Clinical Hepatology (eBook)

Henryk Dancygier is Chief of the Department of Medicine II at the Klinikum Offenbach, and Professor of Medicine at the Goethe University, Frankfurt/Main. He graduated from the University of Heidelberg and trained in Pathology, Internal Medicine, Gastroenterology and Hepatology. He holds degrees from the University of Heidelberg, Frankfurt and the Technical University of Munich and currently is Adjunct Professor of Medicine at the Mount Sinai School of Medicine, New York. Henryk Dancygier is author of a number of books including (English translations) "AIDS – a Clinical Compendium" (1993), "Memorix - Gastroenterology and Hepatology" (1998), "Endosonography in Gastroenterology: Principles, Techniques, Findings" (1999), "Liver Diseases - the ABC of Therapy" (2003) and "Clinical Hepatology – Diagnosis and Therapy of Hepatobiliary Disorders" (2003) that have been translated into several languages and he has also contributed numerous chapters in Medical Textbooks.

Copyright Page 4
Dedication 5
Foreword 6
Preface 7
Volume 2 9
Contents of Volume 2 14
Contributors 19
Part IV: Diseases of the Liver 26
Section X: Developmental Anomalies 27
Chapter 55 28
Malformations and Malpositions of the Liver 28
Riedel’s Lobe 28
Accessory Liver Lobe(s) 28
Ectopy 28
Extraabdominal Location of the Liver 29
Intraabdominal Displacement of the Liver 29
Agenesis 29
Atrophy 29
Zahn’s Grooves 29
“Corset Liver” 29
References 30
Chapter 56 31
Bile Duct Anomalies 31
Congenital Liver Fibrosis 31
Caroli’s Disease and Caroli’s Syndrome 33
Defi nition 33
Pathogenesis 33
Pathology 33
Diagnosis 33
Clinical Manifestations 33
Technical Examinations 33
Differential Diagnosis 33
Course and Prognosis 33
Therapy 34
Von Meyenburg Complexes 34
Biliary Atresia 34
Defi nition 34
Epidemiology 35
Etiology and Pathogenesis 35
Pathology 35
Diagnosis 35
Clinical Manifestations 35
Technical Examinations 36
Prognosis and Treatment 36
References 36
Chapter 57 37
Liver Cysts and Polycystic Liver Disease 37
Liver Cysts 37
Defi nition 37
Epidemiology 37
Etiology 38
Pathogenesis 38
Diagnosis 38
Clinical Manifestations 38
Technical Examinations 38
Differential Diagnosis 38
Complications 39
Natural History and Prognosis 39
Therapy 39
Polycystic Liver Disease 39
Defi nition 39
Epidemiology 39
Etiology and Pathogenesis 39
Pathology 40
Diagnosis 40
Clinical Manifestations 40
Technical Examinations 40
Natural History and Prognosis 40
Therapy 40
References 41
Chapter 58 42
Vascular Anomalies 42
References 43
Section XI: Circulatory and Vascular Disorders 44
Chapter 59 45
Hepatic Veins 45
Acute Hepatic Congestion 45
Chronic Hepatic Congestion 45
Budd-Chiari Syndrome 46
Defi nition 46
Epidemiology 46
Etiology and Pathogenesis 46
Pathology 48
Diagnosis 48
Clinical Manifestations 48
Laboratory Findings 48
Imaging Techniques 48
Prognosis and Treatment 49
Central Hyaline Sclerosis 49
Prolapse of Hepatocytes into the Central Veins 50
References 50
Chapter 60 52
Sinusoids 52
Sinusoidal Dilatation 52
Peliosis Hepatis 53
Defi nition 53
Epidemiology 53
Etiology and Pathogenesis 53
Pathology 53
Diagnosis 53
Signs and Symptoms 53
Laboratory Parameters 53
Imaging Techniques 53
Therapy and Prognosis 54
Sinusoidal Obstruction Syndrome 54
Defi nition 54
Epidemiology 54
Etiology and Pathogenesis 54
Pathology 55
Diagnosis 55
Signs and Symptoms 56
Laboratory Parameters 56
Imaging Techniques 56
Differential Diagnosis 56
Course and Prognosis 56
Treatment 56
Changes of Sinusoidal Contents 57
Perisinusoidal Lesions 57
References 58
Chapter 61 59
Portal Vein 59
Portal Vein Thrombosis 59
Acute Portal Vein Thrombosis 59
Chronic Portal Vein Thrombosis 60
Chapter 62 65
Hepatic Arteries 65
Congentital Anomalies 65
Hepatic Artery Occlusion 65
Hypoxic Hepatitis 66
Defi nition 66
Epidemiology 66
Etiology and Pathogenesis 66
Pathology 66
Diagnosis 67
Clinical Manifestations 67
Laboratory Examinations 67
Imaging Techniques 67
Differential Diagnosis 67
Prognosis and Treatment 67
Ischemic Cholangiopathy 67
Aneurysms 67
Etiology 68
Diagnosis 68
Clinical Manifestations 68
Imaging Techniques 68
Prognosis and Therapy 68
Arterioportal Fistula 68
Arteritis 69
Amyloidosis 70
Vascular Tumors 70
References 70
Section XII: Infectious Liver Diseases 71
Chapter 63 72
Viral Infections by Hepatotropic Viruses 72
63.1 Molecular Biology and Immunobiology of Hepatitis Viruses – Approach to Diagnosis and Therapy 73
Molecular Biology of Hepatitis Viruses 73
Molecular Biology of Hepatitis A Virus 73
Morphology, Genome Organization and Replication 73
Genotypes and Serotypes 74
Molecular Biology of Hepatitis E Virus 75
Morphology and Genome Organization 75
Genotypes and Serotypes 75
Replication of the Hepatitis E Virus 76
Molecular Biology of Hepatitis B Virus 76
Genome Organization 76
HBV Envelope Proteins 77
HBV Capsid Proteins 78
HBV Polymerase 80
HBx-Antigen 80
Genotypes, Serotypes and HBV-Variants 80
HBV-Replication Cycle 80
Hepatitis B Immunology 83
Immune Response of Acute and Reactivated HBV Infection 83
Immune Response in Chronic Hepatitis B 84
Molecular Biology of Hepatitis D Virus 84
Genotypes 85
Hepatitis Delta Antigen 85
Replication 86
Immunology 86
HBV and HDV 87
Molecular Biology of Hepatitis C Virus 87
Genome Organisation 87
HCV-Quasispecies 88
Interferon-sensitivity Determining Region in the NS5A Gene 89
Structural HCV Proteins 89
Non-structural HCV Proteins 89
Genotypes and Subtypes 90
Replication Cycle 90
Diagnostics of Hepatitis Viruses 91
Hepatitis A 91
Anti-HAV-Antibodies and Nucleic Acid Amplification 91
Conclusion for HAV Diagnosis 92
Hepatitis E 92
Anti-HEV Antibodies and Nucleic Acid Amplification 92
Conclusion for HEV Diagnosis 93
Hepatitis B 93
Serological Diagnosis of HBV 93
HBsAg and Anti-HBs-Antibodies 95
PreS-Ag and Anti-PreS-Antibodies 95
Anti-HBc-Antibodies 96
HBeAg and Anti-HBe-Antibodies 96
Molecular Diagnosis of HBV 96
Qualitative HBV-PCR 96
Quantitative Methods for HBV-DNA Measurement 97
Cobas Amplicor™ HBV-Monitor 97
