Artificial Liver

Preface
Contents
Chapter 1: Introduction
1.1 Concept and Classification of Artificial Liver Systems
1.2 Development of Artificial Liver Systems
1.2.1 The 1950s–1960s: The Rise of Artificial Liver Research
1.2.2 The 1970s: The Technology of Hemopurification Encouraged the Development of NBAL
1.2.3 The 1980s–1990s: The Continuous and in-Depth Study of NBAL and the Rise of BAL Research
1.2.4 The Twenty-First Century: New Devices Are Constantly Introduced
1.3 The History of Artificial Liver Research Carried out by Lanjuan Li’s Team at Zhejiang University (ZJU)
1.3.1 Research on the Li-NBAL
1.3.2 Research on Li-BAL
1.3.3 Research on the Li-HAL
1.3.4 Specifications for Artificial Liver System (ALS) Treatment in China
1.4 Summary
References
Chapter 2: Liver Structure
2.1 Anatomy of the Liver
2.1.1 General Description and Topography of the Liver
2.1.1.1 Location of the Liver
2.1.1.2 The Appearance of the Liver
Perihepatic Organs
Hepatic Ligaments
2.1.2 Liver Segments
2.1.2.1 Hepatic Fissure
2.1.2.2 Segmentation of the Liver
2.1.3 Vessel Distribution of the Liver
2.1.4 Biliary System
2.1.5 Lymphatic System and Neural Network
2.1.5.1 Lymphatic System
2.1.5.2 Neural Network
2.2 Hepatic Histology
2.2.1 Hepatic Lobule
2.2.1.1 Classical Lobule
2.2.1.2 Portal Lobule
2.2.1.3 Liver Acinus
2.2.2 Hepatic Sinusoid and Perisinusoidal Space
2.2.3 Hepatocellular Heterogeneity and Non-parenchymal Liver Cell
2.2.3.1 Hepatocellular Heterogeneity
2.2.3.2 Non-Parenchymal Liver Cell
Liver Sinusoidal Endothelial Cells
Hepatic Stellate Cells
Kupffer Cells
Pit Cell
2.2.4 Blood Circulation in the Liver
2.2.5 Bile Flow in the Liver
2.3 Ultrastructure of Liver Cells
2.3.1 Hepatocyte Nucleus
2.3.2 Cytoplasm
2.3.2.1 Mitochondria
2.3.2.2 Endoplasmic Reticulum (ER)
2.3.2.3 Golgi’s Body
2.3.2.4 Lysosomes
2.3.2.5 Peroxidase Microbody
2.3.2.6 Glycogen Particles
2.3.2.7 Cytoskeleton
2.3.3 Cell Membrane
2.3.3.1 Sinusoidal Surface of Liver Cells
2.3.3.2 Bile Duct Surface
2.3.3.3 Adjacent Hepatic Cell Contact Surface
References
Chapter 3: Liver Function
3.1 Energy Metabolism and Its Regulation in the Liver
3.1.1 Glucose Metabolism in the Liver [1, 2]
3.1.1.1 The General Process of the Liver Glucose Metabolism
3.1.1.2 Synthesis and Decomposition of Glycogen
3.1.2 The Fatty Acid Metabolism in the Liver
3.1.3 The Energy Metabolism of Amino Acids
3.1.3.1 Deamination
3.1.3.2 Ammonia Discharge
3.1.3.3 α-Keto Acid Conversion
3.2 Substance Metabolism and Its Function in the Liver
3.2.1 The Synthesis of Protein
3.2.2 The Metabolism of Lipids [3]
3.2.2.1 The Synthesis of Triglycerides
3.2.2.2 The Metabolism of Phospholipids
3.2.2.3 Cholesterol
3.2.2.4 Plasma Lipoprotein
3.2.3 Liver Biotransformation
3.2.4 Bilirubin Metabolism
3.2.5 Bile Acid Metabolism
3.3 The Synthesis and Secretion of Bile
3.3.1 The Composition and Function of Bile
3.3.2 The Formation and Secretion of Bile
3.4 The Immunological Function of Liver
3.4.1 The Liver Immune-Related Cells
3.4.2 Liver-Secreted Immune-Related Proteins
3.4.3 The Removal of Inflammatory Factors from the Liver
References
Chapter 4: Liver Regeneration and Tissue Engineering
4.1 The Process and Regulation of Liver Regeneration
4.1.1 The Basic Process of Liver Regeneration
4.1.2 The Regulatory Effect of Cytokines
4.1.2.1 HGF
4.1.2.2 IL-6
4.1.2.3 TNF
4.1.2.4 EGF and TGF
4.1.2.5 Other Factors
4.2 Liver Tissue Engineering and Liver Regeneration
4.2.1 Seed Cells
4.2.1.1 Hepatocytes
4.2.1.2 Immortalized Hepatocyte Line
4.2.1.3 Stem Cells
4.2.1.4 Hepatic Stem Cells
Embryonic Stem Cells
Mesenchymal Stem Cells
Induced Pluripotent Stem Cells
4.2.2 Biomaterials
4.2.2.1 Natural Biomaterials
Natural Polymers
Decellularized Liver Scaffold
4.2.2.2 Synthetic Polymers
4.2.3 Vascularization
4.3 Clinical Application of Engineered Liver
4.3.1 Cell Transplant
4.3.2 Artificial Liver System
4.3.3 Liver Tissue Engineering
References
Chapter 5: Etiology of Liver Injury
5.1 Infection
5.2 Drugs and Toxicants
5.3 Alcohol
5.4 Heredity and Metabolism
5.5 Autoimmune Liver Disease
5.5.1 Autoimmune Hepatitis (AIH)
5.5.2 Primary Biliary Cirrhosis (PBC)
5.5.3 Primary Sclerosing Cholangitis (PSC)
5.6 Tumor
5.6.1 Benign Tumors
5.6.2 Malignant Tumor
5.7 Others
Reference
Chapter 6: Pathogenesis of Liver Injury and Hepatic Failure
6.1 Summary
6.1.1 Pathogenesis of Liver Failure: Immune-Mediated Cell Injury
6.1.1.1 Humoral Immunity
