Additional Information
Book Details
Abstract
A volume in the popular Pattern Recognition Series, Practical Hepatic Pathology: A Diagnostic Approach features completely updated and reorganized content, resulting in a truly practical guide to understanding liver pathology. Dr. Romil Saxena presents interpretation of liver biopsies according to a pattern-based approach that begins with recognition of the predominant histological pattern of injury, followed by identification of secondary features and appropriate work-up that lead you away from pitfalls to the best diagnosis.
- Unique "visual index" at the beginning of the book references the exact chapter and specific page needed for in-depth diagnostic guidance.
- Superb, high-quality, full-color images illustrate pathognomonic features and common variations.
- Features comprehensive information on major adult and childhood liver diseases, hepatic neoplasms and pre-neoplastic nodules, including clinical features, laboratory tests, imaging findings and differential diagnosis.
- Coverage of the clinical aspects of liver transplantation allows you to understand the pathology and practice of this procedure.
- Virtual Microscope provides your own personal set of over 300 liver slides accessible anywhere, any time on your favorite digital device. Navigate around and zoom in and out to savor these exceptionally high quality whole slide images covering everything from the normal liver to rare challenging cases.
- New section on Evolving Concepts keeps you abreast of new paradigms in liver diseases such as reversal of fibrosis, heterogeneity of cirrhosis, and biphenotypic primary liver cell carcinoma.
- Reorganized Table of Contents is even more intuitive.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Practical Hepatic Pathology | i | ||
| Practical Hepatic Pathology: A Diagnostic Approach | iii | ||
| Copyright | iv | ||
| Dedication | v | ||
| Contributors | vii | ||
| Series Preface | xi | ||
| Preface | xiii | ||
| Acknowledgments | xv | ||
| Contents | xvii | ||
| Pattern-Based Approach to Diagnosis | xix | ||
| Virtual Slide Box | li | ||
| Practical Hepatic Pathology | lxv | ||
| I - Basic Concepts in Liver Pathology | 1 | ||
| 1 - Microscopic Anatomy, Basic Terms, and Elemental Lesions | 3 | ||
| Parenchymal Architecture and Tissue Organization | 3 | ||
| Assessing Parenchymal Architecture in a Biopsy | 6 | ||
| Absence of Portal Tracts | 6 | ||
| Fragmentation | 6 | ||
| Subcapsular Parenchyma | 8 | ||
| Portal Tracts | 8 | ||
| Bile Ducts | 8 | ||
| Hepatic Arteries | 9 | ||
| Portal Veins | 11 | ||
| Hepatic Veins | 11 | ||
| Lobular Parenchyma | 12 | ||
| Hepatocytes | 12 | ||
| Intralobular Biliary Channels | 15 | ||
| Sinusoids | 16 | ||
| Disse Space | 19 | ||
| Electron Microscopy | 20 | ||
| Hepatocytes | 20 | ||
| Sinusoidal Lining Cells | 20 | ||
| Disse Space | 20 | ||
| Utility of Electron Microscopy in Routine Diagnostic Practice | 22 | ||
| Basic Terms and Elemental Lesions | 22 | ||
| Structural | 22 | ||
| Inflammation, Cell Damage, and Necrosis | 22 | ||
| Intracellular Pathology | 23 | ||
| Biliary Lesions | 26 | ||
| Sinusoidal Lesions | 27 | ||
| Suggested Readings | 28 | ||
| References | 28 | ||
| II - Clinical, Laboratory, and Radiologic Features of Liver Disease | 31 | ||
| 2 - Clinical Features of Liver Disease | 33 | ||
| Definitions and Synonyms | 33 | ||
| Acute Liver Disease | 34 | ||
| Etiology | 34 | ||
| Clinical Manifestations | 34 | ||
| Treatment and Prognosis | 35 | ||
| Acute Liver Failure | 35 | ||
| Subacute Liver Failure | 35 | ||
| Chronic Liver Disease | 36 | ||
| Etiology | 36 | ||
| Assessing the Severity of Cirrhosis | 36 | ||
| Clinical Signs (Stigmata) of Chronic Liver Disease | 36 | ||
| Complications of Liver Cirrhosis | 38 | ||
| Variceal Bleeding | 38 | ||
| Ascites | 39 | ||
| Spontaneous Bacterial Peritonitis | 40 | ||
| Hepatorenal Syndrome | 40 | ||
| Hepatic Encephalopathy | 41 | ||
| Hepatopulmonary Syndrome | 41 | ||
| Portopulmonary Hypertension | 41 | ||
| 3 - Laboratory Tests in Liver Disease | 43 | ||
| Liver Tests | 44 | ||
| Transaminases | 44 | ||
| “Biliary” Enzymes | 44 | ||
| Measures of Coagulation | 45 | ||
| Other Tests | 45 | ||
| Approach to Evaluation of Abnormal Liver Tests | 45 | ||
| Laboratory Investigation of Acute Liver Injury | 46 | ||
| Laboratory Investigation of Chronic Liver Disease | 47 | ||
| Laboratory Investigation of Liver Disease in Pregnancy | 48 | ||
| Laboratory Investigation of Liver Abnormalities in Systemic Diseases and Disease of Other Organs | 49 | ||
| Connective Tissue Diseases | 50 | ||
| Endocrine Disorders | 51 | ||
| Infectious Diseases | 51 | ||
