morphogens and Adult Liver Repair 539 Mariana Verdelho Machado and Anna Mae Diehl 44 Liver Repopulation by Cell Transplantation and the Role of Stem Cells in Liver Biology 550 David A. Shafritz and Markus Grompe 45 Liver Regeneration 566 George K. Michalopoulos 46 ß-Catenin Signaling 585 Satdarshan P.S. Monga 47 Polyploidy in Liver Function, Mitochondrial Metabolism, and Cancer 603 Evan R. Delgado, Elizabeth C. Stahl, Nairita Roy, Patrick D. Wilkinson, and Andrew W. Duncan Part Four: Pathobiology of Liver Disease 615 48 Hepatic Encephalopathy 617 Roger F. Butterworth 49 The Kidney in Liver Disease 630 Moshe Levi, Shogo Takahashi, Xiaoxin X. Wang, and Marilyn E. Levi 50 alpha1-Antitrypsin Deficiency 645 David A. Rudnick and David H. Perlmutter 51 Pathophysiology of Portal Hypertension 659 Yasuko Iwakiri and Roberto J. Groszmann 52 Non-alcoholic Fatty Liver Disease: Mechanisms and Treatment 670 Yaron Rotman and Devika Kapuria 53 Alcoholic Liver Disease 682 Bin Gao, Xiaogang Xiang, Lorenzo Leggio, and George F. Koob 54 Drug-Induced Liver Injury 701 Lily Dara and Neil Kaplowitz 55 Oxidative Stress and Inflammation in the Liver 714 John J. Lemasters and Hartmut Jaeschke 56 The Role of Bile Acid-Mediated Inflammation in Cholestatic Liver Injury 728 Shi-Ying Cai, Man Li, and James L. Boyer 57 Toll-like Receptors in Liver Disease 737 So Yeon Kim and Ekihiro Seki Part Five: Liver Cancer 747 58 Experimental Models of Liver Cancer: Genomic Assessment of Experimental Models 749 Sun Young Yim, Jae-Jun Shim, Bo Hwa Sohn, and Ju-Seog Lee 59 Epidemiology of Hepatocellular Carcinoma 758 Hashem B. El-Serag 60 Mutations and Genomic Alterations in Liver Cancer 773 Jessica Zucman-Rossi and Jean-Charles Nault 61 Treatment of Liver Cancer 782 Tim F. Greten Part Six: Hepatitis 793 62 Molecular Biology of Hepatitis Viruses 795 Christoph Seeger, William S. Mason, and Michael M.C. Lai 63 Immune Mechanisms of Viral Clearance and Disease Pathogenesis During Viral Hepatitis 821 Carlo Ferrari, Valeria Barili, Stefania Varchetta, and Mario U. Mondelli 64 Clinical Implications of the Molecular Biology of Hepatitis B Virus 851 Timothy M. Block, Ju-Tao Guo, and W. Thomas London 65 Viral Escape Mechanisms in Hepatitis C and the Clinical Consequences of Persistent Infection 868 Marc G. Ghany, Christopher M. Walker, and 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 889 Gabrielle Vieyres and Thomas Pietschmann 67 Nucleoside Antiviral Agents for HCV: What's Left to Do? 906 Franck Amblard, Seema Mengshetti, Junxing Shi, Sijia Tao, Leda Bassit, and Raymond F. Schinazi 68 Hepatitis E Virus: An Emerging Zoonotic Virus Causing Acute and Chronic Liver Disease 915 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 926 Michael S. Kriss, James R. Burton, Jr., and Hugo R. Rosen 70 Time for the Elimination of Hepatitis C Virus as a Global Health Threat 935 John W. Ward, Alan R. Hinman, and Harvey J. Alter Part Seven: Horizons 953 71 Genome Editing by Targeted Nucleases and the CRISPR/Cas Revolution 955 Shawn M. Burgess 72 Imaging Cellular Proteins and Structures: Smaller, Brighter, and Faster 965 Aubrey V. Weigel and Erik Lee Snapp 73 Liver-Directed Gene Therapy 979 Patrik Asp, Chandan Guha, Namita Roy Chowdhury, and Jayanta Roy Chowdhury 74 Telomeres and Telomerase in Liver Generation and Cirrhosis 992 Sonja C. Schätzlein and K. Lenhard Rudolph 75 Toxins and Biliary Atresia 1000 Michael Pack and Rebecca G. Wells 76 The Dual Role of ABC Transporters in Drug Metabolism and Resistance to Chemotherapy 1007 Jean-Pierre Gillet, Marielle Boonen, Michel Jadot, and Michael M. Gottesman 77 Stem Cell-Derived Liver Cells: From Model System to Therapy 1015 Helmuth Gehart and Hans Clevers 78 Extracellular Vesicles and Exosomes: Biology and Pathobiology 1022 Gyongyi Szabo and Fatemeh Momen-Heravi 79 Integrated Technologies for Liver Tissue Engineering 1028 Tiffany N. Vo, Amanda X. Chen, Quinton B. Smith, Arnav Chhabra and Sangeeta N. Bhatia 80 Pluripotent Stem Cells and Reprogramming: Promise for Therapy 1036 James A. Heslop and Stephen A. Duncan 81 Chromatin Regulation and Transcription Factor Cooperation in Liver Cells 1043 Ido Goldstein 82 Drug Interactions in the Liver 1050 Guruprasad P. Aithal and Gerd A. Kullak-Ublick 83 Metabolic Regulation of Hepatic Growth 1058 Wolfram Goessling 84 The Gut Microbiome and Liver Disease 1062 Lexing Yu, Jasmohan S. Bajaj, and Robert F. Schwabe 85 Lineage Tracing: Efficient Tools to Determine the Fate of Hepatic Cells in Health and Disease 1069 Frédéric Lemaigre 86 The Hepatocyte as a Household for Plasmodium Parasites 1075 Vanessa Zuzarte-Luis and Maria M. Mota Index 1081