Fibrocystic Diseases of the Liver (eBook)

Karen F. Murray, Anne M. Larson (Herausgeber)

eBook Download: PDF

2010 | 2010
XIV, 512 Seiten
Humana Press (Verlag)
978-1-60327-524-8 (ISBN)

Infos

In recent years there have been huge advances in the understanding of the genetic and molecular basis of the fibrocystic diseases. This volume provides a thorough review of fibrocyctic diseases that affect the liver. It contains in-depth discussions of the genetics, molecular biology, pathogenesis, histology, clinical presentations, complications of, treatment, and prognosis of the conditions affecting children and adults, and hence will be the gold-standard reference for these conditions. In addition, the histological features that distinguish these conditions from other potentially fibrosing hepatopathies are illustrated. Conditions with syndromic features involving the kidney or other organ systems are also reviewed. Thorough review of the clinical phenotypes, their presentations, treatment, potential complications of, and prognosis is discussed.

Fibrocystic Diseases of the Liver will be an invaluable resource for hepatologists, gastroenterologists, nephrologists, and hepatic surgeons who care for children and adults with liver disease, as well as basic scientists in molecular genetics, hepatobiliary pathophysiology, hepatology and nephrology.

Inhalt

Preface 8
Contents 10
Contributors 12
Part I Pathophysiology and Development 16
1 Embryology and Development of the Ductal Plate 17
Introduction 18
Liver Specification and Budding 18
Overview of Biliary Tract Development 21
Hepatoblast Differentiation into Biliary Epithelial Cells 23
Biliary Tract Morphogenesis 27
Cilia A Potential Link Between Development and Disease 30
References 32
2 Cholangiocyte Biology as Relevant to Cystic Liver Diseases 36
Introduction 37
Morphology and Secretory Functions of the Normal Biliary Epithelium 39
Cholangiocyte Reaction to Damage 42
Mechanisms of Cystic Liver Diseases: Cilia and Beyond 44
Cellular Mechanisms of Liver Cyst Formation and Growth 46
Altered Biliary Developmental Program (Ductal Plate Malformation) 46
Altered Epithelial Fluid Secretion 47
Cholangiocyte Proliferation 48
Autocrine and Paracrine VEGF Signaling 49
Extracellular Matrix Remodeling 51
New Therapeutic Strategies in Preventing Cyst Growth 52
References 52
3 Cholangiocyte Cilia and Basal Bodies 57
General Introduction to Cilia 58
Structure of Mammalian Cilia 59
Cilia in Normal Cholangiocytes 61
Cilia in Cholangiociliopathies 63
Ciliogenesis 66
Centrosome, Centrioles, and Pericentriolar Material 66
Centrosome Functions 67
Centriole Duplication 68
Centriole Migration and Docking 68
Formation of the Ciliary Axoneme 68
Intraflagellar Transport (IFT) 69
Ciliogenesis in Cholangiocytes 69
Functions of Cholangiocyte Cilia 70
Cholangiocyte Cilia as Mechanosensors 70
Cholangiocyte Cilia as Chemosensors 71
Cholangiocyte Cilia as Osmosensors 72
Ciliary Hypothesis of Cystogenesis 74
Conclusion 75
References 76
4 Genetics of Fibrocystic Diseases of the Liver and Molecular Approaches to Therapy 83
Introduction 84
Autosomal Dominant Polycystic Kidney Disease (ADPKD) 92
Autosomal Recessive Polycystic Kidney Disease (ARPKD) 94
Autosomal Dominant Polycystic Liver Disease (ADPLD) 95
Meckel (Gruber) Syndrome (MKS) 97
Joubert Syndrome 98
