Оглавление
Группа авторов. Autoimmune Liver Disease
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Autoimmune Liver Disease. Management and Clinical Practice
Preface
Contributors
Abbreviations
Introduction The Paradigm and Paradox of Liver Autoimmunity
1 Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree
Abstract
Key Points
Liver Cell Types and Organization
Hepatic Metabolism
Bilirubin Metabolism and Transport
Carbohydrate Metabolism
Lipid Metabolism
Protein Metabolism
Metabolic Zonation
Hepatic Transport Systems
Basolateral (Sinusoidal) Transporters
Apical (Canalicular) Transporters
Drug Metabolism
Bile Formation, Secretion and the Enterohepatic Circulation
Bile Acid Synthesis and Metabolism
Enterohepatic Bile Acid Circulation
Death and Regeneration of Hepatocytes. Cell Death
Liver Regeneration
Cholangiocyte Reaction to Biliary Damage
Protective Role of Biliary HCO3− Secretion
Cholangiocytes and Immunity
Biochemical Markers and Patterns of Hepatic Injury
Hepatocellular Necrosis
Cholestasis
References
2 Concepts of Autoimmunity Relevant to Autoimmune Liver Diseases
Abstract
Key Points
Introduction
Role of Innate and Adaptive Immunity in Autoimmunity in the Context of the Liver as an Immune Organ. Overview
Innate Immunity
Liver as an Innate Immune Organ
Adaptive Immunity and Adaptive Immune Functions of the Liver
Role of the Liver as an Adaptive Immune Organ
Generation and Maintenance of Tolerance to Self‐antigens. Overview
Central Tolerance
Central T‐cell Tolerance
Central B‐cell Tolerance
Peripheral Tolerance
T‐ and B‐cell Clonal Anergy
T‐cell Mediated Immune Regulation
Natural and Inducible T Regulatory Cells
Peripheral B‐cell Regulatory Mechanisms
Regulatory Dendritic Cells
Immunoregulatory Interplay Between Treg and Th17 Cells
Risk Factors for Autoimmune Diseases. Genetics. Complex Genetic and Monogenic Diseases
HLA Risk Alleles
Non‐HLA Gene Associations
Critical Role of Epigenetics. Transcription Factor Enhancers and Super Enhancers
MicroRNAs
Sex and Sex Hormones
Vitamin D and Sunlight Exposure
Loss of Immune Tolerance to Autoantigens and Perpetuation of Autoimmune Diseases. Overview
Role of the Microbiome
Mechanisms of Loss of Tolerance to Autoantigens. Bacterial and Viral Infections
Molecular Mimicry of Autoantigens
Neoantigens
Failure of Apoptosis to Conceal Autoantigens and Eliminate Autoreactive Cells
Immune Deviation of Activated T Cells
T‐cell Receptor Revision in the Periphery
Perpetuation of Autoimmune Diseases
Epigenetics. Enhancers and Super Enhancers
MicroRNA
Epitope Spreading
Tissue Memory T Cells
Cytokines Promoting Chronic Inflammation and Autoimmunity. IL‐12 Family
IL‐20 Receptor Cytokines
Tertiary Lymphoid Structures and Germinal Centers
Epithelial Cell‐induced Transformation of iTreg to Th17 Cells
Prevention of Autoimmunity and Therapeutic Control of Autoimmune Diseases. Overview
Strategies to Prevent Autoimmunity. Vitamin D3
Gut Microbiota Manipulation in Pregnancy and Infancy
Oral Tolerance
Strategies to Treat Established Autoimmune Diseases
Inducible T Regulatory T Cells
Epigenetic Enhancer Regulation
References
3 Genetics and Risk of Autoimmune Liver Diseases
Abstract
Key Points
Introduction
HLA Associations in Autoimmune Liver Disease
Non‐HLA Associations in Autoimmune Liver Disease
Box 3.1 Candidate Genes for Primary Biliary Cholangitis
Box 3.2 Candidate Genes for Primary Sclerosing Cholangitis
Box 3.3 Candidate Genes for Autoimmune Hepatitis
Conclusion
References
4 Autoantibodies and Understanding of Autoimmune Liver Diseases
Abstract
Key Points
Introduction
Methods of Detection
Anti‐nuclear Antibody. History
Immunofluorescence Reactivities and Antigenic Targets
Clinical Significance in Autoimmune Liver Disease
Anti‐smooth Muscle and Anti‐actin Antibodies. History
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance
Anti‐liver‐kidney Microsomal Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance
Anti‐liver Cytosol Type 1 Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance
Anti‐soluble Liver Antigen Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and Clinical Significance
Anti‐neutrophil Cytoplasmic Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance
Anti‐mitochondrial Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance
Anti‐asialoglycoprotein Receptor Antibody. History
Immunofluorescence Reactivities, Antigenic Targets, and their Clinical Significance
Indications for Autoimmune Liver Serology Testing
Concluding Remarks
References
5 Environmental Exposure and Risk in Autoimmune Liver Diseases
Abstract
Key Points
Introduction
Autoimmunity
Interaction of Genes and Environmental Triggers in Autoimmunity
Mechanisms for Triggering Autoimmunity
Primary Biliary Cholangitis
Geo‐epidemiology, Clusters, and Case–Control Studies of PBC
Bacterial Infection and PBC
Xenobiotics and PBC
Viruses in PBC
Autoimmune Hepatitis
Prospectus
References
6 Autoimmune Hepatitis
Abstract
Key Points
Introduction
Definition and Pathophysiology
Epidemiology
Presentation. Adult‐onset AIH
Pediatric‐onset AIH
Diagnosis
Autoimmune Sclerosing Cholangitis
Treatment
Therapeutic Approach in Adults. First‐line Therapy
Withdrawal of Therapy
Second‐line Options
Therapeutic Approach in Children. First‐line Therapy
Withdrawal of Therapy
Second‐line Options
Prognosis. Adulthood
Childhood
References
7 Primary Biliary Cholangitis
Abstract
Key Points
Introduction and Definition
Epidemiology
Etiopathogenesis
Clinical Presentation. Asymptomatic Patients
Symptomatic Patients
Diagnosis
Biochemical Tests
Autoantibodies
Liver Biopsy
Imaging
Differential Diagnosis
Natural History
Disease Course in the UDCA Era
Risk Stratification
Treatment
Ursodeoxycholic Acid
Obeticholic Acid
Fibric Acid Derivatives
Budesonide
Liver Transplantation
Symptom Management
Complications of Liver Disease. Osteoporosis
Advanced Liver Disease. Varices
HCC
Useful Websites
References
8 Primary Sclerosing Cholangitis
Abstract
Key Points
Introduction
Definition
Adult PSC. Epidemiology
Diagnosis
Diagnosis of Variant Phenotypes. Small‐duct PSC
Features of AIH (see also Chapter 6)
Elevated IgG4
Presentation
Malignancy
Cholangiocarcinoma
Gallbladder Cancer
Colorectal Cancer
Prognosis
Risk Stratification: Clinical Characteristics
Natural History Models
ALP and Bilirubin
Non‐invasive Evaluation of Fibrosis
Treatment
Medical Treatment. Ursodeoxycholic Acid
Antibiotics
Immunosuppression
Future Drugs
Bile Acid Therapy
Microbiota Modulators
Anti‐inflammatory Treatment
Antibiotic Therapy
Endoscopic Treatment
Surveillance for Malignancy
Colorectal Cancer: Colonoscopy
Gallbladder Cancer: Ultrasound
Hepatocellular Cancer: Ultrasound
Cholangiocarcinoma
Bone Mineral Density
Juvenile Sclerosing Cholangitis
Epidemiology in Pediatric Disease
Autoimmune Sclerosing Cholangitis
Diagnosis in Children
Clinical Features in Pediatric Disease
Treatment of Pediatric Disease (ASC and Juvenile PSC)
Prognosis in Pediatric Disease
Conclusion
References
9 IgG4‐Related Liver and Biliary Disease
Abstract
Key Points
Introduction and Historical Perspective
Etiology and Pathogenesis of IgG4‐RD. Development and Characteristics of an IgG4 Antibody Response
Antigens That May Drive an IgG4‐RD Response
IgG4 Antibodies and Pathogenesis
Incidence and Prevalence of IgG4‐RD
Clinical Characteristics of IgG4‐related Hepatobiliary Disease. Hepatobiliary Disease
Disease Outside the Hepatobiliary System
Diagnostic Criteria, Histologic Features, and Approach to Diagnosis of IgG4‐related Hepatobiliary Disease. Diagnostic Criteria for AIP and IgG4‐RD
Histologic Diagnosis of IgG4‐related Hepatobiliary Disease
Utility of Blood Tests, Including Serum IgG4 Levels in IgG4‐RD Diagnostics
Common Alternative Diagnoses to Consider
Radiologic Characteristics of Hepatobiliary IgG4‐RD
IgG4‐RD and Relationship with Malignancy
