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A practical guide to autoimmune liver diseases through pathogenesis, diagnosis, and management
In Autoimmune Liver Disease Management and Clinical Practice, practitioners will learn about the current state of autoimmune liver disease and how to focus on their diagnosis and treatment. The four-part book begins with a thorough investigation of current immunological thinking as it relates to the autoimmunity of the liver. It also covers the four major hepatic autoimmune liver diseases in both adults and children, their management and the role of liver transplantation, and learned approaches to patient management and empowerment.
Expert authors in the field have come together to provide a thorough examination of autoimmune liver disease to help support clinicians assisting patients. The text provides an in-depth look at topics including:
● The four major hepatic autoimmune liver diseases, their diagnosis, and potential disease management
● The use (and misuse) of autoantibodies in diagnosis and treatment
● The role and timing of liver transplantation and the impact of recurrent autoimmune liver disease as well as de novo autoimmune hepatitis
● Optimal approaches to managing patients and keeping care personalised
With breadth, depth and current-day relevance, Autoimmune Liver Disease sheds light on recent developments in management of liver disease for practitioners, nurses, and health care professionals.

-도서목차-

Preface xv
Contributors xvii
Abbreviations xxi
Introduction: The Paradigm and Paradox of Liver Autoimmunity 1
M. Eric Gershwin
Section I Scientific Basis of Clinical Autoimmune Liver Diseases 3
1 Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree 5
Marco Carbone and Mario Strazzabosco
Key Points 5
Liver Cell Types and Organization 6
Hepatic Metabolism 7
Bilirubin Metabolism and Transport 7
Carbohydrate Metabolism 7
Lipid Metabolism 8
Protein Metabolism 8
Metabolic Zonation 8
Hepatic Transport Systems 9
Basolateral (Sinusoidal) Transporters 9
Apical (Canalicular) Transporters 11
Drug Metabolism 11
Bile Formation, Secretion and the Enterohepatic Circulation 12
Bile Acid Synthesis and Metabolism 13
Enterohepatic Bile Acid Circulation 13
Death and Regeneration of Hepatocytes 14
Cell Death 14
Liver Regeneration 15
Cholangiocyte Reaction to Biliary Damage 16
Protective Role of Biliary HCO3 − Secretion 16
Cholangiocytes and Immunity 16
Biochemical Markers and Patterns of Hepatic Injury 17
Hepatocellular Necrosis 18
Cholestasis 18
References 20
2 Concepts of Autoimmunity Relevant to Autoimmune Liver Diseases 21
Isaiah G. Roepe and John M. Vierling
Key Points 21
Introduction 22
Role of Innate and Adaptive Immunity in Autoimmunity in the Context of the Liver as an Immune Organ 22
Overview 22
Innate Immunity 23
Liver as an Innate Immune Organ 25
Adaptive Immunity and Adaptive Immune Functions of the Liver 25
Role of the Liver as an Adaptive Immune Organ 28
Generation and Maintenance of Tolerance to Self‐antigens 28
Overview 28
Central Tolerance 29
Central T‐cell Tolerance 29
Central B‐cell Tolerance 29
Peripheral Tolerance 30
T‐ and B‐cell Clonal Anergy 30
T‐cell Mediated Immune Regulation 30
Natural and Inducible T Regulatory Cells 30
Peripheral B‐cell Regulatory Mechanisms 31
Regulatory Dendritic Cells 31
Immunoregulatory Interplay Between Treg and Th17 Cells 31
Risk Factors for Autoimmune Diseases 31
Genetics 31
Complex Genetic and Monogenic Diseases 31
HLA Risk Alleles 32
Non‐HLA Gene Associations 32
Critical Role of Epigenetics 33
Transcription Factor Enhancers and Super Enhancers 33
MicroRNAs 33
Sex and Sex Hormones 33
Vitamin D and Sunlight Exposure 34
