Preface
Contents
Part I: Overview
1: Anatomy and Embryology of the Liver
1.1 Introduction
1.2 Clinical Anatomy of the Liver
1.3 Gross Anatomy and Surfaces of the Liver
1.4 Peritoneum and Ligaments of the Liver
1.5 Vessels and Nerves
1.6 Segmental Anatomy of the Liver
1.7 Extrahepatic Biliary Tract
1.8 Liver Development
1.8.1 Hepatic Competence
1.8.2 Hepatic Induction
1.8.3 Liver Bud Formation and Growth
1.8.4 Hepatoblasts Fate and Function
1.8.5 Differentiation of Hepatocytes and Biliary Epithelial Cells
1.8.6 Hepatic Vascular Development
1.8.7 Morphogenetic Events Accompanying the Liver Growth
1.9 Conclusions
Self Study
Questions
Answers
References
2: Liver Histology
2.1 Introduction: The Microstructure of the Liver
2.2 Hepatic Morpho-functional Units: Hepatic Lobule, Portal Lobule, Hepatic Acinus
2.3 Hepatic Cytotypes
2.3.1 Hepatocytes
2.3.2 Endothelial Cells
2.3.3 Hepatic Stellate Cells
2.3.4 Kupffer Cells
2.3.5 Lymphocytes or Pit Cells
2.4 Cholangiocytes and the Intrahepatic Bile Ducts
2.5 Hepatic Microcirculation
2.6 Microstructure of the Extrahepatic Biliary Tract
2.7 Conclusions
Self Study
Questions
Answer
References
3: Hepatic Progenitor Cells and Biliary Tree Stem Cells
3.1 Hepatic Progenitor Cells: Embryology Derivation and Anatomical Location
3.2 Role of Hepatic Progenitor Cells and Regeneration Pathways in Human Liver Pathologies
3.3 HPCs Activation Is Driven by a Specialized Niche and Signaling Pathways
3.4 Biliary Tree Stem Cells and Peribiliary Glands
3.5 Stem Cells in Regenerative Medicine for Liver Diseases
3.6 Conclusions
Self Study
Questions
Answers
References
4: Hepatocellular Death: Apoptosis, Autophagy, Necrosis and Necroptosis
4.1 Introduction
4.2 Apoptosis
4.3 Autophagy
4.4 Necrosis
4.5 Necroptosis
4.6 The Crosstalk Between Apoptosis, Autophagy, Necrosis and Necroptosis
4.7 Conclusions
Self Study
Questions
Answers
References
5: Liver Inflammation: Short Uptodate
5.1 Introduction
5.2 Liver Inflammation
5.2.1 Macrophages
5.2.2 Dendritic Cells (DCs)
5.2.3 Lymphocytes
5.2.4 Mucosal-Associated Invariant T (MAIT)
5.2.5 Leukocytes
5.2.6 HMGB1 (High Mobility Group Box 1) Protein
5.3 Pathological Liver Inflammation
5.3.1 Cholangiocyte Immune Response
5.3.2 Steatosis and Steatohepatitis
5.3.3 Inflammation in NASH
5.3.4 Metaflammation
5.4 Conclusions
Self Study
Questions
Answers
References
6: Molecular Basis of Fibrogenesis and Angiogenesis During Chronic Liver Disease: Impact of TGF-β and VEGF on Pathogenic Pathways
6.1 Introduction
6.2 Biology of TGF-β Signaling Pathway
6.3 Apoptotic and Fibrotic Effects of TGF-β on Hepatocytes
6.4 Molecular Basis for Phenotypic Changes of HSCs to MyoFBs
6.5 Linkage of VEGF-Induced Angiogenesis with TGF-β-Induced Fibrogenesis
6.6 Endothelial to Mesenchymal Transition (EndoMT) for LC
6.7 Summary and Perspective
Self Study
Questions
Answers
References
7: Hepatotoxicity: Mechanisms of Liver Injury
7.1 Introduction
7.2 Hepatic Injury
7.3 Hepatic Function
7.4 Hyâs Law
7.5 Detecting and Assessing Hepatotoxicity
7.6 Morphologic Pathology
7.7 Direct Hepatotoxins
Self Study
Questions and Answers
References
8: Crosstalk of Molecular Signaling in Hepatocellular Carcinoma
8.1 Introduction
8.2 Receptor Tyrosine Kinases Signaling
8.3 MAPK/ERK Pathway
8.4 PI3K/Akt/mTOR Pathway
8.5 Crosstalk of ERK/MAPK and PI3K/Akt/mTOR Pathway
8.6 Wnt/β-Catenin Signaling
8.7 Crosstalk of Wnt/β-Catenin Pathway with Other Pathways
8.8 TGF-β Signaling
8.9 Crosstalk of TGF-β Signaling with Other Pathways
8.10 JAK/STAT Pathway
8.11 Crosstalk of JAK/STAT Pathway with Other Pathways
8.12 MDM2-p53 Pathway
8.13 Crosstalk of MDM2-p53 Pathway with Other Pathways
8.14 Other Signaling Pathways
8.15 Conclusions and Perspectives
Self Study
Questions
Answers
References
9: Drug Induced Liver Injury: Mechanisms, Diagnosis, and Clinical Management
9.1 Introduction
9.2 Definitions
9.2.1 Idiosyncratic Versus Intrinsic Toxicity
9.3 DILI Mechanisms and Hypothetical Cascade of Events
9.4 Clinical Aspects
9.4.1 Most Implicated Drugs
9.4.2 Genetic and Non-genetic Risk Factors
9.4.3 DILI Signatures for Specific Drugs
9.4.4 Demographics and DILI Characteristics
9.4.5 Clinical Spectrum
9.4.6 Alternative Causes
9.5 Biomarkers
9.6 RUCAM-Based Causality Assessment
9.6.1 Principles
9.6.2 Alternative Approaches of Causality Assessment
9.6.3 Global Usage
9.7 Practical Example
9.8 Conclusions
Self Study
Questions
Answers
References
Further Reading
Related Links/Journals/Book
10: Acquired Metabolic Disorders
10.1 Introduction
10.2 Ornithine Transcarbamylase Deficiency
10.2.1 Brief Historical Overview
10.2.2 Definition of the Disorder
10.2.3 Diagnosis
10.2.4 Treatment
10.3 Porphyria
10.3.1 Brief Historical Overview
10.3.2 Definition of the Disorder
10.3.3 Diagnosis
10.3.4 Treatment
10.4 Hemochromatosis
10.4.1 Brief Historical Overview
10.4.2 Definition of the Disorder
10.4.3 Diagnosis
10.4.4 Treatment
10.5 Alpha 1 Antitrypsin Deficiency
10.5.1 Brief Historical Overview
10.5.2 Definition of the Disorder
10.5.3 Diagnosis
10.5.4 Treatment
10.6 Wilson Disease
10.6.1 Brief Historical Overview
10.6.2 Definition of the Disorder
10.6.3 Diagnosis
10.6.4 Treatment
10.7 Conclusions and Future Perspectives
Self Study
Questions
Answers
References
Further Readings
Ornithine Transcarbamylase Deficiency
Porphyria
Hemochromatosis
Alpha 1 Antitrypsin Deficiency
11: Vascular Disorders of the Liver
11.1 Introduction
11.2 Budd-Chiari Syndrome or Hepatic Venous Outflow Tract Obstruction
11.3 Portal Vein Thrombosis
11.4 Sinusoidal Obstruction Syndrome
11.5 Congenital Vascular Malformations Affecting the Liver
11.5.1 Isolated Congenital Liver Shunts
11.6 Conclusions
Self Study
Questions
Answers
References
12: Liver Ischaemia-Reperfusion Injury
12.1 Introduction
12.1.1 Definitions
12.2 Aetiology
12.2.1 Liver Surgery
12.2.2 Liver Transplantation
12.3 Risk Factors
12.3.1 Liver Surgery
12.3.2 Liver Transplantation
12.4 Pathophysiology
12.4.1 Intracellular Events
12.4.2 Innate Immune Response
12.4.3 Cellular Response
12.4.4 Inflammatory Mediators
12.4.5 Microcirculatory Failure
12.5 Clinical Manifestation
12.5.1 Direct Injury to the Liver
12.5.2 Remote Injury to Other Organs
12.5.2.1 Post-reperfusion Syndrome (PRS)
12.6 Prevention and Treatment
12.6.1 Liver Surgery
