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Drug-Induced Liver Disease
- 3rd Edition - April 18, 2013
- Editors: Neil Kaplowitz, Laurie D. DeLeve
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 3 8 7 8 1 7 - 5
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 8 7 8 1 8 - 2
This field has shown tremendous growth in recent years, primarily due to the recognition that drug-induced liver disease is the most common cause of liver failure and one of the ma… Read more
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Request a sales quoteThis field has shown tremendous growth in recent years, primarily due to the recognition that drug-induced liver disease is the most common cause of liver failure and one of the major contributors to the withdrawal of drugs developed by the pharmaceutical industry. Drug-Induced Liver Disease, 3rd edition is a comprehensive reference that covers mechanisms of injury, diagnosis and management, major hepatotoxins, regulatory perspectives and much more. Written by highly respected authorities, this new edition is an updated and definitive reference for clinicians and scientists in academia, the pharmaceutical industry and government settings. This book contains 4 new chapters on key topics in the area and provides a current and extensive review of the latest developments concerning the toxicology, pharmacology, genetics and immunology of drug-induced liver disease.
- A multi-authored reference work written by leading clinical, academic and industry experts in drug-induced liver disease
- Contains four new chapters on key areas in the field, including one on worldwide drug-induced liver injury networks
- Each chapter has been updated to address the latest research and findings in the field and 16 new chapter authors have been added to this new edition
- Includes coverage of the basic, clinical and practical aspects of drug-induced liver disease to provide the single most comprehensive reference on the subject
This reference is geared primarily towards medical specialists, including gastroenterologists, hepatologists, and pathologists, toxicologists, members of the pharmaceutical industry, and regulators. This book also provides an extensive review of mechanisms of toxicity and of drug safety and would be an excellent reference for students of toxicology, as a secondary audience
Dedication
Preface to the Third Edition
List of Figures
List of Tables
List of Contributors
Part I: Mechanisms of Liver Injury
Chapter 1. Drug-Induced Liver Injury: Introduction and Overview
Introduction
Clinical Overview
Pathogenesis
Diagnosis
Drug Development
Postmarketing Monitoring
Conclusions
References
Chapter 2. Cytochrome P450 Activation of Toxins and Hepatotoxicity
Introduction
Cytochrome P450 Enzymes
Contexts of Toxicity
Bioactivation Reactions
Strategies for Screening in Drug Development
The Issue of Human-Specific Metabolites
Conclusions
References
Chapter 3. Mechanistic Role of Acyl Glucuronides
Introduction
Overview of Major Types of Chemical ReactivitIES of Acyl Glucuronides
Biochemical Aspects of Acyl Glucuronidation
Synthesis, Isolation, and Characterization of Acyl Glucuronides
Stability of Acyl Glucuronides
Reversible Binding of Acyl Glucuronides to Proteins
Covalent Binding of Acyl Glucuronides to Proteins
Stereochemical Aspects of Acyl Glucuronides
Predictability of the Covalent Binding of Acidic Drugs
In Vitro Reactivity Screens Utilizing Nucleophilic Trapping Agents
Potential Toxicological Significance of the Reactive Acyl Glucuronides
Acknowledgment
References
Chapter 4. Oxidant Stress, Antioxidant Defense, and Liver Injury
Introduction
The Major Reactive Oxygen and Nitrogen Species in the Liver and their Sources
Pathophysiological Consequences of Oxidative Stress
Antioxidants
Drug-Induced Oxidative Stress in the Liver
References
Chapter 5. Hepatotoxicity Due to Mitochondrial Injury
Introduction
Overview of Mitochondria
Mitochondrial Permeability Transition
Mitochondria and Drug-Induced Hepatic Steatosis
Conclusion
Acknowledgments
References
Chapter 6. Mechanisms of Cell Death and Relevance to Drug Toxicity
Introduction
Classification of Cell Death
Apoptosis
Autophagy
Necrosis: A Programmed Process?
