Zakim and Boyer’s Hepatology: A Textbook of Liver Disease

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Cleaned hardcover version with correct pagination and bookmarks, as well as correctly rotated pages. Zakim and Boyer's Hepatology......Page 1 Copyright Page......Page 3 Contributors......Page 4 Preface......Page 12 Gross Anatomy......Page 13 Development of the Liver......Page 15 Portal Tracts and the Biliary System......Page 16 The Biliary Tree......Page 18 Cholangiocytes......Page 19 Lobular and Acinar Functional Units......Page 20 Plasma Membrane......Page 21 Endoplasmic Reticulum, Ribosomes, and Golgi Apparatus......Page 22 Lysosomes......Page 23 The Hepatic Sinusoid......Page 24 Sinusoidal Endothelial Cells......Page 25 Stellate Cells......Page 27 Heterogeneity......Page 29 References......Page 30 References......Page 31 Pathways of Bile Acid Synthesis From Cholesterol......Page 35 Bile Acid Conjugation......Page 39 Regulation of Bile Acid Synthesis......Page 40 Defects Involving Reactions to the Steroid Nucleus......Page 41 Oxysterol 7α-Hydroxylase Deficiency......Page 42 3β-Hydroxy-̿5 C27-Steroid Oxidoreductase Deficiency......Page 43 ̿4-3-Oxosteroid 5β-Reductase 䄀䬀刀㄀䐀㄀ Deficiency......Page 44 Sterol 27-Hydroxylase Deficiency: Cerebrotendinous Xanthomatosis......Page 46 Peroxisomal Disorders......Page 47 Bile Acid-CoA Conjugation Defects......Page 48 Enterocyte Bile Acid Physiology......Page 49 Bile Acid Signaling as a Treatment for Nonalcoholic Steatohepatitis......Page 50 References......Page 51 References......Page 52 Historical Perspective and Technology Development......Page 58 Intestinal Barrier......Page 60 How Does the Host Maintain Homeostasis With Continued Exposure to an Enormous Microbial Load?......Page 62 Mucosal and Liver Tolerance......Page 63 Liver and Pattern Recognition Receptors......Page 64 Microbiota, Hepatic Inflammation, and Fibrosis......Page 65 The Intestinal Microbiota as a Mediator of Hepatic Inflammation......Page 66 The Intestinal Microbiota as a Mediator of Hepatic Fibrosis......Page 67 The Intestinal Microbiome and Nonalcoholic Fatty Liver Disease......Page 68 Human Studies......Page 69 Functional and Mechanistic Insights From the Intestinal Microbiome in NAFLD......Page 71 Intestinal Dysbiosis in Alcoholic Liver Disease......Page 74 Corollaries of Intestinal Dysbiosis in Alcoholic Liver Disease......Page 75 The Intestinal Microbiome and Autoimmune Liver Diseases......Page 76 Intestinal Dysbiosis in Experimental Fibrosis and Cirrhosis......Page 77 Intestinal Dysbiosis and Cirrhosis in Clinical Practice......Page 78 Clinical and Metabolic Corollaries of Intestinal Dysbiosis in Cirrhosis......Page 80 The Intestinal Microbiome and Hepatocellular Carcinoma......Page 81 The Intestinal Microbiome and Liver Transplant......Page 82 Interventions to Modulate the Intestinal Microbiome......Page 83 References......Page 86 References......Page 87 Monocytes and Macrophages......Page 93 Dendritic Cells......Page 95 Pattern Recognition Receptors......Page 96 Antigen Presentation and Adaptive Immunity......Page 98 Immune Response in Viral Hepatitis......Page 99 Hepatitis C Virus......Page 100 Hepatitis A Virus and Hepatitis E Virus......Page 101 Inflammation and Immunity in Liver Cancer......Page 102 References......Page 103 References......Page 104 Hepatic Inflammation as a Driver of Hepatic Fibrosis......Page 109 Hepatic Stellate Cells......Page 110 Natural Killer Cells and Natural Killer T Cells......Page 112 Toll-like Receptor Pathway......Page 113 MicroRNAs as Modulators of Liver Inflammation......Page 114 References......Page 115 References......Page 116 Introduction......Page 121 Occlusion of the Portal Veins With Donor Cells......Page 123 Initial Clinical Studies......Page 124 Hepatocyte Transplantation for Acute Liver Failure......Page 125 Hepatocyte Transplantation for Metabolic Liver Disease......Page 126 Patient Selection for Hepatocyte Transplantation......Page 127 Sources of Hepatocytes and Hepatocyte-Like Cells......Page 128 Induced Pluripotent Stem Cells......Page 129 Organoid Culture of Hepatocyte Cells......Page 130 Tracking Donor Cells and Assessment of Cell Function After Transplant......Page 131 Engraftment and Long-Term Repopulation of Recipient Liver With Donor Cells......Page 132 References......Page 134 References......Page 135 Historical Perspective: 100 Years of Liver Function Tests......Page 138 Bilirubin......Page 139 Bile Acids......Page 140 Aminotransferases......Page 141 Alkaline Phosphatase......Page 142 Prothrombin Time and International Normalized Ratio......Page 143 Establishing Abnormal Results......Page 144 Cholestatic and Hepatocellular Injury......Page 145 Acute-on-Chronic Liver Function Test Abnormalities......Page 148 Estimation of Fibrosis Based on Mathematical Scores......Page 149 Correlations Between Liver Function Test Results and Clinical Features......Page 