12.6.1.1 Intermittent Clamping
12.6.1.2 Ischaemic Preconditioning (IPC)
12.6.1.3 Remote Ischaemic Preconditioning (RIPC)
12.6.1.4 Pharmacological Agents
12.7 Liver Transplantation
12.8 Donor Strategies
12.8.1 Donor Optimisation
12.8.2 Normothermic Regional Perfusion (NRP)
12.9 Preservation and Resuscitation
12.9.1 Preservation Solutions
12.9.2 Hypothermic Machine Perfusion (HMP)
12.9.3 Normothermic Machine Perfusion (NMP)
12.10 Recipient Strategies
12.10.1 Washout Techniques
12.10.2 Remote Ischaemic Preconditioning (RIPC)
12.10.3 Pharmacological Agents
12.11 Future Perspectives
Self Study
Questions
Answers
References
13: Autoimmune Hepatitis
13.1 Introduction
13.2 Diagnostic Criteria
13.3 Autoantibody Serology
13.4 Aetiology
13.5 Pathogenesis
13.6 Natural History
13.7 Epidemiology
13.7.1 Histopathological Features
13.7.2 Diagnostic Work Up
13.8 Disease Treatment and Management
13.8.1 Standard Treatment
Self Study
Questions
Answers
References
14: Primary Sclerosing Cholangitis
14.1 Introduction
14.2 Diagnostic Criteria
14.3 Epidemiology
14.4 Natural History
14.5 Serological Features
14.6 Imaging Features
14.7 Histopathological Features
14.8 Autoimmune Hepatitis in PSC
14.9 Extrahepatic Manifestations
14.10 Pathogenesis
14.11 Medical Treatment
Self Study
Questions
Answers
References
15: Parasitic Liver Diseases
15.1 Introduction
15.1.1 Parasitic Liver Diseases: Helminths
15.1.1.1 Schistosomiasis
15.1.2 Echinococcosis
15.1.3 Clonorchiasis and Opisthorchiasis
15.1.4 Fascioliasis
15.1.5 Ascariasis
15.1.6 Visceral Larva Migrans
15.1.7 Hepatic Capillariasis
15.1.8 Ectopic Pinworm Infection
15.1.9 Strongyloidiasis
15.1.10 Fasciolopsiasis
15.1.11 Dicrocoeliasis
15.1.12 Visceral pentastomiasis
15.2 Parasitic Liver Diseases: Protozoa
15.2.1 Amoebiasis
15.2.2 Giardiasis
15.2.3 Cryptosporidiosis
15.2.4 Malaria
15.2.5 Visceral Leishmaniasis
15.2.6 Toxoplasmosis
15.2.7 Babesiosis
15.2.8 Chagasâ Disease (Trypanosomiasis)
15.3 Concluding Remarks and Future Directions
Self Study
Questions
Answers
References
Further Reading
16: Viral Hepatitis B
16.1 Introduction
16.2 HBV Genome
16.3 HBV Genotypes
16.4 HBV Mutation
16.5 HBV Transmission
16.6 Acute Infection
16.7 Chronic Infection
16.8 Genetic Factors Predisposing to Chronic Persistent Infection
16.9 Serological Diagnosis of HBV
16.10 Immune Response
16.11 Fulminant Hepatic Failure
16.12 Chronic Hepatitis, Liver Cirrhosis and Massive Hepatic Necrosis
16.13 Hepatocellular Carcinoma
16.14 HBV Vaccination
16.15 Anti-HBV Therapy
16.16 Pegylated Interferon Alpha (IFN-Îą) Therapy
16.17 Nucleos(t)ide Analogues Therapy
16.18 Combination Therapy
16.19 Future Perspectives
16.20 Conclusion
Self Study
Questions
Answers
References
17: Viral Hepatitis C
17.1 Introduction
17.2 Virology
17.2.1 Taxonomic Classification and Genotypes
17.2.2 Viral Structure
17.2.3 Viral Life Cycle
17.3 Epidemiology
17.4 Transmission
17.5 Diagnosis
17.5.1 Anti-HCV Antibodies
17.5.2 Nucleic Acid Detection
17.5.3 Genotyping
17.5.4 Point of Care and Rapid Tests
17.6 Clinical Manifestations
17.6.1 Acute Hepatitis
17.6.2 Chronic Hepatitis
17.6.3 Hepatic Steatosis
17.6.4 Cirrhosis
17.6.4.1 Ascites
17.6.4.2 Esophageal Varices
17.6.4.3 Hepatic Encephalopathy
17.7 HCC
17.8 Extrahepatic Manifestations
17.8.1 Mixed Cryoglobulinemia
17.8.2 Lymphoproliferative Disorders
17.8.3 Cardiovascular Manifestations
17.8.4 Neurologic and Psychiatric Diseases
17.8.5 Endocrine Diseases
17.9 Natural History
17.10 Treatment
17.10.1 Objectives of Therapy
17.10.2 Direct Antiviral Drugs
17.10.2.1 NS3/4A Protease Inhibitors
17.10.2.2 NS5A Inhibitors
17.10.2.3 NS5B RNA Polymerase Inhibitors
17.10.3 DAA Therapeutic Regimens and Their Clinical Use
17.10.3.1 DAA Treatment and Drug-to-Drug Interaction
17.10.3.2 Post-Treatment Follow-Up
17.11 Treatment of HCV Acute Hepatitis
17.12 Treatment of Particular Patients with HCV
17.12.1 HBV and HIV Co-Infected
17.12.2 End-Stage Liver Disease
17.12.3 Patients with Renal Insufficiency
17.12.4 Non-hepatic Solid Organ Transplantation Patients
17.12.5 Re-treatment of Non-SVR to DAA
17.13 Prevention of HCV Infection
Self Study
Questions
Answers
References
Glossary
18: Non-B, Non-C Viral Hepatitis
18.1 Introduction
18.2 Epidemiology of Non-B/Non-C Viral Hepatitis
18.2.1 HAV Infection
18.2.2 HDV Infection
18.2.3 HEV Infection
18.3 Clinical Presentation and Management of Non-B/Non-C Viral Hepatitis
18.3.1 HAV Infection
18.3.2 HDV Infection
18.3.3 HEV Infection
18.4 Global Burden of Non-B/Non-C Viral Hepatitis
18.5 Summary and Perspectives
Self Study
Question
Answer
References
19: The Microbiome in Liver Diseases
19.1 Introduction
19.2 The Intestinal Microbiome in Liver Diseases
19.3 Summary and Perspectives
Self Study
Question
Answer
References
20: Polycystic Liver Diseases
20.1 Introduction
20.2 Pathogenesis
20.3 Epidemiology
20.4 Signs and Symptoms
20.5 Diagnosis
20.6 Establishing Diagnosis
20.7 Differential Diagnosis
20.8 Natural History and Complications
20.9 Classifications
20.10 Treatment
Self Study
Questions
Answers
References
21: Hepato- and Porto-pulmonary Hypertension
21.1 Introduction
21.2 Porto-Pulmonary Hypertension
21.2.1 Definition
21.2.2 Epidemiology
21.2.3 Pathology
21.2.4 Pathophysiology
21.2.5 Clinical Manifestations
21.2.6 Workup
21.2.7 Pharmacological Treatment
21.2.8 Liver Transplantation in Patients with POPH
21.2.9 Prognosis
21.3 Hepato Pulmonary Syndrome (HPS)
21.3.1 Definition
21.3.2 Epidemiology
21.3.3 Risk Factors
21.3.4 Pathology
21.3.5 Pathophysiology (Fig. 21.1)
21.3.6 Workup
21.3.7 Echocardiography
21.3.8 HPS Classification
21.3.9 HPS Prognosis
21.3.10 HPS Treatment
21.3.11 Pharmacological Treatment
21.3.12 Conclusions
Self Study
Questions
Answers
Future Perspectives
References
Further Reading
22: Hepatic Abscesses
22.1 Definition
22.2 History
22.3 Incidence
22.4 Classification
22.5 Aetiopathogeny
22.6 Diagnosis
22.6.1 Clinical Manifestations
22.6.2 Imaging Explorations
22.6.3 Laboratory Tests
22.6.4 Differential Diagnosis
22.7 Evolution
22.8 Treatment
22.9 Amoebaean Abscesses
Self Study
Questions
Answers
References
23: Liver Cirrhosis
23.1 Introduction
23.2 Epidemiology
23.3 Etiology
23.3.1 Viral Hepatitis
23.3.2 Alcoholic Liver Disease
23.3.3 Non-alcoholic Fatty Liver Disease
23.3.4 Cholestasis
23.3.5 Circulation Disorders
