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 Hadzic 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...