| Neoplastic Diseases | 51 | ||
| Cardiac Diseases | 51 | ||
| Gastrointestinal Diseases | 51 | ||
| 4 - Investigative Imaging of the Liver | 55 | ||
| Commonly Used Imaging Modalities | 55 | ||
| Imaging of Liver Tumors | 57 | ||
| Hemangioma | 57 | ||
| Focal Nodular Hyperplasia | 58 | ||
| Hepatocellular Adenoma | 58 | ||
| Hepatocellular Carcinoma | 59 | ||
| Metastases | 59 | ||
| Cholangiocarcinoma | 59 | ||
| Imaging of Diffuse Liver Disease | 59 | ||
| Hepatic Steatosis | 59 | ||
| Hepatic Fibrosis and Cirrhosis | 60 | ||
| Contrast-Enhanced Sonography | 62 | ||
| Transient Elastography | 62 | ||
| Magnetic Resonance Elastography | 63 | ||
| Summary | 63 | ||
| III - Liver Diseases of Childhood | 67 | ||
| 5 - Liver Diseases of Childhood | 69 | ||
| Neonatal Cholestasis | 69 | ||
| Incidence and Demographics | 70 | ||
| Role of Liver Biopsy in Neonatal Cholestasis | 70 | ||
| Biliary Atresia | 71 | ||
| Incidence and Demographics | 71 | ||
| Clinical Manifestations | 71 | ||
| Radiologic Features | 71 | ||
| Pathology | 72 | ||
| Macroscopic Pathology | 72 | ||
| Microscopic Pathology | 72 | ||
| Differential Diagnosis | 74 | ||
| Treatment and Prognosis | 74 | ||
| Neonatal (Giant Cell) Hepatitis | 76 | ||
| Clinical Manifestations | 76 | ||
| Pathology | 77 | ||
| Differential Diagnosis | 77 | ||
| Treatment and Prognosis | 77 | ||
| Alagille Syndrome | 77 | ||
| Incidence and Demographics | 78 | ||
| Molecular Genetics | 79 | ||
| Clinical Manifestations | 79 | ||
| Gross Pathology | 80 | ||
| Microscopic Pathology | 80 | ||
| Differential Diagnosis | 80 | ||
| Treatment and Prognosis | 81 | ||
| Primary Sclerosing Cholangitis | 81 | ||
| Incidence and Demographics | 81 | ||
| Clinical Manifestations | 81 | ||
| Radiologic Findings | 82 | ||
| Microscopic Pathology | 82 | ||
| Diagnosis | 82 | ||
| Treatment and Prognosis | 82 | ||
| Sclerosing Cholangitis Due to Langerhans Cell Histiocytosis | 83 | ||
| Microscopic Pathology | 84 | ||
| Molecular Pathology | 84 | ||
| Treatment and Prognosis | 85 | ||
| Neonatal Sclerosing Cholangitis | 85 | ||
| IV - Metabolic Diseases of the Liver | 89 | ||
| 6 - Medical Genetics and Biochemistry in Diagnosis and Management | 91 | ||
| Clinical Approach | 91 | ||
| Approach to Biochemical and Genetic Investigation | 93 | ||
| Collection, Storage, and Shipping of Specimens | 93 | ||
| Methodologies Involved in Biochemical and Genetic Testing | 94 | ||
| Tandem Mass Spectrometry | 96 | ||
| Methodologies Used for Specific Biochemical Compounds | 97 | ||
| Amino Acids | 97 | ||
| Organic Acids | 97 | ||
| Proteins | 97 | ||
| Enzymes | 97 | ||
| DNA | 97 | ||
| Very Long Chain Fatty Acids and Related Molecules | 97 | ||
| Treatment and Management | 98 | ||
| Newborn Screening–Related Disorders | 98 | ||
| Other Metabolic Liver Diseases | 98 | ||
| Mitochondrial Disorders | 98 | ||
| Genetic Counseling | 98 | ||
| Suggested Readings | 98 | ||
| References | 99 | ||
| 7 - Histologic Patterns of Metabolic Liver Diseases | 101 | ||
| Handling Liver Biopsy Specimens for Suspected Metabolic Disease | 102 | ||
| Analysis and Reporting of Liver Biopsy Specimens for Suspected Metabolic Disease | 102 | ||
| Histologic Patterns of Metabolic Liver Disease | 102 | ||
| Metabolic Diseases with Normal Liver Histology | 102 | ||
| Metabolic Diseases with an Inflammatory Pattern | 102 | ||
| Metabolic Diseases with Prominent Lobular Cholestasis | 103 | ||
| Bile Ductules Versus Ducts in Metabolic Disease | 104 | ||
| Metabolic Diseases with a Steatotic Pattern | 104 | ||
| Pathology | 106 | ||
| Diagnosis | 106 | ||
| Pathology | 107 | ||
| Diagnosis | 108 | ||
| Reye Syndrome | 108 | ||
| Urea Cycle Defects | 108 | ||
| Clinical Manifestations | 109 | ||
| Pathology | 109 | ||
| Diagnosis | 110 | ||
| Citrin Deficiency | 110 | ||
| Galactosemia | 110 | ||
| Hereditary Fructose Intolerance | 111 | ||
| Lysosomal Storage Disorders | 111 | ||
| Pathology | 112 | ||
| Diagnosis | 112 | ||
| Acid Lipase Deficiency | 112 | ||
| Niemann-Pick Disease, Type C | 112 | ||
| Cystinosis | 115 | ||
| Diagnosis | 116 | ||
| Bile Acid Synthetic Defects | 116 | ||
| Peroxisomal Diseases | 119 | ||
| Clinical Manifestations | 120 | ||
| V - Infectious Diseases of the Liver | 189 | ||
| 13 - Acute Viral Hepatitis | 191 | ||
| Histologic Patterns of Injury in Acute Viral Hepatitis | 192 | ||
| Acute “Lobular” Hepatitis (Prototypical Acute Hepatitis) | 192 | ||
| Gross Pathology | 192 | ||
| Microscopic Pathology | 193 | ||
| Clinicopathologic Course Related to Special Patterns of Hepatic Necrosis and Regeneration | 193 | ||
| Histologic Clues to the Causative Virus | 197 | ||
| Hepatitis A | 197 | ||
