Hepatobiliary Diseases

The last few years have witnessed major developments in molecular biology which have had a significant impact on biomedical knowledge. As a result new concepts in cell biology have emerged, new etiologic agents have been discovered, and new drugs have become available. Furthermore, the world of mediators, cytokines, and humoral factors has enlarged considerably in a relatively short period and this has modified our views of diverse physio­ pathologic processes as well as opened up new therapeutic prospects. In addition, recent technologic advances have revolutionized our diagnostic methodology and have greatly enhanced the power of our therapeutic resources. All these factors have contributed to a substantial remodeling of both liver science and clinical hepatology, and these changes have generated the motivation for the production of the present book, which attempts to give an account of well-known clinical facts in the light of current thinking. It is the fruit of the coordinated work of experts from different countries in three continents. In a sense, it is a manifestation of the fact that inter­ national cooperation is becoming increasingly important not only in the expansion of science but also in its exposition. We hope that Hepatobiliary Diseases will be useful to both students and clinicians and that internists, gastroenterologists, and general practitioners will find in its contents a satifactory coverage of their field of interest.

1 Anatomy and Structure of the Liver and Biliary Tree.- 1 Introduction.- 2 Gross Anatomy.- 3 Light and Electron Microscopy.- 4 Functional Anatomy.- 5 Conclusion.- References.- 2 Biochemical Investigations in the Management of Liver Disease.- 1 Serum Bilirubin.- 2 Interpretation of Bilirubin Levels.- 3 Urinary Bilirubin.- 4 Urinary Urobilinogen.- 5 Aspartate and Alanine Aminotransferases.- 6 Other Tests Indicating the Presence of Hepatocellular Damage or Necrosis.- 7 Alkaline Phosphatases (Liver, Biliary, Tumour, Bone, Intestinal, Placental).- 8 y-Glutamyltransferase.- 9 Plasma Proteins.- 10 Other Tests Sometimes Used to Investigate Liver Function.- 11 Other Tests Which May Be Useful in Managing Patients with Liver Disease.- 12 Tests Used for Research.- 13 The Use of Liver Function Tests.- 14 Applications of Liver Function Tests.- 15 Screening and Profiling.- 16 “Batteries” of Liver Function Tests.- 17 Role of Liver Function Tests in Diagnosis.- 18 Diagnostic Classification of Liver Disease.- 19 Monitoring.- 20 Appendix: Sensitivity, Specificity and Predictive Accuracy.- References.- 3 Molecular Biology of the Liver.- 1 Gene Transcription.- 2 Basic Techniques for the Analysis of Gene Expression.- 3 Regulation of Liver-Specific Genes; Albumin and ?-Fetoprotein.- 4 The Expression of Growth-Associated Genes: Proto-oncogenes, Oncogenes, Growth Factors, and Suppressor Genes.- 5 Gene Expression During Liver Regeneration.- References.- 4 Immunology and the Liver.- 1 The Immune Response.- 2 Role of the Immune System in Liver Disease.- References.- 5 Diagnostic Imaging of the Hepatobiliary System.- 1 Introduction.- 2 Plain Radiographs.- 3 Oral Cholecystography.- 4 Intravenous Cholangiography.- 5 Hepatic Radionuclide Imaging.- 6 Hepatobiliary Ultrasound.- 7 Hepatobiliary Computed Tomography.- 8 Hepatic Magnetic Resonance Imaging.- 9 Hepatic Angiographic Studies.