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Book Details
Abstract
Dr. Rustgi has assembled the leading experts in the management of Heptatitis B to present the current treatment and clinical course for diagnosis and management of the disease. Articles are devoted to: Drug metabolism in the liver; Mechanism of Liver Damage including the RUCAM scale; Drug-induced acute liver failure; Epidemiology and genetic risk factors; Adverse drug reactions: type A (intrinsic or pharmacological) or type B (idiosyncratic); Pathology of injury including phenotypes; The clinical course of drug-induced liver disease; Environmental factors of drug hepatotoxicity; Newer agents in drug hepatotoxicity; Drug hepatotoxicity: herbal products; Drug hepatotoxicity: models including “human on a chip and zebrafish; Acute and chronic liver failure from drugs: impact on the kidney; and Management of acute hepatotoxicity including medical agents and liver support systems. Readers will come away with the cutting edge science behind the latest innovations in the treatment of Hepatitis B.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Drug Hepatotoxicity\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| CONSULTING EDITOR | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Drug-induced Hepatotoxicity…A Topic Where We Don't Know Enough! | vii | ||
| Drug Metabolism in the Liver | vii | ||
| Drug-Induced Liver Disease: Clinical Course | vii | ||
| Mechanisms of Drug-Induced Hepatotoxicity | vii | ||
| Epidemiology and Genetic Risk Factors of Drug Hepatotoxicity | vii | ||
| Adverse Drug Reactions: Type A (Intrinsic) or Type B (Idiosyncratic) | viii | ||
| Phenotypes and Pathology of Drug-Induced Liver Disease | viii | ||
| Drug Hepatotoxicity: Environmental Factors | viii | ||
| Drug Hepatotoxicity: Newer Agents | viii | ||
| Herbal and Dietary Supplement–Induced Liver Injury | ix | ||
| Drug-Induced Acute Liver Failure | ix | ||
| Management of Acute Hepatotoxicity Including Medical Agents and Liver Support Systems | ix | ||
| Drug Metabolism, Drug Interactions, and Drug-Induced Liver Injury in Living Donor Liver Transplant Patients | x | ||
| Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy | x | ||
| CLINICS IN LIVER DISEASE\r | xi | ||
| FORTHCOMING ISSUES | xi | ||
| May 2017 | xi | ||
| August 2017 | xi | ||
| November 2017 | xi | ||
| RECENT ISSUES | xi | ||
| November 2016 | xi | ||
| August 2016 | xi | ||
| May 2016 | xi | ||
| Preface:\rDrug-induced Hepatotoxicity…A Topic Where We Don't Know Enough! | xiii | ||
| Drug Metabolism in the Liver | 1 | ||
| Key points | 1 | ||
| INTRODUCTION | 1 | ||
| DRUG METABOLISM PATHWAYS | 2 | ||
| Phase I Pathway | 2 | ||
| Phase II Pathways | 4 | ||
| Uridine 5'-diphospho-glucuronosyltransferases | 6 | ||
| Sulfotransferases | 6 | ||
| N-acetyltransferases | 7 | ||
| Glutathione S-transferases | 7 | ||
| Thiopurine S-methyltransferases | 8 | ||
| Catechol O-methyltransferases | 8 | ||
| Phase III Pathways | 8 | ||
| SITES OF DRUG METABOLISM | 9 | ||
| Liver | 9 | ||
| Gut | 10 | ||
| Kidney | 11 | ||
| FACTORS AFFECTING THE METABOLISM OF DRUGS | 11 | ||
| Age | 12 | ||
| Gender | 12 | ||
| Pregnancy | 13 | ||
| Liver Diseases | 13 | ||
| Kidney Diseases | 14 | ||
| Diabetes Mellitus | 14 | ||
| Solid Organ Transplantation | 14 | ||