Cell Death in DILI
Conclusions
References
Chapter 7. Role of Membrane Transport in Hepatotoxicity and Pathogenesis of Drug-Induced Cholestasis
Introduction
Bile Formation
Clinical Features of Drug-Induced Cholestasis
Hepatocellular Drug Uptake and Intracellular Drug Concentrations
Mechanisms of BSEP Inhibition
Impact of Elevated Intracellular Bile Salt Levels on Transporter Expression
Susceptibility Factors for Drug-Induced Cholestasis
Conclusions
References
Chapter 8. Liver Sinusoidal Endothelial Cells and Liver Injury
Introduction
Liver Sinusoidal Endothelial Cells
Capillarization, Pseudocapillarization, and Drug Metabolism
Liver Sinusoidal Endothelial Cells and Fibrosis
Bone Marrow Liver Sinusoidal Endothelial Progenitor Cells and Liver Regeneration
Manifestations of Liver Sinusoidal Endothelial Cell Injury
Lesions of Heterogeneous Perfusion
Peliosis Hepatis
Sinusoidal Obstruction Syndrome
Acetaminophen
Gemtuzumab Ozogamicin
Oxaliplatin
Conclusions
References
Chapter 9. Macrophages and Kupffer Cells in Drug-Induced Liver Injury
Introduction
Innate Immune Activation in DILI
Interactions Between Hepatic Macrophages and Other Cells in the Liver During DILI
Danger Signals Generated in Drug-Induced Liver Injury and Their Signaling Pathways
Additional Damps/Pamps Involved in Macrophage Activation in DILI
Complement and Macrophage Activation
Diagnosis and Treatment of Drug-Induced Liver Injury: Can Macrophages Be a Target?
Genetic Susceptibility to DILI
Conclusions
References
Chapter 10. Role of Inflammation in Drug-Induced Liver Injury
Introduction
Inflammation as a Progression Factor in Intrinsic DILI
Inflammation in Idiosyncratic DILI Responses
Exogenously Imposed Inflammation as a Susceptibility Factor for Drug-Induced Liver Injury
Conclusions
Acknowledgments
References
Chapter 11. Role of the Adaptive Immune System in Idiosyncratic Drug-Induced Liver Injury
Introduction
Clinical Characteristics of IDRS
Evidence Suggesting that IDILI is Immune Mediated
Alternative Hypotheses
Toward a Unifying Hypothesis for IDILI
Conclusions
Acknowledgments
References
Chapter 12. Role of Tissue Repair and Death Proteins in Liver Injury
Introduction
Two-Stage Model of Toxicity
Tissue Repair Follows a Dose Response
Dose-Responsive Tissue Repair for Mixtures of Hepatotoxicants
Tissue Repair as a Determinant of the Final Outcome of Toxicity
Relationship Between Higher Initiation of Liver Injury and Tissue Repair
Factors Affecting Tissue Repair
Progression of Liver Injury
Regression of Injury
Significance of Tissue Repair
Significance of Death Proteins in the Spread of Liver Injury
Conclusions
References
Chapter 13. Genetic Factors in the Pathogenesis of Drug-Induced Liver Injury
Introduction
Methods and Approaches Used to Identify Genetic Factors in DILI
Genetic Factors Predicting DILI Susceptibility
Conclusions
References
Part II: Diagnosis and Management
Chapter 14. Clinical Manifestations and Management of Drug-Induced Liver Diseases
Introduction
Susceptibility Factors: Drug-Induced Liver Injury
Clinical Recognition of a Suspected or Probable DILI
Clinical and Laboratory Manifestations
Manifestations of DILI
Nonspecificity of Clinical and Laboratory Manifestations of DILD
Signals of Severe Drug-Induced Liver Injury: The Importance of Hy’s Law
The Important Issue of Drug-Induced Autoimmune Hepatitis
Drugs of Special Interest
Management and Treatment of DILD
Rechallenge
References
Chapter 15. Histopathological Evaluation of Drug-Induced Liver Disease
Introduction
Role of Pathological Evaluation in DILD
Patterns of Injury in DILd
Using Liver Biopsy to Evaluate DILD
Conclusions
Acknowledgments
References
Chapter 16. Risk Factors for Drug-Induced Liver Disease
Introduction
Host-Related Risk Factors
Environmental Risk Factors
Compound-Related Risk Factors
Conclusions
Acknowledgments
References
Chapter 17. Biomarkers for Drug-Induced Liver Injury
Introduction
Current Status of Hepatocellular DILI Biomarkers
The Road to Better DILI Biomarkers
Metabolomics
Transcriptomics
Proteomics
Example of an Application of Novel Biomarkers to a Clinical Trial: Heparins
Serum Protein Adducts
Anti-Liver Antibodies
Lymphocyte Transformation Test
Conclusions
References