- 10 Biliary Invasive Studies.- References.- 6 The Role of Direct Morphologic Methods.- A. Liver Biopsy and Elementary Hepatic Lesions.- 1 Introduction.- 2 Hepatic Architecture and Its Alterations.- 3 Portal Tracts.- 4 The Hepatic Acinus.- References.- B. Laparoscopy.- 1 Indications.- 2 Contraindications.- 3 Complications.- 4 Technique.- 5 Diagnostic Value of Changes Detected by Laparoscopy.- References.- 7 Bilirubin Metabolism and Hyperbilirubinemia.- 1 Introduction.- 2 Chemistry of Bilirubin.- 3 Bilirubin Formation and Plasma Transport.- 4 Hepatocyte Uptake and Intracellular Storage.- 5 Conjugation.- 6 Secretion and Intestinal Fate.- 7 Hyperbilirubinemia.- 8 Dubin-Johnson Sydrome and Rotor’s Syndrome.- References.- 8 Bile Salts, Bile Flow, and Cholestasis.- 1 Bile Salts and the Enterohepatic Circulation: Physiology and Pathophysiology.- 2 Anatomic and Physiologic Bases of Bile Formation.- 3 Cholestasis.- References.- 9 Chronic Hepatitis and Cirrhosis.- A. Chronic Hepatitis.- 1 Pathology.- 2 Etiologic Forms of Chronic Hepatitis.- 3 Pathogenesis.- 4 Clinical Features.- 5 Biochemical Findings.- 6 Diagnosis.- 7 Natural History and Prognosis.- 8 Management.- References.- B. Cirrhosis.- 1 Definition.- 2 Epidemiology.- 3 Classification.- 4 Pathogenesis.- 5 Pathophysiology and Clinical Manifestations.- 6 Metabolic Disturbances.- 7 Systemic Derangements.- 8 Infections and Noninfectious Fever.- 9 Diagnosis.- 10 Prognosis.- 11 Treatment.- References.- 10 Portal-Systemic Encephalopathy.- 1 Introduction.- 2 Pathogenesis.- 3 Clinical Presentation.- 4 Clinical Investigation.- 5 Management.- References.- 11 Portal Hypertension.- 1 Etiology.- 2 Pathophysiology.- 3 Evaluation of the Portal Hypertensive Patient.- 4 Natural History of Esophageal Varices.- 5 Management of Variceal Hemorrhage.- 6 Prevention of Variceal Hemorrhage.- 7 Ectopic Varices.- 8 Portal Hypertensive Gastropathy.- 9 Extrahepatic Portal Hypertension.- 10 Diagnostic and Therapeutic Approach to the Portal Hypertensive Patient.- References.- 12 Ascites and Renal and Electrolyte Abnormalities in Cirrhosis.- 1 Detection of Ascites.- 2 Characteristics of Cirrhotic Ascites.- 3 Factors Involved in Ascites Formation in Cirrhosis.- 4 Mechanism of Renal Function Abnormalities.- 5 Pathogenesis of Ascites and Renal Dysfunction in Cirrhosis.- 6 Reabsorption of Ascites.- 7 Treatment of Ascites.- References.- 13 Viral Hepatitis A and E.- A. Type A Viral Hepatitis.- 1 Introduction.- 2 Etiologic Agent.- 3 Natural History.- 4 Clinical Findings.- 5 Pathology.- 6 Diagnosis.- 7 Treatment.- 8 Epidemiology.- 9 Prevention.- References.- B. Type E Viral Hepatitis.- 1 Introduction.- 2 The Agent of Enterically Transmitted non-A, non-B Hepatitis.- 3 Serologic Assays and Immune Response.- 4 Molecular Cloning of the Viral Genome.- 5 Unanswered Questions.- References.- 14 Viral Hepatitis B and D.- 1 Hepatitis B Virus and Viral Hepatitis B.- 2 Hepatitis D Virus and Viral Hepatitis D.- 3 Laboratory Tests.- 4 Treatment.- 5 Prophylaxis.- References.- 15 Viral Hepatitis C.- 1 Identification of Hepatitis C Virus.- 2 The Virus.- 3 Serologic Markers of Hepatitis C Virus.- 4 Epidemiologic Aspects.- 5 Hepatitis C Virus Infection in Chronic Liver Disease and Hepatocellular Carcinoma.- 6 Pathogenesis of Hepatitis C.- 7 Clinical and Histopathologic Aspects.- 8 Treatment of Hepatitis C Virus Infection.- References.