(PDF) Sherlock’s Diseases of the Liver and Biliary System 13th Edition by Dooley

This is the PDF eBook version for Sherlock’s Diseases of the Liver and Biliary System 13th Edition by James S. Dooley, Anna S. F. Lok, Guadalupe Garcia-Tsao, Massimo Pinzani

Table of Contents

List of Contributors xi

Preface to the Thirteenth 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 3

Anatomy of the biliary tract 4

Surface marking 5

Methods of examination 6

Microanatomy of the liver 7

Hepatic ultrastructure (electron microscopy) and organelle functions 9

Functional heterogeneity of the liver 13

Dynamics of the hepatic microenvironment in physiology and disease 14 Hepatocyte death and regeneration 15 References 16

2 Liver Function in Health and Disease: Clinical Application of Liver Tests 20
George Mells and Graeme Alexander

Bilirubin metabolism 21

Bile acids 23

Lipid and lipoprotein metabolism 26

Amino acid metabolism 28

Plasma proteins 29

Carbohydrate metabolism 31

Markers of hepatocellular injury: the serum transaminases 32

Markers of cholestasis: alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) 33

Haematology in liver disease 34

Effects of ageing on the liver 35

References 36

3 Biopsy of the Liver 39
David Patch and Tu Vinh Luong

Selection and preparation of the patient 39

Techniques 40

Risks and complications 43

Sampling variability 45

Naked-eye appearances 46

Preparation of the specimen 46

Interpretation: a stepwise diagnostic approach 46

Indications 48

Special methods 49

References 50

4 Coagulation in Cirrhosis 53
Nicolas M. Intagliata and Stephen H. Caldwell

Introduction 53

Normal coagulation pathways: a hepatologist’s perspective 54

The coagulation system in cirrhosis 56

Bleeding and thrombosis in cirrhosis 57

Clinical laboratory tests of the coagulation system in cirrhosis 58

Conclusion 60

References 60

5 Acute Liver Failure 62
Shannan R. Tujios and William M. Lee

Definition 62

Epidemiology and aetiologies 63

Clinical features 66

Initial investigations 67

Complications and management of acute liver failure 68

Specific therapies 73

Prognosis 75

Liver transplantation 76

Conclusion 78

References 78

6 Hepatic Fibrogenesis 82
Meena B. Bansal and Scott L. Friedman

Introduction 82

Natural history of hepatic fibrosis 82

Cellular and molecular features of hepatic fibrosis 83

Clinical aspects of hepatic fibrosis 89

Emerging antifibrotic targets and strategies 89

References 90

7 Non-invasive Assessment of Fibrosis and Cirrhosis 93
Avik Majumdar and Massimo Pinzani

Introduction 93

The use of invasive and non-invasive tests 93

Non-invasive tests: specifics 95

Conclusions 102

References 103

8 Hepatic Cirrhosis 107
P. Aiden McCormick and Rajiv Jalan

Definition 107

Causes of cirrhosis 107

Anatomical diagnosis 108

Reversible cirrhosis 110