23.3.6 Drugs and Industrial Poisons
23.3.7 Others
23.4 Pathology
23.5 Clinical Stages and Presentations
23.6 Laboratory Tests
23.7 Imaging
23.8 Diagnosis
23.9 Treatment
23.9.1 Antiviral Treatment
23.9.2 Ascites
23.9.3 Variceal Bleeding
23.9.4 Hepatic Encephalopathy
23.9.5 Hepatorenal Syndrome
23.10 Prognosis
Self Study
Questions
Answers
24: Primary Biliary Cholangitis
24.1 Introduction
24.2 Epidemiology of PBC
24.3 Pathogenesis of PBC
24.3.1 Genetic Factors
24.3.2 Epigenetics
24.3.3 Environmental Factors
24.3.4 The Role of AMA, T Cells and BECs in the Pathogenesis of PBC
24.4 Clinical Presentation
24.5 Diagnosis
24.5.1 Biochemical Findings
24.5.2 Autoantibodies
24.5.3 Histology
24.5.4 Non-invasive Methods for Monitoring Disease Stage
24.6 Natural History of PBC and Treatment
24.6.1 Natural History of PBC in the Pre-UDCA Era
24.6.2 Natural History and Treatment of PBC
24.6.2.1 Medications to Delay Disease Progression
UDCA
Obeticholic Acid
Other Treatment Modalities
Liver Transplantation
24.6.2.2 Active Management of Disease-Related Symptoms
24.7 Variant Syndromes of PBC
24.7.1 AMA Negative PBC
24.7.2 PBC-AIH Variant
24.7.3 Premature Ductopenic Variant
24.8 Staging and Surveying of PBC Patients
24.9 Conclusion/Summary
Self Study
Questions
Answers
References
25: The Paucity of Interlobular Bile Ducts
25.1 Introduction
25.2 Cholangiocyte
25.3 Ductal Plate Remodeling of the Liver
25.4 The Paucity of Interlobular Bile Ducts
25.5 Alagille Syndrome (AGS)
25.6 Williams-Beuren Syndrome (WBS)
25.7 Ivemark Syndrome (IS)
25.8 Zellweger Syndrome
25.9 Major Karyotype Abnormalities
25.10 Alpha-1-Antitrypsin Deficiency
25.11 Cystic Fibrosis
25.12 Virus-Related PIBD
25.13 Sclerosing Cholangitis
25.14 Conclusion
Self Study
Questions
Answers
References
26: Nonalcoholic Fatty Liver Disease: AÂ Wide Spectrum Disease
26.1 Introduction
26.2 Epidemiology
26.2.1 Prevalence and Incidence of NAFL/NASH
26.2.2 Natural History and Risk Factors for NAFL and NASH
26.2.3 Genetic and Epigenetic Factors
26.2.4 Environmental Factors
26.2.5 Lean NAFLD
26.3 Pathogenesis
26.4 Experimental Models
26.5 Diagnosis
26.5.1 Diagnosis of NAFLD
26.5.2 Diagnosis of NASH and Fibrosis
26.6 Treatment
26.7 Conclusions
Self Study
Questions
Answers
References
Related Published Articles
27: Alcoholic Liver Disease
27.1 Introduction
27.2 Malnutrition and Metabolic Dysfunction
27.3 Oxidative Stress
27.4 Genetics/Epigenetics
27.5 Gut Permeability and Endotoxemia
27.6 Treatment of Alcoholic Liver Disease
27.7 Conclusion/Summary
Self Study
Questions
Answers
References
Further Reading and Additional Resources
28: Liver Disease in Pregnancy
28.1 Introduction
28.2 Normal Pregnancy
28.3 Pre-existing or Coincidental Liver Disease During Pregnancy
28.3.1 Acute Viral Hepatitis
28.3.2 Herpes Simplex Virus
28.3.3 Hepatitis B
28.3.4 Hepatitis C
28.3.5 Other Chronic Liver Diseases
28.3.6 Benign Liver Lesion
28.4 Liver Diseases Specific to Pregnancy
28.4.1 Hyperemesis Gravidarum
28.4.2 Intrahepatic Cholestasis of Pregnancy
28.4.3 Preeclampsia/Eclampsia
28.4.4 Acute Fatty Liver of Pregnancy
28.4.5 HELLP
28.4.6 Hepatic Venous Outflow Obstruction (Budd Chiari)
28.5 Special Liver Related Considerations in Pregnancy
28.5.1 Imaging
28.5.2 Liver Biopsy
28.5.3 Endoscopy/ERCP/EUS/Sedation
28.5.4 ERCP
28.6 Cirrhosis and Portal Hypertension
28.7 Liver Transplant
28.8 Conclusion
Self Study
Questions
Answers
References
Normal Pregnancy
Pre-existing or Coincidental Liver Disease During Pregnancy
Liver Diseases Specific to Pregnancy
Special liver Related Considerations in Pregnancy
Cirrhosis and Portal Hypertension
29: Cirrhotic Cardiomyopathy
29.1 Introduction
29.2 Definition
29.3 Epidemiology
29.4 Pathophysiology
29.5 Diagnostic Tests
29.5.1 Echocardiography
29.5.2 Systolic Dysfunction
29.5.3 Diastolic Dysfunction
29.5.4 Cardiac Scintigraphy
29.5.5 Cardiac Magnetic Resonance
29.5.6 Electrophysiological Changes
29.5.7 Cardiac Biomarkers
29.6 Prognosis and Correlation with Liver Disease Severity
29.7 Management Options
29.8 Conclusions
Self Study
Questions
Answers
References
Further Reading
30: Benign Liver Tumours
30.1 Introduction
30.2 Focal Nodular Hyperplasia
30.2.1 Introduction and Epidemiology
30.2.2 Pathogenesis
30.2.3 Pathology
30.2.4 Clinical Features
30.2.5 Diagnosis
30.2.6 Treatment
30.3 Hepatocellular Adenoma
30.3.1 Introduction and Epidemiology
30.3.2 Etiology and Incidence
30.3.3 Pathology
30.3.4 Genotype and Phenotype Classification
30.3.5 Clinical Features
30.3.6 Diagnosis
30.3.7 Treatment
30.4 Hepatic Hemangioma
30.4.1 Introduction and Epidemiology
30.4.2 Pathogenesis
30.4.3 Pathology
30.4.4 Clinical Features
30.4.5 Diagnosis
30.4.6 Treatment
30.5 Cystic Liver Lesions
30.5.1 Introduction
30.6 Simple Hepatic Cysts
30.6.1 Epidemiology and Pathogenesis
30.6.2 Pathology
30.6.3 Clinical Features
30.6.4 Diagnosis
30.6.5 Treatment
30.7 Polycystic Liver Disease
30.7.1 Epidemiology and Pathogenesis
30.7.2 Clinical Features
30.7.3 Diagnosis
30.7.4 Treatment
30.8 Benign Biliary Cystic Tumours (Cystadenoma)
30.8.1 Epidemiology and Pathogenesis
30.8.2 Pathology
30.8.3 Clinical Features
30.8.4 Diagnosis
30.8.5 Treatment
30.9 Conclusions
References
31: Liver Cancer
31.1 Introduction
31.2 Hepatocellular Carcinoma
31.2.1 Epidemiology and Risk Factors
31.2.2 Prevention
31.2.3 Pathogenesis
31.2.4 Diagnosis
31.2.5 Surveillance
31.2.6 Staging
31.2.7 Pathology
31.2.8 Clinical Features
31.2.9 Treatment
31.2.9.1 Liver Surgery
31.2.9.2 Local Ablation
31.2.9.3 Liver Resection vs Local Ablation
31.2.9.4 Transarterial Chemoembolization
31.2.9.5 Radiation Therapy
31.2.9.6 Systemic Therapy
31.3 Intrahepatic Cholangiocellular Carcinoma
31.3.1 Epidemiology and Risk Factors
31.3.2 Molecular Pathogenesis
31.3.3 Pathology and Classification
31.3.4 Clinical Features
31.3.5 Diagnosis
31.3.6 Staging
31.3.7 Treatment
31.3.7.1 Liver Resection and Liver Transplantation
31.3.7.2 Locoregional Therapies
31.3.7.3 Systemic Therapy
31.4 Combined Hepatocellular-Cholangiocarcinoma
Self Study
Questions
Answers
References
32: Acute Liver Failure
32.1 Introduction
32.2 Definition
32.3 Etiology
32.3.1 Etiologies with Possible Indication for Emergency LT
32.3.1.1 Drug-Related Hepatotoxicity
32.3.1.2 Acetaminophen (Paracetamol) Toxicity
