| Preface |
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xv | |
| Contributors |
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xvii | |
| Abbreviations |
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xxi | |
| Introduction: The Paradigm and Paradox of Liver Autoimmunity |
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1 | (2) |
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| Section I Scientific Basis of Clinical Autoimmune Liver Diseases |
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3 | (100) |
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1 Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree |
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5 | (16) |
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5 | (1) |
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Liver Cell Types and Organization |
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6 | (1) |
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7 | (2) |
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Bilirubin Metabolism and Transport |
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7 | (1) |
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7 | (1) |
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8 | (1) |
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8 | (1) |
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8 | (1) |
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Hepatic Transport Systems |
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9 | (2) |
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Basolateral (Sinusoidal) Transporters |
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9 | (2) |
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Apical (Canalicular) Transporters |
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11 | (1) |
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11 | (1) |
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Bile Formation, Secretion and the Enterohepatic Circulation |
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12 | (2) |
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Bile Acid Synthesis and Metabolism |
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13 | (1) |
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Enterohepatic Bile Acid Circulation |
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13 | (1) |
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Death and Regeneration of Hepatocytes |
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14 | (2) |
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14 | (1) |
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15 | (1) |
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Cholangiocyte Reaction to Biliary Damage |
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16 | (1) |
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Protective Role of Biliary HCO3- Secretion |
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16 | (1) |
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Cholangiocytes and Immunity |
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16 | (1) |
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Biochemical Markers and Patterns of Hepatic Injury |
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17 | (3) |
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18 | (1) |
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18 | (2) |
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20 | (1) |
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2 Concepts of Autoimmunity Relevant to Autoimmune Liver Diseases |
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21 | (26) |
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21 | (1) |
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22 | (1) |
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Role of Innate and Adaptive Immunity in Autoimmunity in the Context of the Liver as an Immune Organ |
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22 | (6) |
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22 | (1) |
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23 | (2) |
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Liver as an Innate Immune Organ |
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25 | (1) |
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Adaptive Immunity and Adaptive Immune Functions of the Liver |
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25 | (3) |
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Role of the Liver as an Adaptive Immune Organ |
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28 | (1) |
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Generation and Maintenance of Tolerance to Self-antigens |
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28 | (3) |
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28 | (1) |
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29 | (1) |
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29 | (1) |
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29 | (1) |
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30 | (1) |
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T- and B-cell-Clonal Anergy |
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30 | (1) |
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T-cell Mediated Immune Regulation |
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30 | (1) |
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Natural and Inducible T Regulatory Cells |
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30 | (1) |
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Peripheral B-cell Regulatory Mechanisms |
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31 | (1) |
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Regulatory Dendritic Cells |
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31 | (1) |
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Immunoregulatory Interplay Between Treg and Th17 Cells |
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31 | (1) |
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Risk Factors for Autoimmune Diseases |
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31 | (3) |
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31 | (1) |
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Complex Genetic and Monogenic Diseases |
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31 | (1) |
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32 | (1) |
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Non-HLA Gene Associations |
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32 | (1) |
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Critical Role of Epigenetics |
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33 | (1) |
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Transcription Factor Enhancers and Super Enhancers |
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33 | (1) |
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33 | (1) |
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33 | (1) |
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Vitamin D and Sunlight Exposure |
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34 | (1) |
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Loss of Immune Tolerance to Autoantigens and Perpetuation of Autoimmune Diseases |
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34 | (5) |
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34 | (1) |
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35 | (1) |
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Mechanisms of Loss of Tolerance to Autoantigens |
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35 | (1) |
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Bacterial and Viral Infections |
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35 | (1) |
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Molecular Mimicry of Autoantigens |