Loss of Immune Tolerance to Autoantigens and Perpetuation of Autoimmune Diseases 34
Overview 34
Role of the Microbiome 35
Mechanisms of Loss of Tolerance to Autoantigens 35
Bacterial and Viral Infections 35
Molecular Mimicry of Autoantigens 36
Neoantigens 36
Failure of Apoptosis to Conceal Autoantigens and Eliminate Autoreactive Cells 36
Immune Deviation of Activated T Cells 37
T‐cell Receptor Revision in the Periphery 37
Perpetuation of Autoimmune Diseases 37
Epigenetics 37
Epitope Spreading 38
Tissue Memory T Cells 38
Cytokines Promoting Chronic Inflammation and Autoimmunity 38
Tertiary Lymphoid Structures and Germinal Centers 39
Epithelial Cell‐induced Transformation of iTreg to Th17 Cells 39
Prevention of Autoimmunity and Therapeutic Control of Autoimmune Diseases 39
Overview 39
Strategies to Prevent Autoimmunity 39
Vitamin D3 39
Gut Microbiota Manipulation in Pregnancy and Infancy 39
Oral Tolerance 39
Strategies to Treat Established Autoimmune Diseases 40
Inducible T Regulatory T Cells 40
Epigenetic Enhancer Regulation 40
References 44
3 Genetics and Risk of Autoimmune Liver Diseases 47
George F. Mells
Key Points 47
Introduction 48
HLA Associations in Autoimmune Liver Disease 50
Non‐HLA Associations in Autoimmune Liver Disease 53
Conclusion 61
References 62
4 Autoantibodies and Understanding of Autoimmune Liver Diseases 65
Benedetta Terziroli Beretta‐Piccoli, Giorgina Mieli‐Vergani, and Diego Vergani
Key Points 65
Introduction 66
Methods of Detection 66
Anti‐nuclear Antibody 68
History 68
Immunofluorescence Reactivities and Antigenic Targets 68
Clinical Significance in Autoimmune Liver Disease 70
Ani‐smooth Muscle and Anti‐actin Antibodies 73
History 73
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance 73
Anti‐liver‐kidney Microsomal Antibody 74
History 74
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance 75
Anti‐liver Cytosol Type 1 Antibody 76
History 76
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance 76
Anti‐soluble Liver Antigen Antibody 76
History 76
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance 77
Ani‐neutrophil Cytoplasmic Antibody 77
History 77
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance 77
Anti‐mitochondrial Antibody 78
History 78
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance 78
Anti‐asialoglycoprotein Receptor Antibody 79
History 79
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance 79
Indications for Autoimmune Liver Serology Testing 79
Concluding Remarks 81
References 82
5 Environmental Exposure and Risk in Autoimmune Liver Diseases 83
Ying Qi Li and Andrew L. Mason
Key Points 83
Introduction 84
Autoimmunity 84
Interaction of Genes and Environmental Triggers in Autoimmunity 85
Mechanisms for Triggering Autoimmunity 86
Primary Biliary Cholangitis 89
Geo‐epidemiology, Clusters, and Case–Control Studies of PBC 92
Bacterial Infection and PBC 93
Xenobiotics and PBC 96
Viruses in PBC 97
Autoimmune Hepatitis 99
Prospectus 101
References 102
Section II Autoimmune Liver Diseases and Their Clinical Correlation 103
6 Autoimmune Hepatitis 105
Aliya Gulamhusein and Patrick McKiernan
Key Points 105
Introduction 106
Definition and Pathophysiology 106
Epidemiology 107
Presentation 108
Adult‐onset AIH 108
Pediatric‐onset AIH 109
Diagnosis 109
Autoimmune Sclerosing Cholangitis 112
Treatment 112
Therapeutic Approach in Adults 113
First-line Therapy 113
Withdrawal of Therapy 114
Second‐line Options 114
Therapeutic Approach in Children 115
First-line Therapy 115
Withdrawal of Therapy 115
Second‐line Options 115
Prognosis 116
Adulthood 116
Childhood 116
References 118
7 Primary Biliary Cholangitis 123
Alessio Gerussi and Marco Carbone
Key Points 123
Introduction and Definition 124
Epidemiology 124
Etiopathogenesis 125
