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List of Contributors, xi Preface to the Twelfth Edition, xv Preface to the First Edition, xvi 1 Anatomy and Function, 1 Jay H. Lefkowitch Development of the liver and bile ducts, 1 Anatomy of the liver, 1 Functional liver anatomy: sectors and segments, 3 Anatomical abnormalities of the liver, 4 Anatomy of the biliary tract, 5 Surface marking, 6 Methods of examination, 6 Microanatomy of the liver, 7 Hepatic ultrastructure (electron microscopy) and organelle functions, 11 Functional heterogeneity of the liver, 15 Dynamics of the hepatic microenvironment in physiology and disease, 16 Hepatocyte death and regeneration, 17 2 Assessment of Liver Function, 20 Sandeep Mukherjee & John L. Gollan Selection of biochemical tests, 20 Bile pigments, 21 Serum enzyme tests, 22 Quantitative assessment of hepatic function, 25 Lipid and lipoprotein metabolism, 25 Bile acids, 27 Amino acid metabolism, 30 Plasma proteins, 30 Carbohydrate metabolism, 33 Effects of ageing on the liver, 33 3 Biopsy of the Liver, 36 David Patch & Amar Paul Dhillon Selection and preparation of the patient, 36 Techniques, 37 Risks and complications, 40 Sampling variability, 41 Naked–eye appearances, 43 Preparation of the specimen, 43 Interpretation, 43 Indications, 43 Special methods, 45 4 Haematological Disorders of the Liver, 48 Pramod K. Mistry & Dhanpat Jain The liver and blood coagulation, 50 Haemolytic jaundice, 53 The liver in haemolytic anaemias, 54 The liver in myelo– and lymphoproliferative disease, 57 Leukaemia, 57 Bone marrow transplantation, 57 Lymphoma, 58 Lipid storage diseases, 62 5 Acute Liver Failure, 70 Shannan R. Tujios & William M. Lee Definition, 70 Epidemiology and aetiologies, 71 Clinical features, 74 Initial investigations, 75 Complications and management of acute liver failure, 77 Specific therapies, 84 Prognosis, 86 Liver transplantation, 86 Liver support systems, 88 Conclusion, 88 6 Hepatic Fibrogenesis, 94 Meena B. Bansal & Scott L. Friedman Introduction, 94 Natural history of hepatic fibrosis, 94 Cellular and molecular features of hepatic fibrosis, 95 Clinical aspects of hepatic fibrosis, 100 Emerging antifi brotic targets and strategies, 101 7 Hepatic Cirrhosis, 103 P. Aiden McCormick Definition, 103 Causes of cirrhosis, 103 Anatomical diagnosis, 104 Reversible cirrhosis, 106 Clinical cirrhosis: compensated versus decompensated, 106 Vasodilatation and hyperdynamic circulation, 108 Prognosis (Child???Pugh score, MELD, UKELD), 110 Clinical and pathological associations, 111 Management, 117 8 Hepatic Encephalopathy in Patients with Cirrhosis, 121 Marsha Y. Morgan Classification, 121 Diagnosis, 124 Differential diagnosis, 130 Hepatic encephalopathy and liver transplantation, 131 Prognosis, 131 Pathogenesis, 131 Management of hepatic encephalopathy, 139 Prevention, 146 9 The Hepatic Artery, Portal Venous System and Portal Hypertension: the Hepatic Veins and Liver in Circulatory Failure, 152 Andrew K. Burroughs The hepatic artery, 152 The portal venous system, 156 Haemodynamics of portal hypertension, 160 Clinical features of portal hypertension, 162 Diagnosis of varices, 163 Imaging the portal venous system, 166 Classification of portal hypertension, 171 Extrahepatic portal venous obstruction, 171 Presinusoidal intrahepatic and sinusoidal portal hypertension, 176 Bleeding oesophageal varices, 179 Management of acute variceal bleeding, 181 The hepatic veins, 189 Budd???Chiari (hepatic venous obstruction) syndrome, 191 Circulatory failure, 197 10 Ascites, 210 Guadalupe Garcia–Tsao Mechanisms of ascites formation, 210 Clinical features, 213 Differential diagnosis, 215 Spontaneous bacterial peritonitis, 216 Treatment of cirrhotic ascites, 218 Hyponatraemia, 222 Refractory ascites, 223 Hepatorenal syndrome, 224 Prognosis, 228 11 Jaundice and Cholestasis, 234 Elwyn Elias Introduction, 234 Classification of jaundice, 234 Physiology and pathophysiology, 235 Syndrome of cholestasis, 240 Investigation of the jaundiced patient, 245 Differential diagnosis, 247 Treatment, 249 Familial non–haemolytic hyperbilirubinaemias, 250 12 Gallstones and Benign Biliary Diseases, 257 James S. Dooley Imaging, 258 Composition of gallstones, 261 Formation of cholesterol stones, 261 Factors in cholesterol stone formation, 264 Pigment gallstones, 266 Natural history of gallbladder stones, 266 Acute calculous cholecystitis, 267 Empyema