BardetBiedl Syndrome (BBS) 99
Alagille Syndrome 101
Nephronophthisis (NPHP) 102
Jeune Asphyxiating Thoracic Dystrophy 103
Oral-Facial-Digital Syndrome 103
Molecular Approaches to Therapy 103
References 107
Part II Diagnosis 115
5 Radiologic Findings in the Fibrocystic Diseases 116
Biliary Atresia 117
Autosomal Recessive Polycystic Kidney Disease And Congenital Hepatic Fibrosis 124
Simple Hepatic Cysts And Autosomal Dominant Polycystic Liver Disease 126
Microhamartomas 131
Choledochal Cysts 134
Caroli Disease 138
Summary 141
References 141
6 Pathology of Fibrocystic Diseases of the Liver 144
Introduction 145
Jag1/Notch Sequence and Alagille Syndrome 145
Biliary Atresia 151
Polycystic Kidney Disease 154
Autosomal Recessive Polycystic Kidney Disease (ARPKD) 154
Autosomal Dominant Polycystic Kidney Disease and Polycystic Liver Disease 155
Caroli Disease and Caroli Syndrome 156
Congenital Hepatic Fibrosis 158
Simple Hepatic Cyst 159
Choledochal Cyst 159
Von Meyenburg Complexes (Bile Duct Hamartoma) 161
References 162
Part III Disease States 167
7 Alagille Syndrome and JAGGED1/NOTCH Sequence 168
Introduction 169
Identification of JAGGED1 170
JAGGED1 Mutations in Alagille Syndrome 171
Notch Signaling Pathway 172
GenotypePhenotype Correlations 173
Disease Mechanism in Alagille Syndrome 175
JAGGED1 Expression in Alagille Syndrome 176
Identification of NOTCH2 177
Role of JAGGED1/NOTCH Sequence in Bile Duct Development 179
Role of JAGGED1/NOTCH Sequence in Cardiac Development 181
Role of JAGGED1/NOTCH Sequence in Vascular Development 181
Genetic Testing in Alagille Syndrome 183
Summary 183
References 184
8 Biliary Atresia and the Ductal Plate 188
Biliary Atresia Clinical Perspective 189
Pathogenesis of Biliary Atresia 190
Defective Morphogenesis and Biliary Atresia 192
Embryogenesis and Visceral Isomerism 192
BA and Other Major Congenital Malformations 194
Intrahepatic Bile Duct Development and the Ductal Plate Malformation 194
Immune and Autoimmune Mechanisms Causing Bile Duct Injury and Obstruction 196
T-Cell-Mediated Inflammation 196
Innate Immunity in BA 197
Evidence for Autoimmunity in Biliary Atresia 198
Role of Infectious Agents in Biliary Atresia 200
Clues from the Epidemiology of BA 200
Viruses and BA 201
Conclusions 203
References 204
9 Nephronophthisis and Renal--Hepatic--Pancreatic Dysplasia of Ivemark 209
Introduction 210
Nephronophthisis 210
Clinical Subtypes 211
Juvenile Nephronophthisis 211
Senior--Loken Syndrome 211
Infantile Nephronophthisis 213
Adolescent Nephronophthisis 214
Diagnosis 214
Clinical Care 216
Chronic Kidney Disease Care 216
Factors Affecting Progression 216
End-Stage Renal Disease Care 216
Pathology 217
Genetics and Nephronophthisis 217
Discovery 217
A Shift in Paradigm 217
NPHP1 220
NPHP2/INV 220
NPHP3 220
NPHP4 221
NPHP5/IQCB1 221
NPHP6/CEP-290 (Centrosomal Protein 290 kDa) 221
NPHP7/GLIS2 (Glis Family Zinc Finger Protein 2) 222
Other Genes Associated with Nephronophthisis 222
Evidence for Epistasis and Oligogenic Inheritance 222
Nephronophthisis and the Liver 223
Hepatic Manifestations in Nephronophthisis Syndromes 223
Hepatic Fibrosis and Genetics in Nephronophthisis Syndromes 223
Renal--Hepatic--Pancreatic Dysplasia (RHPD) 224
Summary 225
References 225
10 Meckel and Joubert Syndromes 229
Meckel Syndrome 230
Overview 230
Clinical Diagnosis 231