| Hepatitis E | 197 | ||
| Hepatitis B | 198 | ||
| Hepatitis C | 198 | ||
| Other Viruses Causing Acute Hepatitis | 198 | ||
| Hepatitis D (Delta) Virus | 198 | ||
| Clinical Manifestations and Natural History | 198 | ||
| Pathology | 198 | ||
| Herpesviruses | 198 | ||
| Epstein-Barr Virus | 199 | ||
| Liver Disease Caused by Epstein-Barr Virus. Primary EBV infection occurring in children is largely asymptomatic or minimally sym... | 199 | ||
| Pathology. The most remarkable histopathologic feature of EBV-related hepatitis is the presence of a dense lymphocytic inflammat... | 200 | ||
| Diagnosis. Diagnosis of infectious mononucleosis is established by the detection of heterophilic antibodies to EBV by the Monosp... | 200 | ||
| Cytomegalovirus | 200 | ||
| Liver Disease Caused by Cytomegalovirus. CMV is the most common cause of congenital infection and is reported in 0.2% to 2.2% of... | 200 | ||
| Pathology. Congenital CMV infection may lead to neonatal hepatitis, which is discussed in Chapter 5. Histologically, there is po... | 200 | ||
| Diagnosis. Diagnosis can be made by histology, viral cultures, or serologic tests that detect antibodies or viral proteins. Sero... | 201 | ||
| Human Herpesvirus 6 | 202 | ||
| Herpes Zoster | 202 | ||
| Herpes Simplex Virus Types 1 and 2 | 202 | ||
| Pathology. The histologic findings are distinctive, with randomly distributed, patchy areas of coagulative necrosis that demonst... | 202 | ||
| Adenovirus | 202 | ||
| Pathology | 202 | ||
| Diagnosis | 203 | ||
| Parvovirus | 203 | ||
| Icteric Hemorrhagic Fevers | 203 | ||
| Yellow Fever Virus | 204 | ||
| Liver Disease Caused by Yellow Fever Virus. After 4 to 5 days of incubation, the patient presents with fever, headache, diffuse ... | 204 | ||
| Pathology. The major histologic finding is hemorrhagic hepatocyte necrosis, which is predominantly midzonal (zone 2) but may be ... | 204 | ||
| Diagnosis. Besides epidemiologic and clinical symptoms compatible with yellow fever, serologic enzyme immunoassay must detect Ig... | 204 | ||
| Vaccination and Viscerotropic Disease. The presence of only one serotype of the yellow fever virus enabled the successful develo... | 204 | ||
| Dengue Virus | 205 | ||
| Liver Involvement in Severe Dengue Virus Infections. Severe forms of DENV infection demonstrate high level of viremia leading to... | 206 | ||
| Pathology. A wide spectrum of hepatic histologic changes has been noted in dengue. This comprises fatty change (microvesicular),... | 206 | ||
| Diagnosis | 206 | ||
| Ebola and Marburg Viruses | 206 | ||
| Arenaviruses | 207 | ||
| Hantavirus | 207 | ||
| Suggested Readings | 207 | ||
| References | 207 | ||
| 14 - Hepatitis B | 211 | ||
| Incidence and Demographics | 211 | ||
| Molecular Virology | 211 | ||
| Natural History and Clinical Manifestations | 212 | ||
| Treatment | 213 | ||
| Role of Liver Biopsy in Management of Hepatitis B | 213 | ||
| Microscopic Pathology of Chronic Hepatitis B | 213 | ||
| Portal Changes and Interface Hepatitis | 213 | ||
| Lobular Inflammation, Apoptosis, and Necrosis | 213 | ||
| Ground-Glass Cells and Sanded Nuclei | 214 | ||
| Large Cell and Small Cell Changes | 216 | ||
| Fibrosis and Architectural Distortion | 217 | ||
| Immunohistochemical Stains for Viral Antigens in Chronic Hepatitis B | 218 | ||
| Differential Diagnosis of Chronic Hepatitis B | 218 | ||
| Chronic Hepatitis C | 218 | ||
| Other Chronic Hepatitides | 219 | ||
| Other Chronic Liver Diseases | 219 | ||
| Ground-Glass Cells | 219 | ||
| Practical Approach in Evaluating Liver Biopsy Specimens from Patients with Chronic Hepatitis B | 219 | ||
| Suggested Readings | 220 | ||
| References | 220 | ||
| 15 - Hepatitis C | 223 | ||
| Incidence and Demographics | 223 | ||
| Molecular Virology | 223 | ||
| Natural History and Clinical Manifestations | 224 | ||
| Treatment | 224 | ||
| Role of Liver Biopsy in Management of Hepatitis C | 224 | ||
| Microscopic Pathology of Chronic Hepatitis C | 225 | ||
| Portal Changes and Interface Hepatitis | 225 | ||
| Lobular Inflammation, Apoptosis, and Necrosis | 226 | ||
| Steatosis and Other Cytoplasmic Changes of Hepatocytes | 226 | ||
| Large Cell Change and Small Cell Change | 227 | ||
| Fibrosis and Architectural Distortion | 228 | ||
| Differential Diagnosis of Chronic Hepatitis C | 230 | ||
| Chronic Hepatitides | 230 | ||
| Hereditary Metabolic Disorders | 230 | ||
| Chronic Biliary Diseases | 230 | ||
| Steatohepatitis | 230 | ||
| Malignant Lymphoma | 230 | ||
| Practical Approach in Evaluating Liver Biopsy Specimens from Patients with Chronic Hepatitis C | 230 | ||
| Suggested Readings | 231 | ||
| References | 231 | ||