Clinical Presentation 126
Asymptomatic Patients 126
Symptomatic Patients 126
Diagnosis 127
Biochemical Tests 127
Autoantibodies 128
Liver Biopsy 128
Imaging 130
Differential Diagnosis 130
Natural History 130
Disease Course in the UDCA Era 131
Risk Stratification 132
Treatment 134
Ursodeoxycholic Acid 134
Obeticholic Acid 135
Fibric Acid Derivatives 136
Budesonide 137
Liver Transplantation 137
Symptom Management 137
Complications of Liver Disease 139
Osteoporosis 139
Advanced Liver Disease 140
Varices 140
HCC 140
Useful Websites 141
References 141
8 Primary Sclerosing Cholangitis 143
Mette Vesterhus, Benedetta Terziroli Beretta‐Piccoli, Kirsten Muri Boberg, and Giorgina Mieli‐Vergani
Key Points 143
Introduction 144
Definition 145
Adult PSC 145
Epidemiology 145
Diagnosis 146
Diagnosis of Variant Phenotypes 147
Presentation 147
Malignancy 149
Cholangiocarcinoma 149
Gallbladder Cancer 150
Colorectal Cancer 150
Prognosis 150
Risk Stratification: Clinical Characteristics 150
Natural History Models 151
ALP and Bilirubin 151
Non‐invasive Evaluation of Fibrosis 151
Treatment 152
Medical Treatment 152
Bile Acid Therapy 153
Microbiota Modulators 153
Anti-inflammatory Treatment 154
Antibiotic Therapy 154
Endoscopic Treatment 154
Surveillance for Malignancy 154
Colorectal Cancer: Colonoscopy 155
Gallbladder Cancer: Ultrasound 155
Hepatocellular Cancer: Ultrasound 155
Cholangiocarcinoma 155
Bone Mineral Density 155
Juvenile Sclerosing Cholangitis 155
Epidemiology in Pediatric Disease 155
Autoimmune Sclerosing Cholangitis 156
Diagnosis in Children 156
Clinical Features in Pediatric Disease 158
Treatment of Pediatric Disease (ASC and Juvenile PSC) 158
Prognosis in Pediatric Disease 159
Conclusion 159
References 160
9 IgG4‐Related Liver and Biliary Disease 163
Eleanor Barnes and Emma L. Culver Key Points 163
Introduction and Historical Perspective 164
Etiology and Pathogenesis of IgG4‐RD 165
Development and Characteristics of an IgG4 Antibody Response 165
Antigens That May Drive an IgG4‐RD Response 166
IgG4 Antibodies and Pathogenesis 167
Incidence and Prevalence of IgG4‐RD 167
Clinical Characteristics of IgG4‐related Hepatobiliary Disease 168
Hepatobiliary Disease 168
Disease Outside te Hepatobiliary System 168
Diagnostic Criteria, Histologic Features, and Approach to Diagnosis of IgG4‐related Hepatobiliary Disease 168
Diagnostic Criteria for AIP and IgG4‐RD 168
Histologic Diagnosis of IgG4‐related Hepatobiliary Disease 170
Utility of Blood Tests, Including Serum IgG4 Levels in IgG4‐RD Diagnostics 171
Common Alternative Diagnoses to Consider 172
Radiologic Characteristics of Hepatobiliary IgG4‐RD 173
IgG4‐RD and Relationship with Malignancy 173
Management and Treatment of Patients with IgG4‐RD 174
Monitoring and Follow‐up 175
Conclusions and Future Directions 175
References 177
Section III Specific Clinical Challenges 181
10 Managing Acute and Chronic Seronegative Liver Disease 183
Marcus C. Robertson and Peter C. Hayes
Key Points 183
Introduction 184
An Approach to Seronegative Acute Liver Failure 184
Potential Causes of Seronegative ALF and Features that Suggest an Autoimmune Pathogenesis 185
Clinical Features of Seronegative ALF 188
Risk Stratification in Seronegative ALF 188
Management of Seronegative ALF 189
N‐Acetylcysteine 190
Corticosteroids 190
Emergency Liver Transplantation 191
An Approach to Cryptogenic Chronic Liver Disease 192
Potential Causes of Seronegative Chronic Liver Disease and Features that Suggest an Autoimmune Pathogenesis 192
Non‐alcoholic Fatty Liver Disease 194
Wilson Disease 194
Seronegative Autoimmune Hepatitis 195
Seronegative Primary Biliary Cholangitis 197
Conclusion 197
References 198
11 Managing Pregnant Women with Autoimmune Liver Disease 201