6.1.1.2 Cellular Immunity
Increased Antigen Presentation
Multi-Pathway-Mediated Apoptosis
Changes in Host Cell Autoimmunity
Changes in Cytokines
6.1.2 Pathogenesis of Liver Failure: Ischemia and Hypoxia
6.1.3 Pathogenesis of Liver Failure: Endotoxemia
6.1.3.1 The Structural Characteristics of Endotoxin
6.1.3.2 The Biological Activity of Endotoxin
6.1.3.3 Detection of Endotoxin
6.1.3.4 The Mechanism of Endotoxemia in Liver Failure
Intestinal Endotoxin Production and Increased Intake
Inactivation of Endotoxin in the Liver
6.1.4 Liver Failure and Intestinal Microecology
6.1.4.1 The Microecological Basis of the Liver
Liver Cell Function and Intestinal Microecology
Liver Blood Supply and Intestinal Microecology
Intestinal Circulation and Intestinal Microecology
6.1.4.2 Liver Disease and Intestinal Microecology
Normal Intestinal Microbiota
Intestinal Flora
Intestinal Mucus Layer
Intestinal Epithelial Cell Layer
Intestinal Immune System
Changes of Intestinal Microecology in Liver Disease
6.2 Pathogenesis of Viral Induced Liver Injury/Liver Failure
6.2.1 Summary of the Pathogenesis of Viral Induced Liver Injury/Liver Failure
6.2.1.1 Primary Liver Injury
Immunopathological Effects
Direct Effect of Virus
6.2.1.2 Secondary Liver Injury
6.2.2 The Mechanism of Hepatitis B Virus: Induced Liver Injury and Liver Failure
6.2.2.1 Virus
Direct Effect of Virus
Virus Mutation
HBV Pre-C Gene Mutation
HBV C Gene Mutation
HBV BCP Mutation
HBV Pre-S1/S2 Gene Mutation
HBV S Gene Mutation
6.2.2.2 Host
Mechanism of Liver Necrosis Caused by Cytotoxic T Lymphocytes (CTL) Leading by HBV Infection
CTL-Mediated Hepatocellular Apoptosis
Perforin-Granzyme System (Fig. 6.1)
Fas/FasL System (Fig. 6.2)
TNF/TNFR system (Fig. 6.3)
TRAIL-1 and TRAIL-2/TRAIL-R1 and TRAIL-R2 System
Innate Immunity
Immunosuppression
6.2.3 Pathogenesis of Liver Damage and Liver Failure Caused by Other Common Viral Hepatitis
6.2.3.1 Hepatitis A Virus
6.2.3.2 Hepatitis C Virus
6.2.3.3 Hepatitis D Virus
Consumption of Liver Physiological Enzymes
HDVAg Overexpression
Immune Response
6.2.3.4 Hepatitis E Virus
6.3 Drug Induced Liver Injury/Liver Failure
6.3.1 Drug Biotransformation in Liver
6.3.1.1 Drug Metabolism Reactions
6.3.1.2 Metabolic Enzyme in Drug-Induced Liver Damage
Enzyme in Phase I Reaction
CYP1
CYP2
CYP3
Enzyme in Phase II Reaction
Uridine Diphosphate Glucuronyltransferase
Sulfate Transferase
Glutathione S-Transferase
N-acetyltransferase
Epoxide Hydrolase
6.3.2 Immunological Pathogenesis of Drug-Induced Liver Injury
6.3.3 Mechanism of Cytochrome P450 System Related Drug-Induced Liver Injury
6.3.3.1 Induction and Inhibition of P450 Enzyme System
6.3.3.2 The Mechanism of P450 Enzyme Activity
Environmental Factors
Genetic Factors
Disease Factors
6.4 Other Factors Induced Liver Injury/Liver Failure
6.4.1 Pathogenesis of Liver Injury/Liver Failure Caused by Hepatotoxic Substances
6.4.1.1 Summary
6.4.1.2 Direct and Indirect Hepatotoxic Substances
6.4.1.3 Alcoholic Liver Injury
Ethanol Metabolism Process
The Mechanism of Alcoholic Liver Injury
Ethanol Oxidative Stress
Mitochondrial Toxicity of Ethanol
Cytokines and Other Inflammatory Mediators
Immune Response
Apoptosis Mediated by Multiple Pathways
Ischemia and Hypoxia
6.4.2 The Pathogenesis of Pregnancy Complicated with Liver Failure
6.4.2.1 Individual Factors
6.4.2.2 Environmental Factors
6.4.2.3 Pathological Factors
6.4.3 Pathogenesis of Liver Failure After Trauma, Shock, and Surgery
6.4.3.1 Imbalance of Calcium Homeostasis
6.4.3.2 Lipid Peroxidation
6.4.3.3 Cell Membrane Injury
6.4.3.4 Mitochondria: Associated Cell Damage
6.5 The Pathogenesis of Chronic Liver Failure
6.5.1 The Pathogenesis of Liver Cirrhosis
6.5.1.1 Cirrhosis Caused by Viral Hepatitis
6.5.1.2 Drug or Toxic Induced Liver Cirrhosis
6.5.1.3 Alcoholic Cirrhosis
6.5.1.4 Cholestatic Cirrhosis
6.5.1.5 Schistosomiasis Cirrhosis
6.5.1.6 Cirrhosis Caused by Metabolic Diseases
Hepatolenticular Degeneration
Type IV Glycogen Accumulation Disease
Galactosemia
6.5.2 The Pathogenesis of Chronic Liver Failure
6.5.2.1 Active Cirrhosis
6.5.2.2 Genetic Susceptibility
6.5.2.3 Portal Hypertension and Endotoxemia
6.5.2.4 Hepatocyte Aplasia
6.6 Pathogenesis of Complications of Liver Failure
6.6.1 Pathogenesis of Hepatic Encephalopathy
6.6.1.1 Theory of Ammonia Intoxication
6.6.1.2 Theory of γ-Aminobutyric Acid and Benzodiazepine (GABA/BZ) Complex Receptor
6.6.1.3 Theory of Astrocyte Dysfunction