150 Patients With Abnormal Liver Function Test Results: What to Ask and Assess......Page 152 Signs of Chronic Liver Disease......Page 153 Imaging......Page 154 References......Page 155 References......Page 156 The Value and Meaning of Fibrosis Staging and the Role of Liver Biopsies......Page 162 AST/Platelet Ratio and Fibrosis-4 Indexes......Page 163 FibroMeter......Page 164 Ultrasound......Page 165 Vibration-Controlled Elastography......Page 166 Hepatitis C......Page 167 Nonalcoholic Fatty Liver Disease......Page 169 Cholestatic Diseases......Page 170 References......Page 171 References......Page 172 Wilson Disease......Page 175 α1-Antitrypsin Deficiency......Page 176 Familial Intrahepatic Cholestasis......Page 177 Intrahepatic Cholestasis of Pregnancy as Example......Page 179 Drug-Induced Liver Injury......Page 180 Chronic Viral Hepatitis......Page 181 Next-Generation Sequencing......Page 182 References......Page 183 References......Page 184 Chronic Hepatitis and Cirrhosis......Page 186 Computed Tomography......Page 190 Imaging......Page 192 Liver Cell Adenoma......Page 193 Imaging......Page 195 Imaging......Page 197 Imaging......Page 200 Biliary IPBN......Page 201 Imaging.......Page 202 Imaging......Page 204 References......Page 205 References......Page 207 Imaging Modalities......Page 209 Hemangioma......Page 210 Focal Nodular Hyperplasia......Page 211 Hepatic Adenoma......Page 213 Bile Duct Hamartomas......Page 215 Biliary Cystadenoma......Page 218 Hepatocellular Carcinoma......Page 219 Cholangiocarcinoma......Page 223 Metastases......Page 225 References......Page 228 References......Page 229 Clinical-Pathologic Correlations......Page 231 Tissue Preparation and Stains......Page 232 Approach to Microscopy......Page 233 Acute Hepatitis......Page 234 Fatty Liver Diseases......Page 238 Metabolic Liver Diseases......Page 240 Granulomatous Inflammation in Liver Disease......Page 241 Hepatic Sinusoids......Page 243 Benign Hepatic Lesions/Tumors......Page 244 Malignant Tumors......Page 245 Liver Biopsies in Systemic Disease......Page 246 References......Page 247 References......Page 248 Sepsis/Septic Shock......Page 250 Upper GI Bleeding......Page 252 Acute Acalculous Cholecystitis......Page 253 Prophylaxis for Venous Thromboembolic Disease VTE......Page 254 Procedure Risk of Bleeding in Liver Disease......Page 255 Prognostication......Page 256 References......Page 257 References......Page 258 Ammonia......Page 261 Manganese Deposition......Page 262 Spectrum of Neurocognitive Impairment in Cirrhosis......Page 263 Diagnosis of Hepatic Encephalopathy......Page 264 Abdominal Imaging......Page 265 Paper and Pencil Tests......Page 266 Neurophysiologic Tests......Page 267 Goals for the Management of Hepatic Encephalopathy......Page 268 Metronidazole, Vancomycin, and Paromomycin......Page 270 Nonabsorbable Disaccharides......Page 271 Management of Covert Hepatic Encephalopathy......Page 272 Probiotics......Page 273 Dopaminergic Agents......Page 274 Hepatic Encephalopathy Resistant to Therapy or Persistent Hepatic Encephalopathy......Page 275 Liver Transplantation......Page 276 References......Page 277 References......Page 278 Plasma Volume Expansion......Page 284 Diagnosis......Page 285 Differential Diagnosis......Page 286 Diagnosis......Page 288 Treatment......Page 289 Prophylaxis......Page 290 Sodium Restriction......Page 291 Large-Volume Paracentesis......Page 292 Transjugular Intrahepatic Portosystemic Shunt......Page 293 Treatment of Hyponatremia......Page 294 Prognosis and Natural History......Page 295 References......Page 296 References......Page 297 Physiologic Principles of the Portal Circulation......Page 301 Physiologic Principles of Portal Hypertension......Page 302 Increased Intrahepatic Resistance......Page 303 Increased Splanchnic Blood Flow and the Hyperdynamic Circulatory State......Page 304 Portosystemic Collateral Circulation in Portal Hypertension......Page 305 Portosystemic Collaterals......Page 306 Upper Gastrointestinal Endoscopy......Page 307 Magnetic Resonance Imaging......Page 309 Ultrasound Real-Time Shear Wave Elastography......Page 310 Direct Transhepatic Portal Venous Pressure Measurement......Page 311 Splenomegaly......Page 312 Idiopathic Portal Hypertension......Page 313 Alcoholic Liver Disease......Page 314 Partial Nodular Transformation of the Liver......Page 315 Risk Factors and Natural History of Portal Hypertension?Related Bleeding......Page 316 Portal Hypertensive Gastropathy and Gastric Vascular Ectasia......Page 317 Diagnosis of Portal Hypertension?Related Bleeding......Page 318 β-Adrenergic Blocking Drugs......Page 319 Sclerotherapy......Page 320 Detachable Snares and Clips......Page 321 Esophageal Stents......Page 322 Preprimary Prophylaxis of Variceal Bleeding......Page 323 General Measures......Page 325 Specific Measures......Page 326 Gastric Varices......Page 327 Portal Hypertensive Gastropathy and