Management and Treatment of Patients with IgG4‐RD
Monitoring and Follow‐up
Conclusions and Future Directions
References
10 Managing Acute and Chronic Seronegative Liver Disease
Abstract
Key Points
Introduction
An Approach to Seronegative Acute Liver Failure
Potential Causes of Seronegative ALF and Features that Suggest an Autoimmune Pathogenesis
Clinical Features of Seronegative ALF
Risk Stratification in Seronegative ALF
Management of Seronegative ALF
N‐Acetylcysteine
Corticosteroids
Emergency Liver Transplantation
An Approach to Cryptogenic Chronic Liver Disease
Potential Causes of Seronegative Chronic Liver Disease and Features that Suggest an Autoimmune Pathogenesis
Non‐alcoholic Fatty Liver Disease
Wilson Disease
Seronegative Autoimmune Hepatitis
Seronegative Primary Biliary Cholangitis
Conclusion
References
11 Managing Pregnant Women with Autoimmune Liver Disease
Abstract
Key Points
Introduction
Fertility in AIH
Pregnancy Outcomes in AIH
Liver‐related Outcomes in Pregnancy
Pregnancy in Cirrhosis
Safety of Medication in Pregnancy
Summary
References
12 Bone Health in Patients with Autoimmune Liver Diseases
Abstract
Key Points
Introduction
Prevalence of Osteoporosis and Fractures. Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Autoimmune Hepatitis
Pathogenesis
Assessment of Bone Disease
Prevention and Treatment of Bone Loss. General Measures
Pharmacologic Agents. Bisphosphonates
Other Agents
Summary
References
13 Recurrent Autoimmune Liver Disease and Its Impact on Clinical Practice
Abstract
Key Points
Introduction
Primary Biliary Cholangitis
Recurrence of PBC After LT
Diagnosis of PBC After LT
Risk Factors Associated with PBC Recurrence After LT
Treatment of PBC Recurrence After LT
Prognostic Impact of PBC Recurrence After LT
Primary Sclerosing Cholangitis
Recurrence of PSC After LT
Diagnosis of Recurrence of PSC After LT
Risk Factors Associated with PSC Recurrence After LT
Treatment of PSC Recurrence After LT
Prognostic Impact of PSC Recurrence After LT
Autoimmune Hepatitis
Recurrence of AIH After LT
Risk Factors Associated with AIH Recurrence After LT
Treatment of AIH Recurrence After LT
Prognostic Impact of AIH Recurrence After LT
Conclusions
References
14 Recurrent Autoimmune Liver Disease and its Scientific Significance
Abstract
Key Points
Introduction
Recurrence of PBC
Incidence and Diagnosis of Recurrent PBC
Risk Factors of Recurrent PBC
Impact of Recurrent PBC on Long‐term Outcomes
Recurrence of PSC
Incidence and Diagnosis of Recurrent PSC
Risk Factors of Recurrent PSC
Impact of Recurrent PSC on Long‐term Outcomes
Recurrence of AIH
Incidence and Diagnosis of Recurrent AIH
Risk Factors of Recurrent AIH
Impact of Recurrent AIH on Long‐term Outcomes
Concluding Remarks
References
15 Making Sense of Overlap and Crossover Syndromes
Abstract
Key Points
Introduction
General Considerations
Liver Biopsy
AIH Scores
Genetics
PBC/AIH Overlap Syndrome
Box 15.1 Paris criteria for diagnosing PBC/AIH overlap syndrome
PSC/AIH Overlap Syndrome
Liver Transplantation
Conclusions
References
16 The Role of Extrahepatic Autoimmunity in Autoimmune Liver Disease
Abstract
Key Points
Introduction
Epidemiology
Autoimmune Thyroid Disease
Sjögren Syndrome
Systemic Sclerosis
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Celiac Disease
Inflammatory Bowel Disease
Conclusions
Guidelines for Clinicians
References
17 Symptoms, Chronic Disease, and Patient Management
Abstract
Key Points
Background
Goals of Treatment
Symptoms, Quality of Life, and Health Utility: Key Concepts
Symptoms
Health‐related Quality of Life
Health Utility
Symptoms and Their Management in AILD
Impact of Disease‐modifying Therapy on Symptoms in AILD
Stage‐associated Symptoms
Stage‐independent Symptoms
Pruritus
Fatigue and Cognitive Symptoms
Social Isolation Symptoms
Effective Care Delivery in AILD
References
Index
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