Zakim and Boyer's Hepatology A Textbook of Liver Disease

Author: Arun Sanyal, MBBS, MD, Thomas Boyer, MD, Keith Lindor, MD, Norah Terrault, MD, MPH
Affiliation:
Publisher: Elsevier Health Sciences
Publication Date: 2018
ISBN 10: 032337591X
ISBN 13: 9780323375917
eISBN: 9780323446570
Edition: 7th

Description:

Get the authoritative, up-to-date information you need on liver disease from the 7th Edition of the most trusted reference worldwide. Covering both basic science and recent clinical developments, this revised edition by Drs. Arun J. Sanyal, Thomas D. Boyer, Norah A. Terrault, and Keith D. Lindor, provides an in-depth, comprehensive look at the pathophysiology, diagnostic, and treatment information related to the liver. More than 1,100 figures and tables, many new and in full color, highlight completely updated content throughout. Expert, international authorship and comprehensive, easy-to-access information makes this edition the gold standard in the field of hepatology.

Table of Contents

Front Matter

  • ABOUT
  • Notices
  • Contributors
  • Preface

Section I Basics

    1: Anatomy and Cellular Functions of the Liver

    • Introduction
    • Conclusion
    • References

    2: Bile Acids and Bile Flow: New Functions of Old Molecules

    • Introduction
    • Pathways of Bile Acid Synthesis From Cholesterol
    • Defects in Bile Acid Synthesis Causing Metabolic Liver Disease and Syndromes of Fat-Soluble Vitamin Malabsorption
    • Bile Acids as Signaling Integrators of Metabolism
    • Conclusion
    • References

    3: Intestinal Microbiome and the Liver

    • Historical Perspective and Technology Development
    • General Principles and the Conceptual Construct: the Gut-Liver Axis in Homeostasis and Implications for Liver Diseases
    • Role of the Intestinal Microbiome in Specific Liver Diseases
    • Interventions to Modulate the Intestinal Microbiome
    • Conclusion
    • References

    4: The Liver as an Immune Organ

    • Introduction
    • Immune Cell Populations and Their Function in the Liver
    • Functions of the Immune System in the Liver
    • Inflammation and Innate Immunity in Liver Diseases
    • Autoimmunity in Liver Diseases
    • Liver Fibrosis and Immune Response
    • Inflammation and Immunity in Liver Cancer
    • Conclusion
    • References

    5: The Liver’s Response to Injury: Inflammation and Fibrosis

    • Introduction
    • Hepatic Inflammation as a Driver of Hepatic Fibrosis
    • Cell Types That Participate in Inflammation and Fibrosis
    • Key Pathways in Hepatic Inflammation and Fibrosis
    • MicroRNAs in Hepatic Inflammation and Fibrosis
    • Conclusion
    • References

    6: Stem Cells and Hepatocyte Transplantation

    • Introduction
    • Preclinical and Background Studies Enabling Clinical Translation
    • Integration of Hepatocytes in the Recipient’s Liver
    • Initial Clinical Studies
    • Hepatocyte Transplantation for Acute Liver Failure
    • Hepatocyte Transplantation for Metabolic Liver Disease
    • Patient Selection for Hepatocyte Transplantation
    • Challenges and Solutions Regarding Hepatocyte Transplantation
    • Conclusion
    • References

Section II Management and Assessment of Liver Disease

    7: Approach to Jaundice and Abnormal Liver Function Test Results

    • Introduction
    • Liver Functions Tests: Anatomic, Physiologic, and Pathologic Basis
    • Clinical Approach to Abnormal Liver Function Test Results
    • Conclusion
    • References

    8: Noninvasive Assessment of Disease Progression

    • Introduction
    • Conclusion
    • References

    9: Molecular and Genetics-Based Diagnostics

    • Introduction
    • References

    10: Imaging in Assessment of Liver Disease and Lesions

    • Introduction
    • Diffuse Liver Disease
    • Focal Hepatic Lesions
    • Benign Lesions
    • Neoplastic Lesions
    • Conclusion
    • References

    11: Evaluation of the Hepatic Mass

    • Introduction
    • Imaging Modalities
    • Hemangioma
    • Focal Nodular Hyperplasia
    • Hepatic Adenoma
    • Hepatic Cysts
    • Bile Duct Hamartomas
    • Biliary Cystadenoma
    • Hepatic Abscess
    • Hepatocellular Carcinoma
    • Cholangiocarcinoma
    • Metastases
    • Conclusion
    • References