Gastric Vascular Ectasia......Page 328 References......Page 329 References......Page 330 The Concept of Acute Kidney Injury......Page 333 The RIFLE Diagnostic Criteria for Acute Kidney Injury......Page 334 The Diagnostic Criteria of the ADQI and the International Ascites Club IAC for Acute Kidney Injury in Cirrhosis......Page 335 The RIFLE Diagnostic Criteria......Page 336 The ADQI-IAC Diagnostic Criteria for Acute Kidney Injury......Page 337 Revised Consensus Recommendations of the IAC on the Diagnosis of Acute Kidney Injury in Cirrhosis......Page 338 The Diagnostic Criteria for Hepatorenal Syndrome......Page 339 Splanchnic and Systemic Arterial Vasodilatation of Advanced Cirrhosis and Ascites......Page 340 The Consequences of Splanchnic and Systemic Arterial Vasodilatation......Page 341 The Role of Inflammation......Page 342 Approach to a Patient With Cirrhosis Who Presents With Renal Dysfunction......Page 343 Intrinsic Renal Diseases......Page 344 General Measures......Page 345 Terlipressin......Page 346 Norepinephrine......Page 347 Midodrine......Page 348 The Use of Albumin in Patients With Bacterial Infection......Page 349 Judicious Use of Diuretics......Page 350 References......Page 351 References......Page 352 Echocardiography......Page 357 Clinical Features......Page 358 Management of Cirrhotic Cardiomyopathy......Page 359 Pathogenesis......Page 360 Diagnosis......Page 362 Therapy......Page 364 Epidemiology......Page 365 Treatment......Page 366 Liver Transplant......Page 367 References......Page 368 References......Page 369 The Hemostatic System: Normal Physiology and Pathophysiology in Liver Disease......Page 374 Therapy......Page 376 Therapy......Page 378 Erythrocytes......Page 379 Conclusion......Page 380 References......Page 381 References......Page 382 Causes and Epidemiology......Page 385 Hepatitis A......Page 387 Systemic Viral Infections......Page 388 Acetaminophen......Page 389 Biologic Toxins......Page 391 Early Presentation of the Acute Injury......Page 392 Effects of Acute Liver Failure on Extrahepatic Systems......Page 393 Pulmonary Consequences......Page 394 Breakdown of Host Immune Defenses......Page 395 Neurologic Consequences......Page 396 Intracranial Hypertension and Cerebral Edema......Page 397 N-Acetylcysteine for Acetaminophen Overdose......Page 398 Management of Fluids, Electrolytes, and Acid-Base Abnormalities......Page 400 Pulmonary Complications and Ventilatory Support......Page 401 Management of Acute Kidney Injury......Page 402 Hepatic Encephalopathy, Cerebral Edema, and Intracranial Hypertension......Page 403 Orthotopic Liver Transplantation......Page 405 Assessment of Prognosis: When to Initiate Orthotopic Liver Transplantation Evaluation......Page 406 References......Page 407 References......Page 408 Definition......Page 412 Precipitating Events......Page 413 Pathophysiology......Page 414 Extrahepatic Organ Failure......Page 415 Coagulation Dysfunction......Page 417 General Measures......Page 418 Liver Transplantation......Page 419 References......Page 420 References......Page 421 Introduction......Page 424 Ethanol Metabolism......Page 425 Alcoholic Fatty Liver......Page 427 Infiltration of Neutrophils......Page 428 Alcoholic Hepatitis......Page 429 Alcoholic Fibrosis and Cirrhosis......Page 430 “Second-Hit? Model......Page 431 High-Fat Diet HFD and Ethanol Feeding......Page 432 Therapeutic Targets......Page 433 References......Page 434 References......Page 435 Pattern, Dosage, and Types of Alcohol Consumption and Risk of Alcoholic Liver Disease......Page 438 Genes Influencing Alcohol Metabolism......Page 439 Alcoholic Fatty Liver......Page 440 Hepatitis C......Page 441 Obstructive Sleep Apnea......Page 442 References......Page 443 References......Page 444 Screening for Alcohol Consumption......Page 447 Diagnosis of Alcoholic Hepatitis......Page 448 Modified Discriminant Function Score......Page 449 Lille Score......Page 450 Efficacy of Corticosteroids in Alcoholic Hepatitis Treatment......Page 451 Mechanism of Action......Page 452 Infections in Patients Receiving Corticosteroid Therapy......Page 453 Current Status of Pentoxifylline in the Treatment of Alcoholic Hepatitis......Page 454 Management of Malnutrition......Page 455 Alcohol Abstinence......Page 456 Gut-Liver Axis......Page 457 Controversy Surrounding Liver Transplant in Alcoholic Hepatitis......Page 458 Selection Criteria and Impact on the Donor Pool......Page 459 Antioxidants......Page 460 Evaluation for Comorbidities......Page 461 Graft and Patient Outcomes......Page 462 References......Page 464 References......Page 465 Abbreviations......Page 472 Introduction......Page 473 Making Foie Gras......Page 474 Nonalcoholic Fatty Liver Disease: An Adiposopathy......Page 477 Nonalcoholic Fatty Liver Disease and Insulin Resistance: The Chicken and Egg Paradox......Page 478 Oxidative Stress: Overburning Fat......Page 481 Lipotoxicity: The Ugly