32.3.1.3 Idiosyncratic Drug Reaction
32.3.1.4 Toxin-Related Hepatotoxicity
32.3.1.5 Viral Hepatitis
32.3.1.6 Hepatitis B Virus (HBV)
32.3.1.7 Hepatitis AÂ Virus (HAV)
32.3.1.8 Hepatitis E Virus (HEV)
32.3.1.9 Hepatitis D Virus (HDV)
32.3.1.10 Hepatitis C Virus (HCV)
32.3.1.11 Other Viral Infection
32.3.1.12 Autoimmune Hepatitis
32.3.1.13 Wilson Disease
32.3.1.14 Budd-Chiari Syndrome
32.3.1.15 Pregnancy: Acute Fatty Liver of Pregnancy and HELLP Syndrome
32.3.2 Etiologies with No Indication of LT
32.3.2.1 Malignancies
32.3.2.2 Vascular Causes
32.3.2.3 Portal Vein Thrombosis (PVT)
32.4 Epidemiology
32.5 Pathophysiology
32.6 Diagnosis
32.6.1 Laboratory Evaluation
32.6.2 Imaging Study
32.7 Treatment
32.7.1 General Principles and Organ Specific Management
32.7.2 Treatment for Specific Etiology of ALF
32.7.3 Specific Treatment of ALF
32.7.3.1 Measures to Prevent ICP Elevation
32.7.4 Experimental Therapies
32.7.5 Artificial Liver Support Devices
32.7.6 Liver Transplantation
32.8 Prognosis
32.9 Conclusions
Self Study
Questions
Answers
References
33: Chronic Liver Failure and Acute-on-Chronic Liver Failure
33.1 Introduction
33.2 Pathogenesis of Chronic Liver Failure
33.2.1 Portal Hypertension and Hyperdynamic Circulation
33.2.2 Dysbiosis, Bacterial Translocation and Systemic Inflammation
33.3 Clinical Manifestations
33.3.1 Gastrointestinal Bleeding Secondary to PH
33.3.2 Ascites
33.3.3 Renal Impairment
33.3.4 Immune Dysfunction
33.3.5 Infections
33.3.6 Neurological Manifestations
33.3.7 Cardiopulmonary Complications
33.3.8 Nutrition and Muscle Mass
33.3.9 Bone Disease
33.3.10 Endocrinopathies
33.3.11 Haematological Alterations
33.3.12 Skin Manifestations
33.3.13 Hepatocellular Carcinoma
33.3.14 Acute-on-Chronic Liver Failure
33.4 Conclusions/Summary
Self Study
Questions
Answers
References
Further Reading and Related Links
Part II: Diagnostic Methods
34: History and Physical Examination
34.1 Introduction
34.2 Symptoms of Liver Disease
34.3 Clinical Examination in Liver Disease
34.3.1 Auscultation
34.3.2 Inspection
34.3.3 Palpation
34.3.4 Percussion
34.4 Conclusions/Summary
Self Study
Questions
Answers
References
Further Reading
35: Assessment of Liver Function
35.1 Introduction: Standard Liver Panel
35.1.1 Total Bilirubin
35.1.2 Transaminases
35.1.3 AST/ALT Ratio
35.1.4 Alkaline Phosphatase
35.1.5 Gamma Glutamyl Transpeptidase
35.1.6 Albumin
35.1.7 Other Tests
35.1.7.1 5â˛-Nucleotidase
35.1.7.2 Ceruloplasmin
35.1.7.3 Alpha-Fetoprotein
35.1.7.4 Coagulation Studies
35.1.7.5 Serum Glucose
35.1.8 Lactate Dehydrogenase
35.1.8.1 Elevated Transaminases
35.2 Viral Hepatitis
35.2.1 Hepatitis A
35.2.2 Hepatitis B
35.2.3 Hepatitis C
35.2.4 Hepatitis D
35.2.5 Hepatitis E
35.2.6 Alcohol-Induced Liver Disease
35.2.7 Drug-Induced Liver Injury
35.2.8 Ischemic Hepatitis
35.2.9 Acute Liver Failure
35.2.10 Autoimmune Hepatitis
35.3 Metabolic Liver Disease
35.3.1 Nonalcoholic Fatty Liver Disease
35.3.2 Hereditary Hemochromatosis
35.3.3 Alpha-1 Antitrypsin Deficiency
35.3.4 Wilson Disease
35.4 Cholestatic Liver Diseases
35.4.1 Primary Biliary Cholangitis
35.4.2 Primary Sclerosing Cholangitis
35.5 Complications of Chronic Liver Disease
35.5.1 Cirrhosis
35.6 Complications of Cirrhosis
35.6.1 Portal Hypertension
35.6.2 Esophageal Varices
35.6.3 Gastric Varices and Portal Hypertensive Gastropathy
35.6.4 Hepatic Encephalopathy
35.6.5 Hepatopulmonary Syndrome
35.6.6 Portopulmonary Hypertension
35.6.7 Ascites
35.6.8 Spontaneous Bacterial Peritonitis
35.6.9 Hepatorenal Syndrome
35.6.10 Hepatocellular Carcinoma
35.7 Determining Prognosis
35.7.1 MELD
35.7.2 Child-Turcotte-Pugh
35.8 Future Directions
35.8.1 Cytokeratin 18
35.8.2 MicroRNA
35.8.3 Extracellular Vesicles
Self Study
Questions
Answers
References
36: Noninvasive Biomarkers for Liver Fibrosis
36.1 Introduction
36.2 Extracellular Matrix (ECM) from Normal to Fibrotic Liver
36.3 Liver Biopsy
36.4 Noninvasive Biomarkers of Liver Fibrosis
36.5 Characteristics of Ideal Marker
36.5.1 Indirect Markers
36.5.1.1 Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Ratio (AAR)
36.5.1.2 APRI
36.6 Immune Fibrosis Index (IFI) Score
36.6.1 Prothrombin Time
36.6.2 The FIB-4 Score
36.7 Fibrofast; FIB-5
36.7.1 The NAFLD Fibrosis Score
36.7.2 Fibro Index
36.7.3 FibroTest (FibroSURE in USA)
36.8 Fibro Test Is Calculated as Below
36.8.1 FibroMax
36.9 Serum Leptin and Homeostasis Model Assessment-IR Model
36.9.1 Neutrophil to Lymphocyte Ratio
36.9.2 The PGA Index
36.9.3 The Forns Index
36.10 Forns Index
36.10.1 HepaScore
36.10.2 Platelet Volume and Neutrophil to Lymphocyte Ratio
36.10.3 FibroMeter
36.10.4 SteatoTest
36.10.5 The Proteomics Based Tests
36.11 Direct Noninvasive Biomarkers (NIBMs) for Assessing Liver Fibrosis
36.11.1 Direct Markers Related to Matrix Deposition
36.11.1.1 Procollagen I Carboxy Peptide and Procollagen III Amino Peptide
36.11.1.2 Type IV Collagen
36.11.1.3 Laminin
36.11.1.4 Hyaluronic Acid (HA)
36.11.1.5 YKL-40 (Chondrex)
36.11.2 Direct Markers Linked to Matrix Degradation [Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs)]
36.11.3 Cytokines
36.11.3.1 Transforming Growth Factor (TGF)-β1 and TGFι
36.11.3.2 Connective Tissue Growth Factor (CTGF)
36.11.3.3 Platelet-Derived Growth Factor-Beta
36.11.3.4 Microfibrillar-Associated Protein 4
36.11.3.5 Cytokeratin-18 Fragments
36.11.4 Genetic Markers for Liver Fibrosis
36.12 Combined Direct and Indirect Markers
36.12.1 The Fibrometer Test
36.12.2 Enhanced Liver Fibrosis Test (ELF)
36.12.3 TGF-Ă1, HA, PIIINP and TIMP-1 Panel
36.12.4 Combination of sFas with TGF-Ă1, HA, PIIINP
36.12.5 Fibrospect II Test
36.12.6 SHASTA Index
36.12.7 European Liver Fibrosis Panel (ELF) Test
36.12.8 Hyaluronic Acid Vascular Score
36.13 Consensus Guidelines on Non-invasive Assessment of Hepatic Fibrosis
36.14 Conclusions/Summary
36.15 Future Perspectives for Liver Fibrosis Markers
Self Study
Questions
Answers
References
37: Peritoneal Fluid Analysis
37.1 Introduction
37.2 Ascitic Fluid Analysis: âWhen and Howâ
37.3 Ascites in Cirrhosis vs. Other Conditions: Differential Diagnosis
37.3.1 Ascites with SAAG âĽ1.1 g/dL
37.3.2 Ascites with SAAG <1.1 g/dL
37.4 Conclusion/Summary
Exercises
Case 1
Case 2
References
38: Measurement of the Hepatic Venous Pressure Gradient (HVPG)
38.1 Introduction