- 16 Liver Involvement in Systemic Infection.- 1 Pyogenic Hepatic Abscess.- 2 Systemic Bacterial Infections.- 3 Fungal Infections.- 4 Viruses Other than Hepatitis Virus.- 5 Granulomas of the Liver.- References.- 17 Protozoal and Helminthic Diseases of the Liver and Biliary Tract.- 1 Amebiasis.- 2 Malaria.- 3 Visceral leishmaniasis (Kala-azar).- 4 Ascariasis.- 5 Fascioliasis.- 6 Clonorchiasis and Opisthorchiasis.- 7 Schistosomiasis.- 8 Hydatidosis (Echinococcosis).- 9 Visceral Larva Migrans (Systemic Toxocariasis).- 10 Capillariasis.- 11 Strongyloidiasis.- 12 Pentastomiasis (Porocephaliasis).- 13 Protozoal and Helminthic Diseases in the Liver and Biliary Tract in Acquired Immunodeficiency Syndrome.- References.- 18 The Liver in Pregnancy and in Systemic Diseases.- 1 Liver Diseases and Pregnancy.- 2 Liver Diseases Specific to Pregnancy.- 3 Liver Diseases Occurring During Pregnancy.- 4 Pregnancy in Patients with Liver Disease.- 5 The Liver in Systemic Diseases.- 6 Hematologic Diseases.- 7 Connective Tissue Diseases.- 8 Sarcoidosis.- 9 Amyloidosis.- 10 Inflammatory Bowel Disease.- 11 Thyroid Disease.- References.- 19 Drug-Induced Liver Diseases.- 1 Mechanisms Involved in Acute Hepatitis.- 2 Clinicopathologic Aspects of Acute Hepatitis.- 3 Bland Hepatocellular Cholestasis.- 4 Steatosis.- 5 Subacute Hepatitis, Chronic Hepatitis, and Cirrhosis.- 6 Phospholipidosis and Alcoholic-like Liver Lesions.- 7 Prolonged Cholestasis Due to Rarefaction of Small Bile Ducts.- 8 Sclerosing Cholangitis.- 9 Vascular Lesions.- 10 Hepatic Tumors.- 11 Diagnosis.- 12 Treatment and Prevention.- References.- 20 Alcoholic Liver Disease.- 1 Epidemiologic Aspects of Alcohol Use and Alcoholic Liver Disease.- 2 Patterns and Pathology of Alcoholic Liver Disease.- 3 Ethanol Metabolism.- 4 Pathogenesis of Alcoholic Liver Disease.- 5 Clinical Manifestations of Alcoholic Liver Disease.- 6 Diagnosis and Differential Diagnosis of Alcoholic Liver Diseases.- 7 Treatment and Prognosis of Alcoholic Liver Disease.- References.- 21 Autoimmune Chronic Active Hepatitis.- 1 Definition.- 2 Diagnosis and Classification.- 3 Immunogenetics.- 4 Etiology and Pathogenesis.- 5 Clinical Features and Pathology.- 6 Differential Diagnosis.- 7 Therapy.- References.- 22 Primary Biliary Cirrhosis and Sclerosing Cholangitis.- A. Primary Biliary Cirrhosis.- 1 Epidemiology.- 2 Pathology.- 3 Etiology and Pathogenesis.- 4 Clinical Features.- 5 Laboratory Tests.- 6 Associated Diseases.- 7 Diagnosis.- 8 Differential Diagnosis.- 9 Natural History and Prognosis.- 10 Treatment.- B. Primary Sclerosing Cholangitis.- 1 Etiology and Pathogenesis.- 2 Pathology.- 3 Clinical Features.- 4 Cholangiographie Features.- 5 Associated Diseases.- 6 Diagnosis.- 7 Natural History and Prognosis.- 8 Treatment.- References.- 23 Wilson’s Disease: Pathophysiology and Therapy.- 1 Introduction.- 2 Copper Metabolism.- 3 Wilson’s Disease.- 4 Summary.- References.- 24 Haemochromatosis.- 1 Normal Iron Metabolism.- 2 Definitions and Classification.- 3 Primary (Genetic) Haemochromatosis.- 4 Secondary (Acquired) Haemochromatosis.- References.- 25 ?1-Antitrypsin Deficiency.- 1 Structure and Function of ?1-Antitrypsin.- 2 Genetics and ?1-Antitrypsin Variants.- 3 ?1-Antitrypsin Deficiency and Liver Disease.- References.- 26 The Porphyrias.- 1 Introduction.- 2 Porphyrins and Porphyrinogens.- 3 The Heme Biosynthetic Pathway.