| Medication (Drug-Drug Interactions) | 15 | ||
| Polymorphism | 15 | ||
| SUMMARY | 15 | ||
| REFERENCES | 16 | ||
| Drug-Induced Liver Disease | 21 | ||
| Key points | 21 | ||
| INTRODUCTION | 21 | ||
| DISCUSSION | 22 | ||
| Diagnosis | 22 | ||
| Pattern of Injury | 26 | ||
| Clinical Course | 26 | ||
| Acute Liver Failure, Death, Liver Transplantation | 27 | ||
| Persistent Liver Abnormalities/Chronic Drug-Induced Liver Injury | 30 | ||
| SUMMARY | 32 | ||
| REFERENCES | 32 | ||
| Mechanisms of Drug-Induced Hepatotoxicity | 35 | ||
| Key points | 35 | ||
| CELL DEATH (APOPTOSIS AND NECROSIS) | 37 | ||
| REACTIVE METABOLITE FORMATION (BIOACTIVATION) | 38 | ||
| DRUG TRANSPORTER–MEDIATED DRUG-INDUCED HEPATOTOXICITY | 39 | ||
| IMMUNE-MEDIATED RESPONSE | 39 | ||
| MITOCHONDRIAL DYSFUNCTION | 39 | ||
| ACTIVATION OF STRESS SIGNALING PATHWAYS | 40 | ||
| FACTORS THAT CONTRIBUTE TO DRUG-INDUCED LIVER INJURY | 40 | ||
| Age | 40 | ||
| Gender | 40 | ||
| Genetic Factors | 41 | ||
| Immune Response | 41 | ||
| Daily Dose of Drug and Metabolism | 42 | ||
| Acetaminophen | 42 | ||
| Mechanism | 42 | ||
| Reactive metabolites | 42 | ||
| Oxidative stress | 42 | ||
| Mitochondrial injury | 43 | ||
| Activation of signaling kinase-c-jun N-terminal kinase activation | 43 | ||
| Isoniazid | 43 | ||
| Metabolism and reactive metabolites | 43 | ||
| Immune-mediated mechanisms | 44 | ||
| Risk factors associated with isoniazid -induced hepatotoxicity | 44 | ||
| Nevirapine | 44 | ||
| Reactive metabolites in nevirapine hepatotoxicity | 45 | ||
| Immune-mediated reactions | 45 | ||
| Azoles—ketoconazole | 45 | ||
| Amoxicillin-Clavulanic Acid | 46 | ||
| Troglitazone | 46 | ||
| Herbal Medicines and Dietary Supplements | 47 | ||
| ROUSSEL UCLAF CAUSALITY ASSESSMENT METHOD | 47 | ||
| SUMMARY | 48 | ||
| REFERENCES | 48 | ||
| Epidemiology and Genetic Risk Factors of Drug Hepatotoxicity | 55 | ||
| Key points | 55 | ||
| INTRODUCTION | 55 | ||
| EPIDEMIOLOGY | 55 | ||
| Incidence | 55 | ||
| Pattern of Injury | 58 | ||
| Specific Drugs | 59 | ||
| Herbal and Dietary Supplements | 59 | ||
| Demographic Factors | 60 | ||
| Age | 60 | ||
| Gender | 60 | ||
| Race/ethnicity | 61 | ||
| Daily Dose and Polypharmacy | 61 | ||
| Hospitalization | 61 | ||
| Underlying Liver Disease | 61 | ||
| GENETIC ASSOCIATIONS WITH DRUG-INDUCED LIVER INJURY | 62 | ||
| Background | 62 | ||
| Goals of Genetic Studies | 63 | ||
| Candidate Gene Studies | 63 | ||
| Genome-wide Association Studies and Whole-Genome Sequencing Studies | 65 | ||
| Key Genetic Findings | 67 | ||
| Future Directions for Genetic Analysis of Drug-Induced Liver Injury | 67 | ||
| SUMMARY | 67 | ||
| REFERENCES | 67 | ||
| Adverse Drug Reactions | 73 | ||
| Key points | 73 | ||
| INTRODUCTION | 73 | ||
| TYPE A (INTRINSIC) ADVERSE DRUG REACTIONS | 74 | ||
| TYPE B (IDIOSYNCRATIC) ADVERSE DRUG REACTIONS | 74 | ||
| Risk Factors | 77 | ||
| Presentation and Diagnosis | 78 | ||
| Management | 79 | ||
| Idiosyncratic Reaction Classifications | 79 | ||
| PREDICTING DRUG-INDUCED LIVER INJURY | 80 | ||
| RESOURCES FOR CLINICIANS | 80 | ||
| EVOLUTION OF DRUG-INDUCED INJURY RECOGNITION AND MANAGEMENT | 81 | ||
| Isoniazid | 81 | ||
| Tumor Necrosis Factor-α Antagonists | 82 | ||
| Viral Hepatitis Treatments | 83 | ||
| OTHER EXAMPLES AND MANAGEMENT STRATEGIES FOR IDIOSYNCRATIC DRUG-INDUCED INJURY | 83 | ||