38.2 How and Why to Perform HVPG Measurements
38.3 Methodological Considerations
38.4 Summary and Conclusions
Self Study
Questions
Answers
References
39: Liver Biopsy for Histopathology
39.1 Introduction
39.2 Indications
39.2.1 Parenchymal Liver Diseases
39.2.2 Focal Liver Lesions
39.2.2.1 Benign Lesions
39.2.2.2 Malignant Lesions
Metastases
Primary Liver Tumors
39.3 Contraindications
39.4 Biopsy Technique
39.4.1 Percutaneous Liver Biopsy (PLB)
39.4.1.1 Ultrasound-Guided Percutaneous LB
39.4.1.2 CT-Guided and MRT-Guided Percutaneous LB
39.4.1.3 Fusion Technique
39.4.2 Transjugular Liver Biopsy (TJLB)
39.4.3 Surgical/Laparoscopic biopsy (SLB)
39.5 Post-biopsy Monitoring
39.6 Complications
Self Study
Questions
Answers
References
40: Liver Ultrasonography
40.1 Principles of Liver Ultrasonography
40.2 Normal Liver Ultrasonography
40.2.1 Liver Size
40.2.2 Liver Echostructure
40.2.3 Liver Surface
40.2.4 Liver Vascularization
40.3 Pathologic Aspects in Liver Ultrasonography
40.3.1 Diffuse Liver Disease
40.3.1.1 Fatty Liver
40.3.1.2 Acute Hepatitis
40.3.1.3 Chronic Hepatitis
40.3.1.4 Hepatic Congestion
40.3.1.5 Fibrosis and Cirrhosis
40.3.2 Focal Liver Lesions
40.3.2.1 Benign Focal Liver Lesions
Liver Cysts
Hemangiomas
Liver Cell Adenoma
Focal Nodular Hyperplasia (FNH)
40.3.2.2 Malignant Focal Liver Lesions
Hepatocellular Carcinoma (HCC)
Cholangiocarcinoma (CCC)
Liver Metastases
40.3.3 Vascular Related Pathologies of the Liver
40.3.3.1 Portal Hypertension and Portal Thrombosis
40.3.3.2 Budd-Chiari Syndrome
40.3.3.3 Veno-Occlusive Disease
40.3.3.4 Osler-Weber-Rendu Disease
Self Study
Questions
Answers
References
41: Endoscopy in Hepatic Diseases
41.1 Introduction
41.2 Gastro Esophageal Varices
41.3 Primary Prophylaxis
41.4 Acute Variceal Bleeding
41.5 Endoscopic Therapy for Gastric Varices
41.6 Secondary Prophylaxis
41.7 PHG and GAVE
41.8 Capsule Endoscopy and Enteroscopy
41.9 Endoscopic Retrograde Cholangiopancreatography
41.10 Biliary Complications After Liver Transplantation
41.11 Metabolic and Bariatric Endoscopy for NASH
41.12 Conclusions
Self Study
Questions
Answers
References
42: Dynamic and Multi-phase Contrast-Enhanced CT Scan
42.1 Introduction
42.2 CT Technology Developments
42.3 Hounsfield Units
42.4 Liver Scanning Protocol
42.5 Benign Focal Liver Lesions
42.5.1 Hepatic Cystic Lesions
42.5.2 Benign Hepatic Tumors
42.6 Malignant Hepatic Tumours
42.6.1 Hepatocellular Carcinoma (HCC)
42.6.2 Cholangiocarcinoma
42.6.3 Hepatic Metastases
42.7 Conclusions
Self Study
Questions
Answers
References
43: Patient-Specific 3D Printing in Liver Disease
43.1 Introduction
43.2 Image Post-processing and Segmentation
43.3 3D Printed Liver Models: Dimensional Accuracy
43.4 3D Printed Liver Models: Pre-surgical Planning and Simulation
43.4.1 3D Printed Liver Models in Pre-surgical Planning of Hepatic Tumours
43.4.2 3D Printed Liver Models in Pre-surgical Planning of Liver Transplantation
43.5 3D Printed Liver Models: Medical Education
43.6 3D Printed Liver Models: Limitations and Future Directions
43.7 Summary
Self Study
Questions
Answers
References
Glossary
44: Dynamic Contrast-Enhanced Ultrasonography of the Liver
44.1 Introduction
44.1.1 General Considerations
44.1.2 Safety Considerations
44.1.3 Terminology
44.1.4 CEUS Phases: Examination Technique
44.2 Characterization of Focal Liver Lesions
44.2.1 Benign Liver Lesions
44.2.1.1 Hemangioma
44.2.1.2 Focal Nodular Hyperplasia
44.2.1.3 Hepatocellular Adenoma
44.2.1.4 Focal Fatty Change
44.2.1.5 Liver Abscess
44.2.1.6 Liver Cyst
44.2.1.7 Other Benign Liver Lesions
44.2.2 Malignant Liver Lesions
44.2.2.1 Hepatocellular Carcinoma
44.2.2.2 Cholangiocarcinoma
44.2.2.3 Liver Metastases
44.2.2.4 Lymphoma
44.3 Characterization of Portal Vein Thrombosis
Self Study
Questions
Answers
References
45: Ultrasound Elastography
45.1 Introduction
45.2 Basic Technology of Ultrasound Elastography
45.2.1 Transient Elastography
45.2.2 Point SWE
45.2.3 2D-SWE
45.2.4 Strain Elastography
45.3 Clinical Studies of Ultrasound Elastography
45.4 US Elastography Is Reliable?: Quality Criteria of Ultrasound Elastography
45.5 US Elastography: Limitations and Promises
45.6 Need to Know When Doing US Elastography
45.7 Conclusion
Self Study
Questions
Answers
References
46: MR Elastography and Functional MRI of the Liver
46.1 Magnetic Resonance Elastography
46.1.1 Introduction
46.1.2 Principles
46.1.3 Technical Aspects
46.2 Clinical Applications of MRE
46.2.1 MRE in Staging of Liver Fibrosis
46.2.2 Nonalcoholic Steatohepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD)
46.2.3 Primary Sclerosing Cholangitis
46.2.4 MRE Potential Role in Liver Tumors
46.2.5 Limitations and Pitfalls of MRE
46.3 Functional MRI of the Liver
46.3.1 Introduction
46.3.2 DWI Definition
46.3.3 Principles and Applications of DWI
46.4 Liver-Specific Gadolinium (Gd) Based Contrast Agents
46.4.1 Introduction
46.4.2 Definition and Mechanism
46.4.3 Contrast MR Acquisitions
46.4.4 Indications
46.4.5 Advantage
46.4.6 Pitfalls Using Primovist
46.4.7 Limitations
46.5 Conclusions: Future Perspectives
Self Study
Questions
Answers
References
47: Contrast Enhanced MR imaging of Liver
47.1 Introduction
47.2 Contrast Medium
47.2.1 Extracellular Agents
47.2.1.1 Toxic Effects
47.2.1.2 MR Technical Considerations
47.2.1.3 Dosage
47.2.2 Reticuloendothelial Agents
47.2.2.1 MR Technical Considerations
47.2.2.2 Dosage
47.2.3 Hepatobiliary Agents
47.2.3.1 MR Technical Considerations
47.2.3.2 Dosage
47.2.4 Blood Pool Agents
47.2.5 Combined Agents
47.2.5.1 MR Technical Considerations
47.2.5.2 Dosage
47.3 Diagnosis of Diffuse Liver Diseases with Contrast Enhanced MR
47.4 Diagnosis of Focal Liver Lesions with Contrast Enhanced MR
47.4.1 Hemangiomas
47.4.2 Focal Nodular Hyperplasia (FNH)
47.4.3 Hepatic Cyst
47.4.4 Hepatocellular Adenoma
47.4.5 Malignant Metastatic Tumors
47.4.6 Hepatocellular Carcinoma (HCC)
47.4.7 Intrahepatic Cholangiocarcinoma (ICC)
47.4.8 Diagnostic Pitfalls of Focal Hepatic Disease
47.5 Conclusions/Summary
Self Study
Questions
Answers to the Questions
References
48: Transient Elastography in Chronic Liver Diseases
48.1 Introduction
48.2 Advantages of Transient Elastography
48.3 Limitations of Transient Elastography
48.3.1 Operator Skill
48.3.2 Obesity
48.3.3 Cholestasis