6.6.1.4 Theory of Neurotransmitter
6.6.1.5 Theory of Manganese Ions
6.6.1.6 Theory of Encephaledema
6.6.2 The Pathogenesis of Coagulation Dysfunction
6.6.3 Pathogenesis of Ascites
6.6.3.1 Portal Hypertension
6.6.3.2 Decline of Effective Circulatory Blood Volume
6.6.3.3 Hypoproteinemia
6.6.3.4 Infection
6.6.3.5 Microecological Imbalance
6.6.4 Pathogenesis of Hepatorenal Syndrome
6.6.4.1 Nitric Oxide
6.6.4.2 Endothelin.1
6.6.4.3 Endotoxemia
6.6.4.4 Renin–Angiotensin–Aldosterone System
6.6.4.5 Sympathetic Nervous System
6.6.5 Pathogenesis of Spontaneous Peritonitis
6.6.5.1 Flora Translocation
6.6.5.2 Reticuloendothelial System Activity Declines
6.6.5.3 Decreased Activity of Opsonin in Ascites
6.6.5.4 Neutrophil Dysfunction
References
Chapter 7: Liver Pathology
7.1 Histochemical and Immunohistochemical Stains
7.1.1 Common Histochemical Staining in the Diagnosis of Liver Diseases
7.1.2 Immunohistochemistry of the Liver
7.2 Pathological Changes in the Liver
7.2.1 Basic Pathological Changes in the Liver
7.2.2 Acute Hepatitis
7.2.3 Chronic Hepatitis
7.2.4 Cirrhosis
7.2.5 Cholestasis Liver Disease
7.2.6 Alcoholic Liver Disease (ALD)
7.2.7 Metabolic Liver Disease
7.2.8 Vascular Disease
7.2.9 Starch Denaturation
7.2.10 Liver Tumors
7.3 Pathological Changes in Liver Failure
7.3.1 Acute Liver Failure
7.3.2 Sub-acute Liver Failure
7.3.3 Acute Failure in Chronic Liver Disease
7.3.4 Chronic Liver Failure
References
Chapter 8: Laboratory Evaluation of Liver Failure
8.1 Detection of Pathogenic Infection
8.1.1 Detection of the Virus Infection
8.1.1.1 The Hepatitis Virus
The Hepatitis B Virus
The Hepatitis C Virus
The Hepatitis E Virus
The Hepatitis A Virus
8.1.1.2 The Herpes Virus
The Cytomegalovirus (CMV)
The Epstein-Barr Virus (EBV)
The Herpes Simplex Virus (HSV)
8.1.2 Detection of Bacterial Infection
8.1.2.1 General Bacterial Infection
8.1.2.2 Mycobacterium tuberculosis
8.1.3 Detection of Fungal Infection
8.2 Assessment of Metabolic Balance
8.2.1 Disorders of Water and Electrolyte Metabolism
8.2.1.1 Disorder of Water Metabolism
8.2.1.2 Disorder of Sodium Metabolism
8.2.1.3 Disorder of the Potassium Metabolism
8.2.1.4 Disorders of Others Electrolyte Metabolism
8.2.2 Disorder of the Acid-Base Homeostasis and Blood Gas Analysis
8.3 Evaluation of Hepatorenal Syndrome
8.3.1 Evaluation of Liver Function
8.3.1.1 Total Bilirubin
8.3.1.2 Alanine Aminotransferase and Aspartate Aminotransferase
8.3.1.3 Cholinesterase
8.3.1.4 Alkaline Phosphatase
8.3.1.5 γ-Glutamyl Transpeptidase
8.3.1.6 Lactic Dehydrogenase
8.3.1.7 Albumin, Total Protein, and Prealbumin
8.3.1.8 Glucose
8.3.1.9 Serum Total Cholesterol and Triglyceride
8.3.1.10 Serum Protein Electrophoresis
8.3.2 Evaluation of Renal Function
8.3.2.1 Urea, Creatinine, and Glomerular Filtration Rate
8.3.2.2 Retinol Binding Protein
8.3.2.3 β2-Microglobulin
8.3.2.4 Cystatin C
8.4 Evaluation of Hepatic Encephalopathy
8.4.1 Detection of Blood Ammonia
8.4.2 Detection of Serum Amino Acid
8.4.2.1 Detection of Total Amino Acid
8.4.2.2 Fischer Ratio (BCAA/AAA)
8.4.2.3 Branched Chain Amino Acid and Tyrosine Ratio
8.4.3 Detection of Cerebrospinal Fluid
8.5 Detection of Coagulation
8.5.1 Detection of the Blood Coagulation System
8.5.1.1 Detection of Prothrombin Time
8.5.1.2 Detection of Activated Partial Thromboplastin Time
8.5.1.3 Fibrinogen
8.5.2 Detection of Anticoagulant and the Fibrinolytic System
8.5.3 Detection of Platelet Count and Function
8.5.4 Detection of the Special Coagulation Factor
8.5.4.1 Coagulation Factor II (FII)
8.5.4.2 Coagulation Factor VII
8.5.4.3 Coagulation Factor VIII
8.6 Detection of Anaphylaxis
8.6.1 Detection of Allergen-Specific Antibodies
8.6.1.1 Skin Test
8.6.1.2 Specific IgE Test
8.6.2 Detection of Nonspecific Allergen
8.6.2.1 Detection of Serum Total IgE
8.6.2.2 Detection of Released Active Substances
8.6.2.3 Degranulation Test
8.6.2.4 Detection of Total Complement Activity and C3, C4
8.6.2.5 White Blood Cell Count
References
Chapter 9: Imaging Examination of Liver Failure
9.1 Ultrasonic Diagnosis of Severe Liver Failure
9.1.1 Common Ultrasonic Diagnostic Techniques Applied to Liver Diseases
9.1.1.1 Two-Dimensional Ultrasound
9.1.1.2 Doppler Ultrasound
9.1.1.3 Contrast Enhanced Ultrasound (CEUS)
9.1.1.4 Interventional Ultrasound
9.1.2 Color Doppler Ultrasonography Diagnosis of Liver Failure
9.1.2.1 Acute and Sub-acute Liver Failure