- 4 Classification of the Porphyrias.- 5 Hepatic Porphyrias with Acute Neurovisceral Attacks.- 6 Hepatic Porphyrias without Acute Neurovisceral Attacks.- 7 Erythrohepatic Porphyria or Protoporphyria.- 8 Secondary Porphyrinuria.- References.- 27 Pediatric Metabolic Liver Diseases.- 1 Inborn Errors of Metabolism Associated with Disordered Liver Function or Hepatomegaly.- 2 Congenital or Neonatal Ascites.- 3 Glycogen Storage Diseases.- 4 Hepatic Glycogen Storage Diseases.- 5 Transferase Deficiency Galactosaemia: Galactose-1-phosphate Uridyl Transferase Deficiency.- 6 Epimerase Deficiency Galactosaemia.- 7 Fructosaemia.- 8 Tyrosinaemia.- 9 Urea Cycle Disorders.- 10 Rare Disorders with Hyperammonaemia and Disturbed Amino Acid Metabolism.- 11 Defects in Pyruvate Metabolism Causing Lactic Acidosis.- 12 Disorders with Hyperammonaemia and Massive Fat Accumulation in Hepatocytes.- 13 Defects in Fatty Acid ß-Oxidation.- 14 Abetalipoproteinaemia.- 15 Bile Salt Metabolism.- 16 Defects in Bile Acid Synthesis.- 17 Disorders of Lysosomal Enzymes.- 18 Lipid Storage Disorders.- 19 Mucopolysaccharidosis.- 20 Progressive Neuronal Degeneration of Childhood with Liver Disease.- 21 Indian Childhood Cirrhosis.- 22 Familial Erythrophagocytic Lymphohistiocytosis.- 23 Cystic Fibrosis.- References.- 28 Disordered Embryogenesis of the Hepatobiliary Tract.- 1 Introduction.- 2 Normal Development of the Bile Ducts and the Ductal Plate Malformation.- 3 Anatomic Anomalies of the Bile Ducts.- 4 Atresia of Extrahepatic Bile Ducts.- 5 Paucity of Intrahepatic (Interlobular) Bile Ducts.- 6 Cystic and Dysplastic Lesions.- References.- 29 Fatty Liver Disease and Nutritional Liver Damage.- 1 Introduction.- 2 Fat Metabolism and Fatty Liver.- 3 Reye’s Syndrome.- 4 Fatty Liver Hepatitis (Nonalcoholic Steatohepatitis).- 5 Nutritional Liver Injury.- References.- 30 Circulatory Disorders and Vascular Disease Affecting the Liver.- 1 Effects of Liver Disease on the Systemic Circulation.- 2 Effects of Liver Disease on the Pulmonary Circulation.- 3 Cardiomyopathy Associated with Cirrhosis.- 4 The Effect of Ascites on Cardiac Function.- 5 Endocarditis and Pericarditis.- 6 Atherosclerosis and Arterial Hypertension.- 7 Arteriohepatic Dysplasia Syndrome.- 8 Hereditary Haemorrhagic Telangiectasia.- 9 Arterioportal Fistulae.- 10 Heart Failure.- 11 Hepatic Abnormalities in Other Cardiac Diseases.- 12 Cardiac Surgery.- 13 Hepatic Infarction.- 14 Budd-Chiari Syndrome.- 15 Hepatic Veno-occlusive Disease.- 16 Peliosis Hepatis.- 17 Systemic Vasculitis.- 18 Nodular Regenerative Hyperplasia.- 19 Non-cirrhotic Portal Fibrosis; Idiopathic Portal Hypertension.- References.- 31 Acute Hepatic Failure.- 1 Nomenclature.- 2 Etiology.- 3 Clinical Features.- 4 Prognosis.- 5 Medical Treatment.- 6 Liver Transplantation for Acute Hepatic Failure.- References.- 32 Tumors of the Liver and Biliary Tract.- 1 Malignant Liver Tumors of Adulthood.- 2 Benign Liver Tumors of Adulthood.- 3 Liver Tumors of Childhood.- 4 Tumors of the Gallbladder.- References.- 33 Liver Transplantation.- 1 History of Liver Transplantation.- 2 Indications.- 3 Selection of Patients.- 4 Timing of Transplantation.- 5 Operative and Postoperative Course.- 6 Complications.- 7 Results.- 8 Conclusion.- References.- 34 Gallstones.- 1 Gallstone Formation.- 2 Natural History of Gallstones.- 3 Treatment of Gallstones.- References.