Eleni Theocharidou and Michael A. Heneghan
Key Points 201
Introduction 202
Fertility in AIH 202
Pregnancy Outcomes in AIH 202
Liver‐related Outcomes in Pregnancy 206
Pregnancy in Cirrhosis 209
Safety of Medication in Pregnancy 210
Summary 213
References 214
12 Bone Health in Patients with Autoimmune Liver Diseases 219
Albert Parés and Núria Guañabens
Key Points 219
Introduction 220
Prevalence of Osteoporosis and Fractures 222
Primary Biliary Cholangitis 222
Primary Sclerosing Cholangitis 223
Autoimmune Hepatitis 223
Pathogenesis 224
Assessment of Bone Disease 226
Prevention and Treatment of Bone Loss 227
General Measures 227
Pharmacologic Agents 227
Bisphosphonates 227
Other Agents 229
Summary 230
References 231
Section IV Transplantation and Its Role in Autoimmune Liver Disease 233
13 Recurrent Autoimmune Liver Disease and Its Impact on Clinical Practice 235
Carlos Moctezuma‐Velázquez and Aldo J. Montano‐Loza
Key Points 235
Introduction 236
Primary Biliary Cholangitis 236
Recurrence of PBC After LT 236
Diagnosis of PBC After LT 236
Risk Factors Associated with PBC Recurrence After LT 237
Treatment of PBC Recurrence After LT 238
Prognostic Impact of PBC Recurrence After LT 239
Primary Sclerosing Cholangitis 239
Recurrence of PSC After LT 240
Diagnosis of Recurrence of PSC After LT 240
Risk Factors Associated with PSC Recurrence After LT 240
Treatment of PSC Recurrence After LT 241
Prognostic Impact of PSC Recurrence After LT 241
Autoimmune Hepatitis 241
Recurrence of AIH After LT 242
Risk Factors Associated with AIH Recurrence After LT 242
Treatment of AIH Recurrence After LT 243
Prognostic Impact of AIH Recurrence After LT 243
Conclusions 243References 244
14 Recurrent Autoimmune Liver Disease and its Scientific Significance 247
Atsushi Tanaka, Patrick S.C. Leung, and M. Eric Gershwin
Key Points 247
Introduction 247
Recurrence of PBC 248
Incidence and Diagnosis of Recurrent PBC 249
Risk Factors of Recurrent PBC 250
Impact of Recurrent PBC on Long‐term Outcomes 250
Recurrence of PSC 251
Incidence and Diagnosis of Recurrent PSC 252
Risk Factors of Recurrent PSC 253
Impact of Recurrent PSC on Long‐term Outcomes 254
Recurrence of AIH 254
Incidence and Diagnosis of Recurrent AIH 254
Risk Factors of Recurrent AIH 255
Impact of Recurrent AIH on Long‐term Outcomes 255
Concluding Remarks 256
References 257
Section V Controversies in Autoimmune Liver Diseases 263
15 Making Sense of Overlap and Crossover Syndromes 265
Olivier Chazouillères
Key Points 265
Introduction 266
General Considerations 267
Liver Biopsy 268
AIH Scores 269
Genetics 269
PBC/AIH Overlap Syndrome 269
PSC/AIH Overlap Syndrome 272
Liver Transplantation 273
Conclusions 274
References 275
16 The Role of Extrahepatic Autoimmunity in Autoimmune Liver Disease 277
Ewa Wunsch and Piotr Milkiewicz
Key Points 277
Introduction 278
Epidemiology 278
Autoimmune Thyroid Disease 279
Sjogren Syndrome 279
Systemic Sclerosis 280
Systemic Lupus Erythematosus 281
Rheumatoid Arthritis 282
Celiac Disease 283
Inflammatory Bowel Disease 284
Conclusions 286
Guidelines for Clinicians 287
References 288
17 Symptoms, Chronic Disease, and Patient Management 289
David Jones
Key Points 289
Background 290
Goals of Treatment 290
Symptoms, Quality of Life, and Health Utility: Key Concepts 291
Symptoms 291
Health‐related Quality of Life 292
Health Utility 292
Symptoms and Their Management in AILD 292
Impact of Disease‐modifying Therapy on Symptoms in AILD 292
Stage‐associated Symptoms 293
Stage‐independent Symptoms 293
Pruritus 293
Fatigue and Cognitive Symptoms 295
Social Isolation Symptoms 298
Effective Care Delivery in AILD 299
References 300
Index 301

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