Molecular Genetics of MKS 236
Outcome and Management of MKS 240
Joubert Syndrome and Related Disorders 241
Overview 241
Clinical Diagnosis 241
Molecular Genetics of JSRD 249
Outcome and Management of JSRD 254
Conclusions: MKS and JSRD are Ciliopathies 256
References 256
11 Bardet-Biedl and Jeune Syndromes 265
Introduction 266
Overview 266
Structure and Function of Cilia 267
BardetBiedl Syndrome 268
Overview 268
Clinical Features of BBS 270
Rod--Cone Dystrophy 270
Obesity 274
Postaxial Polydactyly 274
Renal Manifestations 275
Hepatic Involvement in Bardet--Biedl Syndrome 275
Craniofacial Dysmorphism in BBS 275
Hirschsprung's Disease in BBS 277
Molecular Genetics of BBS 277
Jeune Syndrome 281
Clinical Diagnosis of JATD 281
Skeletal Findings 281
Respiratory Insufficiency 282
Retinal Degeneration 283
Cystic Renal Disease 283
Liver Disease 283
Natural History 283
Molecular Genetics of Jeune Syndrome 287
Conclusion 287
References 288
12 Congenital Disorders of Glycosylation and Their Effects on the Liver 294
Introduction 295
Glycosylation Introduction 295
History Glycosylation Disorders 296
N-Linked Glycosylation 296
Clinical Presentation of Classical CDG 301
CDG and Liver Disease General Features 301
Features of the Respective CDG Subtypes 302
PMM2 Deficiency (CDG-Ia) 302
PMI/MPI Deficiency (CDG-Ib) 306
Autosomal Dominant Polycystic Liver Disease (ADPLD) 308
ALG6 Deficiency (CDG-Ic) 309
NOT56L Deficiency (CDG-Id) 309
DPM1 Deficiency (CDG-Ie) 310
MPDU1 Deficiency (CDG-If) 310
ALG12 Deficiency (CDG-Ig) 310
ALG8 Deficiency (CDG-Ih) 311
ALG2 Deficiency (CDG-Ii) 311
DPAGT1 Deficiency (CDG-Ij) 312
HMT1 Deficiency (CDG-Ik) 312
DIBD1 Deficiency (CDG-IL) 312
DK1 Deficiency (CDG-Im) 312
RFT-1 Deficiency (CDG-In) 313
Deficiencies in the Oligosaccharyltransferase Complex (N33/TUSC3 or IAP Deficiencies) 313
Untyped Type I Defects (CDG-Ix) 313
MGAT2 Deficiency (CDG-IIa) 313
GLS1 Deficiency (CDG-IIb) 314
SLC35C1 Deficiency (CDG-IIc Leukocyte Adhesion Deficiency Type II [LADII])
B4GALT1 Deficiency (CDG-IId) 315
COG Subunit Deficiencies (CDG-IIe, -IIg, and -IIh) 315
SLC35A1 Deficiency (CDG-IIf) 316
Untyped CDGs (CDG-IIx) 316
Conclusions 317
References 318
13 Autosomal Recessive Polycystic Kidney Disease 325
Introduction 326
Genetics and Pathogenesis 326
Pathology 327
Clinical Manifestations 329
Diagnosis 330
Clinical Management 331
Prognosis 333
References 333
14 Caroli Disease, Caroli Syndrome, and Congenital Hepatic Fibrosis 337
Introduction 338
Caroli Disease and Caroli Syndrome 338
Genetics 339
Epidemiology 339
Pathogenesis 339
Pathology 340
Clinical Manifestations 340
Diagnosis 341
Differential Diagnosis 344
Associated Conditions 345
Complications 345
Treatment 345
Medical Treatment 345
Surgical Treatment 348
Prognosis 348
Congenital Hepatic Fibrosis 348
Pathogenesis 352
Pathology 352
Clinical Manifestations 353
Portal Hypertensive CHF 353
Cholangitic CHF 354
Mixed Type 354
Laboratory Findings 355
Physical Examination 355
Diagnosis 355
Imaging 356
Therapy 357
References 360
15 Simple Hepatic Cysts/Choledochal Cysts 365
Simple Hepatic Cysts 365
Epidemiology 366
Pathogenesis 366
Clinical Features and Diagnosis 366
Surgical Management 367
Choledochal Cysts 369
Epidemiology 369
Classification 369
Pathogenesis 370
Diagnosis and Clinical Features 370
Surgical Management 372
References 373