Clinical cirrhosis: compensated versus

decompensated 110

Prognosis (Child–Pugh score, MELD, UKELD) 111

Clinical and pathological associations 112

Management 119

Acute-on-chronic liver failure 120

References 123

9 Ascites 127
Guadalupe Garcia-Tsao

Mechanisms of ascites formation 127

Clinical features 130

Differential diagnosis 132

Spontaneous bacterial peritonitis 132

Treatment of cirrhotic ascites 134

Hyponatraemia 138

Refractory ascites 139

Hepatorenal syndrome 141

Prognosis 144

References 145

10 Hepatic Encephalopathy in Patients with Cirrhosis 151
Marsha Y. Morgan

Clinical Features 151

Classification 153

Prevalence and consequences 154

Diagnosis 154

Diagnostic comorbidities, confounders, and alternatives 160

Pathogenesis 161

Management 167

Prevention 174

References 174

11 Portal Hypertension in Cirrhosis 180
Jaime Bosch and Annalisa Berzigotti

Introduction 180

Pathophysiology and rational basis of therapy 185

Evaluation and diagnosis 188

Natural history and prognosis 194

Management 196

Treatment of portal hypertension according to clinical scenarios 200

References 205

12 Vascular Disorders of the Liver and Extrahepatic Portal Hypertension 209
Dominique-Charles Valla

Hepatic artery occlusion 209

Aneurysms of the hepatic artery 210

Hepatic arterioportal fistula 211

Hepatic vascular malformations in hereditary haemorrhagic telangiectasia 212

Congenital portosystemic shunts – Abernethy malformation 213

Budd–Chiari syndrome – hepatic venous outflow tract obstruction 214

Extrahepatic portal vein obstruction – portal vein thrombosis and portal cavernoma in the absence of cirrhosis 217

Portal vein thrombosis in patients with cirrhosis 220

Idiopathic non-cirrhotic intrahepatic portal hypertension 221

Hypoxic hepatitis 223

Congestive cardiac hepatopathy 223

Non-obstructive sinusoidal dilation (NOSD) and peliosis 225

References 226

13 Jaundice and Cholestasis 231
Peter L. M. Jansen

Introduction 231

Mechanics of bile formation 233

Syndrome of cholestasis 238

Causes of isolated hyperbilirubinaemia 239

Causes of cholestatic and hepatocellular jaundice 242

Consequences of cholestasis and their management 244

Investigation of the jaundiced patient 247

Decisions to be made in the jaundiced patient Management of cholestatic disorders 251

References 251

14 Gallstones and Benign Biliary Disease 256
James S. Dooley, Kurinchi S. Gurusamy, and Brian R. Davidson

Introduction 256

Imaging the gallbladder and biliary tract 256

Gallstones 259

Symptoms and complications of gallstones 264

Cholecystectomy 266

Complicated acute gallbladder disease 268

Percutaneous cholecystostomy 269

Asymptomatic gallbladder stones 269

Non-surgical treatment of gallstones in the gallbladder 269 Common bile duct stones 270 Acute gallstone pancreatitis 272 Large common duct stones 272 Mirizzi syndrome 273