and the Beast......Page 483 Endoplasmic Reticulum Stress: A Tree Born Crooked Cannot Straighten Its Trunk......Page 484 Sterile Inflammation: When the Aggressor Is Fat......Page 486 Dysbiota: The Unwanted Guests......Page 488 Fibrogenesis: To Heal or to Scar......Page 490 References......Page 493 References......Page 494 Introduction......Page 508 Prevalence......Page 509 Causes of and Conditions Associated With Nonalcoholic Fatty Liver Disease......Page 510 Progression to Advanced Liver Fibrosis and Cirrhosis in Nonalcoholic Fatty Liver Disease......Page 511 Modifiers of Progression of Nonalcoholic Fatty Liver Disease......Page 512 Genetic Modifiers of Nonalcoholic Fatty Liver Disease......Page 513 Signs on Physical Examination......Page 515 Grading and Staging of the Severity of Nonalcoholic Fatty Liver Disease in Clinical Practice......Page 516 Diagnostic Approach to Nonalcoholic Fatty Liver Disease......Page 518 Risk Stratification and Staging of Nonalcoholic Fatty Liver Disease......Page 519 References......Page 522 References......Page 523 Treatment......Page 526 Exercise......Page 527 Insulin-Sensitizing Medications......Page 528 Conclusion......Page 529 References......Page 531 References......Page 532 Model Systems......Page 534 Envelope Glycoproteins......Page 535 The Virus and Its Life Cycle......Page 537 Overview......Page 541 Cellular Immunity......Page 542 Immunoregulation......Page 544 Cytotoxic T Cells......Page 545 T Cell?Mediated Injury......Page 546 Chemokines in Recruitment of Immune Cells Into the Liver......Page 547 Conclusion......Page 548 References......Page 549 References......Page 550 Discovery of Hepatitis C Virus......Page 558 Receipt of Infected Blood or Blood Products......Page 559 Sexual Transmission......Page 560 Natural History of Acute Hepatitis C Infection......Page 561 United States......Page 562 Natural History of Chronic Hepatitis C......Page 563 Prevalence of Hepatitis C Virus......Page 566 Hepatitis C Virus Genotypes......Page 569 Confirmatory Testing......Page 571 Screening to Prevent Hepatitis C Virus?Related Transmission and Disease......Page 572 Primary Prevention......Page 573 Conclusion......Page 574 References......Page 575 References......Page 576 The Evolution of Hepatitis C Virus Therapies......Page 584 Ribavirin......Page 585 Goals of Hepatitis C Virus Treatment......Page 588 Candidacy for Antiviral Therapy and Pretreatment Assessments......Page 589 Hepatitis C Virus Treatment Regimens......Page 590 Ledipasvir and Sofosbuvir......Page 591 Paritaprevir/Ritonavir, Ombitasvir, and Dasabuvir......Page 592 Simeprevir and Sofosbuvir......Page 593 Genotype-3 Regimens......Page 594 Sofosbuvir and Ribavirin......Page 595 Monitoring During and After Hepatitis C Virus Therapy......Page 596 Direct-Acting Antiviral Resistance......Page 597 HIV-HCV Coinfection......Page 599 Acute Hepatitis C Virus......Page 600 References......Page 601 References......Page 602 Hepatitis B Virus: Host and Model Systems......Page 605 Hepatitis B Virus Structure, Genome, and Proteins......Page 606 The Hepatitis B Virus Life Cycle......Page 607 Capsid Formation, Maturation, and Secretion......Page 608 The Immunologic Profile of Hepatitis B Virus Control......Page 609 The Impact of Age in the Pathogenesis of Hepatitis B Virus?Mediated Hepatitis......Page 611 Liver Damage Pathogenesis During Hepatitis B Virus Infection......Page 612 References......Page 614 References......Page 615 Changing Epidemiology......Page 620 Percutaneous......Page 621 Hepatitis B Surface Antigen and Hepatitis B Surface Antibody......Page 622 Hepatitis B Core Antigen and Hepatitis B Core Antibody......Page 623 Hepatitis B e Antigen and Hepatitis B e Antibody......Page 624 Laboratory Findings......Page 625 Clinical Manifestations......Page 626 Immune-Tolerant Phase......Page 627 Reactivation Phase HBeAg-Negative Chronic Hepatitis......Page 628 Hepatocellular Carcinoma......Page 629 References......Page 630 References......Page 631 Phases of Chronic Hepatitis B Virus Infection......Page 635 Treatment Indication......Page 636 Treatment End Points......Page 637 Resistance......Page 638 Safety......Page 640 Lamivudine......Page 641 Is a Finite Duration of Nucleoside/Nucleotide Analog Therapy Possible?......Page 642 Prevention of Antiviral Drug Resistance......Page 643 Hepatitis B e Antigen?Positive Patients......Page 644 Hepatitis B e Antigen?Negative Patients......Page 645 New Treatments......Page 646 Pregnancy......Page 647 Immune Suppression......Page 648 Vaccination......Page 649 References......Page 650 References......Page 651 Virology......Page 656 Epidemiology of Hepatitis Delta Virus Infection......Page 659 Diagnosis and Diagnostic Tests......Page 661 Monitoring and Surveillance......Page 662 Nucleoside/Nucleotide Analogs......Page 664 New Drug Therapies......Page 665 References......Page 666 References......Page 667 Molecular Virology......Page 