Title Details

Andrew Burroughs is a Consultant Physician and Hepatologist at the Royal Free Hospital, Liver Transplantation and Hepato-biliary Medicine Unit. He qualified in Liverpool with a MB ChB Honours in 1976, gained his MRCP in 1978 and FRCP in 1991. He is a Fellow of the European Board of Gastroenterology. He has been Scientific Secretary of the European Association for the Study of the Liver 1997-1999. He continues his association with EASL as administrative secretary until 2001. He is a council member of the United European Gastroenterology Federation until 2002, and a council member of the International Association for the Study of the Liver. He is a member of the MRC advisory board in the UK, from 1997 onwards. He was a member of Council of the British Society of Gastroenterology from 1992 to 1995. Andrew Burroughs main research interests are portal hypertension, variceal bleeding and coagulopathy, primary biliary cirrhosis, prognosis in liver disease and liver transplantation. He has published over 200 peer-reviewed articles.

Anna Lok is a Professor of Internal Medicine and the Director of Clinical Hepatology at the University of Michigan Medical Center. Her research focuses on the epidemiology and treatment of hepatitis B and C viruses. Millions of people worldwide are infected and are at risk for hepatitis-associated cirrhosis and hepatocellular carcinoma. Dr. Lok has made seminal contributions to our understanding of the natural history of hepatitis B and the role of hepatitis B virus genotypes and variants in the outcome of chronic hepatitis B infection. She has also made contributions to the treatment of hepatitis-induced diseases. She is currently testing new antiviral therapies for hepatitis B, developing cost-effective methods for preventing recurrent hepatitis B infection following liver transplantation, and studying the long-term effects of interferon treatment in patients with hepatitis C. During her distinguished career, she has received numerous awards for research and teaching.

Jenny Heathcote, Toronto Western Hospital, Canada.

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