Intrahepatic gallstones 274

Haemobilia 274

Functional gallbladder and sphincter of Oddi disorders 274

Other gallbladder pathologies 276

Relationships to malignant change 279

Benign biliary strictures 279

Anastomotic strictures following biliary surgery 282

IgG4-related sclerosing cholangitis 283

Chronic pancreatitis 283

References 284

15 Malignant Biliary Diseases 294
Rahul S. Koti and John Bridgewater

Carcinoma of the gallbladder 294

Carcinoma of the bile duct (cholangiocarcinoma) 296

Other biliary malignancies 301 Metastases at the hilum 301

Ampullary and periampullary carcinomas 301

Conclusion 305

References 305

16 Fibropolycystic Liver Diseases and Congenital Biliary Abnormalities 308
Nedim Had?ic and Mario Strazzabosco

Overview 308

Polycystic liver disease 309

Fibropolycystic diseases 313

Autosomal recessive polycystic kidney disease 314

Congenital hepatic fibrosis 314

Caroli disease 316

Microhamartomas (von Meyenberg complexes) Choledochal cysts 318

Solitary non-parasitic liver cyst 320

Congenital anomalies of the biliary tract 321

References 324

17 Primary Biliary Cholangitis 328
David E. J. Jones

Clinical features 328

Diagnosis 329

Epidemiology 333

Aetiology and pathogenesis 334

Management 335

Prognosis 337

References 338

18 Sclerosing Cholangitis 341
Tom Hemming Karlsen and Kirsten Muri Boberg

Introduction 341

Primary sclerosing cholangitis 341

Secondary sclerosing cholangitis 350

Sclerosing cholangitis in systemic inflammatory

diseases 351

References 351

19 Autoimmune Hepatitis and Overlap Syndromes 355
Ashnila Janmohamed and Gideon M. Hirschfield

Introduction 355

Disease overview 356

Biological determinants of disease 357

Disease presentation 359

Laboratory features 361

Imaging 363

Liver biopsy and histological features 363

Differential diagnosis 365

Diagnostic dilemmas 366

Making a diagnosis in practice 367

Management strategies 368

Pretreatment and on-treatment considerations 371

Treatment challenges and alternative agents 371

Pregnancy and autoimmune hepatitis 372

The elderly and autoimmune hepatitis 372

Childhood-onset autoimmune hepatitis 373

Autoimmune hepatitis and liver transplantation 373

Overlap syndromes 374

Conclusion 377

References 377

20 Enterically Transmitted Viral Hepatitis: Hepatitis A and Hepatitis E 380
Rinjal D. Brahmbhatt and Anna S. F. Lok

General features of enterically transmitted viral hepatitis 380

Hepatitis A virus 385

Hepatitis E virus 389

References 391

21 Hepatitis B 395
Anna S. F. Lok

Introduction 395

Hepatitis B virus 395

Immune response and mechanisms of hepatic injury 398

Epidemiology 399

Prevention 400

Diagnosis 402

Clinical manifestations 404

Natural history 405

Treatment 408

HBV and HCV coinfection 414

HBV and HDV coinfection 414

HBV and HIV coinfection 414

References 415

22 Hepatitis D 421
Patrizia Farci and Grazia Anna Niro

History 421

Hepatitis D virus 421

Epidemiology 422

Pathogenesis 425

Modes of infection and clinical course 425

Diagnosis 428

Treatment 429

Prevention 432

References 432

23 Hepatitis C 436
Geoffrey Dusheiko

Introduction 436

Epidemiology 436

Virology 438

Pathology and pathogenesis 439

Diagnostic tests for hepatitis C 440

Acute hepatitis C 441

Chronic hepatitis C 441

References 459

24 Drug-Induced Liver Injury 468
Frank W. DiPaola and Robert J. Fontana

Introduction 468

Epidemiology 468

Complications of DILI 469

Classification of hepatotoxicity 469

Drug metabolism and pharmacokinetics 469

Hepatic drug metabolism 471

Molecular mechanisms in drug-induced liver injury 472

Non-genetic risk factors for DILI 473

Diagnosis of DILI 474

Medical management 478

Pharmacogenetic risk factors 478

Potential immunological mechanisms in idiosyncratic DILI 479

Liver injury from specific drugs 479

References 486

25 Alcohol and the Liver 494
Stephen Stewart and Ewan Forrest

Introduction 494

Alcohol metabolism 494

Pathogenesis 496

Susceptibility 497

Histological features 498

Clinical features 501

Clinical syndromes 503

Prognosis 504

Treatment 506

Conclusions 507

References 508

26 Iron Overload States 511
Paul Adams and Heinz Zoller

Normal iron physiology 511

Iron overload and liver damage 515

Genetic haemochromatosis 516

Other iron storage diseases 521

References 523

27 Wilson Disease 526
Eve A. Roberts and Karl Heinz Weiss

Molecular genetics: pathogenesis 527

Pathology 528

Clinical picture 529

Laboratory tests 532

Genetic strategies 533

Diagnostic difficulties 533

Treatment 533

Prognosis 536

Non-Wilsonian copper-related cirrhosis 536

References 536

28 Non-Alcoholic Fatty Liver Disease 540
Timothy Hardy and Christopher P. Day

Introduction 540

Further definitions, terminology, and diagnosis 541

Liver biopsy, classification of NAFLD, and non- invasive markers of NASH and fibrosis 541