| 16 - Chronic Hepatitis: Grading and Staging | 233 | ||
| Need for Grading and Staging | 233 | ||
| General Principles of Grading and Staging | 234 | ||
| Grading and Staging Systems | 234 | ||
| Histologic Activity Index | 235 | ||
| Grading Systems | 235 | ||
| Scheuer System | 235 | ||
| Batts and Ludwig System | 235 | ||
| VI - Granulomatous Diseases of the Liver | 287 | ||
| 19 - Hepatic Granulomas: Differential Diagnosis | 289 | ||
| Histologic Patterns of Hepatic Granulomas | 290 | ||
| Epithelioid Granulomas | 290 | ||
| Suppurative Granulomas (Granulomas with Central Microabscess) | 291 | ||
| Microgranulomas | 291 | ||
| Lipogranulomas | 291 | ||
| Foamy Macrophage Aggregates | 291 | ||
| Fibrin-Ring Granulomas | 292 | ||
| Specific Granulomatous Diseases | 292 | ||
| Tuberculosis | 292 | ||
| Pathology | 293 | ||
| Diagnosis | 293 | ||
| Other Mycobacteria | 293 | ||
| Brucellosis | 294 | ||
| VII - Autoimmune Hepatitis | 307 | ||
| 21 - Autoimmune Hepatitis and Overlap Syndromes | 309 | ||
| Definitions and Synonyms | 309 | ||
| Incidence and Demographics | 309 | ||
| Clinical Manifestations | 310 | ||
| Laboratory Findings | 310 | ||
| Microscopic Pathology | 310 | ||
| Portal Changes and Interface Hepatitis | 310 | ||
| Lobular Inflammation and Damage | 311 | ||
| Cholestasis | 312 | ||
| Fibrosis | 312 | ||
| Overlap Syndromes | 312 | ||
| Overlap with Primary Biliary Cholangitis | 312 | ||
| Overlap with Primary Sclerosing Cholangitis | 312 | ||
| Grading and Staging of Autoimmune Hepatitis | 313 | ||
| Differential Diagnosis | 313 | ||
| Acute or Chronic Viral Hepatitis | 314 | ||
| Celiac Disease | 314 | ||
| Drug-Induced Liver Injury | 314 | ||
| Hereditary Metabolic Diseases | 314 | ||
| Primary Biliary Cholangitis | 314 | ||
| Genetics | 314 | ||
| Treatment and Prognosis | 314 | ||
| Suggested Readings | 315 | ||
| References | 315 | ||
| VIII - Drug- and Toxin-Induced Liver Injury | 317 | ||
| 22 - Metabolism of Drugs and Xenobiotics | 319 | ||
| General Considerations in Drug Metabolism | 319 | ||
| Factors Affecting Bioavailability of Drugs | 320 | ||
| Enzyme Induction and Inhibition | 320 | ||
| Enzyme Polymorphisms | 320 | ||
| Disease States | 321 | ||
| Clinically Significant Drug-Metabolizing Enzymes and Transporters | 321 | ||
| Cytochrome P450 Enzymes | 321 | ||
| CYP1A2 | 321 | ||
| CYP2B6 | 321 | ||
| CYP2C | 322 | ||
| CYP2D6 | 322 | ||
| CYP3A | 322 | ||
| Conjugating Enzymes | 322 | ||
| Drug Transporters/Phase III Enzymes | 324 | ||
| Role of Drug Metabolism in Drug-Induced Liver Injury | 324 | ||
| Alcohol Use and Risk of Drug-Induced Liver Injury | 325 | ||
| Suggested Readings | 325 | ||
| References | 325 | ||
| 23 - Liver Injury Due to Drugs and Herbal Agents | 327 | ||
| Brief Historical Overview | 327 | ||
| Incidence and Demographics | 328 | ||
| Clinical Manifestations | 330 | ||
| Microscopic Pathology | 331 | ||
| Necroinflammatory Patterns (Figures 23.1 to 23.8) | 331 | ||
| Cholestatic Patterns (Figures 23.9 to 23.15) | 353 | ||
| Steatotic Patterns (Figures 23.16 to 23.19) | 357 | ||
| Vascular Injury Patterns (Figures 23.20 to 23.22) | 361 | ||
| Pigments and Other Cytoplasmic Changes | 363 | ||
| Neoplasms | 364 | ||
| Grading and Staging | 364 | ||
| Differential Diagnosis | 365 | ||
| Establishing Causality | 365 | ||
| Ancillary Diagnostic Studies | 366 | ||
| Genetics | 367 | ||
| Treatment and Prognosis | 367 | ||
| Figure Acknowledgments | 368 | ||
| Suggested Readings | 368 | ||
| References | 368 | ||
| 24 - Alcohol-Induced Liver Disease | 371 | ||
| Incidence and Demographics | 372 | ||
| Clinical Manifestations | 372 | ||
| Noninvasive Assessment of Alcoholic Liver Disease | 373 | ||
| Blood Tests | 373 | ||
| Imaging Studies | 373 | ||
| Gross Pathology | 373 | ||
| Microscopic Pathology | 373 | ||
| Alcoholic Fatty Liver | 375 | ||
| Alcoholic Steatohepatitis | 376 | ||
| Cirrhosis | 379 | ||
| Histologic Variants | 380 | ||
| Portal Tract Changes | 380 | ||
| Iron Overload | 381 | ||
| Other Changes in Hepatocytes | 381 | ||
| Grading and Staging | 382 | ||
| Role of Liver Biopsy | 382 | ||
| Focal Liver Lesions in Alcoholic Liver Disease | 382 | ||
| Hepatocellular Carcinoma | 382 | ||
| Other Focal Lesions | 383 | ||
| Differential Diagnosis | 383 | ||
| Classical Histologic Features of Alcoholic Liver Disease | 383 | ||
| Other Histologic Variants of Alcoholic Liver Disease | 384 | ||
| Interactions with Other Liver Diseases | 384 | ||
| Genetics | 384 | ||
| Treatment and Prognosis | 385 | ||
| Suggested Readings | 386 | ||
| References | 386 | ||
| IX - Disorders of the Bile Ducts, BileFormation, and Secretion | 391 | ||
| 25 - Fibrocystic Liver Diseases | 393 | ||