Branched HBV-DNA (bDNA) Assay 98
Real Time PCR: Cobas Ampliprep/Cobas TaqMan Assay 98
Real Time PCR: Abbott RealTime HBV Assay 99
Real Time PCR: Artus HBV PCR Kit 99
Conclusion for HBV Diagnosis 99
Acute HBV Infection 99
Chronic HBV Infection 99
Hepatitis D 100
Hepatitis Delta Serology 100
Molecular Diagnosis of Hepatitis Delta 101
Morphological HDV Diagnosis 102
Conclusion for HDV Diagnosis 102
Hepatitis C 102
Serological HCV Diagnostics 103
Enzyme Immunoassays (IgG and IgM) 103
Confirmation Tests 103
Molecular Based HCV Detection Methods 104
Qualitative HCV-RNA Detection 104
Reverse Transcription-Polymerase Chain Reaction (RT-PCR) 104
Qualitative RT-PCR (Amplicor™ HCV 2.0, Roche Diagnostics) 105
Transcription-Mediated Amplification (TMA, Versant™, Siemens) 105
Quantitative HCV-RNA Detection 106
Cobas Amplicor™ HCV-Monitor (Roche Diagnostics) 106
Branched DNA-Hybridising Assay (Versant™ HCV-RNAAssay (bDNA), Siemens) 106
HCV-SuperQuant™ (National Genetics Institute, NGI) 106
Real-Time Based HCV-RNA Detection Assays 106
COBAS TaqMan (CAP/CTM, Roche Diagnostics) 107
Abbott RealTime HCV Test (North Chicago, IL, USA) 107
HCV Typing Methods 107
Genotyping by Sequence Analysis 107
Reverse Hybridizing Assay (Versant™ HCV Genotype 2.0 System (LiPA), Siemens) 108
Trugene (TRUGENE® HCV 5’NC Genotyping Kit, Siemens) 108
Morphological 108
Conclusion for HCV Diagnosis 108
Immunological and Direct Antiviral Treatment Approaches in Viral Hepatitis 108
Chronic Hepatitis B 109
Nucleos(t)ide Analogs 109
Lamivudine 109
Adefovir Dipivoxil 109
Tenofovir 110
Entecavir 110
Telbivudine 110
Immunomodulatory Drugs 110
Protein Vaccination 110
DNA Vaccination (Genetic Immunization, Genetic Vaccination) 111
Monoclonal Antibodies 111
Adoptive T Cell Transfer 111
Drugs Specific Against Viral RNA/DNA 111
Antisense-Oligonucleotides 111
Ribozymes 112
Dominant-Negative Mutants 112
Chronic Hepatitis C 113
Inhibitors of the Inosine Monophosphate Dehydrogenase 113
VX-497 113
Ribavirin 113
CpG-Oligo(deoxy)nucleotides 113
Vaccinations 114
DNA Vaccines 114
Protein Vaccines 114
Epitope Vaccine 114
Amantadine and Rimantadine 115
Specific Enzyme Inhibitors 115
Helicase Inhibitors 116
Protease Inhibitors 116
Polymerase Inhibitors 116
Drugs Specifically Directed Against Viral RNA 117
Inhibitors of the Internal Ribosome Entry Site 117
Antisense-Oligodeoxynucleotides 117
Ribozymes 118
References 118
63.2 Pathology of Acute and Chronic Viral Hepatitis 121
General Features of Acute Viral Hepatitis 121
General Features of Chronic Viral Hepatitis 123
Pathology of Specific Hepatitis Viruses 125
Hepatitis A Virus (HAV) 125
Hepatitis B Virus (HBV) 126
Hepatitis C Virus (HCV) 127
Hepatitis D Virus (HDV) 130
Hepatitis E Virus (HEV) 130
Grading and Staging of Chronic Hepatitis 130
References 132
63.3 Hepatitis A to E. Epidemiology, Clinical Manifestations, Prevention and Therapy 134
Hepatitis A 135
Epidemiology 135
Pathogenesis 137
Clinical Presentation 137
Symptoms and Signs 137
Laboratory Findings 138
Diagnosis 138
Differential Diagnosis 139
Natural Course and Prognosis 140
Cholestatic Hepatitis 140
Relapsing Hepatitis 140
Fulminant Hepatitis and Acute Liver Failure 140
Prevention 141
Passive Immunization 141
Active Immunization 142
Therapy 143
References 143
Hepatitis B 144
Definition 144
Epidemiology 144
Pathogenesis 146
Hepatitis B Stages 147
Clinical Manifestations 148
Acute Hepatitis B 148
Chronic Hepatitis B 148
Extrahepatic Manifestations 149
HBV-associated Glomerulonephritis 149
Polyarteritis Nodosa 150
Diagnosis 150
Differential Diagnosis 150
Major Patterns of Chronic Hepatitis B 151
HBeAg-Positive Chronic Hepatitis B 151
HBeAg-negative Chronic Hepatitis B 152
Inactive HBsAg Carrier State 153
Occult Hepatitis B Virus infection 153
Natural Course and Prognosis 154
Acute Hepatitis B 154
Fulminant Hepatitis B 155
Chronic Hepatitis B 155
Age 155
Immunosuppression 156
HBV Genotype 156
Viral Load 156
Coinfections 157
Spontaneous Resolution 158
HBeAg Seroconversion 158
HBsAg Seroconversion 158
Hepatitis Flares 158
Liver Fibrosis and Cirrhosis 159
Hepatocellular Carcinoma 159
Prevention 160
Passive Immunization 160
Active Immunization (Vaccination) 161
Suppression of HBV-Reactivation 162
Treatment 162
Treatment of Acute Hepatitis B 162
Treatment of Chronic Hepatitis B 162
Goals of Therapy 163
Indications 164
Drugs Used in the Treatment of Hepatitis B 164
Interferons 165
Standard Interferon 165
Pegylated Interferon 166
Nucleosides and Nucleotides 169
Lamivudine 169
Adefovir Dipivoxil 171
Entecavir 173
Telbivudine 174
Tenofovir, Emtricitabine, Clevudine 174
Combination Therapy 175
Special Therapeutic Problems 176
Liver Cirrhosis 176
Coinfection with Other Viruses 176
HBV-Induced Glomerulonephritis 177
Children 177
Asian Patients 177
Liver Transplantation 177
Nonresponders and Drug Resistance 178
References 181
Hepatitis C 189
Epidemiology 189
Transmission 190
Pathogenesis 190
Clinical Manifestations and Diagnosis 192
Acute Hepatitis C 193
Chronic Hepatitis C 193
Extrahepatic Manifestations of Chronic Hepatitis C 194
Mixed Cryoglobulinemia 194
Glomerulonephritis 195
Polyarteritis Nodosa 195
Porphyria Cutanea Tarda 196
Sjögren’s Syndrome 196
Sarcoidosis 196
Thyroid Disorders 196
Dermatologic Disorders 196
Metabolic Manifestations 197
Hematologic-Oncologic Disorders 197
Nervous System and Psychiatric Disorders 198
Others 198
Differential Diagnosis 198
Natural Course and Prognosis 198
Chronic Hepatitis C with Persistently Normal Aminotransferases 200
Hepatitis C and Pregnancy 200
Hepatitis C in Children 200
Coinfection with HBV 200
Coinfection with GBV-C/HGV 200
Coinfection with HIV 201
a1-Antitrypsin Deficiency 201
Porphyria Cutanea Tarda 201
Diabetes Mellitus 201
Prevention 201
Approach to Accidental Exposure (Needle Stick Injury) 201
Therapy 202
Therapy of Acute Hepatitis C 202
Therapy of Chronic Hepatitis C 202
Definitions of Response to Treatment 202
Drugs used in the Treatment of Chronic Hepatitis C 202