    12: Assessment of Liver Histology

    • Introduction
    • Morphologic Lesions of Hepatitis
    • Cholestatic Lesions
    • Hepatic Parenchymal Manifestations of Vascular Lesions
    • Conclusion
    • References

    13: Critical Care Management of Patients With Liver Disease

    • Introduction
    • Sepsis/Septic Shock
    • Altered Mental Status
    • Upper GI Bleeding
    • General Critical Care Issues
    • ICU Jaundice and Liver Function Test (LFT) Abnormalities (see Chapter 57)
    • Hypoxic/Ischemic Hepatitis (Shock Liver)
    • Acute Acalculous Cholecystitis
    • Prophylaxis for Venous Thromboembolic Disease (VTE)
    • Primary SBP Prophylaxis
    • Acid-Base and Electrolyte Disorders in Cirrhosis
    • Procedure Risk of Bleeding in Liver Disease
    • Prognostication
    • Conclusion
    • References

Section III Clinical Consequences of Chronic Liver Disease

    14: Neurologic Consequences of Liver Disease

    • Introduction
    • Historical Background
    • Pathogenesis of Hepatic Encephalopathy
    • Spectrum and Nomenclature of Hepatic Encephalopathy
    • Spectrum of Neurocognitive Impairment in Cirrhosis
    • Importance of Hepatic Encephalopathy
    • Diagnosis of Hepatic Encephalopathy
    • Management and Treatment of Hepatic Encephalopathy
    • Hepatic Encephalopathy Resistant to Therapy or Persistent Hepatic Encephalopathy
    • Nutrition
    • Liver Transplantation
    • References

    15: Ascites and Hyponatremia

    • Introduction
    • Epidemiology
    • Pathogenesis
    • Clinical Features
    • Diagnosis
    • Differential Diagnosis
    • Associated Conditions
    • Disease Complication: Spontaneous Bacterial Peritonitis
    • Treatment of Ascites
    • Treatment of Conditions Associated With Ascites
    • Prognosis and Natural History
    • Conclusion
    • References

    16: Portal Hypertension Related to Bleeding

    • Anatomy of the Portal Venous System
    • Physiologic Principles of the Portal Circulation
    • Portal Hypertension
    • Conclusion
    • References

    17: Renal Failure in Cirrhosis

    • Introduction
    • Measurement of Renal Function
    • The Concept of Acute Kidney Injury
    • The Application of the Various AKI Diagnostic Criteria to Cirrhotic Patients
    • How Well Do These Various Diagnostic Criteria of AKI Serve Cirrhotic Patients?
    • Revised Consensus Recommendations of the IAC on the Diagnosis of Acute Kidney Injury in Cirrhosis
    • The Diagnostic Criteria for Hepatorenal Syndrome
    • Pathophysiology of Acute Kidney Injury and Hepatorenal Syndrome
    • Approach to a Patient With Cirrhosis Who Presents With Renal Dysfunction
    • Differential Diagnoses of Acute Kidney Injury
    • Treatment of AKI
    • Prevention of Hepatorenal Syndrome–Acute Kidney Injury
    • Chronic Kidney Disease in Cirrhosis
    • Conclusion
    • References

    18: Cardiopulmonary Complications of Cirrhosis

    • Introduction
    • Definition and Diagnosis of Cirrhotic Cardiomyopathy
    • Natural History and Epidemiology
    • Pathogenesis of Cirrhotic Cardiomyopathy
    • Clinical Features
    • Management of Cirrhotic Cardiomyopathy
    • Pulmonary Vascular Complications in Liver Disease
    • Conclusion
    • References

    19: The Hemostatic and Hematopoietic System in Liver Disease

    • Introduction
    • Conclusion
    • References

    20: Acute Liver Failure

    • Introduction
    • Causes and Epidemiology
    • Pathogenesis of the Syndrome of Acute Liver Failure
    • Cardiovascular Consequences
    • Pulmonary Consequences
    • Renal and Electrolyte Disturbances
    • Hematologic Disturbances
    • Breakdown of Host Immune Defenses
    • Gastrointestinal Consequences
    • Neurologic Consequences
    • Hepatic Encephalopathy
    • Intracranial Hypertension and Cerebral Edema
    • Management of Acute Liver Failure
    • References