| 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors | 83 | ||
| Herbal and Alternative Medicine | 84 | ||
| SUMMARY | 84 | ||
| REFERENCES | 84 | ||
| Phenotypes and Pathology of Drug-Induced Liver Disease | 89 | ||
| Key points | 89 | ||
| CLINICAL SYNDROMES AND HISTOLOGIC CORRELATES | 89 | ||
| DIAGNOSIS OF DRUG-INDUCED LIVER DISEASE | 91 | ||
| MORPHOLOGIC FEATURES THAT SUGGEST DRUG-INDUCED LIVER INJURY | 95 | ||
| REFERENCES | 100 | ||
| Drug Hepatotoxicity | 103 | ||
| Key points | 103 | ||
| INTRODUCTION | 103 | ||
| GEOGRAPHIC VARIATION | 104 | ||
| EXCESSIVE ALCOHOL CONSUMPTION | 105 | ||
| SMOKING | 106 | ||
| INFECTION AND INFLAMMATION | 107 | ||
| CIRCADIAN RHYTHM AND THE HEPATIC CLOCK | 108 | ||
| GUT MICROBIOME | 108 | ||
| ENVIRONMENTAL POLLUTION | 108 | ||
| SUMMARY | 109 | ||
| REFERENCES | 109 | ||
| Drug Hepatotoxicity | 115 | ||
| Key points | 115 | ||
| INTRODUCTION | 115 | ||
| ANTIBIOTICS | 116 | ||
| Amoxicillin/Clavulanate | 116 | ||
| Cephalosporins | 116 | ||
| Azithromycin | 117 | ||
| Quinolones | 117 | ||
| Newer Antiretrovirals | 117 | ||
| MOLECULAR TARGETED THERAPY | 119 | ||
| Tyrosine Kinase Inhibitors | 119 | ||
| Monoclonal Antibodies | 119 | ||
| CARDIOVASCULAR AGENTS | 123 | ||
| Novel or Non–Vitamin K Oral Anticoagulants | 123 | ||
| Newer Antiplatelet Agents | 124 | ||
| NEWER ANTIDIABETIC AGENTS | 125 | ||
| CENTRAL NERVOUS SYSTEM AGENTS | 125 | ||
| Newer Antiepileptic Drugs | 125 | ||
| Newer Antidepressants | 126 | ||
| Newer Antipsychotic Agents | 127 | ||
| REFERENCES | 127 | ||
| Herbal and Dietary Supplement–Induced Liver Injury | 135 | ||
| Key points | 135 | ||
| INTRODUCTION | 135 | ||
| Epidemiology | 135 | ||
| REGULATION AND QUALITY CONTROL | 137 | ||
| CLINICAL PRESENTATION AND DIAGNOSIS | 137 | ||
| PATTERN OF INJURY | 138 | ||
| UNIQUE ASPECTS OF HERBAL AND DIETARY SUPPLEMENT–INDUCED LIVER INJURY | 139 | ||
| HEPATOTOXICITY ASSOCIATED WITH SPECIFIC HERBAL AND DIETARY SUPPLEMENTS | 139 | ||
| Anabolics | 139 | ||
| Black Cohosh | 141 | ||
| Germander | 141 | ||
| Green Tea | 142 | ||
| Pyrrolizidine Alkaloids | 142 | ||
| Kava Kava | 142 | ||
| Traditional Chinese Medicine | 142 | ||
| PROPRIETARY MIXES | 143 | ||
| Herbalife | 143 | ||
| OxyELITE Pro | 143 | ||
| Hydroxycut | 143 | ||
| Move Free Advanced | 143 | ||
| SUMMARY | 144 | ||
| REFERENCES | 144 | ||
| Drug-Induced Acute Liver Failure | 151 | ||
| Key points | 151 | ||
| INTRODUCTION | 151 | ||
| CLINICAL FEATURES | 152 | ||
| Encephalopathy | 152 | ||
| Coagulopathy | 153 | ||
| Other Manifestations | 153 | ||
| DIAGNOSIS | 153 | ||
| Definition | 153 | ||
| Establishing Diagnosis | 154 | ||
| MANAGEMENT | 154 | ||
| Identification of the High-Risk Individual | 154 | ||
| Treatment of Drug-Induced Liver Injury | 155 | ||
| Specific Measures | 155 | ||
| Hepatic encephalopathy and cerebral edema | 155 | ||
| Coagulopathy | 156 | ||
| Sepsis | 156 | ||
| Metabolic derangements and renal failure | 157 | ||
| Circulatory and respiratory issues | 157 | ||
| Liver-Assist Devices | 157 | ||
| Liver Transplantation | 158 | ||
| SUMMARY | 158 | ||
| REFERENCES | 158 | ||
| Management of Acute Hepatotoxicity Including Medical Agents and Liver Support Systems | 163 | ||
| Key points | 163 | ||
| INTRODUCTION | 163 | ||