48.3.4 Alanine Aminotransferase Flares
48.3.5 Narrow Intercostal Space
48.3.6 Hepatic Congestion
48.3.7 Food Intake
48.3.8 Steatosis
48.3.9 Ascites
48.3.9.1 Validation of Transient Elastography in Liver Fibrosis Assessment
48.4 Normal Values of Liver Stiffness on TE
48.5 Transient Elastography in Chronic Liver Diseases
48.6 Transient Elastography and HCV
48.7 Transient Elastography and CHB
48.8 Transient Elastography and Portal Hypertension
48.9 Transient Elastography and Autoimmune Hepatitis
48.10 Transient Elastography and NAFLD
48.11 Transient Elastography and Hepatocellular Carcinoma
48.12 Transient Elastography and Acute Cellular Rejection Following Liver Transplantation
48.13 Transient Elastography and Alcoholic Liver Disease
48.14 Controlled Attenuation Parameter (CAP)
48.15 Transient Elastography and Postoperative Outcomes
48.16 Conclusions/Summary
48.17 Future Perspectives for Liver FibroScan
Self Study
Questions
Answers
References
49: Portal Venography
49.1 Introduction
49.2 Noninvasive Imaging of the Portal System
49.2.1 Ultrasonography (US)
49.2.2 Computed Tomography
49.2.3 Magnetic Resonance Imaging
49.3 Invasive Imaging of the Portal System
49.3.1 Wedged Hepatic Venography
49.3.2 Percutaneous Splenoportography
49.3.3 Transhepatic Portography
49.3.4 Arterial Portography
49.4 Conclusion
Self Study
Questions
Answers
References
50: Minilaparoscopy and Conventional Laparoscopy
50.1 Introduction
50.2 Indications
50.3 Surgical technique
50.3.1 Access to the Abdominal Cavity, Pneumoperitoneum, Exposition of the Operative Field
50.3.2 Parenchymal Transection
50.4 Procedures
50.5 Comparison of Single Incision and Multi Port Laparoscopic Surgery
50.6 Future Perspectives
50.7 Conclusion
Self Study
Questions
Answers
References
Part III: Treatment
51: Medical Nutrition Therapy in Liver Disease
51.1 Introduction
51.1.1 General Principles of Nutritional Medical Intervention in Liver Diseases (LDs)
51.2 Nutrition Assessment
51.2.1 Anthropometric and Body Composition Assessment
51.2.1.1 Measurement of Height and Weight
51.2.1.2 Determination of Body Mass Index (BMI)
51.2.1.3 Other Anthropometric Evaluations
51.2.1.4 Determination of the Energetic Balance
51.2.1.5 The Composite Score
51.2.2 Biochemical Data
51.2.2.1 Biochemical Data Regarding the Nutritional Status
51.2.2.2 Specific Lab Determinations for Liver Disease
51.2.3 Nutrition: Physical Evaluation
51.2.4 Patientâs History
51.3 Nutritional Intervention in LD
51.3.1 Related Issues Regarding Liver Physiopathology
51.3.2 Nutritional Intervention in Acute Liver Diseases
51.3.3 Nutritional Intervention in CLD
51.3.3.1 Nutritional Intervention in ALD
51.3.3.2 Nutritional Intervention in NAFLD, NASH
51.3.3.3 Nutritional Intervention in Cirrhosis
Sodium Restriction in the Diet and the Management of Ascites
Portal Hypertension
Hyponatremia
Glucose Alteration
Hepato-Renal Syndrome
Osteopenia
51.3.3.4 Nutritional Intervention in Liver Transplantation
51.4 Conclusions
Self Study
Questions
Answers
References
52: Molecular Targets in Liver Disease
52.1 Protein Kinases
52.1.1 Receptor Tyrosine Kinases
52.1.1.1 Vascular Endothelial Growth Factor Receptors
52.1.1.2 Platelet-Derived Growth Factor Receptors
52.1.1.3 Hepatocyte Growth Factor Receptor c-MET
52.1.1.4 c-MET Structure and Activation
52.1.1.5 c-MET Downstream Signaling
52.1.1.6 c-MET Regulation
52.1.2 Intracellular Serine/Threonine Kinases: RAF Kinases
52.1.2.1 RAF Activation and Regulation
52.1.2.2 RAF Signaling
52.1.3 Drugs Targeting Protein Kinases in HCC
52.2 Nuclear Receptors
52.2.1 General Structure and Activation
52.2.1.1 Structure
52.2.1.2 Activation
52.2.2 Farnesoid X Receptors
52.2.2.1 Structure and Activation
52.2.2.2 FXRs in Cholestasis
52.2.2.3 FXRs in Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)
52.2.2.4 Drugs Targeting FXRs
52.2.3 Peroxisome Proliferator-Activated Receptors
52.2.3.1 Structure and Activation
52.2.3.2 Drugs Targeting PPARs
52.2.4 Glucocorticoid Receptors
52.3 Novel Therapeutic Targets
52.3.1 Takeda G Protein-Coupled Receptor 5 (TGR5, Gpbar-1, M-BAR)
52.3.2 Cell Death Protein-1 Checkpoint Inhibitors
52.3.3 Metabotropic Glutamate Receptors
52.4 Summary
Self Study
Questions
Answers
References
Further Reading
53: Specific Medications for Chronic Viral Hepatitis
53.1 Introduction
53.2 Hepatitis B Virus (HBV) Infection
53.2.1 Treatment Strategies for HBV
53.2.1.1 Interferon (IFN)
53.2.1.2 Nucleos(t)ide Analogues (NAs)
53.2.1.3 HBV in Pregnancy
53.2.1.4 HBV in Children
53.3 Hepatitis C Virus (HCV) Infection
53.3.1 Treatment Strategies for HCV
53.3.1.1 Ribavirin
53.3.1.2 Direct-Acting Antivirals (DAAs)
Sofosbuvir
Combination Regimens
Sofosbuvir and Ledipasvir
Sofosbuvir and Velpatasvir
Sofosbuvir, Velpatasvir and Voxilaprevir
Ritonavir-Boosted Paritaprevir, Ombitasvir and Dasabuvir
Grazoprevir and Elbasvir
Glecaprevir and Pibrentasvir
53.4 Future Perspectives for Hepatitis Treatment
53.4.1 Future Treatment Options for HBV
53.4.2 Future Perspectives for the Treatment of HCV
Self Study
Questions
Answers
References
54: Portal Vein Embolization (PVE) and Partial TIPE ALPPS: Beyond the Limitations of PVE
54.1 Introduction
54.2 History
54.3 Mechanism of PVE-Induced Hypertrophy
54.4 Approaches to the Portal Vein for PVE
54.4.1 TIPE Technique
54.4.2 PTPE Technique (Fig. 54.1)
54.5 Embolic Materials
54.6 Potential Complications of PVE
54.6.1 Bleeding
54.6.2 Portal Thrombosis and Coil Migration
54.6.3 Bile Leakage
54.7 Outcomes of PVE
54.8 Beyond the Limitations of PVE: Associating Liver Partition and Portal Vein Embolization for Staged Hepatectomy
Self Study
Question
Answers
References
55: Endoscopic and Pharmacological Treatment of Esophageal Varices
55.1 Introduction
55.2 Pathophysiology and Endoscopic Characteristics of Esophageal Varices
55.3 Screening of EVs in Cirrhotic Patients
55.4 Pharmacological Treatment in the Prevention and Management of Variceal Bleeding
55.4.1 Non-selective Beta-Blockers (NSBBs)
55.4.2 Carvedilol
55.4.3 Terlipressin
55.4.4 Somatostatin and Its Analogues
55.4.5 Simvastatin
55.5 Endoscopic Treatments of Esophageal Varices
55.5.1 Sclerotherapy
55.5.2 Endoscopic Variceal Band Ligation (EVBL)
55.5.3 Other Endoscopic Treatments
55.6 Overall Management of Esophageal Varices