    21: Acute-on-Chronic Liver Failure

    • Introduction
    • Definition
    • Precipitating Events
    • Prevalence
    • Natural History
    • Economic Burden
    • Pathophysiology
    • Prognostic Models
    • Potential Prognostic Biomarkers
    • Management of ACLF
    • Conclusion
    • References

Section IV Specific Diseases

    22: Epidemiology and Pathogenesis of Alcoholic Liver Disease

    • Introduction
    • Epidemiology of Alcoholic Liver Disease
    • Ethanol Metabolism
    • Alcoholic Fatty Liver
    • Alcoholic Steatohepatitis
    • Alcoholic Hepatitis
    • Alcoholic Fibrosis and Cirrhosis
    • Alcoholic Liver Cancer
    • Risk Factors for Alcoholic Liver Disease
    • Animal Models of Alcoholic Liver Disease
    • Comorbid Conditions
    • Therapeutic Targets
    • Conclusion
    • References

    23: Natural History and Cofactors of Alcoholic Liver Disease

    • Introduction
    • Pattern, Dosage, and Types of Alcohol Consumption and Risk of Alcoholic Liver Disease
    • Natural History of Alcoholic Liver Disease
    • Special Considerations for Factors Influencing the Natural History of Alcoholic Liver Disease
    • Conclusion
    • References

    24: Prevention and Management of Alcoholic Liver Disease

    • Prevention of Alcoholic Liver Disease
    • Treatment of Alcoholic Liver Disease
    • Treatment of Alcoholic Cirrhosis
    • Conclusion
    • References

    25: Pathogenesis of Nonalcoholic Fatty Liver Disease

    • Introduction
    • Making Foie Gras
    • Nonalcoholic Fatty Liver Disease: An Adiposopathy
    • Nonalcoholic Fatty Liver Disease and Insulin Resistance: The Chicken and Egg Paradox
    • Oxidative Stress: Overburning Fat
    • Lipotoxicity: The Ugly and the Beast
    • Endoplasmic Reticulum Stress: A Tree Born Crooked Cannot Straighten Its Trunk
    • Autophagy: The Ouroboros Housekeeper
    • Sterile Inflammation: When the Aggressor Is Fat
    • Dysbiota: The Unwanted Guests
    • Cell Death: A Cry for Help
    • Fibrogenesis: To Heal or to Scar
    • Conclusion
    • References

    26: Epidemiology, Natural History, and Evaluation of Nonalcoholic Fatty Liver Disease

    • Introduction
    • Epidemiology
    • Natural History of Nonalcoholic Fatty Liver Disease
    • Modifiers of Progression of Nonalcoholic Fatty Liver Disease
    • Clinical Features of Nonalcoholic Fatty Liver Disease
    • Evaluation of Nonalcoholic Fatty Liver Disease
    • References

    27: Management of Nonalcoholic Fatty Liver Disease and Metabolic Syndrome

    • Introduction
    • Associated Conditions
    • Treatment
    • Conclusion
    • References

    28: Virology and Pathogenesis of Hepatitis C

    • Introduction
    • Overview of the Virion
    • Model Systems
    • Structure and Function of the Viral Proteins
    • The Virus and Its Life Cycle
    • Pathogenesis of Hepatitis C Virus Infection
    • Conclusion
    • References

    29: Epidemiology, Natural History, and Diagnosis of Hepatitis C

    • Discovery of Hepatitis C Virus
    • Hepatitis C Virus Transmission
    • Natural History of Acute Hepatitis C Infection
    • Natural History of Chronic Hepatitis C
    • Hepatitis C Virus in Children
    • Conclusion
    • References

    30: Treatment of Hepatitis C

    • Introduction
    • The Evolution of Hepatitis C Virus Therapies
    • Goals of Hepatitis C Virus Treatment
    • Candidacy for Antiviral Therapy and Pretreatment Assessments
    • Hepatitis C Virus Treatment Regimens
    • Monitoring During and After Hepatitis C Virus Therapy
    • Special Populations
    • Conclusion
    • References

    31: Virology and Pathogenesis of Hepatitis B

    • Introduction
    • Hepatitis B Virus: Host and Model Systems
    • Hepatitis B Virus Biology
    • Immunopathogenesis of Hepatitis B Virus Infection
    • Conclusion
    • References