| Ductal Plate | 393 | ||
| Ductal Plate Malformation | 394 | ||
| von Meyenburg Complex (Microhamartoma, Biliary Hamartoma) | 395 | ||
| Polycystic Liver | 396 | ||
| Autosomal Dominant Polycystic Kidney Disease | 396 | ||
| Autosomal Dominant Polycystic Liver Disease | 396 | ||
| Clinical Manifestations | 396 | ||
| Macroscopic Pathology | 397 | ||
| Microscopic Pathology | 397 | ||
| Treatment | 397 | ||
| Solitary (Nonparasitic) Bile Duct Cysts | 397 | ||
| Autosomal Recessive Polycystic Kidney Disease/Congenital Hepatic Fibrosis | 397 | ||
| Clinical Manifestations | 398 | ||
| Macroscopic Pathology | 399 | ||
| Microscopic Pathology | 399 | ||
| Treatment | 399 | ||
| Caroli Disease | 399 | ||
| Clinical Manifestations | 400 | ||
| Macroscopic Pathology | 402 | ||
| Microscopic Pathology | 402 | ||
| Treatment | 402 | ||
| Choledochal Cysts | 402 | ||
| Clinical Manifestations | 403 | ||
| Macroscopic Pathology | 403 | ||
| Microscopic Pathology | 403 | ||
| Treatment | 405 | ||
| Suggested Readings | 406 | ||
| References | 406 | ||
| 26 - Primary Biliary Cholangitis | 409 | ||
| Incidence and Demographics | 409 | ||
| Clinical Manifestations | 410 | ||
| Laboratory Findings | 410 | ||
| Liver Enzymes and Immunoglobulins | 410 | ||
| Autoantibodies | 410 | ||
| Antimitochondrial Antibodies | 410 | ||
| Antinuclear Antibodies | 410 | ||
| Other Autoantibodies | 410 | ||
| Radiologic Features | 410 | ||
| Pathology | 410 | ||
| Gross Pathology | 410 | ||
| Microscopic Pathology | 410 | ||
| Nonsuppurative Cholangitis. Nonsuppurative cholangitis is the hallmark of PBC.17,18 However, the distribution is heterogeneous e... | 410 | ||
| Ductular Reaction. Ductular reaction often accompanies the bile duct injury and results from metaplasia of periportal hepatocyte... | 410 | ||
| Bile Duct Loss and Ductopenia. Bile duct loss and ductopenia occur with disease progression, primarily involving the small intra... | 410 | ||
| Portal Inflammation | 412 | ||
| Hepatic Parenchymal Changes | 412 | ||
| Encroachment of the Limiting Plate. The inflammatory cells often spill over from the portal tract into the adjacent parenchyma (... | 412 | ||
| Cholate Stasis. This finding becomes more prominent with disease progression but may not be seen in all cases on needle biopsies... | 412 | ||
| Copper Deposition. Copper is excreted in the bile and copper accumulation occurs in the liver in chronic cholestasis of any etio... | 414 | ||
| Keratin7 Expression. Periportal hepatocytes may strongly express K7 by immunohistochemistry, reflecting acquisition of a biliary... | 414 | ||
| Cholestasis. Although biochemical cholestasis is present early in the disease, cholestasis at the morphologic level occurs years... | 414 | ||
| Fibrosis. Progressive ductular reaction and cholate stasis is accompanied by fibrosis. In early stages, periportal fibrosis may ... | 414 | ||
| Diagnosis | 415 | ||
| Staging | 415 | ||
| Differential Diagnosis | 415 | ||
| Mechanical Large Bile Duct Obstruction | 415 | ||
| Primary Sclerosing Cholangitis | 415 | ||
| Adverse Drug Reaction | 416 | ||
| Autoimmune Hepatitis | 416 | ||
| Viral Hepatitis | 416 | ||
| Granulomatous Inflammation | 418 | ||
| Treatment and Prognosis | 418 | ||
| Variants and Special Diagnostic Considerations | 419 | ||
| Antimitochondrial Antibody–Negative Primary Biliary Cholangitis | 419 | ||
| Asymptomatic Patients with Positive Antimitochondrial Antibody | 419 | ||
| Primary Biliary Cholangitis–Autoimmune Hepatitis Overlap Syndrome | 419 | ||
| Recurrent Primary Biliary Cholangitis in Allograft Liver | 419 | ||
| Nodular Regenerative Hyperplasia | 420 | ||
| Suggested Readings | 420 | ||
| References | 420 | ||
| 27 - Primary Sclerosing Cholangitis | 423 | ||
| Incidence and Demographics | 424 | ||
| Clinical Manifestations | 424 | ||
| Laboratory Findings | 424 | ||
| Radiologic Features | 424 | ||
| Gross Pathology | 424 | ||
| Microscopic Pathology | 425 | ||
| Large (Hilar/Parahilar) Bile Ducts | 425 | ||
| Small (Septal/Interlobular) Bile Ducts | 427 | ||
| Small Peripheral Portal Tracts | 427 | ||
| Parenchymal Changes | 427 | ||
| Gallbladder | 427 | ||
| Grading of Primary Sclerosing Cholangitis | 427 | ||
| Differential Diagnosis | 427 | ||
| Primary Biliary Cholangitis | 427 | ||
| Autoimmune Hepatitis | 429 | ||
| Immunoglobulin G4–Related Sclerosing Cholangitis | 429 | ||
| Hepatolithiasis and Recurrent Pyogenic Cholangitis | 429 | ||
| Secondary Sclerosing Cholangitis | 429 | ||
| Other Chronic Liver Diseases | 429 | ||
| Dominant Stricture | 429 | ||
| Genetics | 429 | ||
| Treatment and Prognosis | 430 | ||
| Secondary (Acquired) Sclerosing Cholangitis | 430 | ||