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36 | (1) |
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36 | (1) |
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Failure of Apoptosis to Conceal Autoantigens and Eliminate Autoreactive Cells |
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36 | (1) |
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Immune Deviation of Activated T Cells |
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37 | (1) |
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T-cell Receptor Revision in the Periphery |
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37 | (1) |
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Perpetuation of Autoimmune Diseases |
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37 | (1) |
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37 | (1) |
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38 | (1) |
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38 | (1) |
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Cytokines Promoting Chronic Inflammation and Autoimmunity |
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38 | (1) |
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Tertiary Lymphoid Structures and Germinal Centers |
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39 | (1) |
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Epithelial Cell-induced Transformation of iTreg to Th17 Cells |
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39 | (1) |
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Prevention of Autoimmunity and Therapeutic Control of Autoimmune Diseases |
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39 | (5) |
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39 | (1) |
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Strategies to Prevent Autoimmunity |
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39 | (1) |
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39 | (1) |
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Gut Microbiota Manipulation in Pregnancy and Infancy |
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39 | (1) |
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39 | (1) |
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Strategies to Treat Established Autoimmune Diseases |
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40 | (1) |
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Inducible T Regulatory T Cells |
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40 | (1) |
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Epigenetic Enhancer Regulation |
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40 | (4) |
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44 | (3) |
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3 Genetics and Risk of Autoimmune Liver Diseases |
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47 | (18) |
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47 | (1) |
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48 | (2) |
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HLA Associations in Autoimmune Liver Disease |
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50 | (3) |
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Non-HLA Associations in Autoimmune Liver Disease |
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53 | (8) |
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61 | (1) |
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62 | (3) |
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4 Autoantibodies and Understanding of Autoimmune Liver Diseases |
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65 | (18) |
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Benedetto Terziroli Beretta-Piccoli |
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65 | (1) |
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66 | (1) |
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66 | (2) |
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68 | (5) |
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68 | (1) |
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Immunofluorescence Reactivities and Antigenic Targets |
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68 | (2) |
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Clinical Significance in Autoimmune Liver Disease |
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70 | (3) |
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Anti-smooth Muscle and Anti-actin Antibodies |
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73 | (1) |
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73 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance |
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73 | (1) |
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Anti-liver-kidney Microsomal Antibody |
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74 | (2) |
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74 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance |
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75 | (1) |
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Anti-liver Cytosol Type 1 Antibody |
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76 | (1) |
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76 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance |
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76 | (1) |
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Anti-soluble Liver Antigen Antibody |
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76 | (1) |
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76 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance |
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77 | (1) |
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Anti-neutrophil Cytoplasmic Antibody |
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77 | (1) |
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77 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance |
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77 | (1) |
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Anti-mitochondrial Antibody |
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78 | (1) |
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78 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance |
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78 | (1) |
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Anti-asialoglycoprotein Receptor Antibody |
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79 | (1) |
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79 | (1) |
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Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance |
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79 | (1) |
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Indications for Autoimmune Liver Serology Testing |
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79 | (2) |
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81 | (1) |
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82 | (1) |
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5 Environmental Exposure and Risk in Autoimmune Liver Diseases |
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83 | (20) |
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83 | (1) |
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84 | (1) |
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84 | (5) |
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Interaction of Genes and Environmental Triggers in Autoimmunity |
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85 | (1) |
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Mechanisms for Triggering Autoimmunity |
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86 | (3) |
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Primary Biliary Cholangitis |
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89 | (10) |