671 Epidemiology......Page 672 Clinical Course......Page 675 Diagnosis......Page 676 Treatment of Acute Infection......Page 677 Vaccination......Page 678 References......Page 680 References......Page 681 Genome Organization and Proteins......Page 685 Genetic Heterogeneity......Page 686 Sporadic Zoonotic Hepatitis E......Page 687 Seroepidemiology......Page 688 Incidence......Page 689 Chronic Hepatitis E Virus Infection......Page 691 Extrahepatic Complications......Page 692 Laboratory Testing......Page 693 Chronic Hepatitis E Virus Infections in Solid Organ Transplant Patients......Page 694 Chronic Hepatitis E Virus Infection of Patients With Hematologic Disease......Page 695 Conclusion......Page 696 References......Page 697 References......Page 698 Epidemiology of Liver Disease in Those With HIV Infection......Page 702 Mechanisms of Liver Disease Unique to HIV......Page 703 Liver Biopsy and Noninvasive Markers of Liver Disease Severity......Page 704 Fibrosis 4 Score......Page 705 Panels and Radiologic Modalities......Page 706 Noninvasive Markers in HIV-Infected Patients and Long-Term Outcomes......Page 707 Hepatitis B......Page 708 Hepatitis D......Page 711 Epstein Barr Virus EBV......Page 712 Parasitic Infections......Page 713 Granulomatous Processes......Page 714 Nonalcoholic Fatty Liver Disease......Page 715 Hepatotoxic Drugs and Drug-Drug Interactions......Page 716 Hepatic Malignancies Associated With HIV......Page 719 AIDS Cholangiopathy......Page 720 References......Page 721 References......Page 722 Epstein-Barr Virus......Page 729 Cytomegalovirus......Page 730 Herpes Simplex Virus......Page 731 Human Herpesviruses......Page 733 Adenoviruses......Page 734 Influenza......Page 735 Rubella......Page 736 Dengue Fever......Page 737 Lassa Fever......Page 738 Ebola Virus Disease......Page 739 References......Page 740 References......Page 741 Introduction......Page 744 Schistosomiasis......Page 745 Diagnosis......Page 746 Praziquantel......Page 747 Clinical Manifestations......Page 748 Introduction......Page 749 Diagnosis......Page 750 Clinical Manifestations......Page 751 Clonorchiasis and Opisthorchiasis......Page 752 Ascaris lumbricoides......Page 753 References......Page 754 References......Page 755 Abbreviations......Page 759 Epidemiology......Page 760 Etiology, Pathogenesis, and Pathophysiology......Page 761 Clinical Manifestations, Diagnosis, and Management......Page 762 Disseminated Bacterial Infections With Involvement of the Liver......Page 764 Risk Factors for Bacterial Infections......Page 765 Immune Tolerance in Liver Disease......Page 766 Biliary Strictures......Page 767 Multidrug Resistant Bacterial Infections in LT Population......Page 768 Cryptococcus Species......Page 769 Pathogenesis of Liver Disease: the Bloodborne Route......Page 770 Treatment of Fungal Liver Disease......Page 771 References......Page 772 References......Page 773 Genetic Factors in Disease Pathogenesis......Page 777 Clinical Presentation......Page 779 Autoantibodies......Page 780 Smooth Muscle Autoantibodies......Page 781 Liver Kidney Microsomal Autoantibodies......Page 783 Diagnosis......Page 784 Remission Induction......Page 786 Maintenance Therapy......Page 787 Quality of Life......Page 788 Autoimmune Hepatitis and Pregnancy......Page 789 Autoimmune Hepatitis and Cholestatic Liver Diseases Overlap Syndromes......Page 790 Cancer Risk and Surveillance......Page 791 References......Page 792 References......Page 793 Incidence and Prevalence......Page 796 Predisposing Factors......Page 797 Etiopathogenesis......Page 798 Genetics......Page 799 Fatigue......Page 800 Pruritus......Page 801 Diagnosis......Page 802 Imaging Studies......Page 803 Natural History of Untreated Patients......Page 804 Ursodeoxycholic Acid......Page 805 Obeticholic Acid......Page 807 Fatigue......Page 808 Recurrent Primary Biliary Cholangitis......Page 809 Antimitochondrial Antibody?Negative Primary Biliary Cholangitis......Page 810 References......Page 811 References......Page 812 Variants of Sclerosing Cholangitis......Page 815 PSC?Autoimmune Hepatitis Overlap......Page 816 Secondary Sclerosing Cholangitis......Page 817 Genetic and Environmental Risks......Page 818 Immune Responses in Primary Sclerosing Cholangitis......Page 821 Lymphocyte Trafficking......Page 822 Diagnostic Criteria......Page 823 Laboratory Tests......Page 824 Imaging......Page 825 Inflammatory Bowel Disease in PSC......Page 826 Natural History......Page 827 Risk Prediction in PSC......Page 828 Pretransplant Management......Page 829 Pharmacotherapy......Page 831 Cancer Screening for Cholangiocarcinoma, Gallbladder Cancer, and Colorectal Cancer......Page 833 Transplant for Primary Sclerosing Cholangitis......Page 834 Posttransplant Management of PSC......Page 835 References......Page 836 References......Page 837 Diagnosis of BCS......Page 844 Etiology......Page 843 Diagnosis of Underlying Cause of