Chapter 18. Causality Assessment
Introduction
Diagnosis in the Clinical Setting
Minimal Elements for Drug-Induced Liver Injury Diagnosis and Publishing
Causality Assessment
Conclusions
References
Part III: Hepatotoxicity of Specific Drugs
Chapter 19. Mechanisms of Acetaminophen-Induced Liver Disease
Introduction
Reactive Metabolite Formation
Protein Covalent Binding
Toxicity Occurs in Two Phases
Alterations in Calcium Metabolism
Oxidative Stress and Toxicity
Mitochondrial Permeability Transition
Antioxidant Defense Mechanisms
Cell Signaling and Mitochondrial Permeability Transition
Hepatic Inflammation
Genomics, Proteomics, and Metabolomics
Conclusions
Acknowledgments
References
Chapter 20. Acetaminophen: Pathology and Clinical Presentation of Hepatotoxicity
Introduction
Pharmacology of Acetaminophen
Availability of Acetaminophen and Considerations on Regulation
Clinical Presentation of Acetaminophen Toxicity
Definitions of Toxicity
Biomarkers of Toxicity
Patient Variability and Acetaminophen Toxicity
Acknowledgments
References
Chapter 21. Mechanisms Underlying the Hepatotoxicity of Nonsteroidal Antiinflammatory Drugs
NSAID Hepatotoxicity: A Paradigm of IDILI
Toxicokinetic Determinants of NSAID Hepatotoxicity: Disposition and Metabolism
Toxicodynamic Determinants of NSAID Hepatotoxicity: Cellular and Molecular Mechanisms
Patient-Specific Determinants of Susceptibility to NSAID Hepatotoxicity
Conclusions
References
Chapter 22. Nonsteroidal Antiinflammatory Drugs and Leukotriene Receptor Antagonists
Introduction
Incidence of NSAID-Induced Hepatic Injury
Effect of Rheumatic Diseases on the Liver
Clinical and Biochemical Spectrum of NSAID-Induced Hepatic Injury
Hepatic Injury Due to Individual NSAIDs
Hepatic Injury Due to DMARDS
Hepatotoxicity of Leukotriene Receptor Antagonists
Hepatotoxicity of Agents Used in the Treatment of Gout
Monitoring for NSAID and Other Antiinflammatory Drug-Induced Hepatic Injury
References
Chapter 23. Mechanism, Pathology, and Clinical Presentation of Hepatotoxicity of Anesthetic Agents
Introduction
Clinical Features of Volatile Anesthetic-Induced Hepatotoxicity
Metabolism of Volatile Anesthetics
Adaptive Immune Responses in Patients with AnesthetIc-Induced Liver Injury
Animal Models
Hydrochlorofluorocarbon Refrigerants
Mechanism of Volatile Anesthetic-Induced Liver Injury and Basis of Individual Susceptibility
Conclusions
References
Chapter 24. Anticonvulsant Agents
Introduction
Carbamazepine
Oxcarbazepine
Phenytoin
Phenobarbital
Valproic Acid
Felbamate
Lamotrigine
Management
References
Chapter 25. Hepatotoxicity of Psychotropic Drugs and Drugs of Abuse
Introduction
Epidemiological Aspects of Psychotropic Hepatotoxicity
Identification of Drug-Induced Liver Injury Caused by Psychotropic Agents
Factors that Contribute to the Hepatotoxicity of Psychotropic Agents
Antidepressants
Neuroleptic Agents
Anxiolytic Agents
Psychostimulating Agents
Thymoregulating Agents
Herbal Medicines
Illegal and Recreational Compounds
Conclusions
References
Chapter 26. Hepatotoxicity of Antimicrobials and Antifungal Agents
Introduction
Antibacterial Agents
Antifungal Agents
Conclusions
References
Chapter 27. Hepatotoxicity of Antitubercular Drugs
Introduction
Incidence of Hepatotoxicity
Mechanism of Hepatotoxicity
Hepatotoxicity of Individual Drugs
Hepatotoxicity with Multidrug Antitubercular Therapy
Risk Factors for Antitubercular Therapy Hepatotoxicity
Clinical, Biochemical, and Histological Features
Management, Including Referral for Liver Transplant
Alternative Therapy for Underlying Tuberculosis and Reintroduction of Antitubercular Therapy
Antitubercular Therapy in Patients with Underlying Liver Disease
Hepatotoxicity of Antitubercular Therapy in Liver Transplant Recipients
Recommendations for Monitoring Patients While on ATT
Conclusions
References
Chapter 28. Hepatotoxicity of Antiviral Agents
Introduction
Antiretroviral Drugs
Incidence and Risk Factors for HAART-Related DILI: The Drug and the Host
Clinical Presentations of HAART-Related DILI and their Mechanisms
Hepatitis Treatments
Herpesviridae Treatment
Influenza Virus Treatments
References
Chapter 29. Hepatotoxicity of Cardiovascular and Antidiabetic Drugs