Combination Treatment 203
Results of Treatment 205
Individualizing Treatment 205
New Approaches to Treatment 206
Therapeutic Problems in Special Patient Populations 206
Patients with Persistently Normal Aminotransferase Levels (PNALT) 206
Nonresponders and Relapsers 206
Liver Cirrhosis 208
Recurrent Disease after Liver Transplantation 208
End-Stage Renal Disease 208
Children 208
Ethnic Groups 209
Intravenous Drug Users 209
References 209
Hepatitis D 217
Epidemiology 217
Pathogenesis 217
Clinical Manifestations 218
Diagnosis 218
Natural Course and Prognosis 218
Prevention 219
Therapy 219
References 219
Hepatitis E 220
Epidemiology 220
Pathogenesis 221
Clinical Presentation 221
Diagnosis 221
Differential Diagnosis 221
Natural Course and Prognosis 221
Prevention 221
Therapy 222
References 222
Chapter 64 223
Viral Infections by Nonhepatotropic Viruses 223
Herpes Viruses 223
Herpes Simplex Virus 1 and 2 223
Human Herpesvirus 6 and 7 224
Human Herpesvirus 8 225
Varicella-Zoster Virus 225
Cytomegalovirus 225
Epstein-Barr Virus 226
Adenoviruses 227
Enteroviruses 227
Paramyxoviruses 227
Togaviruses 227
Arboviruses 228
Yellow Fever Virus 228
Dengue Virus 228
Hantavirus 228
Arenaviruses 228
Lassavirus 228
Junin- and Machupovirus 229
Filoviruses 229
Marburg Virus 229
Ebola Virus 229
Parvoviruses 229
Coronaviruses 229
References 229
Chapter 65 231
Bacterial Liver Abscess and Other Bacterial Infections 231
Bacterial Liver Abscess 232
Definition 232
Epidemiology 232
Etiology and Pathogenesis 232
Diagnosis 233
Clinical Manifestations 233
Technical Investigations 233
Differential Diagnosis 234
Course and Prognosis 234
Therapy 234
Actinomycetaceae 235
Bartonellae 235
Borreliae 235
Brucellae 236
Burkholderia pseudomallei 236
Campylobacter Species 236
Chlamydiae 236
Clostridium perfringens 236
Ehrlichiae 237
Francisella tularensis 237
Gonococci 237
Legionella pneumophila 237
Leptospira 237
Listeria monocytogenes 238
Mycobacteria 238
Mycoplasma pneumoniae 239
Pneumococci 239
Rickettsiae 239
Salmonellae 239
Shigellae 240
Staphylococcus aureus 240
Treponema pallidum 240
Tropheryma whipplei 241
Yersiniae 241
References 241
Chapter 66 243
Amebic Liver Abscess and Other Protozoal Diseases 243
Amebiasis 243
Definition 243
Epidemiology 243
Etiology, Pathogenesis and Pathology 244
Diagnosis 244
Clinical Manifestations 244
Technical Investigations 244
Differential Diagnosis 245
Course and Prognosis 245
Therapy 245
Babesiosis 246
Cryptosporidiosis 246
Giardiasis 246
Leishmaniasis 246
Malaria 247
Pathology 247
Clinical Manifestations 247
Toxoplasmosis 247
References 248
Chapter 67 249
Helminthic Infections 249
Hepatic Schistosomiasis (Bilharziasis) 249
Definition 249
Epidemiology 249
Pathogenesis 250
Pathology 250
Diagnosis 250
Clinical Manifestations 250
Technical Investigations 251
Differential Diagnosis 251
Course and Prognosis 251
Therapy 251
Fascioliasis 252
Dicroceliasis 252
Clonorchiasis and Opisthorchiasis 252
Echinococcosis (Hydatid Disease) 253
Definition 253
Epidemiology 253
Pathogenesis 253
Pathology 253
Diagnosis 254
Clinical Manifestations 254
Technical Investigations 254
Differential Diagnosis 254
Complications 255
Course and Prognosis 255
Therapy 255
Ascariasis 256
Toxocariasis (Visceral Larva Migrans) 256
Capillariasis 257
Enterobiasis 257
Strongyloidiasis 257
References 258
Chapter 68 259
Fungal Infections 259
Candidiasis 259
Aspergillosis 260
Mucormycosis (Phycomycosis Zygomycosis)
Cryptococcosis 260
Histoplasmosis 260
Coccidioidomycosis, Blastomycosis, and Paracoccidiomycosis 260
Penicilliosis 261
References 261
Section XIII: Hepatobiliary Diseases in HIV-Infected Patients 262
Chapter 69 263
Infections 263
HIV Infection 263
Viral Hepatitis 263
Hepatitis A 264
Hepatitis B 264
Hepatitis D 265
Hepatitis C 265
Effects of HIV Infection on Chronic Hepatitis C 265
Effects of Chronic Hepatitis C on HIV Infection 266
Diseases of other Systems in HCV/HIV Coinfected Patients 266
Hepatitis E 266
Hepatitis G 266
Opportunistic Infections 267
References 267
Chapter 70 270
Neoplastic Diseases 270
Hepatocellular Carcinoma 270
Kaposi’s Sarcoma 270
Malignant Lymphomas 271
References 271
Chapter 71 272
Drug-Induced Liver Injury 272
Nucleosidic Reverse Transcriptase Inhibitors 273
Non-nucleosidic Reverse Transcriptase Inhibitors 273
Protease Inhibitors 273
References 273
Section XIV: Autoimmune Liver Diseases 275
Chapter 72 277
Autoimmune Hepatitis 277
Definition 277
Epidemiology 277
Etiology and Pathogenesis 278
Immunologic Factors 278
Genetic Factors 278
Pathology 279
Diagnosis 279
Autoimmune Hepatitis Type I 280
Autoimmune Hepatitis Type II 280
Autoimmune Hepatitis Type III 282
Clinical Presentation 282
Laboratory Findings 283
Imaging Tools 284
Differential Diagnosis 284
Course and Prognosis 285
Therapy 285
References 288
Chapter 73 291
Primary Biliary Cirrhosis 291
Definition 291
Epidemiology 291
Etiology and Pathogenesis 292
Genetic Factors 292
Environmental Factors 292
Immunologic Factors 292
Pathology 293
Diagnosis 293
Clinical Presentation 293
Extrahepatic Diseases 295
Laboratory Findings 295
Imaging Tools 296
Differential Diagnosis 296
Natural Course and Prognosis 296
Therapy 297
References 299
Chapter 74 304
Autoimmune Cholangitis 304
References 304
Chapter 75 306
Primary Sclerosing Cholangitis 306
Definition 306
Epidemiology 306
Etiology and Pathogenesis 307
Pathology 307
Diagnosis 308
Clinical Manifestations 308
Extrahepatic Diseases 309
Laboratory Findings 309
Imaging Tools 309
Differential Diagnosis 310
Course and Prognosis 311
Therapy 312
References 312
Chapter 76 315
Biliary Ductopenia (Vanishing Bile Duct Syndrome) 315
Defi nition 315
Epidemiology 315
Etiology and Pathogenesis 315
Pathology 317
Diagnosis 318
Laboratory Findings 318
Imaging Techniques 318
Differential Diagnosis 318
Course and Prognosis 318
Therapy 318
References 318
Chapter 77 319
Autoimmune Overlap Syndromes 319
Overlap Between AIH and PBC 320
Overlap Between AIH and PSC 320
Overlap Between PBC and PSC 320
References 321