| Suggested Readings | 430 | ||
| References | 430 | ||
| 28 - Loss of Intrahepatic Bile Ducts | 433 | ||
| Microscopic Pathology of Loss of Intrahepatic Bile Ducts | 434 | ||
| Pitfalls in Microscopic Diagnosis | 434 | ||
| Liver Diseases Leading to Loss of Intrahepatic Bile Ducts | 435 | ||
| Primary Biliary Cholangitis | 435 | ||
| Microscopic Pathology | 435 | ||
| Primary Sclerosing Cholangitis | 436 | ||
| Microscopic Pathology | 437 | ||
| Secondary Sclerosing Cholangitis | 437 | ||
| Sarcoidosis | 437 | ||
| Acute and Chronic Liver Allograft Rejection | 438 | ||
| Microscopic Pathology | 438 | ||
| Recurrent Primary Biliary Cholangitis and Primary Sclerosing Cholangitis in Liver Allografts | 439 | ||
| Graft-versus-Host Disease | 439 | ||
| Acute Graft-versus-Host Disease | 439 | ||
| Chronic Graft-versus-Host Disease | 439 | ||
| Microscopic Pathology | 440 | ||
| Ischemic Cholangiopathy | 440 | ||
| Microscopic Pathology | 441 | ||
| Drug-Induced Loss of Intrahepatic Bile Ducts | 442 | ||
| Microscopic Pathology | 442 | ||
| Idiopathic Adulthood Ductopenia | 443 | ||
| Suggested Readings | 443 | ||
| References | 443 | ||
| 29A - Intrahepatic Cholestasis | 445 | ||
| Transporter Proteins | 445 | ||
| Basolateral (Sinusoidal) Membrane Transporters | 446 | ||
| Apical (Canalicular) Membrane Transporters | 447 | ||
| Bile Salt Export Pump (ABCB11) | 447 | ||
| Multidrug Resistance 1 (ABCB1) | 447 | ||
| Multidrug Resistance 3 Phospholipid Transporter (ABCB4) | 447 | ||
| Multidrug Resistance 2 (ABCC2) | 449 | ||
| Hepatic Basolateral ABC-Transporter Proteins | 449 | ||
| Electroneutral Anion Exchanger | 449 | ||
| Other Hepatocyte Transporters | 449 | ||
| Bile Acids | 449 | ||
| Bile Acid Functions | 450 | ||
| Bile Acid Signaling | 450 | ||
| Enterohepatic Circulation of Bile | 450 | ||
| Cholangiocyte Modification of Bile | 451 | ||
| Ileal Transport of Bile Acids | 451 | ||
| 29B - Intrahepatic Cholestasis | 453 | ||
| Progressive Familial Intrahepatic Cholestasis | 454 | ||
| Etiopathogenesis | 454 | ||
| Incidence and Demographics | 455 | ||
| Clinical Manifestations (Table 29B.2) | 455 | ||
| Laboratory Findings | 455 | ||
| Microscopic Findings | 456 | ||
| PFIC-1 | 456 | ||
| PFIC-2 | 456 | ||
| PFIC-3 | 457 | ||
| Immunohistochemistry | 458 | ||
| Electron Microscopy | 459 | ||
| Treatment (see Table 29B.2) | 459 | ||
| Miscellaneous Causes of “Low-GGT” Intrahepatic Cholestasis | 459 | ||
| Miscellaneous Causes of “High-GGT” Intrahepatic Cholestasis | 460 | ||
| Differential Diagnosis | 460 | ||
| “Benign” Recurrent Intrahepatic Cholestasis | 460 | ||
| Etiopathogenesis | 460 | ||
| Clinical Manifestations | 460 | ||
| X - Vascular Disorders of the Liver | 465 | ||
| 30 - Vascular Disorders of the Liver | 467 | ||
| Differential Diagnosis of Sinusoidal Congestion | 467 | ||
| Budd-Chiari Syndrome | 468 | ||
| Etiopathogenesis | 468 | ||
| Incidence and Demographics | 468 | ||
| Clinical Manifestations | 469 | ||
| Laboratory Findings | 469 | ||
| Radiologic Features | 469 | ||
| Gross Pathology | 469 | ||
| Microscopic Pathology | 469 | ||
| Treatment and Prognosis | 469 | ||
| Congestive Hepatopathy | 470 | ||
| Etiopathogenesis | 470 | ||
| Incidence and Demographics | 470 | ||
| Clinical Manifestations | 470 | ||
| Laboratory Findings | 470 | ||
| Radiologic Features | 470 | ||
| Gross Pathology | 471 | ||
| Microscopic Pathology | 471 | ||
| Treatment and Prognosis | 471 | ||
| Sinusoidal Obstruction Syndrome/Veno-occlusive Disease | 472 | ||
| Etiopathogenesis | 472 | ||
| Incidence and Demographics | 472 | ||
| Clinical Manifestations | 472 | ||
| Laboratory Findings | 472 | ||
| Radiologic Features | 472 | ||
| Gross Pathology | 472 | ||
| Microscopic Pathology | 472 | ||
| Treatment and Prognosis | 473 | ||
| Sickle Cell Disease | 473 | ||
| Etiopathogenesis | 473 | ||
| Incidence and Demographics | 474 | ||
| Clinical Manifestations | 474 | ||
| Laboratory Findings | 474 | ||
| Radiologic Features | 474 | ||
| Gross Pathology | 474 | ||
| Microscopic Pathology | 474 | ||
| Treatment and Prognosis | 474 | ||
| Preeclampsia | 474 | ||
| XI - Tumors and Tumor-like Lesionsof the Liver | 485 | ||
| 31 - Premalignant and Early Malignant Hepatocellular Lesions in Chronic Hepatitis/Cirrhosis | 487 | ||
| Clinical Setting and Target Population: Surveillance | 488 | ||
| Nomenclature | 488 | ||
| Dysplastic Foci | 490 | ||
| Dysplastic Nodules | 490 | ||
| Small Hepatocellular Carcinoma | 491 | ||
| Dysplastic Nodules as Hepatocellular Carcinoma Precursors | 491 | ||
| Natural History of Premalignant Lesions | 493 | ||
| Dysplastic Nodules and Early Hepatocellular Carcinoma: Role of Imaging | 494 | ||