Introduction
Cardiovascular Drugs
Antidiabetic Drugs
Other Agents
Conclusions
References
Chapter 30. Cancer Chemotherapy
Introduction
Hepatic Metabolism of Anticancer Drugs
Liver Toxicity and Hematopoietic Stem Cell Transplantation
Hepatotoxicity by Anticancer Therapy
Selected Anticancer Drugs and Modalities
Conclusions
References
Chapter 31. Hepatotoxicity of Immunosuppressive Drugs
Classification of Immunosuppressive Agents
Hepatotoxicity of Immunosuppressives in Current Clinical Practice
Conclusions
References
Chapter 32. Hepatotoxicity Related to Methotrexate
Introduction
Acute DILI
Methotrexate-Associated Chronic Liver Disease
Pathogenesis of Methotrexate-Associated Chronic Liver Disease
Monitoring for Methotrexate-Associated Chronic Liver Disease
Conclusions
References
Chapter 33. Adverse Effects of Hormones and Hormone Antagonists on the Liver
Introduction
Oral Contraceptive Steroids
Anabolic Androgenic Steroids
Estrogen Receptor Antagonists
Antiandrogens
Corticosteroids
Antithyroid Drugs
Conclusions
References
Chapter 34. Mushroom Poisoning: A Clinical Model of Toxin-Induced Centrilobular Necrosis
Introduction
Amanita: The Mushrooms
The Toxins
Amanita Poisoning: Manifestations
Liver Lesions
Prognosis
Management
Conclusions
Acknowledgment
References
Chapter 35. Hepatotoxicity of Herbals and Dietary Supplements
Introduction
Epidemiology of and Expenditure on Herbals and Dietary Supplements
Origin and Production of Herbals and Botanicals for Medicinal Purposes
Regulation of Dietary Supplements
The Use of Herbal Products to Treat Liver Disease
Liver Injury Caused by Herbals and Dietary Supplements
Causality Assessment for Hepatotoxicity Due to Herbals and Dietary Supplements
Limitations of Causality Assessment for Hepatotoxicity Due to Herbals and Dietary Supplements
Herbal Products Associated with Liver Injury
Dietary Supplements Associated with Liver Injury
Natural Toxins
Conclusions
References
Chapter 36. Occupational and Environmental Hepatotoxicity
Introduction
Types of Injuries
Types of Exposures
Susceptibility to Injury
Testing for Occupational Hepatotoxicity
Mechanisms of Injury
Hepatotoxic Chemicals
Halogenated Aromatic Hydrocarbons
Halogenated Aliphatic Hydrocarbons
Chlorinated Ethylenes
N-Substituted Amides
Organochlorine Pesticides, Insecticides, and Herbicides
Miscellaneous Hepatotoxins
Hydraulic Fracturing
Conclusions
References
Chapter 37. Chronic Liver Disease from Drugs
Introduction
Autoimmune Hepatitis Triggered by Drugs
Vanishing Bile Duct Syndrome Associated with Drugs
Liver Cirrhosis Associated with Drugs
Incidence of Chronic Liver Test Abnormalities After DILI
Possible Long-Term Consequences of DILI on the Liver
Conclusions
References
Part IV: Future Directions
Chapter 38. Regulatory Perspectives
Introduction
Regulatory and Scientific Challenges in the Assessment of Drug-Induced Liver Injury Risk
Assessment of DILI Risk in Clinical Trials
Identification and Characterization of DILI Risk in the Postmarket: A Life Cycle Approach
Evaluation of Postmarketing DILI Cases
Postmarketing DILI Surveillance Tools
Risk Management of DILI
DILI and the FDAs Role in the Safe Use of Drugs and Biological Agents
Future Directions Surrounding DILI: Interface between Science and Regulation
References
Chapter 39. Drug-Induced Liver Injury Research Networks
Introduction
Prospective Studies of DILI
Prospective DILI Registries
Retrospective Pharmacoepidemiological Studies of DILI
Acknowledgments
References
Chapter 40. LiverTox: A Website on Drug-Induced Liver Injury
Introduction
Introductory Sections
Drug Records
Interactive Section
Conclusions
Acknowledgments
References
Index
- No. of pages: 776
- Language: English
- Edition: 3
- Published: April 18, 2013
- Imprint: Academic Press
- Hardback ISBN: 9780123878175
- eBook ISBN: 9780123878182
NK
Neil Kaplowitz
Affiliations and expertise
MD, Professor of Medicine, Chief, Division of Gastrointestinal and Liver Disease, University of Southern California, Keck School of MedicineLD
Laurie D. DeLeve
Affiliations and expertise
MD, PhD, Professor of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California Keck School of MedicineRead Drug-Induced Liver Disease on ScienceDirect