Section XV: Acute Liver Failure 322
Chapter 78 323
Acute Liver Failure 323
Defi nition 323
Epidemiology 323
Etiology 323
Prognosis 324
General Considerations 325
Special Entities 326
Acetaminophen Intoxication 326
Mushroom Poisoning 326
Drug-Induced Liver Injury 327
Viral Hepatitis 327
Wilson’s Disease 328
Autoimmune Hepatitis 329
Acute Fatty Liver of Pregnancy 329
Budd-Chiari Syndrome 329
Indeterminate Etiology 329
Therapy 329
General Considerations 329
Encephalopathy and Cerebral Edema 330
Diagnosis of Increased Intracranial Pressure 330
General Therapeutic Measures in Cerebral Hypertension 331
Drug Therapy of Intracranial Hypertension 331
Supportive Therapy in Intracranial Hypertension 332
Infections in Acute Liver Failure 332
Multi-Organ-Failure in Acute Liver Failure 333
Aspects of Cardiovascular System and Hemodynamics 333
Renal Failure 333
Coagulation Disorders 334
Metabolic Disorders in Acute Liver Failure 334
Basic Aspects of Nutrition in Acute Liver Failure 334
Liver Replacement Therapies 335
Liver Transplantation and Prognosis 335
References 336
Section XVI: Liver Cirrhosis and Sequelae 339
Chapter 79 340
Liver Cirrhosis 340
Defi nition 340
Epidemiology 340
Etiology and Pathogenesis 341
Cell Death 341
Fibrosis and Circulatory Disturbances 342
Disturbances in Hepatocyte Growth and Proliferation 342
Pathology 343
Macroscopical Findings 343
Micronodular Cirrhosis 343
Macronodular Cirrhosis 344
Mixed Forms 345
Histological Findings 345
Diagnosis 346
Clinical Manifestations 346
Laboratory Findings 350
Imaging Techniques 351
Differential Diagnosis 352
Course and Prognosis 353
Therapy 354
References 355
Chapter 80 357
Complications of Liver Cirrhosis 357
80.1 Ascites, Varices, Portal Hypertensive Gastroenteropathy 359
Ascites 359
General Measures 360
Bed Rest 360
Diet 360
Diuretics 360
Potassium-Sparing Diuretics 361
Loop Diuretics 361
Practical Approach to Diuretic Therapy 362
Large-Volume Paracentesis 362
Practical Approach to Paracentesis 363
Refractory Ascites 363
Therapy of Refractory Ascites 364
Outlook 365
Esophageal Varices 366
Defi nition 366
Epidemiology 366
Anatomy, Etiology and Pathophysiology 366
Diagnosis 367
Course and Prognosis 368
Predictors of Variceal Bleeding 368
Prophylaxis and Therapy 369
“Preprimary” Prophylaxis 369
Primary Bleeding Prophylaxis 370
Therapy of Acute Variceal Hemorrhage 372
Prevention of Recurrent Variceal Hemorrhage 374
Gastric Varices 375
Portal Hypertensive Gastropathy 376
Defi nition 376
Epidemiology 376
Etiology and Pathogenesis 376
Pathology 376
Clinical Manifestations and Diagnosis 376
Differential Diagnosis 377
Course and Prognosis 377
Portal Hypertensive Entero-, Colo- and Biliopathy 378
References 378
Ascites 378
Esophageal Varices 380
Gastric Varices 383
Portal Hypertensive Gastropathy 383
Portal Hypertensive Entero-, Colo- and Biliopathy 383
80.2 Bacterial Infections 384
Spontaneous Bacterial Peritonitis 384
Defi nition 384
Epidemiology 384
Etiology and Pathogenesis 384
Diagnosis 385
Clinical Manifestations 385
Laboratory Findings 385
Differential Diagnosis 386
Course and Prognosis 386
Prophylaxis and Therapy 386
Primary Prophylaxis 386
Therapy 387
Secondary Prophylaxis 388
References 388
80.3 Hepatorenal Syndrome 389
Defi nition 389
Epidemiology 389
Etiology and Pathogenesis 389
Clinical Manifestations and Diagnosis 391
Type 1 Hepatorenal Syndrome 391
Type 2 Hepatorenal Syndrome 391
Differential Diagnosis 392
Course and Prognosis 392
Therapy 393
Drug Therapy 393
TIPS 393
Hemodialysis 393
Liver Transplantation 394
References 394
80.4 Hepatic Encephalopathy 395
Defi nition 395
Epidemiology 395
Etiology and Pathogenesis 395
Neurotoxins and Impaired Astrocyte Function 397
Amino Acid Imbalance and False Neurotransmitters 399
Pathology 400
Diagnosis 400
Clinical Manifestations 400
Minimal Hepatic Encephalopathy 400
Overt Hepatic Encephalopathy 400
Technical Investigations 401
Differential Diagnosis 402
Course and Prognosis 402
Therapy 402
General Measures and Elimination of Precipitating Factors 402
Ammonia-Lowering Strategies 404
Orthotopic Liver Transplantation 405
References 405
80.5 Pulmonary Complications 407
Hepatopulmonary Syndrome 407
Defi nition 407
Epidemiology 407
Etiology and Pathogenesis 407
Pathology 408
Clinical Manifestations and Diagnosis 408
Differential Diagnosis 409
Course and Prognosis 409
Therapy 409
Portopulmonary Hypertension 410
Defi nition 410
Epidemiology 410
Etiology and Pathogenesis 410
Pathology 411
Clinical Manifestations and Diagnosis 411
Differential Diagnosis 411
Course and Prognosis 411
Therapy 411
Hepatic Hydrothorax 412
Defi nition 412
Epidemiology 412
Pathogenesis 412
Clinical Manifestations and Diagnosis 412
Course and Prognosis 412
Therapy 412
References 412
Section XVII: Genetic and Metabolic Liver Disorders 422
Chapter 81 423
Wilson’s Disease 423
Defi nition and Epidemiology 423
Etiology and Pathogenesis 423
Diagnosis 424
Clinical Presentation 424
Diagnostic Findings 425
Family Screening 427
Differential Diagnosis 427
Prognosis 427
Treatment 428
Medical Treatment 428
Liver Transplantation 430
References 430
Chapter 82 432
Hereditary Hemochromatosis and Iron Overload 432
Defi nition and Classifi cation of Iron Overload Diseases 433
Type 1 HFE Hemochromatosis 434
History 434
Epidemiology 434
Etiology and Pathogenesis 435
Diagnosis 435
Laboratory Tests 435
Liver Biopsy and Determination of Liver Iron Concentration 436
Deferoxamine Testing and Ferrokinetic Measurements 436
Computed Tomography (CT), Magnetic Resonance Tomography (MRT) and Biomagnetometry 437
Genetic Tests 437
Early Diagnosis and Screening 437
Differential Diagnosis 439
Complications of Iron Overload 439
Liver cirrhosis 439
Liver Carcinoma 440
Association of Hemochromatosis with other Liver Diseases 440
Diabetes mellitus 441
Heart Disease 442
Arthropathy 442
Endocrine Abnormalities 443
Skin 443
Other Potential Complications 443
Therapy 443
Phlebotomy 443
Iron Removal by Chelators 444
Diet 444
Liver Transplantation 445
