James S. Dooley, The Royal Free Hospital, London, UK.

Anna S. Lok, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.

Guadalupe Garcia-Tsao, Yale University School of Medicine, VA-CT Healthcare System, CT, USA.

Massimo Pinzani, UCL Institute for Liver and Digestive Health, London, UK.

List of Contributors xi Preface to the Thirteenth Edition xv Preface to the First Edition xvi 1. Anatomy and Function 1Jay 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 20George 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 gammäglutamyl transferase (GGT) 33 Haematology in liver disease 34 Effects of ageing on the liver 35 References 36 3 Biopsy of the Liver 39David 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 53Nicolas 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 62Shannan 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 82Meena 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 93Avik 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 107P. 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 127Guadalupe GarciäTsao 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 151Marsha 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 180Jaime 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 209Dominique¿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 231Peter 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 256James 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 294Rahul 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 308Nedim Had?i¿ 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 328David E. J. Jones Clinical features 328 Diagnosis 329 Epidemiology 333 Aetiology and pathogenesis 334 Management 335 Prognosis 337 References 338 18 Sclerosing Cholangitis 341Tom 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 355Ashnila 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 380Rinjal 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 395Anna 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 421Patrizia 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 436Geoffrey 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 468Frank 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 494Stephen 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 511Paul 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 526Eve 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...