55.6.1 Primary Prophylaxis
55.6.2 Acute Bleeding
55.6.3 Secondary Prophylaxis
55.7 Conclusions
Self Study
Questions
Answers
References
56: Procedure for Gastric Variceal Bleeding: From BRTO to PARTO to CARTO, Three Decades of Progress
56.1 Introduction
56.2 Techniques and Outcomes of BRTO
56.2.1 Patients
56.2.2 Outcomes of BRTO
56.2.3 BRTO vs. Endoscopic Treatment
56.2.4 Conventional BRTO: Technique
56.2.5 The Occlusion-Balloon: Dwell-Time and Rupture
56.2.6 Sclerosants and Transvenous Obliteration
56.3 Modified BRTO
56.3.1 PARTO
56.3.2 CARTO
56.4 More Indications for BRTO
56.4.1 BRTO, PARTO, CARTO: Hepatic Encephalopathy and Synthetic Function
56.5 Summary
Self Study
Questions
Answers
References
57: Endoscopy and Endoscopic Ultrasound for the Evaluation and Treatment of Gastric and Ectopic Varices
57.1 Introduction
57.2 Gastric Varices
57.2.1 Endoscopic Treatment
57.2.2 The Role of Endoscopic Ultrasound
57.3 Ectopic Varices
57.3.1 Duodenal and Jejunal Varices
57.3.2 Choledochal Varices
57.3.3 Rectal and Colonic Varices
57.4 Conclusions
Self Study
Questions
Answers
References
58: Portacaval Shunting for Portal Hypertension
58.1 Overview of Portal Hypertension
58.2 Current Treatment Options
58.2.1 Surgical Shunts
58.2.2 Percutaneous Shunts
58.2.2.1 Transjugular Intrahepatic Portosystemic Shunt (TIPS)
58.2.2.2 Direct Intrahepatic Portacaval Shunt (DIPS)
58.2.2.3 Percutaneous Mesocaval Shunt
58.3 Comparison of Available Portocaval Shunting Procedures (Table 58.1)
58.4 Future Directions
Self Study
Questions
Answers
References
59: Systemic Therapy of Advanced Liver Cancer
59.1 Introduction
59.2 Conventional Chemotherapy for Advanced HCC
59.3 Molecularly Targeted Therapy
59.4 Immunotherapy
59.5 Future Perspective and Biomarkers
Self Study
Questions
Answers
References
60: Embolization Therapy for Liver Cancer
60.1 Introduction
60.2 Indications
60.3 Technique
60.4 Technical Advances
60.5 Methods
60.5.1 cTACE
60.5.2 DEB-TACE
60.5.3 Comparison of DEB-TACE and cTACE
60.5.4 DSM-TACE
Self Study
Questions
Answers
References
61: Ablation of Hepatocellular Carcinoma
61.1 Introduction
61.2 Indications
61.2.1 At-Risk Localizations and Adverse Events
61.2.2 Tumor Size
61.3 Technical Aspects
61.3.1 Radiofrequency-Ablation (RFA)
61.3.2 Microwave Ablation (MWA)
61.3.3 Irreversible Electroporation (IRE)
Self-Study
Questions
Answers
References
62: Laparoscopic Liver Resection
62.1 Introduction
62.2 Indications
62.2.1 Benign Disease
62.2.1.1 Simple Liver Cyst
62.2.2 Primary Malignant Disease
62.2.2.1 Hepatocellular Carcinoma
62.2.2.2 Intrahepatic Cholangiocarcinoma
62.2.3 Metastatic Disease
62.3 Preparation
62.4 Surgical Technique
62.4.1 Wedge Resection
62.4.2 Anatomical Segmentectomy
62.4.3 Left Lateral Lobectomy
62.4.4 Left Hepatectomy
62.4.5 Right Hepatectomy
62.5 Peri-operative Management
62.5.1 Pain Management
62.5.2 NG Tubes, Abdominal Drains
62.6 Conclusion
Self Study
Questions
Answers
References
63: New Loco Regional Approaches to Treat Liver Cancer
63.1 Introduction
63.2 Ablative Techniques
63.2.1 Radiofrequency Ablation
63.2.2 Microwave Ablation
63.2.3 Cryoablation
63.2.4 Irreversible Electroporation (IRE)
63.2.5 Chemical Ablation
63.3 Endovascular Techniques
63.3.1 TACE
63.3.2 Bland Embolization
63.3.3 Y-90
63.3.4 Stereotactic Body Radiotherapy (SBRT)
63.4 Immunotherapy
63.5 Conclusion
Self Study
Questions
Answers
References
64: Hepatic Encephalopathy
64.1 Developments in Pathophysiologic Understanding
64.1.1 The Role of Ammonia in the Pathogenesis of HE Occurring in ALF, Cirrhosis and Chronic Porto-Systemic Shunting
64.1.1.1 In ALF
64.1.1.2 In Cirrhosis and Chronic Porto-Systemic Shunting
64.1.2 The Role of Inflammation in the Pathogenesis of HE Occurring in ALF, Cirrhosis and Chronic Porto-Systemic Shunting
64.1.3 The Two-Phase Roles of Ammonia and Inflammation in the Pathogenesis of HE Occurring in ACLF
64.2 Management
64.2.1 Treatment of HE in ALF (Table 64.3)
64.2.2 Treatment of HE in Cirrhosis (Table 64.4)
64.2.2.1 Reducing the Intestinal Production and Systemic Absorption of Ammonia
64.2.2.2 Increasing the Systemic Metabolism of Ammonia
64.2.2.3 Reducing Systemic Inflammation by Modulation of the Intestinal Microbiome
64.2.3 HE in Chronic Portal-Systemic Shunting
64.2.4 HE in Acute on Chronic Liver Failure (ACLF)
Self Study
Question
Answers
References
65: Management of Ascites
65.1 Introduction
65.2 Classification and Management of Ascites
65.2.1 Uncomplicated Ascites
65.2.1.1 Sodium Intake Restriction
65.2.1.2 Diuretics
65.2.1.3 Complications of Diuretic Therapy
65.2.2 Large Ascites
65.2.3 Refractory Ascites
65.2.3.1 Liver Transplantation (LT)
65.2.3.2 Vasoconstrictors
65.2.3.3 Other Treatments
65.2.3.4 Transjugular Intrahepatic Portosystemic Shunts (TIPS)
65.3 Hyponatremia
65.3.1 Management of Hyponatremia
65.4 Spontaneous Bacterial Peritonitis (SBP)
65.4.1 Management of SBP: Antibiotic Treatment
65.4.2 Prophylaxis of SBP
65.5 Hepatorenal Syndrome (HRS)
65.5.1 Management of HRS
65.6 Conclusions/Summary
Self-Study
Questions
Answers
References
66: Extracorporeal Non cellular Liver Assisted Devices
66.1 Introduction
66.2 Types of Extracorporeal Liver Assisted Devices
66.3 Molecular Adsorbent Recirculating Systems (MARS)
66.4 Prometheus System
66.5 Single Pass Albumin Dialysis (SPAD)
66.6 Selective Plasma Filtration Therapy (SEPET)
66.7 Discussion
66.8 Conclusion
Self Study
Questions
Answers
References
67: Extracorporeal Cellular Liver Assisted Devices
67.1 Introduction
67.2 Bioartificial Liver Support (BALS)
67.3 Extracorporeal Liver Assist Device
67.3.1 Extracorporeal Circuit
67.3.2 Studies
67.4 HepatAssistâ˘
67.4.1 Extracorporeal Circuit
67.4.2 Studies
67.5 Modular Extracorporeal Liver Support System (MELS)
67.5.1 Extracorporeal Circuit
67.5.2 Studies
67.6 Bioartificial Liver Support System (BLSS)
67.6.1 Extracorporeal Circuit
67.6.2 Studies
67.7 Conclusions
Self Study
Question
Answer
References
68: Liver Transplantation for Acute and Chronic Liver Failure
68.1 Introduction
68.2 Liver Allocation
68.3 Orthotopic Liver Transplantation
68.4 Indications for Liver Transplantation
68.5 Transplantation Evaluation and Listing
68.6 Important Medical Concerns for Listing
68.6.1 Age
68.6.2 Obesity
68.6.3 Coronary Artery Disease
68.6.4 Porto-Pulmonary Hypertension