    32: Epidemiology, Diagnosis, and Natural History of Hepatitis B

    • Introduction
    • Epidemiology
    • Diagnosis
    • Natural History
    • Conclusion
    • References

    33: Treatment of Hepatitis B

    • Introduction
    • Indications for Treatment
    • Treatment End Points
    • Nucleoside/Nucleotide Analogs
    • Pegylated Interferon
    • New Treatments
    • Management of Chronic Hepatitis B in Special Populations
    • Vaccination
    • Conclusion
    • References

    34: Hepatitis D

    • Introduction
    • Historical Perspective
    • Virology
    • Experimental Models for Study of Hepatitis Delta Virus
    • Epidemiology of Hepatitis Delta Virus Infection
    • Diagnosis and Diagnostic Tests
    • Clinical Features and Natural History of Hepatitis Delta Virus Infection
    • Monitoring and Surveillance
    • Prevention and Treatment
    • References

    35: Hepatitis A

    • Introduction
    • Molecular Virology
    • Pathogenesis
    • Epidemiology
    • Clinical Course
    • Diagnosis
    • Treatment of Acute Infection
    • Prevention
    • Conclusion
    • References

    36: Hepatitis E

    • Introduction
    • History of Hepatitis E
    • Virology
    • Epidemiology
    • Acute Hepatitis E Virus Infection
    • Chronic Hepatitis E Virus Infection
    • Complications of Hepatitis E Virus Infection
    • Diagnosis
    • Treatment
    • Hepatitis E Virus and the Blood Supply
    • Prevention
    • Conclusion
    • References

Section V Liver and Other Infections

    37: HIV and the Liver

    • Introduction
    • Epidemiology of Liver Disease in Those With HIV Infection
    • Mechanisms of Liver Disease Unique to HIV
    • Liver Biopsy and Noninvasive Markers of Liver Disease Severity
    • Viral Hepatitis in Those With HIV Infection
    • Conclusion
    • Acknowledgments
    • References

    38: Liver Disease Associated With Systemic Viral Infection

    • Introduction
    • Opportunistic Viral Infections (Table 38-1)
    • Systemic Viral Infections (Table 38-2)
    • Viral Hemorrhagic Fevers (Table 38-3)
    • Conclusion
    • References

    39: Parasitic Liver Disease

    • Introduction
    • Schistosomiasis
    • Echinococcosis (Echinococcus granulosus and Echinococcus multilocularis)
    • Amebiasis
    • Hepatobiliary Parasites
    • Ascaris lumbricoides
    • Human Immunodeficiency Virus and Parasitic Infections
    • Conclusion
    • References

    40: Bacterial and Miscellaneous Infections of the Liver

    • Introduction
    • Bacterial Infections in Cirrhosis
    • Pyogenic Liver Abscess
    • Peliosis Hepatis
    • Disseminated Bacterial Infections With Involvement of the Liver
    • Bacterial Infections in Liver Transplant Recipients
    • Fungal Infection Prophylaxis in Liver Transplant Recipients
    • Commonly Encountered Fungal Infections of the Liver
    • Conclusion
    • References

Section VI Immune Diseases and the Liver

    41: Autoimmune Hepatitis

    • Introduction
    • History and Epidemiology
    • Clinical Presentation
    • Histology
    • Diagnosis
    • Treatment and Management
    • Conclusion
    • References

    42: Primary Biliary Cholangitis

    • Introduction
    • Epidemiology
    • Treatment
    • Conclusion
    • References

    43: Primary and Secondary Sclerosing Cholangitis

    • Introduction
    • Variants of Sclerosing Cholangitis
    • Epidemiology
    • Pathogenesis
    • Clinical Features
    • Natural History
    • Pretransplant Management
    • Transplant for Primary Sclerosing Cholangitis
    • Conclusion
    • References

Section VII Vascular Diseases of the Liver

    44: Budd-Chiari Syndrome and Sinusoidal Obstruction Syndrome

    • Introduction
    • Conclusion
    • References

    45: Portal and Splenic Vein Thrombosis

    • Introduction
    • Portal Vein Thrombosis in the Absence of Underlying Liver Disease
    • Portal Vein Thrombosis in Patients With Cirrhosis
    • Portal Vein Thrombosis in Children
    • Isolated Splenic Vein Thrombosis
    • Conclusion
    • References