Prognosis 445
Juvenile Hereditary Hemochromatosis 445
Prevalence 445
Pathophysiology 445
Natural History 446
Diagnosis 446
Treatment 446
Transferrin Receptor 2 (TFR2)-Related Type 3 Hemochromatosis 447
Prevalence 447
Pathophysiology 447
Natural History 447
Diagnosis 448
Therapy 448
Type 4 Hemochromatosis–Ferroportin Disease 448
Prevalence and Pathophysiology 448
Natural History 449
Diagnosis 450
Therapy 450
Pathophysiology 450
Diagnosis 451
Therapy 451
References 452
Chapter 83 458
alpha1-Antitrypsin Defi ciency 458
Defi nition 459
Epidemiology 459
Etiology and Pathogenesis 459
Pathology 460
Clinical Manifestations 460
Laboratory Findings 462
Therapy 462
References 463
Chapter 84 464
Porphyrias 464
Abbreviations 464
Defi nition 464
Epidemiology 465
Etiology and Pathogenesis 466
Acute Porphyrias 466
Acute Intermittent Porphyria 467
Variegate Porphyria 467
Hereditary Coproporphyria 467
Doss-Porphyria (ALADP) (Delta-Aminolevulinic Acid-Dehydratase-Defect) 467
Non-acute Porphyrias 468
Porphyria Cutanea Tarda 468
Erythropoietic and X-linked Protoporphyria 469
Congenital Erythropoietic Porphyria (Guenther’s Disease) 469
Pathology 469
Porphyria Cutanea Tarda 470
Erythropoietic Protoporphyria 471
Clinical Manifestations 471
Acute Porphyrias 471
Non-acute Porphyrias 473
Porphyria Cutanea Tarda 473
Hepatoerythropoietic Porphyria 473
Erythropoietic Protoporphyria 473
Congenital Erythropoietic Porphyria (Günther’s Disease) 474
Diagnosis 474
Acute Porphyrias 474
Non-acute Potphyrias 475
Chronic Hepatic Porphyria and Porphyria Cutanea Tarda 475
Erythropoietic Protoporphyria 475
Differential Diagnosis 475
Acute Hepatic Porphyrias 475
Chronic Hepatic Porphyria and Porphyria Cutanea Tarda 475
Therapy and Prognosis 476
Acute Porphyrias 476
Non-acute Porphyrias 477
Chronic Hepatic Porphyria and Porphyria Cutanea Tarda 477
Erythropoietic Protoporphyria 477
Congenital Erythropoietic Porphyria 478
References 478
Chapter 85 480
Inherited Syndromes of Intrahepatic Cholestasis 480
Alagille’s Syndrome (Arteriohepatic Dysplasia) 480
Liver 480
Cardiovascular System 481
Facies 481
Ocular Changes 481
Skeletal Anomalies 481
Other Changes 481
Progressive Familial Intrahepatic Cholestasis 481
PFIC 1 484
Benign Recurrent Intrahepatic Cholestasis Type 1 (BRIC 1 Summerskill–Tygstrup–Walsh Syndrome)
PFIC 2 and BRIC 2 485
PFIC 3 485
References 485
Chapter 86 487
Cystic Fibrosis 487
Defi nition 487
Epidemiology 487
Etiology and Pathogenesis 487
Pathology 488
Clinical Manifestations 488
Course and Prognosis 488
Therapy 489
References 489
Chapter 87 490
Amyloidosis 490
Defi nition 490
Classifi cation 491
Development and Deposition of Amyloid 491
AL-Amyloid 491
AA-Amyloid 491
Hepatic Amyloidosis 492
Pathology 492
Diagnosis 492
Clinical Manifestations 492
Laboratory Investigations 493
Differential Diagnosis 493
Course and Prognosis 493
Therapy 493
References 493
Chapter 88 495
Alcoholic Liver Disease 495
Introduction 496
Metabolism of Alcohol 498
Gastric First Pass Metabolism of Ethanol 498
Hepatic Alcohol Metabolism 500
Alcohol Dehydrogenase 500
Hepatic Microsomal Ethanol Oxidizing System 501
Hepatic Catalase 503
Hepatic Acetaldehyde Dehydrogenase 503
Bacterial Metabolism of Ethanol 503
Alcoholic Liver Disease 504
Epidemiology 504
Natural Course 504
Risk Factors 504
Alcoholic Fatty Liver 505
Defi nition 505
Epidemiology 506
Pathogenesis 506
Histopathology 507
Clinical and Laboratory Findings 508
Differential Diagnosis 509
Complications 509
Prognosis 510
Therapy 510
Alcoholic Steatohepatitis 511
Defi nition 511
Pathophysiology 511
Histopathology 518
Clinical Findings 519
Laboratory Findings 520
Imaging 520
Differential Diagnosis 520
Complications 521
Natural Course and Prognosis 521
Therapy 522
Drugs 524
Alcoholic Cirrhosis 526
Defi nition 526
Epidemiology 526
Pathogenesis 526
Histopathology 528
Clinical Findings 528
Differential Diagnosis 529
Natural Course and Prognosis 529
Therapy 529
Hepatocellular Carcinoma 530
Epidemiology 530
Pathogenesis 531
Clinical Findings, Diagnosis and Therapy 532
References 532
Chapter 89 536
Nonalcoholic Fatty Liver Disease 536
Defi nition 536
Epidemiology 536
Etiology 537
Pathogenesis 538
NAFLD Associated with Obesity and Metabolic Syndrome 538
The Way to Steatosis 539
From Steatosis to Steatohepatitis 541
NAFLD Associated with Chronic Hepatitis C Virus Infection 543
Pathology 544
Diagnosis 546
Clinical Manifestations 546
Laboratory Findings 547
Imaging Techniques 547
Differential Diagnosis 548
Natural Course and Prognosis 548
Therapy 549
Lifestyle Modifi cations 549
Pharmacological Therapy 549
Bariatric Surgery 557
References 557
Chapter 90 563
Other Metabolic Diseases: Tabellary Overview 563
References 568
Chapter 91 569
Malnutrition and Nutrition in Liver Disease 569
Defi nition 570
Prevalence 571
Malnutrition 571
Obesity 571
Pathophysiology of Malnutrition 572
Nutrient Intake 572
Absorption 572
Alcohol 572
Protein Metabolism 572
Energy Metabolism 573
Molecular Mechanisms 574
Prognosis 575
Nutritional Assessment 576
Clinical Features 577
Medical History 577
Physical Examination 577
Nutritional Requirements 578
Nitrogen 578
Energy 578
Vitamins 579
Specifi c Alterations in Liver Disease 579
Accelerated Starvation 579
Hepatic Encephalopathy 579
Protein Restriction 580
Non-essential Amino Acids 580
Salt Restriction 580
Alcohol Related Alterations 581
Obesity 581
Nutritional Management 581
Goals 581
Specifi c Patient Populations 581
Cirrhosis 581
Alcoholic Hepatitis 581
Fulminant Hepatic Failure 581
Weight Loss 583
Liver Transplant 583
Principles and Practical Implementation 583
Glucose Requirement 583
Route of Nutrient Administration 583
Parenteral Nutrition 584
Branched Chain Amino Acids 584
Dietary Supplements 584
Summary 585
References 586
Section XVIII: Drug-Induced and Toxic Liver Disease 590
Chapter 92 591
Hepatic Drug Metabolism and Drug Toxicity 591
Factors Affecting Hepatic Drug Metabolism and Drug Toxicity 591
Gender 592
Genetic Factors 592