| Premalignant and Early Malignant Hepatocellular Nodules in Daily Clinical Practice | 494 | ||
| Basic Histopathologic Features (Elementary Lesions) | 494 | ||
| Parenchymal Changes | 494 | ||
| Nonparenchymal Changes | 495 | ||
| Key Diagnostic Points | 495 | ||
| Stromal Invasion | 495 | ||
| Biomarkers | 497 | ||
| Nodule in Nodule | 498 | ||
| Liver Biopsy | 499 | ||
| Diagnostic Criteria in Liver Biopsy | 499 | ||
| Nodule Management | 503 | ||
| Suggested Readings | 504 | ||
| References | 504 | ||
| 32 - Benign Hepatocellular Tumors | 507 | ||
| Definitions and Synonyms | 507 | ||
| Focal Nodular Hyperplasia | 507 | ||
| Hepatocellular Adenoma | 508 | ||
| Incidence and Demographics | 508 | ||
| Clinical Manifestations | 508 | ||
| Radiologic Features | 509 | ||
| Focal Nodular Hyperplasia | 509 | ||
| Ultrasonography and Contrast-Enhanced Ultrasound | 509 | ||
| Magnetic Resonance Imaging | 509 | ||
| Hepatocellular Adenoma | 510 | ||
| Ultrasonography and Contrast-Enhanced Ultrasound | 510 | ||
| Magnetic Resonance Imaging | 510 | ||
| Differential Diagnosis | 511 | ||
| Gross Pathology | 512 | ||
| Microscopic Pathology | 512 | ||
| Focal Nodular Hyperplasia | 512 | ||
| Hepatocellular Adenoma | 515 | ||
| Genotype-Phenotype Classification of Hepatocellular Adenoma | 515 | ||
| HNF1α-Inactivated Hepatocellular Adenoma | 515 | ||
| β-Catenin–Activated Hepatocellular Adenoma | 518 | ||
| Inflammatory Hepatocellular Adenoma | 518 | ||
| Hepatocellular Adenoma, Not Otherwise Specified | 520 | ||
| Immunohistochemistry | 520 | ||
| Histologic Variants | 520 | ||
| Differential Diagnosis | 522 | ||
| Genetics | 525 | ||
| HNF1α-Inactivated Hepatocellular Adenoma: HNF1A Gene | 526 | ||
| β-Catenin–Activated Hepatocellular Adenoma: CTNNB1 Gene | 526 | ||
| Inflammatory Hepatocellular Adenoma | 526 | ||
| Telomerase Reverse Transcriptase Promoter | 526 | ||
| Treatment | 526 | ||
| Focal Nodular Hyperplasia | 526 | ||
| Hepatocellular Adenoma | 526 | ||
| References | 526 | ||
| 33 - Hepatocellular Carcinoma | 529 | ||
| Epidemiology and Risk Factors | 530 | ||
| Hepatotropic Viruses | 530 | ||
| Other Etiologic Factors | 530 | ||
| Clinical Manifestations | 531 | ||
| Gross Pathology | 531 | ||
| Microscopic Pathology | 532 | ||
| Tumor Cells | 532 | ||
| Growth Patterns | 533 | ||
| Immunohistochemistry | 533 | ||
| Histologic Variants | 535 | ||
| Fibrolamellar Hepatocellular Carcinoma | 535 | ||
| Clear Cell Hepatocellular Carcinoma | 537 | ||
| Steatohepatitic Hepatocellular Carcinoma | 537 | ||
| Sarcomatoid Hepatocellular Carcinoma | 537 | ||
| Sclerosing Hepatocellular Carcinoma | 537 | ||
| Grading and Other Prognostic Factors | 538 | ||
| Differential Diagnosis | 538 | ||
| Molecular Genetics | 539 | ||
| Natural History and Treatment | 540 | ||
| Suggested Readings | 540 | ||
| References | 540 | ||
| 34 - Benign and Malignant Tumors of Bile Ducts | 545 | ||
| Benign Tumors or Tumor-like Lesions | 545 | ||
| Solitary Bile Duct Cyst | 545 | ||
| Clinical Manifestations | 545 | ||
| Pathology | 545 | ||
| XII - Liver Transplantation | 603 | ||
| 37 - Clinical Aspects of Liver Transplantation | 605 | ||
| History of Liver Transplantation | 606 | ||
| Current Trends | 607 | ||
| Indications in Adults | 607 | ||
| Hepatitis C | 607 | ||
| Hepatitis B and Hepatitis A | 609 | ||
| Nonalcoholic Fatty Liver Disease | 609 | ||
| Alcoholic Liver Disease | 609 | ||
| Autoimmune Hepatitis | 609 | ||
| Cholestatic Liver Disease | 609 | ||
| Primary Biliary Cholangitis | 609 | ||
| Primary Sclerosing Cholangitis | 610 | ||
| Hepatocellular Carcinoma | 610 | ||
| Acute Liver Failure | 610 | ||
| Indications in Children | 611 | ||
| Patient Evaluation | 611 | ||
| Elderly Patients | 612 | ||
| Obese Patients | 612 | ||
| Patients with Substance Abuse | 612 | ||
| Patients with Comorbidities | 613 | ||
| Retransplantation | 613 | ||
| Pediatric Patients | 613 | ||
| Donor and Allograft Evaluation | 614 | ||
| Extended Criteria Donors | 614 | ||
| Physiologic Extended Criteria Donors | 615 | ||
| Medical History Extended Criteria Donors | 616 | ||
| Partial Liver Allografts | 617 | ||
| Liver Allograft Allocation | 617 | ||
| Organ Matching | 618 | ||
| Donor and Recipient Operation | 618 | ||
| Organ Procurement from Deceased Donors | 618 | ||
| Liver Transplant Operation | 619 | ||
| Preparation of Allograft | 619 | ||
| Recipient Hepatectomy | 619 | ||
| Implantation of Allograft | 619 | ||
| Closure of Abdomen | 620 | ||
| Anesthesia | 620 | ||
| Posttransplant Course | 620 | ||
| Surgical Complications | 620 | ||
| Primary Nonfunction | 620 | ||
| Biliary Complications | 621 | ||
| Hepatic Outflow Obstruction | 621 | ||