9.1.2.2 Chronic and Acute Liver Failure
9.1.2.3 Chronic Liver Failure
9.1.3 Contrast-Enhanced Ultrasonography in the Diagnosis of Liver Failure
9.1.4 Interventional Ultrasound in the Diagnosis of Liver Failure
9.1.4.1 Ultrasound Guided Fine-Needle Biopsy
9.1.4.2 Ultrasound guided Primary Liver Cancer Radiofrequency Ablation
9.2 CT and MR Examinations of the Liver
9.2.1 Indications and Contraindications
9.2.2 Patient Preparation
9.2.3 Multidetector Computed Tomography
9.2.3.1 Unenhanced Axial CT Scan
9.2.3.2 Enhanced CT Scan
9.2.3.3 Computed Tomography Angiography (CTA)
9.2.3.4 Computed Tomography Perfusion (CTP)
9.2.3.5 Post-processing
Multi-planar Reformation (MPR)
Curved Planar Reconstruction (CPR)
Maximum Intensity Projection (MIP)
Shaded Surface Display (SSD)
Volume Rendering (VR)
CT Virtual Endoscopy (CTVE)
Volumetric Measurement
9.2.4 Magnetic Resonance Imaging
9.2.4.1 Protocols
9.2.4.2 Intravenous Agents
9.2.4.3 Magnetic Resonance Angiography (MRA)
9.2.4.4 Magnetic Resonance Cholangiopancreatography (MRCP)
9.2.4.5 Functional Magnetic Resonance Imaging (fMRI)
Diffusion-Weighted Imaging (DWI)
Perfusion Weighted Imaging (PWI)
Magnetic Resonance Spectroscopy (MRS)
Magnetic Resonance Elastography (MRE)
9.3 Normal CT and MR Appearances of the Liver
9.3.1 Liver Parenchyma
9.3.2 The Hepatic Vessels and Bile Ducts
9.3.3 Hepatic Ligaments and Fissures
9.3.4 Hepatic Segmental Division
9.3.4.1 Hepatic Fissure
9.3.4.2 Hepatic Vein
9.3.4.3 Portal Vein
9.3.4.4 Other Anatomical Landmarks
9.4 CT, MRI Findings of Liver Failure
9.4.1 Imaging Manifestations of Liver Failure and Major Complications
9.4.1.1 Imaging Findings of Acute Liver Failure (ALF)
9.4.1.2 Imaging Findings of Chronic Liver Failure (ALF)
Liver Morphological Changes
Liver Parenchyma Changes
Secondary Changes
Autoimmune Liver Failure
Complications of Liver Failure
Precautions for CT and MRI in Patients with Liver Failure
9.4.2 Liver failure, the Application of Imaging Examination Before and After Transplant
9.4.2.1 Imaging Evaluation Before the Operation of Liver Failure
9.4.2.2 Imaging Evaluation After Liver Transplant
Biliary Complications
Vascular Complications
Neurological Complications
Other Complications After a Liver Transplant
References
Chapter 10: Diagnosis of Liver Failure
10.1 The Definition and Classification of Liver Failure
10.1.1 The Development of the Definition of Liver Failure and Its Classification
10.1.2 Classification of Clinical Diagnosis of Liver Failure
10.2 Stage of Liver Failure
10.3 The Diagnosis of Liver Failure
10.3.1 Etiological Diagnosis of Liver Failure
10.3.2 The Clinical Diagnosis of Liver Failure
10.3.3 Laboratory Examination and Diagnosis of Liver Failure
10.3.4 Early Detection of Liver Failure
10.4 The Dynamics of Liver Function and Prognosis of Liver Failure
10.4.1 The BES of the Dynamic Changes of the Liver Functions and the Prognosis of Liver Failure
10.4.2 The BBS of the Dynamic Changes in the Liver Functions and the Prognosis of Liver Failure
10.5 The Significance of the Immune Molecules in the Diagnosis of Liver Failure
10.6 Prognosis of Liver Failure
References
Chapter 11: Internal Medical Treatment of Liver Failure
11.1 Medical Monitoring
11.1.1 General Monitoring
11.1.2 Analysis of the Initial Laboratory Index
11.1.3 Laboratory Index About the Change in Conditions
11.1.4 Invasive Hemodynamic Monitoring
11.1.5 Intracranial Pressure Monitoring
11.2 Specific Nutrition and Metabolic Support Therapy
11.2.1 Principles of Specific Nutrition and Metabolic Support Therapy
11.2.2 Enteral Nutrition
11.2.3 Total Parenteral Nutrition
11.2.4 Supplemental Parenteral Nutrition
11.2.5 The Application of Special Nutrients
11.3 Targeting Etiologies and Pathogenesis
11.3.1 Viral Hepatitis
11.3.2 Acetaminophen Hepatotoxicity
11.3.3 Other Drug-Induced Liver Injury
11.3.4 Mushroom Poisoning
11.3.5 Wilson’s Disease
11.3.6 Autoimmune Hepatitis
11.3.7 Acute Fatty Liver of Pregnancy/HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelet Counts)
11.4 Promote the Growth of Hepatocytes and the Removal of Jaundice
11.4.1 Principles of the Application of Liver Protection Drugs in the Treatment of Liver Failure
11.4.2 Promote the Growth of Hepatocytes
11.4.3 The Application of Prostaglandin E1
11.4.4 The Application of Glycyrrhizic Acid Preparation
11.4.5 The Application of Detoxification and Hepato-Protective Drugs
11.4.6 The Application of Cholecystagogue