Section VIII Tumors of the Liver

    46: Hepatocellular Carcinoma

    • Introduction
    • Epidemiology
    • Risk Factors
    • Prevention
    • Pathogenesis
    • Hepatocellular Carcinoma Surveillance
    • Viral Hepatitis
    • Staging
    • Pathology
    • Histologic Variants
    • Radiology
    • Treatment
    • Conclusion
    • References

    47: Cholangiocarcinoma

    • Introduction
    • Epidemiology and Risk Factors
    • Molecular Pathogenesis
    • Pathology and Classification
    • Clinical Presentation and Diagnosis
    • Therapy
    • Conclusion
    • References

    48: Other Malignant Hepatic Tumors

    • Introduction
    • Fibrolamellar Hepatocellular Carcinoma
    • Hepatoblastoma
    • Biliary Cystadenocarcinoma
    • Hepatic Epithelioid Hemangioendothelioma
    • Angiosarcoma
    • Hepatic Lymphoma
    • Hepatic Metastasis
    • Conclusion
    • References

    49: Benign Liver Tumors

    • Introduction
    • Hepatic Hemangiomas
    • Focal Nodular Hyperplasia
    • Hepatocellular Adenoma
    • Nodular Regenerative Hyperplasia
    • Conclusion
    • References

Section IX Liver Transplantation

    50: Pretransplant Evaluation and Care

    • Introduction
    • Pretransplant Evaluation
    • Repeated Transplant: Recurrent Disease and Graft Failure
    • Contraindications for Liver Transplantation: Absolute and Relative
    • Monitoring and Management
    • Allocation and Distribution Systems
    • Donor Liver Choices
    • Conclusion
    • References

    51: Transplantation of the Liver

    • Introduction
    • Indications and Contraindications to Liver Transplantation
    • Candidate Evaluation and Listing
    • Liver Transplantation: Deceased and Living Donors
    • Liver Transplantation: The Recipient Operation
    • Early Postoperative Complications of Liver Transplantation
    • Current Outcomes of Liver Transplantation
    • Conclusion
    • References

    52: Post–Liver Transplant Management

    • Introduction
    • Morbidity and Mortality After Liver Transplantation
    • Approach to the Care of the Liver Transplant Recipient
    • Complications Occurring After Liver Transplantation
    • Reproductive Health
    • Repeated Transplantation
    • Conclusion
    • References

    53: Recurrent Primary Disease After Liver Transplantation

    • Introduction
    • Hepatitis B and Liver Transplantation
    • Hepatitis C and Liver Transplantation
    • Primary Biliary Cholangitis and Liver Transplantation
    • Primary Sclerosing Cholangitis and Liver Transplantation
    • Autoimmune Hepatitis and Liver Transplantation
    • Nonalcoholic Fatty Liver and Liver Transplantation
    • Alcoholic Liver Disease and Liver Transplantation
    • Metabolic Liver Diseases and Liver Transplantation
    • Conclusion
    • References

Section X Liver Affected by Other Conditions or Diseases

    54: The Liver in Pregnancy

    • Introduction
    • Changes in Liver Anatomy and Function During Normal Pregnancy
    • Liver-Related Symptoms and Physical Examination in Pregnancy
    • Hepatobiliary Ultrasonography in Pregnancy
    • Liver Diseases Not Specific to Pregnancy
    • Pregnancy and Vascular Liver Diseases
    • Portal Vein Thrombosis in Pregnancy
    • Budd-Chiari Syndrome and Pregnancy
    • Hereditary Hemorrhagic Telangiectasia
    • Cirrhosis and Portal Hypertension
    • Management of Variceal Bleeding
    • Management of Labor and Delivery
    • Hepatobiliary Disease During Pregnancy
    • Pregnancy and Liver Transplant
    • The Evaluation of a Liver Mass During Pregnancy
    • Liver Diseases Unique to Pregnancy
    • Consultation of Liver Patient Regarding Pregnancy
    • References