| Rejection | 621 | ||
| Infections | 621 | ||
| Long-Term Renal Failure | 621 | ||
| Malignancy | 621 | ||
| Complications in Pediatric Recipients | 622 | ||
| Posttransplant Immunosuppression | 622 | ||
| Immunosuppression Agents | 622 | ||
| Cyclosporine | 622 | ||
| Tacrolimus | 623 | ||
| Sirolimus/Everolimus | 624 | ||
| Mycophenolate Mofetil | 624 | ||
| Azathioprine | 624 | ||
| Prednisone | 624 | ||
| Induction Therapy | 624 | ||
| Rabbit Antithymocyte Globulin | 624 | ||
| Alemtuzumab | 625 | ||
| Daclizumab | 625 | ||
| Posttransplant Prophylaxis and Treatment of Infections | 625 | ||
| References | 625 | ||
| 38 - Pathology of Liver Transplantation | 629 | ||
| Evaluation of Donor Biopsies | 630 | ||
| Preservation–Reperfusion Injury | 633 | ||
| Clinical Manifestations | 633 | ||
| Microscopic Pathology | 633 | ||
| Differential Diagnosis | 634 | ||
| Rejection | 634 | ||
| Terminology | 634 | ||
| Clinical Manifestations | 635 | ||
| Microscopic Pathology | 635 | ||
| Hyperacute Rejection. Liver biopsies are not performed in the majority of cases of hyperacute humoral rejection because of rapid... | 635 | ||
| Acute Antibody-Mediated Rejection. Histologic features associated with acute AMR consist of endothelial cell hypertrophy, promin... | 636 | ||
| Cellular Rejection. Cellular rejection occurring in the early posttransplant period (acute cellular rejection) demonstrates a cl... | 636 | ||
| Chronic Rejection. The ischemic/fibrotic process of chronic rejection affects the bile ducts and the arteries of the liver allog... | 639 | ||
| Chronic Antibody-Mediated Rejection. Although chronic AMR (cAMR) has not been fully characterized, it has been shown that LT rec... | 641 | ||
| Treatment | 642 | ||
| Central Perivenulitis | 642 | ||
| Recurrent Diseases | 643 | ||
| Recurrent Hepatitis C | 643 | ||
| Clinical Considerations | 643 | ||
| Microscopic Pathology | 645 | ||
| Differential Diagnosis | 646 | ||
| Acute Cellular Rejection. The most clinically significant differential diagnostic problem is the distinction of acute cellular r... | 646 | ||
| Other Conditions. Acute hepatitis C in the allograft has to be distinguished from drug-induced hepatitis. This distinction relie... | 646 | ||
| Recurrent Hepatitis B | 647 | ||
| Clinical Considerations | 647 | ||
| Microscopic Pathology | 647 | ||
| Differential Diagnosis | 648 | ||
| Recurrent Autoimmune Hepatitis | 648 | ||
| Clinical Considerations | 648 | ||
| Microscopic Pathology | 649 | ||
| Differential Diagnosis | 649 | ||
| Recurrent Primary Biliary Cholangitis | 649 | ||
| Clinical Considerations | 649 | ||
| Microscopic Pathology | 650 | ||
| Differential Diagnosis | 650 | ||
| Recurrent Primary Sclerosing Cholangitis | 650 | ||
| Clinical Considerations | 650 | ||
| Microscopic Pathology | 651 | ||
| Differential Diagnosis | 651 | ||
| Recurrent Nonalcoholic Steatohepatitis | 651 | ||
| Clinical Considerations | 651 | ||
| XIII - Evolving Concepts in Liver Pathology | 663 | ||
| 39 - Biphenotypic Primary Liver Carcinoma | 665 | ||
| Microscopic Pathology: A Group of Heterogeneous Tumors | 665 | ||
| Epidemiology and Prognosis | 666 | ||
| 40 - Regression of Liver Fibrosis: From Myth to Reality | 671 | ||
| Mechanisms of Fibrogenesis | 671 | ||
| Morphologic Patterns of Fibrosis | 672 | ||
| Regression of Fibrosis | 672 | ||
| Regression of Cirrhosis | 672 | ||
| Histologic Assessment of Regression of Fibrosis | 673 | ||
| Conventional Scoring Systems | 673 | ||
| Image Analysis Systems | 673 | ||
| Histologic Assessment of Regression of Cirrhosis | 674 | ||
| Hepatic Repair Complex | 674 | ||
| Suggested Readings | 676 | ||
| References | 676 | ||
| 41 - Cirrhosis: A Term in Need of a Makeover | 679 | ||
| What Is Wrong with the Current Concept of Cirrhosis? | 679 | ||
| Cirrhosis Is Not a Homogeneous Disease | 680 | ||
| Variations in Gross Morphology | 680 | ||
| Variations in Microscopic Pathology | 680 | ||
| Clinical Staging and Prognostication of Cirrhosis | 681 | ||
| Pathologic Staging of Cirrhosis | 683 | ||
| Regression of Cirrhosis | 683 | ||
| Histologic Assessment of Regression of Cirrhosis | 684 | ||
| Is Cirrhosis a Primarily Fibrotic Process? | 684 | ||
| Acknowledgments | 684 | ||
| Suggested Readings | 684 | ||
| Index | 687 | ||
| A | 687 | ||
| B | 690 | ||
| C | 692 | ||
| D | 695 | ||
| E | 697 | ||
| F | 697 | ||
| G | 699 | ||
| H | 700 | ||
| I | 704 | ||
| J | 707 | ||
| K | 707 | ||
| L | 707 | ||
| M | 710 | ||
| N | 712 | ||
| O | 713 | ||
| P | 714 | ||
| Q | 718 | ||
| R | 718 | ||
| S | 718 | ||
| T | 720 | ||
| U | 721 | ||
| V | 721 | ||
| W | 722 | ||
| X | 722 | ||
| Y | 722 | ||
| Z | 722 |