Gilbert’s Syndrome and Pharmacogenomic Risk 594
Simultaneous Exposure to Several Drugs 597
Biliary Excretion of Drugs 597
Impact of Liver Disease 598
References 600
Chapter 93 602
Drug- and Toxin-Induced Liver Injury 602
Defi nition 602
Diagnosis 603
Clinical Manifestations 603
Hepatotoxic Liver Injury 603
Idiosyncratic Liver Injury 604
Laboratory Findings 604
Histological Patterns of Injury 604
Therapy 607
References 609
Section XIX: Granulomatous Liver Diseases 611
Chapter 94 612
Hepatic Granulomas 612
Defi nition 612
Epidemiology 612
Etiology 612
Pathogenesis and Pathology 613
Diagnosis 614
Clinical Manifestations 614
Laboratory Findings 614
Imaging Techniques 614
Differential Diagnosis 614
Course and Prognosis 615
Therapy 615
References 615
Chapter 95 616
Sarcoidosis of the Liver 616
Defi nition 616
Epidemiology 616
Pathogenesis 616
Pathology 617
Diagnosis 617
Clinical Manifestations 617
Laboratory Findings 618
Imaging Techniques 618
Differential Diagnosis 618
Course and Prognosis 618
Therapy 619
References 619
Section XX: Interaction Between the Liver and Other Organ Systems 620
Chapter 96 621
Effects of Chronic Liver Disease on Other Organs: Tabellary Overview 621
References 622
Chapter 97 623
Hepatic Involvement in Extrahepatic Disease: Tabellary Overview 623
References 628
Section XXI: Pregnancy-Specific Liver Diseases 630
Chapter 98 632
Intrahepatic Cholestasis of Pregnancy 632
Defi nition 632
Epidemiology 632
Etiology and Pathogenesis 633
Pathology 633
Diagnosis 633
Clinical Manifestations 633
Laboratory Findings 633
Imaging Techniques 634
Differential Diagnosis 634
Course and Prognosis 634
Therapy 635
References 635
Chapter 99 637
Acute Fatty Liver of Pregnancy 637
Defi nition 637
Epidemiology 637
Etiology and Pathogenesis 637
Pathology 638
Diagnosis 638
Clinical Manifestations 638
Laboratory Findings 638
Imaging Techniques 638
Differential Diagnosis 638
Course and Prognosis 639
Therapy 639
References 640
Chapter 100 641
The Liver in Toxemia of Pregnancy 641
Defi nition 641
Epidemiology 641
Etiology and Pathogenesis 641
Pathology 642
Diagnosis 642
Clinical Manifestations 642
Laboratory Findings 642
Imaging Techniques 642
Complications 642
HELLP Syndrome 642
Prognosis and Therapy 643
References 643
Section XXII: Primary Tumors of the Liver and Intrahepatic Bile Ducts 644
Chapter 101 645
Benign Tumors 645
Introduction 647
References 647
101.1 Hepatocellular Adenoma 648
Defi nition 648
Epidemiology 648
Etiology 648
Pathogenesis 648
Pathology 649
Diagnosis 649
Clinical Manifestations 649
Laboratory Findings 650
Imaging Techniques 650
Differential Diagnosis 650
Prognosis and Therapy 651
References 651
101.2 Nodular Regenerative Hyperplasia 652
Defi nition 652
Epidemiology 652
Etiology 652
Pathogenesis 653
Pathology 653
Diagnosis 654
Clinical Manifestations 654
Laboratory Findings 654
Imaging Techniques 654
Differential Diagnosis 654
Natural History and Prognosis 654
Therapy 655
References 655
101.3 Focal Nodular Hyperplasia 656
Defi nition 656
Epidemiology 656
Etiology and Pathogenesis 656
Pathology 656
Diagnosis 657
Clinical Manifestations 657
Laboratory Findings 658
Imaging Techniques 658
Differential Diagnosis 658
Natural History and Prognosis 659
Therapy 659
References 659
101.4 Bile Duct Adenoma 660
Defi nition 660
Histology 660
Clinical Manifestations 660
Differential Diagnosis 660
Therapy 661
References 661
101.5 Biliary Cystadenoma 661
Defi nition and Epidemiology 661
Pathology 661
Diagnosis 661
Clinical Manifestations 661
Laboratory Findings 662
Imaging Techniques 662
Differential Diagnosis 662
References 662
101.6 Biliary Papillomatosis 663
Defi nition 663
Epidemiology, Etiology and Pathogenesis 663
Diagnosis 663
Clinical Manifestations 663
Laboratory Findings 663
Imaging Techniques 663
Differential Diagnosis 663
Prognosis 663
Therapy 663
References 664
101.7 Hemangioma 664
Defi nition 664
Epidemiology 664
Pathology 664
Diagnosis 664
Clinical Manifestations 664
Laboratory Findings 665
Imaging Techniques 665
Differential Diagnosis 666
Natural History and Prognosis 666
Treatment 667
References 667
101.8 Infantile Hemangioendothelioma 667
Defi nition and Epidemiology 667
Pathology 667
Diagnosis 667
Clinical Manifestations 667
Laboratory Findings 668
Imaging Techniques 668
Therapy 668
References 668
101.9 Lymphangioma and Hepatic Lymphangiomatosis 669
References 669
101.10 Mesenchymal Hamartoma 669
References 669
101.11 Lipomatous Tumors 670
Lipoma 670
Pseudolipoma 670
Focal Steatosis 670
Angiomyolipoma 670
Defi nition and Epidemiology 670
Pathology 670
Diagnosis 672
Clinical Manifestations 672
Laboratory Findings 672
Imaging Methods 672
References 672
101.12 Fibrous Tumors 673
Solitary Fibrous Tumor 673
Infl ammatory Pseudotumor 673
Defi nition and Epidemiology 673
Etiology and Pathogenesis 673
Pathology 674
Diagnosis 674
Clinical Manifestations 674
Laboratory Findings 674
Imaging Techniques 674
Differential Diagnosis 675
Therapy and Prognosis 675
References 675
101.13 Various Rare Tumors 676
References 676
Chapter 102 677
Malignant Tumors 677
102.1 Hepatocellular Carcinoma 679
Defi nition 679
Epidemiology 679
Etiology 680
Pathogenesis 682
Chronic Hepatitis B Virus Infection 683
Chronic Hepatitis C Virus Infection 684
Liver Cirrhosis 684
Alcoholic Liver Disease 684
Nonalcoholic Fatty Liver Disease 684
Afl atoxin B1 and Other Toxins 684
Pathology 685
Macroregenerative Nodules 685
Liver Cell Dysplasia 685
Large Cell Dysplasia 685
Small Cell Dysplasia 686
Dysplastic Foci 686
Dysplastic Nodules 686
Low Grade Dysplastic Nodules 686
High Grade Dysplastic Nodules 686
Progression from Dysplasia to Hepatocellular Carcinoma 686
Hepatocellular Carcinoma 687
Gross Anatomy 687
Microscopic Anatomy 687
Clinical Manifestations 689
Diagnosis 689
Laboratory Findings 689
alpha1-Fetoprotein 690
Des-gamma-Carboxy-Prothrombin 690
Novel Markers 690
Imaging Techniques 691
Approach to a Hepatic Mass in a Cirrhotic Liver 691
Lesions Less Than 1 cm in Diameter 693
Lesions 1–2 cm in Diameter 693