11.4.7 The Application of Essential Phospholipids
11.4.8 Application of Silymarin
11.4.9 The Application of Intestinal Microecological Regulators
11.4.10 The Application of Other Drugs for Liver Protection
11.5 The Prevention and Treatment of Complications
11.5.1 Prevention and Treatment of Hepatic Encephalopathy and Cerebral Edema
11.5.2 Prevention and Treatment of Bleeding
11.5.3 The Prevention and Treatment of Infection
11.5.4 The Prevention and Treatment of Hemodynamic Abnormalities and the Hepatorenal Syndrome
11.5.5 Prevention and Therapy of Water, Electrolyte, and Acid–Base Balance Disorders
11.5.6 Prevention and Treatment of Abnormal Glucose Metabolism
11.5.7 Prevention and Treatment of Hepatic-Lung Syndrome
11.5.8 The Prevention and Treatment of Disseminated Intravascular Coagulation (DIC)
11.5.9 Prevention and Treatment of Other Complications
References
Chapter 12: Mechanism for the Functioning of the Artificial Liver
12.1 Artificial Liver and Liver Functions
12.1.1 Normal Liver Functions
12.1.2 Various Types of Artificial Liver and the Recovery of Liver Functions
12.1.2.1 Non-biological Artificial Liver and the Recovery of Liver Functions
Plasma Exchange
Blood/Plasma Perfusion and Bilirubin Adsorption
Plasma Diafiltration
The Combination of the Use of Multiple Non-biological Artificial Liver Treatments
12.1.2.2 Biological Artificial Liver and Recovery of Liver Functions
Effect of Animal Liver Cells-Based Biological Artificial Liver on the Recovery of Liver Functions
Effect of Liver Tumor Cells-Based Biological Artificial Liver on the Recovery of Liver Functions
Effect of the Immortalized Human Hepatocyte Line-Based Biological Artificial Liver on the Recovery of Liver Functions
12.1.2.3 Hybrid Liver Support Systems and Recovery of Liver Functions
12.2 Artificial Liver and Toxic Metabolites
12.2.1 Toxic Metabolites in Liver Failure
12.2.1.1 Ammonia
The Cause for Hyperammonia
The Toxic Effects of the Central Nervous System
12.2.1.2 Medium Molecular Substance
12.2.1.3 Pseudo-Neurotransmitters
12.2.1.4 Mercaptan
12.2.1.5 Short-Chain Fatty Acid
12.2.1.6 Phenols
12.2.1.7 Aromatic Amino Acid
12.2.1.8 Gamma-Aminobutyric Acid and Endogenous Benzodiazepine Substances
12.2.1.9 Bilirubin
12.2.1.10 Bile Acids
12.2.1.11 Other Toxic Substances
12.2.2 Artificial Liver and the Removal of Toxic Metabolites
12.2.2.1 Hemodialysis and Removal of Toxic Metabolites
12.2.2.2 Hemofiltration and Removal of Toxic Metabolites
12.2.2.3 Hemoperfusion and Removal of Toxic Metabolites
12.2.2.4 Plasmapheresis and Removal of Toxic Metabolites
12.2.2.5 Biological Artificial Liver and Removal of Toxic Metabolites
12.3 Artificial Liver and Microecology
12.3.1 Mechanism and Clinical Significance of Microecological Imbalance in Liver Failure
12.3.1.1 The Mechanism of the Microecological Imbalance in Liver Failure
Nutrient Deficiency
The Reduction or the Composition Changed in Bile Secretion
Endotoxemia
Portal Hypertension and Portal Shunt
pH Changed in the Intestinal Tract
Ischemia-Reperfusion Injury
Neurohormonal Factors
Irrational Use of Antibiotics
12.3.1.2 Clinical Significance of Microecological Imbalance of Liver Failure
Secondary Infection
Endotoxemia
High Dynamic Circulation and Upper Gastrointestinal Bleeding
Hepatic Encephalopathy
Hepatorenal Syndrome
12.3.2 The Reconstruction Effect of Artificial Liver on Microecological Imbalance
12.3.2.1 Scavenging Action
12.3.2.2 Supplementary Function
12.3.3 Artificial Liver and Endotoxin
12.3.3.1 Clinical Manifestations of Endotoxemia
Fever
Disseminated Intravascular Coagulation
Acute Gastric Mucosa Erosive Bleeding
Hepatic Ascites and Ascites Infection
Local Allergic Reaction (Shwartzman Response)
The Hepatorenal Syndrome
Endotoxin and Hepatic Encephalopathy
Metabolic Disorders
Other Damage Caused by Endotoxin
12.3.4 Artificial Liver and Removal of Endotoxin
12.3.4.1 Non-Bio-artificial Liver of Hematodialysis, Hemofiltration, and Endotoxin Removal
12.3.4.2 Non-Bio-artificial Liver of Hemoperfusion and Endotoxin Removal
Nonselective Blood Adsorption
Selective Blood Adsorption
Specific Immune Adsorption
12.3.4.3 Plasma Exchange and Endotoxin Removal of Non-biological Artificial Liver
12.4 Artificial Liver and the Internal Environment
12.4.1 Normal Internal Environment
12.4.1.1 Normal Metabolism of Water and Sodium
Body Fluid
Distribution and Capacity of the Body Fluid