    55: Nutrition and the Liver

    • Introduction
    • What Is Sarcopenia in Cirrhosis?
    • How Is Sarcopenia Diagnosed in Cirrhosis?
    • Clinical Significance of Sarcopenia in Cirrhosis
    • Contributors to Sarcopenia in Cirrhosis
    • Mechanisms of Sarcopenia in Cirrhosis
    • Therapeutic Options for Sarcopenia
    • Post–Liver Transplant Sarcopenia
    • Nonalcoholic Fatty Liver Disease and Nutrition
    • Conclusion
    • References

    56: Drug-Induced Liver Injury

    • Introduction
    • Epidemiology, Common Causes, and Clinical Risk Factors
    • Causality Assessment
    • Mechanisms of Hepatic Injury Due to Drugs and Chemicals
    • Immunologic Mechanisms of Drug-Induced Liver Injury
    • Clinicopathologic Patterns of Drug-Induced Liver Injury
    • Macrovesicular or Mixed Microvesicular and Macrovesicular Steatosis
    • Predictable Versus Unpredictable Drug-Induced Liver Injury
    • Drug-Induced Liver Injury Due To Specific Agents
    • Liver Injury Due to Immune Checkpoint Inhibitors
    • Botanicals, Herbal Products, and Dietary Supplements
    • Conclusion
    • Acknowledgments
    • References

    57: Preoperative and Postoperative Hepatic Dysfunctions

    • Introduction
    • Preoperative Liver Dysfunction
    • Postoperative Liver Dysfunction
    • Anesthetic-Induced Liver Injury
    • Ischemic Hepatitis
    • Acute Viral Hepatitis
    • Drug-Induced Hepatitis
    • Benign Postoperative Cholestasis
    • Bile Duct Obstruction
    • Evaluation of Patients With Postoperative Liver Dysfunction
    • References

Section XI Inherited and Pediatric Liver Diseases

    58: Bilirubin Metabolism and Its Disorders

    • Introduction
    • Jaundice as an Indicator of Hepatic Dysfunction
    • Formation of Bilirubin
    • Potential Beneficial Effects of Products of Heme Breakdown
    • Measurement of Bilirubin Production
    • Chemistry of Bilirubin
    • Photochemistry of Bilirubin
    • Bilirubin Toxicity
    • Disposition of Bilirubin
    • The Role of Albumin
    • Hepatic Bilirubin Uptake
    • Storage of Bilirubin Within the Hepatocyte
    • Conjugation of Bilirubin
    • Enzyme-Catalyzed Glucuronidation of Bilirubin
    • Latency of Uridine Diphosphoglucuronate Glucuronosyltransferases
    • Multiple Forms of Uridine Diphosphoglucuronate Glucuronosyltransferases
    • Organization of the UGT1A Gene Family
    • Bile Canalicular Secretion of Bilirubin Conjugates and Related Organic Anions
    • Quantification of Bilirubin
    • The Nature and Significance of Bilirubin in Body Fluids and Tissues
    • Disorders of Bilirubin Metabolism
    • Acknowledgments
    • References

    59: Wilson Disease

    • Introduction
    • Epidemiology: Incidence and Geographic Distribution
    • Pathogenesis
    • Clinical Manifestations
    • Treatment
    • Special Situations
    • Prognosis and Natural History
    • Conclusion
    • References

    60: Hemochromatosis

    • Introduction
    • Historical Aspects
    • Hepcidin, the Hemochromatosis Hormone
    • The Genetic and Pathogenic Basis for Hemochromatosis
    • Genetics and Epidemiology
    • The Clinical Spectrum of Hemochromatosis
    • Conclusion
    • Acknowledgments
    • References

    61: α1-Antitrypsin Deficiency

    • Introduction
    • Conclusion
    • References

    62: Approach to and Evaluation of Metabolic Liver Diseases

    • Introduction
    • General Approach and Clinical Evaluations
    • Diagnostics for Metabolic Liver Diseases
    • References

    63: Pediatric Cholestatic Syndromes

    • Introduction
    • Intrahepatic Disease
    • Extrahepatic Disorders
    • General Treatment of Children With Cholestasis
    • References

    64: Fibrocystic Diseases of the Liver

    • Introduction
    • Biology of Fibrocystic Liver Diseases
    • Histopathology of Fibrocystic Liver Diseases
    • Clinical Manifestations and Treatment of Fibrocystic Liver Diseases
    • References

    65: Viral Hepatitis in Children

    • Introduction
    • Conclusion
    • References