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Geo-epidemiology, Clusters, and Case-Control Studies of PBC |
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92 | (1) |
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Bacterial Infection and PBC |
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93 | (3) |
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96 | (1) |
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97 | (2) |
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99 | (2) |
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101 | (1) |
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102 | (1) |
| Section II Autoimmune Liver Diseases and Their Clinical Correlation |
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103 | (78) |
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105 | (18) |
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105 | (1) |
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106 | (1) |
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Definition and Pathophysiology |
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106 | (1) |
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107 | (1) |
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108 | (1) |
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108 | (1) |
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109 | (1) |
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109 | (3) |
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Autoimmune Sclerosing Cholangitis |
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112 | (1) |
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112 | (4) |
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Therapeutic Approach in Adults |
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113 | (1) |
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113 | (1) |
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114 | (1) |
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114 | (1) |
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Therapeutic Approach in Children |
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115 | (1) |
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115 | (1) |
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115 | (1) |
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115 | (1) |
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116 | (2) |
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116 | (1) |
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116 | (2) |
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118 | (5) |
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7 Primary Biliary Cholangitis |
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123 | (20) |
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123 | (1) |
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Introduction and Definition |
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124 | (1) |
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124 | (1) |
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125 | (1) |
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126 | (1) |
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126 | (1) |
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126 | (1) |
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127 | (3) |
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127 | (1) |
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128 | (1) |
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128 | (2) |
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130 | (1) |
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130 | (1) |
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130 | (1) |
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Disease Course in the UDCA Era |
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131 | (1) |
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132 | (2) |
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134 | (5) |
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134 | (1) |
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135 | (1) |
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136 | (1) |
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137 | (1) |
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137 | (1) |
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137 | (2) |
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Complications of Liver Disease |
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139 | (2) |
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139 | (1) |
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140 | (1) |
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140 | (1) |
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140 | (1) |
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141 | (1) |
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141 | (2) |
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8 Primary Sclerosing Cholangitis |
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143 | (20) |
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Benedetta Terziroli Beretta-Piccoli |
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143 | (1) |
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144 | (1) |
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145 | (1) |
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145 | (10) |
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145 | (1) |
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146 | (1) |
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Diagnosis of Variant Phenotypes |
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147 | (1) |
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147 | (2) |
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149 | (1) |
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149 | (1) |
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150 | (1) |
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150 | (1) |
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150 | (1) |
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Risk Stratification: Clinical Characteristics |
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150 | (1) |
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151 | (1) |
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151 | (1) |
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Non-invasive Evaluation of Fibrosis |
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151 | (1) |
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152 | (1) |
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152 | (1) |
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153 | (1) |
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153 | (1) |
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Anti-inflammatory Treatment |
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154 | (1) |
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154 | (1) |
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154 | (1) |
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Surveillance for Malignancy |
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154 | (1) |
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Colorectal Cancer: Colonoscopy |
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155 | (1) |
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Gallbladder Cancer: Ultrasound |
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155 | (1) |
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Hepatocellular Cancer: Ultrasound |
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155 | (1) |
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155 | (1) |
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155 | (1) |
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Juvenile Sclerosing Cholangitis |
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155 | (4) |