The Main Electrolytes and Their Distribution in the Body Fluid
Osmotic Pressure of Body Fluid
The Balance of Water and Sodium
12.4.1.2 Normal Regulation of Water and Sodium Metabolism
Normal Regulation of Water Metabolism
The Normal Regulation of Sodium Metabolism
Normal Regulation of Potassium Metabolism
Acid–Base Balance
12.4.2 Internal Environmental Changes in Liver Failure
12.4.2.1 Water Retention
12.4.2.2 Disturbances of Sodium Metabolism
True Hyponatremia
Diluted Hyponatremia
12.4.2.3 Disturbances of the Potassium Metabolism
12.4.2.4 The Common Causes of Hyperkalemia Are
12.4.2.5 Disorders of the Metabolism of Chlorine, Phosphorus, Calcium, and Magnesium
12.4.2.6 Disturbance of the Acid–Base Metabolism
Respiratory Alkalosis
Respiratory Alkalosis Complicated by Metabolic Alkalosis
Metabolic Acidosis Complicated by Respiratory Alkalosis
Respiratory Acidosis Complicated with Metabolic Acidosis
Triple Imbalance of Acid–Base Balance
12.4.3 Artificial Liver and Water, Electrolyte, Acid–Base Balance
12.4.3.1 Hemodialysis
12.4.3.2 Hemofiltration
12.4.3.3 Plasma Perfusion
12.4.3.4 Plasma Exchange
12.5 Cytokines in Artificial Liver Support Systems
12.5.1 Cytokines
12.5.2 Cytokines and Acute Liver Failure
12.5.2.1 Interferons
12.5.2.2 Tumor Necrosis Factor
12.5.2.3 Interleukin-6
12.5.3 Cytokines in Artificial Liver Support Systems
12.5.3.1 Plasma Exchange
12.5.3.2 Plasma Filtration
12.5.3.3 Plasma Perfusion
12.5.3.4 Bio-artificial Liver Support System
References
Chapter 13: Non-bioartificial Liver
13.1 Membrane Filter and Absorber
13.1.1 Dialyzer
13.1.1.1 Materials and Parameters
13.1.1.2 Properties
Celluloid Membrane
Copper Imitation Membrane
Acetate Fiber Membrane
Polyacrylonitrile Membrane
13.1.2 Hemofilter
13.1.2.1 Materials and Parameters
13.1.2.2 Properties
13.1.3 Membrane Plasma Separator
13.1.3.1 Materials and Parameters
13.1.3.2 Properties
13.1.4 Adsorber
13.1.4.1 Materials and Parameters
Activated Carbon
Resin
13.1.5 Albumin Dialyzer
13.2 Li-NBAL
13.2.1 Plasma Exchange
13.2.1.1 Mechanisms
13.2.1.2 Types of PE
Nonselective Plasma Separation
Selective Plasma Separation
13.2.1.3 Displacement Liquid
13.2.1.4 Exchange Volume and Frequency of the PE
13.2.1.5 Indication of PE
13.2.1.6 Clinical Use and Evaluation of Efficacy
13.2.2 Hemofiltration
13.2.2.1 Mechanisms of the Treatment
13.2.2.2 Types of Hemofiltration
13.2.2.3 Displacement Liquid
Components of Displacement Liquid
Supply Approach of Displacement Fluids
13.2.2.4 Indication of Hemofiltration
13.2.3 Plasma Exchange and Hemofiltration (Hemodiafiltration)
13.2.3.1 Mechanisms of the Treatment
13.2.3.2 Clinical Use
13.2.4 Hemoperfusion
13.2.4.1 Mechanisms of the Treatment
13.2.4.2 Indication of Hemoperfusion
13.2.4.3 Clinical Use
13.2.5 Plasma Exchange and Plasma Adsorption
13.2.5.1 Mechanisms of the Treatment
13.2.6 Plasma Diafiltration
13.2.6.1 Mechanisms of the Treatment
13.2.6.2 Clinical Use
13.2.7 Li-ALS (Li-NBAL 2.0)
13.3 Other Non-biological Artificial Livers
13.3.1 MARS
13.3.1.1 Frame Composition
13.3.1.2 Components of MARS
13.3.1.3 Clinical Use
Preparation of MARS Before Treatment
Implementation of the MARS Treatment
MARS Treatment Indications and Treatment Regimens
Contraindications for the MARS Treatment
Complications and Countermeasures of the MARS Treatment
13.3.1.4 Clinical Application Research
13.3.2 Prometheus
13.3.2.1 Treatment Principles and Components
13.3.2.2 Clinical Efficacy and Evaluation
13.4 Indications and Contraindications for Artificial Liver Systems in Liver Failure
13.4.1 Indications
13.4.2 Management of the Complications of Liver Failure
13.4.2.1 Hepatorenal Syndrome
13.4.2.2 Hepatic Encephalopathy
13.4.2.3 Severe Fluid and Electrolyte Disorder
13.4.2.4 Systemic Inflammatory Response Syndrome
References
Chapter 14: Operation and Management of Artificial Liver Support Systems
14.1 Management of the Non-biological Artificial Liver System
14.1.1 The Safety Management System
14.1.1.1 The Basic Requirements of Medical Institutions
14.1.1.2 Partition and Requirements of the Artificial Liver Treatment Center
The Treatment Room for the Artificial Liver System
The Warehouse
Medical Staff Office and Living Room
14.1.1.3 Contaminated Areas
14.1.1.4 Security Management
14.1.2 Usage and Maintenance of Hardware Equipment
14.1.3 Staffing and Training
14.1.3.1 Staffing
14.1.3.2 Training
14.1.4 Disinfection and Isolation Management System