Lesions Larger Than 2 cm in Diameter 693
Differential Diagnosis 693
Prognosis and Staging 693
TNM System 695
Okuda Staging System 695
Cancer of the Liver Italian Program 696
Barcelona Clinic Liver Cancer Staging Classifi cation 697
Other Scoring Systems 697
Comparison of Different Staging Systems 697
Prevention and Screening 698
Therapy 698
Surgical Resection 698
Liver Transplantation 699
Locally Ablative Techniques 699
Transarterial Chemoembolization 700
Radiofrequency Ablation 700
Percutaneous Ethanol Injection 700
Medical Therapy 701
Systemic Chemotherapy 701
Hormonal Therapy 701
Molecularly Targeted Therapy 701
References 701
102.2 Fibrolamellar Carcinoma 709
Defi nition 709
Epidemiology 709
Etiology and Pathogenesis 709
Pathology 709
Diagnosis 709
Differential Diagnosis 709
Prognosis and Treatment 710
References 710
102.3 Hepatoblastoma 710
Defi nition 710
Epidemiology 710
Etiology and Pathogenesis 710
Pathology 710
Diagnosis 711
Clinical Manifestations 711
Technical Investigations 711
Course and Prognosis 711
Therapy 711
References 711
102.4 Angiosarcoma 712
Defi nition 712
Epidemiology 712
Etiology and Pathogenesis 712
Pathology 712
Diagnosis 713
Clinical Manifestations 713
Laboratory Findings 713
Imaging Techniques 713
Differential Diagnosis 713
Course and Prognosis 713
Therapy 714
References 714
102.5 Epithelioid Hemangioendothelioma 715
Defi nition 715
Epidemiology 715
Etiology and Pathogenesis 715
Diagnosis 716
Clinical Manifestations 716
Laboratory Findings 716
Imaging Techniques 716
Differential Diagnosis 716
Course and Prognosis 716
Therapy 716
References 717
102.6 Embryonal Sarcoma 717
Defi nition 717
Epidemiology 717
Etiology and Pathogenesis 717
Pathology 717
Diagnosis 718
Clinical Manifestations 718
Laboratory Findings 718
Imaging Techniques 718
Differential Diagnosis 718
Course and Prognosis 718
Therapy 718
References 718
102.7 Primary Hepatic Malignant Lymphoma 719
Epidemiology 719
Pathogenesis 719
Pathology 719
Diagnosis 719
Clinical Manifestations 719
Laboratory Findings 719
Imaging Techniques 720
Differential Diagnosis 720
Course and Prognosis 720
Therapy 720
References 720
102.8 Various Rare Tumors 721
Malignant Fibrous Histiocytoma 721
Kaposi’s Sarcoma 721
Other Rare Tumors 722
References 722
Section XXIII: Liver Transplantation and Surgery in Liver Disease 723
Chapter 103 724
Liver Transplantation: Indications, Preoperative Evaluation and Posttransplantation Management 724
History 725
Philosophy 725
The Evaluation Process 726
Listing for Transplantation 726
Scoring Systems and Prioritization on the Waiting List 727
Impact of MELD on Outcomes and Transplant Benefi t 727
Indications for Transplantation 728
Minimal Listing Criteria 728
Alcoholic Liver Disease 729
Viral Hepatitis 730
Hepatitis C 730
Hepatitis B 730
Cholestatic Liver Disease 731
Malignant Diseases of the Liver 731
Cholangiocarcinoma 732
Hepatocellular Carcinoma 732
Metabolic Liver Disease 735
Vascular Disease of the Liver 735
Fulminant Hepatic Failure 735
Indications for Liver Transplant in the Child 736
Pediatric Cholestatic Diseases 736
Pediatric Metabolic Liver Diseases 737
Hepatic Malignancy in Children 737
Retransplantation in Children 737
Evaluation and Listing 737
Contraindications to Liver Transplant 739
Age 739
Psychosocial Contraindications 740
Cardiopulmonary Contraindications 740
Infectious Contraindications 740
HIV Infection 740
Other Infectious Contraindications 741
The Waiting List 741
Management on the Waiting List 741
Timing of Transplantation 741
Delisting Criteria 742
Living Donor Liver Transplantation 742
The Posttransplant Period 743
The Perioperative Period 743
Immunosuppression 744
Rejection 746
New Onset Diabetes Mellitus Following Transplant 746
Arterial Hypertension 746
Hyperlipidemia 747
Biliary Complications 747
Vascular Complications 747
Recurrent Disease 747
Infection 748
Conclusion 749
References 750
Chapter 104 753
Risk of Surgery in Patients with Liver Disease 753
Effects of Surgery on the Liver 753
Liver Biochemical Tests 753
Hepatic Blood Flow and Hemodynamic Effects 754
Hypoxemia 754
Hepatic Metabolism of Anesthetic Agents 755
Operative Risk in Patients with Liver Disease 755
Challenges in Estimating Operative Risk 755
Preoperative Screening 756
Conditions for Which Elective Surgery is Contraindicated 757
Acute Hepatitis 757
Acute Alcoholic Hepatitis 757
Acute Liver Failure 758
Surgery in Patients with Chronic Liver Disease 758
Chronic Viral Hepatitis 758
Nonalcoholic Fatty Liver Disease (NAFLD) 759
Other Causes of Chronic Liver Disease 759
Cirrhosis 760
Operative Risk Stratifi cation by Child Class 760
Operative Risk Stratifi cation by MELD Score 761
Operative Risk Associated with Specifi c Types of Surgery 761
Endoscopic Procedures 764
Ascites 765
Renal Dysfunction 765
Encephalopathy 765
Nutrition 766
Postoperative Monitoring 766
References 766
Section XXIV: Gene Therapy 770
Chapter 105 771
A Look to the Future: Gene Therapy in Liver Diseases 771
Genetic Classifi cation of Diseases 771
Gene Therapy of Liver Diseases 772
Gene Repair 772
Gene Substitution 772
Hepatocyte Transplantation 773
Block of Gene Expression or Function 773
Ribozymes 773
Small Interfering RNA 774
Antisense Oligonucleotides 774
Interfering Peptides or Proteins 774
DNA Vaccination 775
Gene Augmentation 775
Suicide Gene Therapy 775
Antiangiogenic Gene Therapy 776
Oncolytic Viruses 776
Immune Therapy 776
AFP-Specifi c Immune Therapy 776
Immune Therapy with Antigen Presenting Cells 776
Cytokine Gene Therapy 776
Molecular Prevention of Liver Diseases 776
Summary and Perspectives 777
References 777
Part V: Diseases of the Gallbladder and Extrahepatic Bile Ducts 781
Section XXV: Anatomy, Histology and Physiology 782
Chapter 106 783
Gross and Microscopic Anatomy 783
Embryonic Development 783
Gallbladder 783
Extrahepatic Bile Ducts 784
References 787
Chapter 107 788
Physiology of the Gallbladder and the Extrahepatic Bile Ducts 788
Physiology of the Gallbladder 788