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Epidemiology in Pediatric Disease |
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155 | (1) |
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Autoimmune Sclerosing Cholangitis |
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156 | (1) |
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156 | (2) |
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Clinical Features in Pediatric Disease |
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158 | (1) |
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Treatment of Pediatric Disease (ASC and Juvenile PSC) |
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158 | (1) |
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Prognosis in Pediatric Disease |
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159 | (1) |
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159 | (1) |
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160 | (3) |
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9 IgG4-Related Liver and Biliary Disease |
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163 | (18) |
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163 | (1) |
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Introduction and Historical Perspective |
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164 | (1) |
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Etiology and Pathogenesis of IgG4-RD |
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165 | (2) |
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Development and Characteristics of an IgG |
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G4 | |
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165 | (1) |
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Antigens That May Drive an IgG4-RD Response |
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166 | (1) |
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IgG4 Antibodies and Pathogenesis |
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167 | (1) |
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Incidence and Prevalence of IgG4-RD |
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167 | (1) |
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Clinical Characteristics of IgG4-related Hepatobiliary Disease |
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168 | (1) |
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168 | (1) |
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Disease Outside the Hepatobiliary System |
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168 | (1) |
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Diagnostic Criteria, Histologic Features, and Approach to Diagnosis of IgG4-related Hepatobiliary Disease |
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168 | (5) |
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Diagnostic Criteria for AIP and IgG4-RD |
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168 | (2) |
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Histologic Diagnosis of IgG4-related Hepatobiliary Disease |
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170 | (1) |
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Utility of Blood Tests, Including Serum IgG4 Levels in IgG4-RD Diagnostics |
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171 | (1) |
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Common Alternative Diagnoses to Consider |
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172 | (1) |
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Radiologic Characteristics of Hepatobiliary IgG4-RD |
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173 | (1) |
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IgG4-RD and Relationship with Malignancy |
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173 | (1) |
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Management and Treatment of Patients with IgG4-RD |
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174 | (1) |
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175 | (1) |
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Conclusions and Future Directions |
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175 | (2) |
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177 | (4) |
| Section III Specific Clinical Challenges |
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181 | (52) |
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10 Managing Acute and Chronic Seronegative Liver Disease |
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183 | (18) |
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183 | (1) |
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184 | (1) |
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An Approach to Seronegative Acute Liver Failure |
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184 | (1) |
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Potential Causes of Seronegative ALF and Features that Suggest an Autoimmune Pathogenesis |
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185 | (3) |
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Clinical Features of Seronegative ALF |
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188 | (1) |
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Risk Stratification in Seronegative ALF |
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188 | (1) |
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Management of Seronegative ALF |
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189 | (3) |
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190 | (1) |
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190 | (1) |
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Emergency Liver Transplantation |
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191 | (1) |
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An Approach to Cryptogenic Chronic Liver Disease |
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192 | (5) |
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Potential Causes of Seronegative Chronic Liver Disease and Features that Suggest an Autoimmune Pathogenesis |
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192 | (2) |
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Non-alcoholic Fatty Liver Disease |
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194 | (1) |
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194 | (1) |
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Seronegative Autoimmune Hepatitis |
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195 | (2) |
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Seronegative Primary Biliary Cholangitis |
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197 | (1) |
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197 | (1) |
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198 | (3) |
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11 Managing Pregnant Women with Autoimmune Liver Disease |
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201 | (18) |
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201 | (1) |
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202 | (1) |
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202 | (1) |
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Pregnancy Outcomes in AIH |
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202 | (4) |
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Liver-related Outcomes in Pregnancy |
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206 | (3) |
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209 | (1) |
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Safety of Medication in Pregnancy |
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210 | (3) |
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213 | (1) |
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214 | (5) |
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12 Bone Health in Patients with Autoimmune Liver Diseases |