14.1.5 System for the Management of Disposable Medical Items
14.2 Operation and Nursing of Non-bioartificial Liver Support Therapy
14.2.1 Pre-treatment Nursing
14.2.1.1 Pre-treatment Special Assessment
14.2.1.2 Preparation Before Treatment
14.2.1.3 Health Education
14.2.2 In-Treatment Nursing
14.2.3 Post-treatment Nursing
14.2.4 Operation and Nursing of Different Methods of Non-bioartificial Liver Systems
14.2.4.1 Li-ALS
14.2.4.2 MARS
14.2.5 Operational Process of Artificial Liver Catheterization
14.3 Anticoagulation Method
14.3.1 Introduction
14.3.2 Principles of Anticoagulation
14.3.3 Method of Heparin Anticoagulation
14.3.3.1 Unfractionated Heparin
14.3.3.2 Low Molecular Weight Heparin
14.3.3.3 Anticoagulation for Li-ALS
Anticoagulate with Heparin
Conventional Heparin
Limited Heparin
Heparin In Vitro
Treatment Without Heparin
Other Anticoagulants
Local Citrate Anticoagulation
Anticoagulation with Argatroban
14.3.4 Anticoagulation Management During Artificial Liver Treatment
References
Chapter 15: Artificial Liver Support System: Complications and Prevention
15.1 Bleeding and Clot Formation
15.1.1 Bleeding
15.1.2 Blood Clotting of the Extracorporeal Liver Device
15.2 Hypotension
15.2.1 Reduction of Effective Blood Volume
15.2.2 Blood Loss
15.2.3 Cardiogenic
15.2.4 Allergic Reaction to Medications or Plasma
15.2.5 Hemoperfusion Syndrome
15.2.6 Vasoactive Substances and Hypotensive Shock
15.3 Secondary Infections
15.3.1 Artificial Liver Catheter-Related Infections
15.3.1.1 Incidence
15.3.1.2 Pathogens
15.3.1.3 Clinical Manifestation
15.3.1.4 Management and Prevention of Infections of the Vascular Accesses
Prevention of Intravenous Catheter Infections
Antibiotics Therapy
15.3.2 Hematogenous Infections in Artificial Liver Patients
15.3.2.1 HCV Infections
15.3.2.2 HIV Infections
15.4 Allergic Reactions
15.4.1 Plasma Substitutes
15.4.1.1 Reaction Mechanism
Allergic Reaction
Anaphylactoid Reaction
Clinical Manifestation
15.4.1.2 Diagnosis and Treatment
15.4.2 Allergic Reaction to Protamine
15.4.3 Allergic Reaction to Fresh Frozen Plasma
15.5 Hemolysis
15.5.1 Etiology and Mechanism
15.5.2 Clinical Manifestations
15.5.3 Management and Prevention
15.6 Other Complications
15.6.1 Dialysis Disequilibrium Syndrome
15.6.1.1 Etiology
15.6.1.2 Clinical Manifestations
15.6.1.3 Treatment and Prevention
15.6.2 Air Embolus
15.6.2.1 Etiology
15.6.2.2 Clinical Manifestations
15.6.2.3 Treatment
15.6.3 Microthrombus
15.6.4 Deletion Syndrome
15.6.5 Destruction of the Physical Component of the Blood
References
Chapter 16: Efficacy and Its Evaluation of Non-bioartificial Liver
16.1 Criteria and Indicators of Efficacy of Non-bioartificial Liver
16.1.1 Criteria of Short-Term Efficacy
16.1.1.1 Effectiveness Before and After Treatment
16.1.1.2 Cure Rate and Improvement Rate of Patients
16.1.2 Criteria of Long-Term Efficacy
16.2 The Efficacy of Non-bioartificial Liver
16.2.1 Short-Term Efficacy
16.2.2 Long-Term Efficacy
16.3 MELD for Predication of Curative Effect in Liver Failure Treatment Via Non-bioartificial Liver
16.3.1 History
16.3.1.1 MELD
16.3.1.2 MELD-Na
16.3.1.3 MESO Index
16.3.1.4 iMELD
16.3.2 Advantage of MELD
16.3.3 Application
16.3.3.1 Esophageal Variceal Bleeding
16.3.3.2 Spontaneous Bacterial Peritonitis
16.3.3.3 Hepatorenal Syndrome
16.3.3.4 Viral Hepatitis
16.3.3.5 Alcoholic Hepatitis
16.3.3.6 Hepatocellular Carcinoma
16.3.3.7 Liver Transplantation
Assessing Patient Survival and Allocation of Liver Transplantation
Evaluation of the Survival Rate of Patients After Liver Transplantation
Pediatric Liver Transplantation
Application of MELD in Liver Transplantation for Hepatocellular Carcinoma
16.3.4 MELD in Prognostic Criteria for End-Stage Liver Disease
16.3.5 The MELD in Efficacy Prediction for Liver Failure Treatment Using Non-bioartificial Liver
References
Chapter 17: Bio-Artificial Liver
17.1 The Principle of the Bio-Artificial Liver
17.2 The Bio-Artificial Liver System
17.2.1 The Li-BAL System
17.2.1.1 Cell Sources of Hepatocytes for the Bio-artificial Liver (BAL)
17.2.1.2 Bioreactor
17.2.1.3 The Construction of the Li-BAL System
17.2.1.4 The Evaluation of the Li-BAL System
17.2.2 The Bio-Artificial Liver Support System
17.2.2.1 Source of Hepatocytes
17.2.2.2 The Bioreactor
17.2.2.3 BLSS Construction
17.2.2.4 The Evaluation of the BLSS
17.2.3 The Extracorporeal Liver Assist Device
17.2.3.1 Hepatocytes Source
17.2.3.2 Reactor