of the gallbladder, 269 Emphysematous cholecystitis, 269 Chronic calculous cholecystitis, 269 Acalculous cholecystitis, 270 Cholecystectomy, 271 Postcholecystectomy bile duct damage, 273 Postcholecystectomy syndromes, 275 Non–surgical treatment of gallstones in the gallbladder, 276 Other gallbladder pathology, 277 Biliary fi stulae, 279 Gallstone ileus, 280 Bile peritonitis, 280 Association between cholecystectomy and colorectal cancer, 281 Common duct stones, 281 Management of duct stones, 282 Haemobilia, 285 Bile duct???bowel anastomotic stricture, 285 Chronic pancreatitis, 286 Primary sclerosing cholangitis and autoimmune pancreatitis, 287 Bile duct pathology following liver transplantation, 287 13 Malignant Biliary Diseases, 294 Rahul S. Koti & Brian R. Davidson Carcinoma of the gallbladder, 294 Carcinoma of the bile duct (cholangiocarcinoma), 296 Intrahepatic cholangiocarcinoma, 302 Other biliary malignancies, 302 Metastases at the hilum, 302 Periampullary carcinoma, 302 Conclusions, 308 14 Cysts and Congenital Biliary Abnormalities, 312 Giorgina Mieli–Vergani & Nedim Hadzic Fibropolycystic diseases, 312 Adult polycystic disease, 314 Congenital hepatic fibrosis, 316 Caroli's disease, 318 Microhamartoma (von Meyenberg complexes), 319 Choledochal cysts, 320 Congenital anomalies of the biliary tract, 322 15 Primary Biliary Cirrhosis, 329 Margaret F. Bassendine Clinical features, 329 Diagnosis, 332 Aetiology, 335 Epidemiology and genetics, 336 Treatment, 337 Prognosis, 338 16 Sclerosing Cholangitis, 342 Simon Rushbrook & Roger W. Chapman Introduction, 342 Primary sclerosing cholangitis, 342 Secondary sclerosing cholangitis, 348 References, 350 17 Enterically Transmitted Viral Hepatitis: Hepatitis A and Hepatitis E, 353 Peter Karayiannis & Howard C. Thomas General features of enterically transmitted viral hepatitis, 353 Hepatitis A virus, 358 Hepatitis E virus, 362 18 Hepatitis B, 367 Anna S. F. Lok Introduction, 367 Hepatitis B virus, 367 Immune response and mechanisms of hepatic injury, 369 Epidemiology, 370 Prevention, 371 Diagnosis, 374 Clinical manifestations, 376 Natural history, 377 Treatment, 380 19 Hepatitis D, 393 Patrizia Farci History, 393 Hepatitis D virus, 393 Epidemiology, 395 Pathogenesis, 396 Modes of infection and clinical course, 396 Diagnosis, 399 Treatment, 400 Prevention, 403 20 Hepatitis C, 406 Geoffrey Dusheiko Introduction, 406 Epidemiology, 406 Virology, 408 Pathology and pathogenesis, 409 Diagnostic tests for hepatitis C, 410 Acute hepatitis C, 411 Chronic hepatitis C, 412 21 Hepatitis due to Non–A???E Viruses, 427 Antonio Craxì & Rosa Di Stefano General features of non–A???E hepatitides, 427 Hepatotropic viruses, 429 Systemic viral infections that often cause transient liver involvement, 431 22 HIV and the Liver, 438 Marion G. Peters & Vincent Soriano Viral hepatitis and human immunodefi ciency virus (HIV) infection, 438 Cirrhosis and liver transplantation, 444 HIV–associated opportunistic infections and the liver, 444 HIV–associated neoplasms of the liver, 446 Antiretroviral–related liver injury in HIV, 446 23 Autoimmune Hepatitis and Overlap Syndromes, 452 Gideon M. Hirschfield & E. Jenny Heathcote Introduction, 452 Disease overview, 452 Biological determinants of disease, 454 Disease presentation, 455 Laboratory features, 457 Imaging, 459 Liver biopsy and histological features, 459 Differential diagnosis, 461 Diagnostic dilemmas, 463 Making a diagnosis in practice, 463 Management strategies, 464 Pregnancy and autoimmune hepatitis, 468 Contraception choices for patients with autoimmune hepatitis, 469 The elderly and autoimmune hepatitis, 469 Childhood–onset autoimmune hepatitis, 469 Autoimmune hepatitis and liver transplantation, 471 Overlap syndromes, 471 Conclusion, 475 24 Drug–Induced Liver Injury, 478 Leonard B. Seeff & Robert J. Fontana Introduction, 478 Worldwide epidemiology, 479 Expressions of hepatotoxicity, 481 Classification of hepatotoxicity, 482 Predictors of susceptibility and outcome in druginduced liver injury, 483 Mechanisms of injury, drug metabolism and pharmacokinetics, 484 Diagnostic approaches and causality assessment of drug–induced liver injury, 487 Clinical and biochemical presentations of drug–induced liver disease, 488 Assessment of suspected drug–induced liver disease, 489 Assessing causality for drug–induced liver disease, 489 Medical management, 491 Liver injury from specifi c drugs, 