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219 | (14) |
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219 | (1) |
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220 | (2) |
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Prevalence of Osteoporosis and Fractures |
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222 | (2) |
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Primary Biliary Cholangitis |
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222 | (1) |
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Primary Sclerosing Cholangitis |
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223 | (1) |
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223 | (1) |
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224 | (2) |
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Assessment of Bone Disease |
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226 | (1) |
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Prevention and Treatment of Bone Loss |
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227 | (3) |
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227 | (1) |
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227 | (1) |
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227 | (1) |
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229 | (1) |
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230 | (1) |
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231 | (2) |
| Section IV Transplantation and Its Role in Autoimmune Liver Disease |
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233 | (30) |
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13 Recurrent Autoimmune Liver Disease and Its Impact on Clinical Practice |
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235 | (12) |
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Carlos Moctezuma-Velazquez |
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235 | (1) |
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236 | (1) |
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Primary Biliary Cholangitis |
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236 | (3) |
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Recurrence of PBC After LT |
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236 | (1) |
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Diagnosis of PBC After LT |
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236 | (1) |
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Risk Factors Associated with PBC Recurrence After LT |
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237 | (1) |
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Treatment of PBC Recurrence After LT |
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238 | (1) |
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Prognostic Impact of PBC Recurrence After LT |
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239 | (1) |
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Primary Sclerosing Cholangitis |
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239 | (2) |
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Recurrence of PSC After LT |
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240 | (1) |
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Diagnosis of Recurrence of PSC After LT |
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240 | (1) |
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Risk Factors Associated with PSC Recurrence After LT |
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240 | (1) |
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Treatment of PSC Recurrence After LT |
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241 | (1) |
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Prognostic Impact of PSC Recurrence After LT |
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241 | (1) |
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241 | (2) |
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Recurrence of AIH After LT |
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242 | (1) |
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Risk Factors Associated with AIH Recurrence After LT |
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242 | (1) |
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Treatment of AIH Recurrence After LT |
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243 | (1) |
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Prognostic Impact of AIH Recurrence After LT |
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243 | (1) |
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243 | (1) |
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244 | (3) |
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14 Recurrent Autoimmune Liver Disease and its Scientific Significance |
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247 | (16) |
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247 | (1) |
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247 | (1) |
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248 | (3) |
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Incidence and Diagnosis of Recurrent PBC |
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249 | (1) |
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Risk Factors of Recurrent PBC |
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250 | (1) |
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Impact of Recurrent PBC on Long-term Outcomes |
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250 | (1) |
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251 | (3) |
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Incidence and Diagnosis of Recurrent PSC |
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252 | (1) |
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Risk Factors of Recurrent PSC |
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253 | (1) |
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Impact of Recurrent PSC on Long-term Outcomes |
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254 | (1) |
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254 | (2) |
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Incidence and Diagnosis of Recurrent AIH |
|
|
254 | (1) |
|
Risk Factors of Recurrent AIH |
|
|
255 | (1) |
|
Impact of Recurrent AIH on Long-term Outcomes |
|
|
255 | (1) |
|
|
|
256 | (1) |
|
|
|
257 | (6) |
| Section V Controversies in Autoimmune Liver Diseases |
|
263 | (38) |
|
15 Making Sense of Overlap and Crossover Syndromes |
|
|
265 | (12) |
|
|
|
|
|
265 | (1) |
|
|
|
266 | (1) |
|
|
|
267 | (2) |
|
|
|
268 | (1) |
|
|
|
269 | (1) |
|
|
|
269 | (1) |
|
|
|
269 | (3) |
|
|
|
272 | (1) |
|
|
|
273 | (1) |
|
|
|
274 | (1) |
|
|
|
275 | (2) |
|
16 The Role of Extrahepatic Autoimmunity in Autoimmune Liver Disease |
|
|
277 | (12) |
|
|
|
|
|
|
|
277 | (1) |
|
|
|
278 | (1) |
|
|
|
278 | (1) |
|
Autoimmune Thyroid Disease |
|
|
279 | (1) |
|
|
|
279 | (1) |
|
|
|
280 | (1) |
|
Systemic Lupus Erythematosus |
|
|
281 | (1) |
|
|
|
282 | (1) |
|
|
|
283 | (1) |
|
Inflammatory Bowel Disease |
|
|
284 | (2) |
|
|
|
286 | (1) |
|
Guidelines for Clinicians |
|
|
287 | (1) |
|
|
|
288 | (1) |
|
17 Symptoms, Chronic Disease, and Patient Management |
|
|
289 | (12) |
|
|
|
|
|
289 | (1) |
|
|
|
290 | (1) |
|
|
|
290 | (1) |
|
Symptoms, Quality of Life, and Health Utility: Key Concepts |
|
|
291 | (1) |
|
|
|
291 | (1) |
|
Health-related Quality of Life |
|
|
292 | (1) |
|
|
|
292 | (1) |
|
Symptoms and Their Management in AILD |
|
|
292 | (7) |
|
Impact of Disease-modifying Therapy on Symptoms in AILD |
|
|
292 | (1) |
|
Stage-associated Symptoms |
|
|
293 | (1) |
|
Stage-independent Symptoms |
|
|
293 | (1) |
|
|
|
293 | (1) |
|
Fatigue and Cognitive Symptoms |
|
|
295 | (1) |
|
Social Isolation Symptoms |
|
|
298 | (1) |
|
Effective Care Delivery in AILD |
|
|
299 | (1) |
|
|
|
300 | (1) |
| Index |
|
301 | |