Clinical features 543

Laboratory testing 544

Epidemiology 545

Ethnic variation in NAFLD 545

Pathogenesis of NASH 545

Natural history of NAFLD 550

NAFLD and hepatocellular carcinoma (HCC) 551

Therapy for non-alcoholic fatty liver disease 552

Other forms of NAFLD 554

References 555

29 Nutrition and Chronic Liver Disease 561
Manuela Merli

Introduction 561

Epidemiology and general characteristics 562

Causes of malnutrition 562

Consequences of malnutrition 564

Diagnosis and assessment 565

Treatment and management 568

References 570

30 Pregnancy and the Liver 572
Rachel H. Westbrook and Catherine Williamson

Introduction 572

Normal physiology in pregnancy 572

Pregnancy-related liver diseases 573

Pre-existing liver diseases and pregnancy 578

Liver transplantation and pregnancy 580

Liver disease coincidentally

arising with pregnancy 581

Conclusion 582

References 582

31 The Liver in the Neonate, in Infancy, and Childhood 588
Susan M. Siew and Deirdre A. Kelly

Investigation of liver disease in children 588

Neonatal jaundice 589

Neonatal unconjugated hyperbilirubinaemia 589

Neonatal liver disease (conjugated hyperbilirubinaemia) 591

Neonatal hepatitis 594

Inherited disease in the neonate 596

Genetic cholestatic syndromes 598

Structural abnormalities: biliary atresia and choledochal cyst 600

Acute liver failure in infancy 602

Liver disease in older children 605

Metabolic disease in older children 607

Cirrhosis and portal hypertension 613

Liver transplantation 613

Tumours of the liver 614

References 615

32 The Liver in Systemic Diseases 622
James S. Dooley and Christopher McNamara

Collagen-vascular and autoimmune disorders 622

Hepatic granulomas 624

Sarcoidosis 626

The liver in endocrine disorders 628

Amyloidosis 629

Porphyrias 632

The liver in haemolytic anaemias 634

The liver in myelo- and lymphoproliferative disease 638

Bone marrow transplantation 639

Lymphoma 640

Extramedullary haemopoiesis 642

Rare haematological disorders that may involve the liver 643

Lipid storage diseases 643

Non-metastatic complications of malignancy 646

References 646

33 The Liver in Infections 652
Sanjay Bhagani and Ian Cropley

Introduction 652

Jaundice of infections 652

Pyogenic liver abscess 652

Hepatic amoebiasis 655

Tuberculosis of the liver 657

Hepatic actinomycosis 659

Syphilis of the liver 659

Perihepatitis 660

Leptospirosis 660

Relapsing fever 663

Lyme disease 663

Rickettsial infections 663

Fungal infections 664

Schistosomiasis (bilharzia) 665

Malaria 667

Kala-azar (visceral leishmaniasis) 668

Echinococcosis (hydatid disease) 668

Ascariasis 673

Strongyloides stercoralis 674

Trichinosis 674

Toxocara canis (visceral larva migrans) 674

Liver flukes 675

References 676

34 Imaging of the Liver and Diagnostic Approach of Space-Occupying Lesions 682
Neil H. Davies and Dominic Yu

Ultrasound 682

Computed tomography 683

Magnetic resonance imaging 685

Radioisotope scanning 688

Positron emission tomography 691

MR spectroscopy 691

Conclusions and choice of imaging technique 691

References 691

35 Benign Liver Tumours 693
Ian R. Wanless

Diagnosis of focal liver lesions 693

Hepatocellular lesions 693

Biliary and cystic lesions 699

Mesenchymal tumours 700

References 701

36 Primary Malignant Neoplasms of the Liver 705
Adam Doyle and Morris Sherman

Hepatocellular carcinoma 705

Intrahepatic cholangiocarcinoma 718

Other malignant neoplasms of the liver 721

Other sarcomas 722

References 722

37 Hepatic Transplantation 730
Lindsay Y. King and Carl L. Berg

Selection of patients 730

Candidates 732

Absolute and relative contraindications 737

General preparation of the patient 738

Donor selection and operation 738

The recipient operation 739

Immunosuppression 742

Postoperative course 743

Post-transplantation complications 744

Conclusion 751

References 752

38 Hepatic Transplantation and HBV, HCV, and HIV Infections 758
Norah A. Terrault

Introduction 758

Hepatitis B and liver transplantation 759

Hepatitis C and liver transplantation 763

HIV and liver transplantation 770

References 773

Index 781