491 25 Alcohol and the Liver, 507 Stephen Stewart & Chris Day Introduction, 507 Alcohol metabolism, 507 Pathogenesis, 508 Susceptibility, 510 Histological features, 511 Clinical features, 513 Clinical syndromes, 516 Prognosis, 517 Treatment, 517 26 Iron Overload States, 521 Paul Adams Normal iron metabolism, 521 Iron overload and liver damage, 523 Genetic haemochromatosis, 523 Other iron storage diseases, 530 27 Wilson's Disease, 534 Eve A. Roberts Molecular genetics: pathogenesis, 534 Pathology, 536 Clinical picture, 537 Genetic strategies, 539 Diagnostic diffi culties, 540 Treatment, 540 Prognosis, 542 Indian childhood cirrhosis, 543 28 Non–alcoholic Fatty Liver Disease and Nutrition, 546 Stephen H. Caldwell & Curtis K. Argo Introduction, 546 Clinical features, 548 Laboratory testing, 549 Mitochondriopathies and lipodystrophy, 549 Epidemiology of non–alcoholic fatty liver disease, 549 Pathogenesis of non–alcoholic fatty liver disease and non–alcoholic steatohepatitis, 550 The natural history of non–alcoholic fatty liver disease (non–alcoholic steatohepatitis and non–NASH fatty liver), 556 Therapy of non–alcoholic fatty liver disease, 558 Other forms of non–alcoholic fatty liver, 560 29 The Liver in the Neonate, in Infancy and Childhood, 568 Deirdre A. Kelly Investigation of liver disease in children, 568 Neonatal jaundice, 569 Neonatal liver disease (conjugated hyperbilirubinaemia), 571 Neonatal hepatitis syndrome, 574 Inherited disease in the neonate, 576 Genetic cholestatic syndromes, 578 Structural abnormalities: biliary atresia and choledochal cyst, 580 Acute liver failure in infancy, 583 Liver disease in older children, 585 Metabolic disease in older children, 587 Cirrhosis and portal hypertension, 594 Liver transplantation, 594 Tumours of the liver, 595 30 The Liver in Pregnancy, 602 Andrew K. Burroughs & E. Jenny Heathcote Normal pregnancy, 602 Liver disease in pregnancy, 602 Diseases specifi c to pregnancy, 602 Diseases of late pregnancy, 603 Pregnancy in those with acute or chronic liver disease, 608 Hepatotoxic drugs and the pregnant woman, 609 Pre–existing liver disease, 610 Pregnancy in liver transplant recipients, 611 31 The Liver in Systemic Disease, 615 Humphrey J. F. Hodgson Collagen–vascular and autoimmune disorders, 615 Hepatic granulomas, 616 The liver in diabetes mellitus, 622 Liver and thyroid, 622 Liver and adrenal, 623 Liver and growth hormone, 623 Amyloidosis, 623 Porphyrias, 626 Non–metastatic complications of malignancy, 628 Bone–marrow/stem cell transplantation; graft–versushost disease, 629 32 The Liver in Infections, 632 Christopher C. Kibbler Introduction, 632 Jaundice of infections, 632 Pyogenic liver abscess, 632 Hepatic amoebiasis, 635 Tuberculosis of the liver, 637 Hepatic actinomycosis, 638 Syphilis of the liver, 639 Perihepatitis, 640 Leptospirosis, 640 Relapsing fever, 643 Lyme disease, 643 Rickettsial infections, 643 Fungal infections, 644 Schistosomiasis (bilharzia), 645 Malaria, 647 Kala–azar (visceral leishmaniasis), 648 Hydatid disease, 648 Ascariasis, 652 Strongyloides stercoralis, 654 Trichinosis, 654 Toxocara canis (visceral larva migrans), 654 Liver fl ukes, 654 33 Space–Occupying Lesions: the Diagnostic Approach, 660 Neil H. Davies & Dominic Yu Ultrasound, 660 Computed tomography, 661 Magnetic resonance imaging, 663 Radioisotope scanning, 666 Positron emission tomography, 667 MR spectroscopy, 668 Conclusions and choice of imaging technique, 669 34 Benign Liver Tumours, 671 Ian R. Wanless Diagnosis of focal liver lesions, 671 Hepatocellular tumours, 671 Biliary and cystic lesions, 676 Mesenchymal tumours, 677 35 Primary Malignant Neoplasms of the Liver, 681 Morris Sherman Hepatocellular carcinoma, 681 Cholangiocarcinoma, 696 Other malignant neoplasms of the liver, 698 36 Hepatic Transplantation, 704 Andrew K. Burroughs & James O'Beirne Selection of patients, 704 Candidates: outcome, 706 Absolute and relative contraindications, 712 General preparation of the patient, 713 Donor selection and operation, 713 The recipient operation, 714 Immunosuppression, 716 Postoperative course, 717 Post–transplantation complications, 718 Conclusion, 726 37 Liver Transplantation in Patients with Hepatitis B, C or HIV Infection, 731 Norah Terrault Introduction, 731 Hepatitis B and liver transplantation, 731 Hepatitis C and liver transplantation, 735 HIV and liver transplantation, 740 References, 741 Index, 747