Thrombosis......Page 845 Portosystemic Shunting......Page 846 Risk Factors and Epidemiology......Page 847 Pathogenesis......Page 848 Diagnosis......Page 849 Treatment......Page 850 References......Page 851 References......Page 852 Inherited Thrombophilia......Page 856 Local Factors......Page 857 Acute Portal Vein Thrombosis......Page 858 Acute Portal Vein Thrombosis......Page 859 Chronic Portal Vein Thrombosis......Page 860 Pregnancy......Page 861 Transjugular Intrahepatic Portosystemic Shunt......Page 862 Surgery......Page 863 References......Page 864 References......Page 865 Epidemiology......Page 868 Risk Factors......Page 869 Hepatitis B......Page 870 Diabetes......Page 871 Aflatoxin......Page 872 Phosphoinositide 3-Kinase?AKT?Mammalian Target of Rapamycin Pathway......Page 873 Epidermal Growth Factor Receptor Pathway......Page 874 Viral Hepatitis......Page 875 Staging......Page 878 Pathology......Page 879 Fibrolamellar Hepatocellular Carcinoma......Page 880 Radiology......Page 881 Hepatic Resection......Page 882 Liver Transplantation......Page 885 Liver-Directed Therapy......Page 886 Ablative Therapy......Page 887 Transcatheter Arterial Chemoembolization......Page 888 Selective Internal Radiation Therapy......Page 889 Systemic Therapy......Page 890 Tyrosine Kinase Inhibitors......Page 891 References......Page 892 References......Page 893 Epidemiology......Page 902 Risk Factors......Page 903 Molecular Pathogenesis......Page 904 Perihilar and Distal CCA......Page 907 Staging......Page 909 Therapy......Page 911 Biliary Stents......Page 912 Systemic Therapy......Page 913 Locoregional Therapies......Page 914 Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma......Page 915 References......Page 916 References......Page 917 Pathogenesis......Page 921 Treatment and Prognosis......Page 922 Pathology......Page 924 Clinical Features......Page 925 Angiosarcoma......Page 926 Treatment and Prognosis......Page 927 Pathogenesis and Pathology......Page 928 Hepatic Metastasis From Colorectal Cancer......Page 929 Hepatic Metastasis From Neuroendocrine Tumors......Page 931 References......Page 932 References......Page 933 Pathology......Page 936 Ultrasonography and Contrast-Enhanced Ultrasonography......Page 937 Diagnostic Workup......Page 938 Treatment......Page 939 Prognosis and Natural History......Page 940 Pathology......Page 941 Ultrasonography and Contrast-Enhanced Ultrasonography......Page 942 Associated Conditions......Page 943 Hepatocellular Adenoma Classification......Page 945 Clinical Features......Page 946 Treatment......Page 947 Epidemiology......Page 948 Imaging Findings......Page 949 Conclusion......Page 950 References......Page 951 References......Page 952 Pretransplant Evaluation......Page 956 Timing of Referral for Evaluation......Page 957 Exploring Alternatives to Liver Transplantation......Page 961 Acute Liver Failure......Page 962 Nonalcoholic Steatohepatitis......Page 963 Hepatocellular Carcinoma......Page 964 Repeated Transplant: Recurrent Disease and Graft Failure......Page 965 Cardiovascular Disease......Page 966 Infection......Page 967 Psychosocial Issues......Page 968 Allocation and Distribution Systems......Page 969 Conclusion......Page 970 References......Page 971 References......Page 972 Brief History of Liver Transplantation......Page 977 Contraindications......Page 978 Assessment of Disease Severity and Waitlist Stratification......Page 980 Candidates With Hepatocellular Carcinoma......Page 981 Organ Procurement Operation......Page 982 Reduced-Sized and Split Livers......Page 983 Living Donor: Preoperative Evaluation and Planning......Page 984 Living Donor: Hepatectomy......Page 985 Recipient Hepatectomy......Page 986 Venous, Arterial, and Biliary Anastomoses......Page 988 Postoperative Bleeding......Page 989 Technical Complications: Biliary......Page 990 Current Outcomes of Liver Transplantation......Page 991 References......Page 992 References......Page 993 The First 90 Days......Page 996 Beyond the First 90 Days......Page 997 Allograft Immune Response......Page 998 Acute Allograft Rejection......Page 1001 Antibody-Mediated Rejection......Page 1002 Use of Immunosuppressive Medications......Page 1003 Biliary Complications......Page 1005 Obesity......Page 1006 Renal Disease......Page 1007 Infectious Disease Complications......Page 1008 Reproductive Health......Page 1009 References......Page 1010 References......Page 1011 Hepatitis B and Liver Transplantation......Page 1013 Natural History After Liver Transplantation......Page 1014 Pathology of Hepatitis B After Liver Transplantation......Page 1015 Pretransplant Antiviral Treatment......Page 1017 Historical Perspective......Page 1018 Prophylaxis Using Hepatitis B Immunoglobulin Plus Nucleoside/Nucleotide Analog Therapy......Page 1019 Treatment of Recurrent Hepatitis B Virus Disease......Page 1020 Human Immunodeficiency Virus?Coinfected Patients......Page 1021 Hepatitis D