17.2.3.3 The construction of the ELAD System
17.2.3.4 The Evaluation of the ELAD System
17.2.4 Radial Flow Biological Artificial Liver System
17.2.5 The Amsterdam Medical Center Bio-Artificial Liver
17.3 Animal Models for Evaluating Bio-Artificial Liver
17.3.1 The Surgical Model
17.3.1.1 The Total Hepatectomy Model
17.3.1.2 Partial Liver Resection Model
17.3.1.3 The Hepatic Blood Flow Blocking Model
17.3.2 The Chemical Model
17.3.2.1 The Acetaminophen Drug Model
17.3.2.2 D-galactosamine
References
Chapter 18: Hybrid Artificial Liver
18.1 Construction of Hybrid Artificial Liver
18.1.1 Construction of HAL
18.1.1.1 HepatAssist System
18.1.1.2 Modular Extracorporeal Liver Support (MELS)
18.1.1.3 Amsterdam Medical Center-bioartificial Liver (AMC-BAL)
18.1.1.4 Li-hybrid Artificial Liver Support System (Li-HAL)
18.1.2 Hybrid Artificial Liver Support Device
18.1.2.1 Circulation Path
18.1.2.2 Heating System
18.1.2.3 Monitoring System
18.2 Animal Experiment Evaluation Using the Hybrid Artificial Liver (HAL)
18.3 Hybrid Artificial Liver Clinical Trials
18.3.1 HepatAssist System
18.3.2 Modular Extracorporeal Liver Support (MELS) System
18.3.3 Amsterdam Medical Center-bioartificial Liver (AMC-BAL) System
18.3.4 Li-hybrid Artificial Liver Support System (Li-HAL)
References
Chapter 19: Cell Transplantation Therapy for Liver Failure
19.1 The Basic Study of Hepatocyte Transplantation
19.1.1 The Sources and Species of the Transplanted Cells
19.1.1.1 Human Hepatocytes
19.1.1.2 Xenogeneic Hepatocytes
19.1.1.3 Tumor Cell Lines
19.1.1.4 Stem Cells
Hepatic Oval Cells
Small Hepatocyte-Like Progenitor Cells
Embryonic Stem Cells
Mesenchymal Stem Cells
Induced Pluripotent Stem Cells
19.1.1.5 Immortalized Hepatocytes
19.1.2 Transplantation Routes for Cell Transplantation
19.1.2.1 Cell Transplantation In Situ
Cell Transplantation in Liver
Cell Transplantation in Spleen
19.1.2.2 Heterotopic Cell Transplantation
Cell Transplantation into the Peritoneal Cavity
Cell Transplantation into Other Tissues and Organs
19.1.3 Appropriate Cell Numbers for Transplantation
19.1.4 The Isolation and Culture of Hepatocytes
19.2 Clinical Application of Cell Transplantation
19.2.1 The Indications and Contraindications of Liver Cell Transplantation
19.2.1.1 Indications
19.2.1.2 Contraindication
19.2.2 Preliminary Clinical Application of Hepatocyte Transplantation
19.2.2.1 Treatments of Inherited Metabolic Liver Diseases
19.2.2.2 Hepatocellular Therapy for Liver Failure
19.2.2.3 Use of Oval Liver Cells
19.2.3 Treatment of Complications After Hepatocellular Transplantation
19.2.3.1 Hepatic Veno-Occlusive Disease
19.2.3.2 Infection
19.2.3.3 Immune Rejection of Transplanted Liver Cells
19.2.3.4 Hepatic Encephalopathy
19.3 Problems and Prospects of Hepatocyte Transplantation
References
Chapter 20: Artificial Liver and Liver Transplantation
20.1 A Brief Introduction to Liver Transplantation
20.2 Indications for Liver Transplantation, Contraindications and Timing of Surgery
20.2.1 Indications of Liver Transplantation
20.2.2 Contraindications of Liver Transplantation
20.2.3 The Timing of the Liver Transplant
20.3 The Application of Liver Transplantation to Treat Liver Failure
20.3.1 The Indications of Liver Transplantation to Treat Liver Failure
20.3.2 The Prognosis of Liver Transplantation in Patients with Acute Liver Failure
20.3.3 The Application of the Artificial Liver Support System in the Preoperative and Perioperative Period
20.3.4 The Application of ALSS in the Postoperative Period
20.3.4.1 Delayed Recovery of Liver Function Following Liver Transplantation
20.3.4.2 The Primary Graft Lack of Function Following Liver Transplantation
References
Chapter 21: Four Clinical Cases
21.1 Case 1: Li-ALS Treatment for Viral Liver Failure
21.2 Case 2: Li-ALS Treatment for Drug-induced Liver Failure
21.3 Case 3: Li-ALS Treatment for Acute Fatty Liver of Pregnancy
21.4 Case 4: Li-ALS Therapy for Human Infection with H7N9 Influenza A Virus
Chapter 22: Prospect
22.1 The Present Situation and Controversies on the Medical Treatment of Liver Failure
22.2 The Developments and Prospects of Artificial Liver Therapy
22.2.1 The Optimization and Innovation of Non-biological Artificial Liver
22.2.2 Problems and Breakthroughs in Bioartificial and Hybrid Artificial Liver Support Systems
22.2.3 Problems and Hopes for Liver Transplantation and Stem Cell Transplantation
References