68.6.5 Hepatopulmonary Syndrome
68.6.6 Renal Dysfunction
68.6.7 Tobacco Use
68.6.8 Absolute Contraindications to Transplantation
68.7 Early Post-Liver Transplant Complications
68.8 Immunosuppression
68.9 Acute and Chronic Rejection
68.9.1 Long-Term Outcomes and Reoccurrence of Disease
68.9.2 Long-Term Concerns After Liver Transplantation
68.10 Hypertension
68.11 Obesity
68.12 Diabetes Mellitus
68.13 Dyslipidemia
68.14 Kidney Disease
68.15 Osteopenia
68.16 Malignancy
68.17 Conclusion
Self Study
Questions
Answers
References
69: Surgical Complications Following Liver Transplant and Their Management
69.1 Introduction
69.2 Surgical Complications
69.2.1 Haemorrhage
69.2.1.1 Methods of Ensuring Haemostasis During Transplant
69.2.1.2 Post transplant Monitoring of Clotting and Administration of Clotting Factors
69.2.1.3 Detection, Quantifying and Treating Post op Haemorrhage
69.2.2 Vascular Complications
69.2.2.1 Hepatic Artery Thrombosis (HAT)
Incidence and Presentation
Diagnosis and Treatment of Early HAT
Diagnosis of HAT
Treatment of Early HAT
Treatment of Late HAT
69.2.2.2 Hepatic Artery Stenosis
Diagnosis
Treatment
69.2.2.3 Hepatic Artery Pseudoaneurysms
69.2.2.4 Portal Vein Thrombosis (PVT)
69.2.2.5 Portal Vein Stenosis
69.2.2.6 Concurrent Hepatic Artery and Portal Vein Thrombosis
69.2.2.7 Vena Cava Complications
69.2.3 Biliary Complications
69.2.3.1 Biliary Reconstruction Techniques
69.2.3.2 Diagnosis of Biliary Complications
69.2.3.3 Bile Leaks
69.2.3.4 Biliary Strictures
Anastomotic Strictures
Nonanastomotic Biliary Strictures
69.2.4 Intra-abdominal Infections
69.2.5 Wound Complications
69.3 Conclusion
Self Study
Questions
Answers
References
70: Anaesthesia for Liver Transplantation
70.1 Introduction
70.2 Preoperative Considerations
70.2.1 Frailty, Sarcopenia and Poor Functional Capacity
70.2.2 Cardiorespiratory Pathology
70.2.3 Diabetes Mellitus
70.2.4 Chronic Kidney Disease
70.2.5 Coagulopathy and Anaemia
70.3 Intraoperative Care
70.3.1 Anaesthetic Choice
70.3.2 Vascular Access
70.3.3 Haemodynamic Monitoring
70.3.4 Point of Care Testing
70.3.5 Induction and Maintenance
70.3.6 Fluid Management and Transfusion
70.4 Key Intraoperative Priorities
70.4.1 Dissection Phase
70.4.2 Anhepatic Phase
70.4.3 Reperfusion Phase
70.5 Immediate Postoperative Care
70.6 Discussion of Adjuvant Drugs
70.7 Living Donor Liver Transplantation in Adults
70.7.1 LDLT Recipients
70.7.2 Donor Preoperative Assessment
70.7.3 Intraoperative Care of the Living Donor
70.7.4 Recipient and Donor Outcomes
Self Study
Questions
Answers
References
71: Surgery in Liver Disease
71.1 Introduction
71.2 Surgical Anatomy of the Liver
71.2.1 Avoiding Blood Loss During Liver Surgery
71.3 Physiological Changes of Liver Disease and Implications for Surgery
71.3.1 Altered Circulation
71.3.2 Drug Clearance and Hepatic Encephalopathy
71.3.3 Clotting and Blood Loss
71.3.4 Nutrition, Obesity and Sarcopenia
71.3.5 Hepato-Renal Syndrome (HRS)
71.3.6 Sepsis in Cirrhotic Patients, Particularly SBP
71.4 Pre-operative Management for Cirrhotic Patients
71.4.1 Auto-Transfusion and Cell Salvage
71.4.2 Pre-operative TIPPS
71.5 Classifying Severity of Liver Disease
71.5.1 CTP Score
71.5.2 MELD Score
71.6 Emergency Surgery in Cirrhotic Patients
71.7 Elective Surgery in Patients with Abnormal Liver Function
71.8 Hepatic Resection in Cirrhotic Patients
71.8.1 Selection of Surgical Procedure
71.8.2 Evaluation of Liver Function and Functional Reserve
71.8.3 Other Methods of Predicting Postoperative Liver Failure
71.8.4 Importance of AFP Levels in Patients with Suspected HCC
71.9 Non-hepatic Surgery in Cirrhotic Patients
71.9.1 Umbilical Hernia Repair (UHR)
71.9.1.1 Emergency UHR
71.9.1.2 Elective
71.9.2 Cholecystectomy
71.9.2.1 Emergency
71.9.2.2 Elective
71.9.3 Colorectal Surgery
71.9.4 Cardiac Surgery
71.10 Avoiding Futile Operations
71.11 Summary
Self Study
Questions
Answers
References
72: Robotic Liver Resection
72.1 Introduction
72.2 Indications
72.3 Operative Technique
72.3.1 Patient Positioning and Port Placement
72.3.2 Lobectomy (Right and Left Hepatectomy)
72.3.3 Segmentectomy (Follow Segmental Anatomy)
72.3.4 Wedge Resection
72.3.5 Near-Infrared Fluorescence Imaging
72.4 Outcomes of Robotic Liver Resection
72.4.1 Post-operative Outcomes
72.4.2 Long-Term Oncologic Outcomes
72.4.3 Comparative Outcomes: Robotic vs. Open
72.4.4 Comparative Outcomes: Robotic vs. Laparoscopic
72.4.5 Learning-Curve
72.4.6 Financial Impact
72.5 Conclusion
Self Study
Questions
Answers
References
73: Cardiac Surgery Risks in Liver Dysfunction
73.1 Introduction
73.2 Advanced Liver Dysfunction Physiopathological Changes Relevant for Cardiac Surgery
73.2.1 Haemostasis and Coagulation Disorders
73.2.2 Renal Function Impairment
73.2.3 Cardiovascular Alterations
73.2.4 Disorders of the Immune System
73.2.5 Pulmonary Disorders
73.2.6 Liver Function Deterioration
73.3 Cardiac Surgery Risks and Outcome in Patients with Advanced Liver Dysfunction
73.4 Preoperative Preparation of Cirrhotic Patients Prior to Major Cardiac Surgery
73.5 Anaesthetic Management of Patients with Advanced Liver Dysfunction Undergoing Cardiac Surgery
73.6 Operative Management of Cirrhotic Patients Undergoing Major Cardiac Surgery. Cardiopulmonary Bypass and Liver Dysfunction
73.7 Postoperative Care of Cirrhotic Patients After Major Cardiac Surgery
73.8 Endovascular Procedures in Cirrhotic Patients
73.9 Early Ischemic Liver Injury After Cardiac Surgery
73.10 Conclusion
Self Study
Questions
Answers
References
74: Future Approaches in Liver Disorders: Regenerative Medicine
74.1 Introduction
74.2 Liver Architecture and Its Regeneration
74.2.1 Cell Therapy
74.2.2 Human Primary Hepatocytes
74.2.3 Hepatocyte Like-Cells (HLCs)
74.2.4 Cellular Reprogramming
74.2.5 Pluripotent Stem Cells (PSCs)
74.2.6 Mesenchymal Stem Cells (MSCs)
74.2.7 Embryonic Stem Cells (ESCs)
74.2.8 Hematopoietic Stem Cells (HSCs)
74.2.9 Human Fibroblasts
74.3 Liver Tissue/Organ Engineering
74.3.1 Scaffold-Based Systems
74.3.2 Organoid Technology
74.3.3 Microencapsulation Technique
74.3.4 Bioprinting in the Fabrication of 3D Liver Tissues (Bioprinted Liver Tissues)
74.4 Bioartificial Liver (BAL)
74.5 Gene Therapy
74.6 Conclusions
Self Study
Questions
Answers
References