Bile Storage and Excretion 788
Gallbladder Motility 789
Physiology of the Extrahepatic Bile Ducts 789
Physiology of the Sphincter of Oddi 790
References 791
Section XXVI: Developmental Anomalies 792
Chapter 108 793
Anomalies of the Gallbladder and the Cystic Duct 793
Numerical Anomalies of the Gallbladder 793
Positional Anomalies of the Gallbladder 794
Internal and External Morphological Anomalies of the Gallbladder 795
Anomalies of the Cystic Duct 795
References 796
Chapter 109 797
Anomalies of the Extrahepatic Bile Ducts 797
Anomalies in the Number and/or Course of the Extrahepatic Bile Ducts 797
Form Anomalies of the Extrahepatic Bile Ducts 798
Congenital Bile Duct Cysts 798
Congenital Biliary Atresia and Stenosis 799
References 800
Chapter 110 801
Benign Strictures of the Extrahepatic Bile Ducts 801
References for Chapters 108, 109, 110 801
Section XXVII: Motility Disorders 803
Chapter 111 804
Motility Disorders of the Bile Ducts and Postcholecystectomy Syndrome 804
Postcholecystectomy Syndrome 804
Defi nition and Epidemiology 804
Etiology and Pathogenesis 804
Clinical Presentation and Diagnosis 805
Differential Diagnosis 805
Bile Duct Stones 808
Long Cystic Duct with Retained Stone 808
Bile Duct Strictures 808
Stenosis and Tumors of the Papilla 808
Sphincter of Oddi Dysfunction 808
Diagnostic Procedures 808
Sphincter of Oddi Manometry 810
Pharmacologic Provocation Tests 810
ERCP, MRCP 810
Abdominal Ultrasound with Provocation Tests 812
Hepatobiliary Scintigraphy 812
Probatory Stent Placement 812
Botulinum Toxin Injection (BoTox) 813
Sphincter of Oddi Dyskinesia 814
SOD Type I 814
SOD Type II 815
SOD Type III 815
Clinical Course and Prognosis 816
Therapy 816
Endoscopic Interventional Therapy 817
References 817
Section XXVIII: Gallstones 819
Chapter 112 820
Gallbladder Stones 820
Epidemiology 820
Etiology and Pathogenesis 822
Cholesterol Stones 822
Black Pigment Stones 825
Brown Pigment Stones 826
Gallbladder Sludge 828
Diagnosis 828
Ultrasound 828
Radiological Techniques 828
Natural Course 830
Asymptomatic Cholelithiasis 831
Symptomatic Cholelithiasis 831
Complications of Cholecystolithiasis 832
Acute Bacterial Cholecystitis 832
Gallbladder Empyema and Hydrops 834
Emphysematous Cholecystitis 834
Chronic Cholecystitis 834
Chalk Milk Bile, Porcelain Gallbladder 834
Mirizzi Syndrome 835
Stone Perforation and Stone Ileus 835
Gallbladder Carcinoma 835
Biliary Pancreatitis 835
Gallstone Prophylaxis 835
Therapy 836
Oral Litholysis 836
Extracorporeal Shock Wave Lithotripsy 837
Contact Litholysis 838
Cholecystectomy 838
Postcholecystectomy Syndrome 839
Treatment of Cholecystitis and Its Complications 839
Cholecystectomy 839
Cholecystolithotomy, Cholecystostomy 840
References 840
Chapter 113 841
Bile Duct Stones 841
Epidemiology 841
Clinics 842
Diagnosis 842
Ultrasound 842
Radiologic Techniques 842
Complications 843
Cholangitis 844
Liver Abscess 844
Biliary Pancreatitis 844
Bile Duct Carcinoma 845
Treatment of Choledocholithiasis and Cholangitis 845
Endoscopic Stone Extraction 845
Adjuvant Treatment Procedures 846
Treatment of Cholangitis 847
Surgery for Bile Duct Stones 848
Therapy of Hepatolithiasis 848
Cholelitholysis 848
References 849
Section XXIX: Infectious Disorders 851
Chapter 114 852
Biliary Infections 852
Bacterial Cholangitis 852
Pathogenesis 852
Bacteria in Bile 852
Bile Duct Obstruction 853
Diagnosis 853
Treatment 854
Antibiotic Treatment 854
Decompression of Bile Ducts 855
Prophylaxis 856
Fungal Cholangitis 857
Diagnosis 857
Treatment 857
Parasitic Cholangitis 857
Pathogenesis 857
Diagnosis and Treatment 857
Nematode Cholangitis 857
Trematode Cholangitis 858
HIV Cholangiopathy 858
Pathogenesis 859
Diagnosis 859
Treatment 859
References 860
Section XXX: Tumors of the Gallbladder and Extrahepatic Bile Ducts 862
Chapter 115 863
Benign Tumors 863
Benign Tumors of the Gallbladder 863
Defi nition 863
Epidemiology 863
Etiology and Pathogenesis 864
Pathology 864
Clinical Manifestations 865
Diagnosis 865
Differential Diagnosis 866
Therapy and Prognosis 866
Benign Tumors of the Extrahepatic Bile Ducts 867
Defi nition 867
Epidemiology 867
Etiology and Pathogenesis 867
Pathology 868
Clinical Manifestations 868
Diagnosis 868
Differential Diagnosis 869
Therapy and Prognosis 869
Benign Tumors of the Ampulla of Vater 870
Defi nition 870
Epidemiology 870
Etiology and Pathogenesis 870
Pathology 870
Clinical Manifestations 871
Diagnosis 871
Differential Diagnosis 871
Therapy and Prognosis 872
References 873
Chapter 116 876
Malignant Tumors 876
Gallbladder Cancer 876
Defi nition 876
Epidemiology 876
Etiology and Pathogenesis 877
Pathology 878
Clinical Manifestations 878
Diagnosis 878
Differential Diagnosis 879
Therapy and Prognosis 879
Curative Treatment 879
Palliative Treatment 880
Recurrent Gallbladder Cancer 881
Extrahepatic Cholangiocarcinoma 881
Defi nition 881
Epidemiology 881
Etiology and Pathogenesis 883
Pathology 884
Differential Diagnosis 886
Therapy and Prognosis 887
Curative Treatment for Hilar Cholangiocarcinoma 887
Preoperative Biliary Drainage 888
Resection of Hilar Cholangiocarcinoma 888
Liver Transplantation for Hilar Cholangiocarcinoma 890
Resection of Distal Cholangiocarcinoma 890
Neoadjuvant and Adjuvant Therapy 891
Palliative Management 893
Stenting for Extrahepatic Cholangiocarcinoma 893
Photodynamic Therapy (PDT) for Hilar Cholangiocarcinoma 895
Surgical Palliation 898
Palliative Chemotherapy 898
Palliative Radiotherapy 900
Palliative Chemoradiation 900
Future Directions of Palliation 904
Progress in PDT 904
Progress in Chemotherapy 905
Molecular Targeted Therapy 906
Recurrent Extrahepatic Cholangiocarcinoma 908
Management of Tumor Complications 908
Prognostic Indicators in Patients with Hilar Cholangiocarcinoma 908
Malignant Tumors of the Ampulla of Vater 909
Defi nition 909
Epidemiology 909
Etiology and Pathogenesis 909
Pathology 909
Clinical Manifestations 909
Diagnosis 909
Differential Diagnosis 910
Therapy and Prognosis 911
References 911
Index 924