Virus?Coinfected Patients......Page 1022 Natural History After Liver Transplantation......Page 1023 Assessment of Hepatic Fibrosis in Liver Transplant Recipients......Page 1024 Pathology of Hepatitis C After Liver Transplant......Page 1025 Factors Associated With Disease Progression and Graft Loss......Page 1026 Donor- and Peritransplant-Related Factors......Page 1027 Transplantation-Related Factors......Page 1028 Induction Antibody Therapy......Page 1029 Prevention and Treatment of Recurrent Disease......Page 1030 To Achieve Cure......Page 1031 Posttransplant Therapy......Page 1032 Significant Fibrosis/Compensated Cirrhosis......Page 1033 Severe Early Recurrent Hepatitis C Virus Infection and Decompensated Cirrhosis......Page 1034 Natural History After Liver Transplantation......Page 1035 Risk Factors for Recurrent Primary Biliary Cholangitis......Page 1036 Natural History After Liver Transplantation......Page 1037 Management of Recurrent Primary Sclerosing Cholangitis......Page 1038 Risk Factors for Recurrent Autoimmune Hepatitis......Page 1039 Natural History After Liver Transplantation......Page 1040 Diagnosis of Recurrent Nonalcoholic Fatty Liver Disease......Page 1041 Natural History After Liver Transplantation......Page 1042 Hemochromatosis......Page 1043 References......Page 1044 References......Page 1045 Liver Anatomy and Histology......Page 1059 Drug Metabolism......Page 1060 Bilirubin......Page 1061 Changes in Liver Function Test Values......Page 1062 Hepatitis A......Page 1063 Hepatitis B......Page 1064 Hepatitis E......Page 1065 Pregnancy and Vascular Liver Diseases......Page 1066 Budd-Chiari Syndrome and Pregnancy......Page 1067 Management of Labor and Delivery......Page 1068 Hepatobiliary Disease During Pregnancy......Page 1069 The Evaluation of a Liver Mass During Pregnancy......Page 1070 Management......Page 1071 Diagnosis......Page 1072 Diagnosis......Page 1073 Acute Fatty Liver of Pregnancy......Page 1074 Diagnosis......Page 1075 Differential Diagnosis......Page 1076 Future Pregnancies......Page 1077 Reference......Page 1078 References......Page 1079 What Is Sarcopenia in Cirrhosis?......Page 1084 Clinical Significance of Sarcopenia in Cirrhosis......Page 1085 Mechanisms of Sarcopenia in Cirrhosis......Page 1086 Therapeutic Options for Sarcopenia......Page 1087 Exercise and Physical Activity......Page 1088 Conclusion......Page 1089 Reference......Page 1090 References......Page 1091 Introduction......Page 1094 Epidemiology, Common Causes, and Clinical Risk Factors......Page 1096 Apoptosis and Necrosis......Page 1097 Bioactivation of Xenobiotic Agents......Page 1098 Role of Glutathione in Chemical Detoxification of Reactive Electrophiles......Page 1099 Oxidative Stress and Free-Radical Reactions in Hepatotoxicity......Page 1100 Immunologic Mechanisms of Drug-Induced Liver Injury......Page 1102 Hepatocellular Hepatitic Pattern of Injury......Page 1103 Mixed Pattern of Injury......Page 1107 Macrovesicular or Mixed Microvesicular and Macrovesicular Steatosis......Page 1108 Anesthetics......Page 1109 Anticonvulsants......Page 1110 Antipsychotics: Second Generation......Page 1114 Agents Used in the Treatment of Parkinson Disease, Migraines, and Alzheimer Disease......Page 1115 Sulfonylureas......Page 1116 α-Glucosidase Inhibitors......Page 1117 Amphotericin B......Page 1118 Antimalarials......Page 1119 Ethambutol......Page 1120 Nucleoside Analog Reverse Transcriptase Inhibitors......Page 1121 Protease Inhibitors......Page 1122 Amoxicillin?Clavulanic Acid......Page 1123 Macrolides......Page 1124 Other Antibiotics......Page 1125 Antiarrhythmic Drugs......Page 1126 Hydroxymethylglutaryl-Coenzyme a Reductase Inhibitors Statins......Page 1128 Nonsteroidal Antiinflammatory Drugs and Acetaminophen......Page 1130 Antimetabolites......Page 1133 Nitrosoureas Carmustine, Lomustine, Semustine, Streptozocin......Page 1136 Biologic Response Modulators......Page 1137 Some Botanicals, Herbal Products, and Dietary Supplements Associated With Liver Injury......Page 1138 Acknowledgments......Page 1139 References......Page 1140 References......Page 1141 Preoperative Liver Dysfunction......Page 1158 Postoperative Liver Dysfunction......Page 1160 Drug-Induced Hepatitis......Page 1161 Bile Duct Obstruction......Page 1162 References......Page 1163 References......Page 1164 Formation of Bilirubin......Page 1166 Opening of the Heme Ring by Heme Oxygenase......Page 1167 Measurement of Bilirubin Production......Page 1168 Absorption Spectra and Circular Dichroism of Bilirubin IXα......Page 1169 Bilirubin Encephalopathy in Gunn Rats......Page 1170 Biochemical Basis of Bilirubin Toxicity......Page 1172 Disposition of Bilirubin......Page 1173 The Role of Albumin......Page 1174 Transporters......Page 1175 Acquired and Inherited Abnormalities of Hepatic Bilirubin Uptake......Page 1176 Multiple Forms of Uridine Diphosphoglucuronate Glucuronosyltransferases......Page 