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.
Table of contents
Introduction: The Paradigm and Paradox of Liver Autoimmunity, 00
Section I Scientific Basis of Clinical Autoimmune Liver Diseases
1 Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree
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
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
Peripheral Tolerance
Risk Factors for Autoimmune Diseases
Genetics
Critical Role of Epigenetics
Sex and Sex Hormones
Vitamin D and Sunlight Exposure
Loss of Immune Tolerance to Autoantigens and Perpetuation of Autoimmune Diseases
Overview
Mechanisms of Loss of Tolerance to Autoantigens
Perpetuation of Autoimmune Diseases
Prevention of Autoimmunity and Therapeutic Control of Autoimmune Diseases
Overview
Strategies to Prevent Autoimmunity
Strategies to Treat Established Autoimmune Diseases
References
3 Genetics and Risk of Autoimmune Liver Diseases
Key Points
Introduction
HLA Associations in Autoimmune Liver Disease
Non-HLA Associations in Autoimmune Liver Disease
Conclusion
References
4 Autoantibodies and Understanding of Autoimmune Liver Diseases
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
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
Section II Autoimmune Liver Diseases and Their Clinical Correlation
6 Autoimmune Hepatitis
Key Points
Introduction
Definition and Pathophysiology
Epidemiology
Presentation
Adult-onset AIH
Pediatric-onset AIH
Diagnosis
Autoimmune Sclerosing Cholangitis
Treatment
Therapeutic Approach in Adults
Therapeutic Approach in Children
Prognosis
Adulthood
Childhood
References
7 Primary Biliary Cholangitis
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
References
Useful Websites
8 Primary Sclerosing Cholangitis
Key Points
Introduction
Definition
Adult PSC
Epidemiology
Diagnosis
Presentation
Malignancy
Prognosis
Treatment
Surveillance for Malignancy
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-associated Disease
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
Section III Specific Clinical Challenges
10 Managing Acute and Chronic Seronegative Liver Disease
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
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
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
Summary
References
Section IV Transplantation and Its Role in Autoimmune Liver Disease
13 Recurrent Autoimmune Liver Disease and Its Impact on Clinical Practice
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
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
Section V Controversies in Autoimmune Liver Diseases
15 Making Sense of Overlap and Crossover Syndromes
Key Points
Introduction
General Considerations
Liver Biopsy
AIH Scores
Genetics
PBC/AIH Overlap Syndrome
PSC/AIH Overlap Syndrome
Liver Transplantation
Conclusions
References
16 The Role of Extrahepatic Autoimmunity in Autoimmune Liver Disease
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
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
Effective Care Delivery in AILD
References