16 Autosomal Dominant Polycystic Liver Disease 376
Definition 377
Genetics 377
ADPLD with ADPKD 377
ADPLD Without ADPKD 378
Pathogenesis 378
Proliferation 379
Secretion 379
Matrix Remodeling and Neovascularization 379
Estrogen 380
Epidemiology 380
Clinical Manifestations 381
Hepatic Manifestations 381
Extrahepatic Manifestations 382
Pathology 382
Gross Examination 382
Microscopic Examination 383
Natural History 383
Diagnosis and Differential Diagnosis 383
Treatment 384
Interventional Managements 384
Non-interventional Management 386
Investigational Treatments: Ongoing Clinical Trials 387
Summary 387
References 387
17 Echinococcal/Hydatid Cysts of the Liver 392
History 393
Microbiology and Life Cycle 393
Epidemiology 396
Prevention 396
Clinical Manifestations 398
Diagnosis 400
Management 405
References 412
18 Miscellaneous Cystic Lesions of the Liver 415
Introduction 416
Biliary Hamartoma (Von Meyenburg Complex) 416
Ciliated Hepatic Foregut Cyst 421
Cavernous Hemangioma 423
Peliosis Hepatis 426
Peribiliary Cysts 427
Other Cystic Conditions of the Liver and Biliary Tract 428
References 430
Part IV Complications 437
19 Vascular Complications of Fibrocystic Liver Disease 438
Introduction 439
Hepatic Vascular Complications 440
Portal Hypertension 440
Hepatic Venous Outflow Obstruction 442
Extrahepatic Vascular Complications of Fibrocystic Liver Disease 443
Intracranial Aneurysms 444
Other Aneurysms 445
Cardiac Abnormalities 445
Conclusion 446
References 446
20 Biliary Cystadenoma and Cystadenocarcinoma 448
Introduction 449
Pathology 450
Macroscopic Appearance 450
Microscopic Appearance 450
Immunohistochemistry 453
New Proposed Classification 453
Etiology 454
Clinical Presentation 455
Diagnosis 456
Therapy 459
Prognosis 460
References 461
21 Cholangitis 465
Introduction 466
Pathogenesis 467
Clinical Manifestations 471
Diagnosis 472
Treatment 474
Summary 479
References 479
Part V Surgical Management 483
22 Surgical Management of Fibrocystic Liver Disease 484
Introduction 485
Simple Hepatic Cysts 485
Choledochal Cysts 486
Carolis Disease and Carolis Syndrome 487
Congenital Hepatic Fibrosis 487
Polycystic Liver Disease 488
Autosomal Dominant Polycystic Kidney Disease (ADPKD) 488
Autosomal Dominant Polycystic Liver Disease 489
Other Congenital Syndromes Associated with Fibrocystic Liver Disease 489
Biliary Atresia 490
Echinococcal Cysts/Hydatid Cysts of the Liver 491
Cystadenoma and Cystadenocarcinoma 492
Conclusion 492
References 493
Subject Index 495

Produkt-Details

• Erscheint lt. Verlag: 23.7.2010
• Reihe/Serie: Clinical Gastroenterology
• Reihe/Serie: Clinical Gastroenterology
• Zusatzinfo: XIV, 512 p. 161 illus., 70 illus. in color.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Chirurgie ► Viszeralchirurgie
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Gastroenterologie
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Hepatologie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pädiatrie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Urologie
• Schlagworte: abdominal surgery • Cholangiocyte • Cystadenoma • Fibrocystic • gastroenterology • Hepatic Cyst • hepatology • Joubert Syndrome • kidney • Kidney Disease • Liver • liver disease • Nephrology • pathophysiology • Physiology
• ISBN-10: 1-60327-524-X / 160327524X
• ISBN-13: 978-1-60327-524-8 / 9781603275248