| CHARACTERIZATION OF DRUG-INDUCED LIVER INJURY | 164 | ||
| Workup and Differential Diagnosis | 164 | ||
| Histopathologic Features of Drug-Induced Liver Injury and the Role of Liver Biopsy | 165 | ||
| Differentiation of Drug-Induced Liver Injury from Autoimmune Hepatitis | 165 | ||
| Determination of Causality | 165 | ||
| MANAGEMENT OF DRUG-INDUCED LIVER INJURY | 166 | ||
| Drugs That Have Antidotes | 166 | ||
| Acetaminophen | 166 | ||
| Amanita phalloides | 168 | ||
| Valproic acid | 169 | ||
| Additional Pharmacologic Therapeutics | 170 | ||
| Steroids | 170 | ||
| Ursodeoxycholic acid | 170 | ||
| Cholestyramine | 170 | ||
| N-acetylcysteine | 170 | ||
| Symptom Management | 171 | ||
| Rechallenging | 171 | ||
| EXTRACORPOREAL LIVER SUPPORT SYSTEMS | 171 | ||
| Artificial Liver Support Systems | 171 | ||
| Molecular adsorbent reticulating system | 171 | ||
| Fractionated plasma and adsorption | 172 | ||
| Single-pass albumin dialysis | 172 | ||
| High-volume plasma exchange | 173 | ||
| Bioartificial Liver Support Systems | 173 | ||
| Extracorporeal liver assist device | 174 | ||
| Porcine hepatocyte-based bioartificial liver | 174 | ||
| Emerging Therapies | 175 | ||
| SUMMARY | 175 | ||
| REFERENCES | 175 | ||
| Drug Metabolism, Drug Interactions, and Drug-Induced Liver Injury in Living Donor Liver Transplant Patients | 181 | ||
| Key points | 181 | ||
| INTRODUCTION | 181 | ||
| DRUG THERAPY IN LIVING DONOR LIVER TRANSPLANT PATIENTS | 182 | ||
| Immunosuppression | 182 | ||
| Calcineurin Inhibitors | 183 | ||
| Mycophenolic Acid | 186 | ||
| Mammalian Target of Rapamycin Inhibitors | 186 | ||
| PHYSIOLOGIC CHANGES AFFECTING PHARMACOKINETICS AFTER LIVING DONOR LIVER TRANSPLANT | 186 | ||
| Liver Regeneration | 186 | ||
| Graft Size | 187 | ||
| Liver Ischemia/Reperfusion Injury | 187 | ||
| PHARMACOKINETIC CHANGES IN LIVING DONOR LIVER TRANSPLANT | 188 | ||
| PHARMACOKINETICS OF CERTAIN MEDICATIONS IN LIVING DONOR LIVER TRANSPLANT PATIENTS | 188 | ||
| Tacrolimus | 188 | ||
| Cyclosporine A | 189 | ||
| Mycophenolic Acid | 189 | ||
| Sirolimus (Rapamycin)/Everolimus | 190 | ||
| IDIOSYNCRATIC DRUG-INDUCED LIVER INJURY IN THE LIVING DONOR LIVER TRANSPLANT SETTING | 190 | ||
| HEPATOTOXICITY OF FREQUENTLY USED DRUGS IN LIVING DONOR LIVER TRANSPLANT RECIPIENTS AND DRUG INTERACTIONS | 191 | ||
| Immunosuppressants | 191 | ||
| Antibiotics | 192 | ||
| Antifungals | 192 | ||
| Antiviral Agents | 192 | ||
| Other Agents | 192 | ||
| SUMMARY | 192 | ||
| REFERENCES | 193 | ||
| Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy | 197 | ||
| Key points | 197 | ||
| CURRENT STATUS OF DRUG HEPATOTOXICITY PREDICTION USING MAMMALIAN IN VIVO MODELS | 199 | ||
| IN VITRO MODELS FOR PREDICTING DRUG-INDUCED HEPATOTOXICITY | 201 | ||
| PAST EXPERIENCES WITH IN VITRO LIVER ABSORPTION, DISTRIBUTION, METABOLISM, EXCRETION, AND TOXICITY MODELS PREDICTING HUMAN ... | 203 | ||
| ZEBRAFISH LARVAE AS A LOW-COST, MEDIUM-THROUGHPUT, WHOLE-ORGANISM PLATFORM TO PREDICT DRUG HEPATOTOXICITY | 203 | ||
| CASE STUDY: USING “FIT-FOR-PURPOSE” ASSAY EVALUATIONS TO RANK-ORDER COMPOUNDS | 206 | ||
| EMERGENCE OF HUMAN TISSUE AND ORGAN MODELS | 207 | ||
| PROSPECTUS: MOVING TO THE FUTURE: INTEGRATING THE HUMAN LIVER ON A CHIP, COMPUTATIONAL MODELS, AND QUANTITATIVE SYSTEMS PHA ... | 208 | ||
| REFERENCES | 210 |