1177 Organization of the UGT1A Gene Family......Page 1178 Transport of Bile Acids and Non?Bile Acid Organic Anions......Page 1179 Fate of Bilirubin in the Gastrointestinal Tract......Page 1180 Chromatographic Analysis of Bilirubin Species as Intact Tetrapyrroles: Thin-Layer and High-Pressure Liquid Chromatography......Page 1181 Bilirubin in Cerebrospinal Fluid......Page 1182 Maternal Serum Jaundice Lucey-Driscoll Syndrome.......Page 1183 Laboratory Tests.......Page 1184 Animal Models of Crigler-Najjar Syndrome Type 1: The Gunn Rat.......Page 1185 Hepatocyte Transplant.......Page 1186 Molecular Mechanism and Inheritance.......Page 1187 Organic Anion Transport.......Page 1188 Acquired Defects of Hepatobiliary Transport......Page 1189 Organic Anion Transport.......Page 1190 TR? Rats and Eisai Hyperbilirubinemic Rats.......Page 1191 The Genetic and Mechanistic Basis of Rotor Syndrome.......Page 1192 References......Page 1193 References......Page 1194 Copper Pathway......Page 1202 Basic Defect......Page 1203 Copper Transport and Homeostasis in Hepatocytes......Page 1204 Hepatic Involvement......Page 1205 Neurologic Involvement......Page 1206 Involvement of Other Systems......Page 1207 Biochemical Diagnostic Features......Page 1208 Diagnosis by Mutation Analysis......Page 1209 Specific Mutations and Clinical Features......Page 1210 Genetic Differential Diagnosis......Page 1211 Chelation......Page 1212 Induction of Metallothioneins and Interference With Copper Absorption......Page 1213 Liver Transplantation......Page 1214 Wilsonian Fulminant Hepatic Failure......Page 1215 References......Page 1216 References......Page 1217 Historical Aspects......Page 1221 The Iron-Sensing Machinery......Page 1223 The Common Pathogenic Basis of All Forms of Hemochromatosis......Page 1226 Genetics and Epidemiology......Page 1229 The Low Penetrance of HFE C282Y Homozygotes......Page 1231 Acquired Hemochromatosis......Page 1233 Suspecting and Diagnosing Hemochromatosis......Page 1234 Management......Page 1236 Atransferrinemia/Hypotransferrinemia......Page 1237 Porphyria Cutanea Tarda......Page 1238 References......Page 1239 References......Page 1240 Pathogenesis......Page 1246 Clinical Features......Page 1250 Diagnosis......Page 1252 Treatment......Page 1253 References......Page 1256 References......Page 1257 General Approach and Clinical Evaluations......Page 1260 Infancy......Page 1261 Childhood......Page 1262 Adulthood......Page 1263 References......Page 1264 References......Page 1265 Congenital Syphilis......Page 1266 Rubella......Page 1267 Varicella-Zoster Virus......Page 1268 Clinical Manifestations and Outcomes of α1-Antitrypsin Deficiency–Associated Liver Disease......Page 1269 Diagnosis......Page 1270 Treatment......Page 1271 Clinical Manifestations and Hepatic Pathology......Page 1272 Clinical Manifestations......Page 1273 Familial Intrahepatic Cholestasis 1 Deficiency, or Progressive Familial Intrahepatic Cholestasis Type 1 OMIM 211600......Page 1274 Treatment......Page 1275 Management and Prognosis......Page 1276 Clinical Features......Page 1277 Clinical Features......Page 1278 Cholestasis Associated With Inspissated Bile......Page 1279 Pathogenic Mechanisms of Disease......Page 1280 Surgical Management of Biliary Atresia......Page 1281 General Treatment of Children With Cholestasis......Page 1282 Nutritional Therapy......Page 1283 References......Page 1284 References......Page 1285 Ductal Plate Malformation Hypothesis......Page 1292 Primary Cilia Contribute to Cystogenesis......Page 1294 PKD1 and Polycystin 1......Page 1295 LRP5 and Lrp5......Page 1296 Mechanisms for Polycystin 1?Polycystin 2?Fibrocystin Complexes to Influence Cell Proliferation......Page 1297 Cytokines and Growth Factors Involved in Hepatic Cystogenesis......Page 1299 Autosomal Dominant Polycystic Liver Disease......Page 1300 Caroli Disease......Page 1301 Choledochal Cysts......Page 1302 Natural History......Page 1303 Clinical Features......Page 1304 Medical Treatments......Page 1306 Characteristics......Page 1307 Treatment......Page 1308 Clinical Features......Page 1309 Characteristics......Page 1310 References......Page 1311 References......Page 1312 General......Page 1318 Acute Liver Failure......Page 1319 Cytomegalovirus......Page 1320 Hepatitis E Virus......Page 1321 Parvovirus B19......Page 1322 Epidemiology......Page 1323 Natural History......Page 1324 Treatment......Page 1325 Nucleotide Analog Family: Lamivudine, Adefovir Dipivoxil, and Entecavir......Page 1326 Epidemiology......Page 1327 Natural History......Page 1328 Conclusion......Page 1330 References......Page 1331 References......Page 1332 A......Page 1335 B......Page 1337 C......Page 1338 D......Page 1340 F......Page 1342 H......Page 1343 I......Page 1347 L......Page 1348 M......Page 1350 N......Page 1351 P......Page 1352 R......Page 1354 S......Page 1355 T......Page 1356 V......Page 1357 Z......Page 1358