Schiff's Diseases of the Liver

Name: Schiff's Diseases of the Liver
Brand: Wiley-Blackwell
Price: 231.99 EUR
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Eugene R. Schiff Willis C. Maddrey K. Rajender Reddy(Herausgeber*in)

Wiley-Blackwell (Verlag)

12. Auflage

Erschienen am 8. September 2017

1232 Seiten

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Intro
Schiff's Diseases of the Liver
Contents
Contributors
Foreword
Preface
About the Companion Website
PART I Overview: Clinical Fundamentals of Hepatology
1 History Taking and Physical Examination for the Patient with Liver Disease
Abnormal liver biochemical test levels or known liver disease
History taking
Physical examination
Jaundice
Known or suspected compensated or decompensated cirrhosis
History taking
Physical examination
References
2 Laboratory Tests, Noninvasive Markers of Fibrosis, Liver Biopsy, and Laparoscopy
Introduction
Tests used for detection of injury to hepatocytes
Aminotransferases
Glutamate dehydrogenase
Isocitrate dehydrogenase
Lactate dehydrogenase
Enzymes for detection of cholestasis
Alkaline phosphatase
5'-Nucleotidase
Gamma-glutamyltransferase
Bilirubin
Urinary bilirubin
Bile salts
Test of liver synthetic function
Prothrombin time
Albumin
Quantitative liver function tests
Breath tests
Dye tests
Dual cholate test
Use of liver function tests
Noninvasive markers of fibrosis
Liver biopsy
Roles of liver biopsy
Percutaneous liver biopsy
Transvenous liver biopsy
Endoscopic ultrasound-guided transgastric liver biopsy
Laparoscopy of the liver and laparoscopic liver biopsy
Complications of liver biopsy
Complications of diagnostic laparoscopy
Further reading
References
3 Noninvasive and Invasive Imaging of the Liver and Biliary Tract
Noninvasive imaging of liver and biliary tract
Ultrasound
Computed tomography
Nuclear medicine and positron emission tomography
Magnetic resonance imaging
Elastography
Noninvasive imaging of nonalcoholic fatty liver disease
Noninvasive imaging of hepatic iron deposition
Noninvasive hepatic vascular imaging
Noninvasive imaging in the screening of hepatocellular carcinoma
Noninvasive imaging of primary sclerosing cholangitis
Noninvasive imaging of choledocholithiasis
Noninvasive imaging of metastases
Invasive imaging of liver and biliary tract
Hepatic arteriography and portalhepatic venography
Percutaneous transhepatic cholangiography
Endoscopic imaging of the hepatobiliary system
Endoscopic retrograde cholangiopancreatography
Cholangioscopy
Cholangiography
Choledocholithiasis
Biliary strictures
Biliary leaks/fistulae
Congenital conditions
Endoscopic ultrasound
References
PART II General Considerations
4 Physioanatomic Considerations
Surface anatomy
Segmental anatomy
Embryology
Large vessels of the liver
Portal veins
Hepatic veins
Hepatic arteries
Hepatic collateral circulation
Lymphatics
Nerves
Biliary system
Large ducts and gallbladder
Intrahepatic ducts
Variations and surgical implications
Microanatomy
Normal human histology
Hepatocytes
Endothelial cells and sinusoids
Formation of lymph
Biliary tree
Stellate cells
Kupffer cells
Liver-associated lymphocytes
Stroma
Three-dimensional organization of the liver
Hepatocellular heterogeneity
Control of hepatic microcirculation
Pathogenesis of chronic liver disease
Vascular lesions
Parenchymal extinction lesions
Role of pressure gradients
Mechanisms of vascular obstruction and therapeutic significance
Regression of cirrhosis
Further reading
References
5 Bilirubin Metabolism and Jaundice
Introduction
Sources, structure, and plasma transport of bilirubin
Bilirubin production from heme
Possible cytoprotective effects of the heme oxygenase/biliverdin reductase pathway
Quantitative aspects of bilirubin production
Structure of bilirubin-IXa
Other bilirubin isomers
Bilirubin in plasma
Hepatic disposition of bilirubin
Bilirubin uptake
Intracellular binding
Bilirubin glucuronidation
Canalicular excretion of bilirubin
Fate of bilirubin in the gastrointestinal tract
Bilirubin in the urine
Clinical physiology of bilirubin
Measurement of plasma bilirubin concentration
Normal ranges
Hyperbilirubinemia and jaundice
Causes and consequences of hyperbilirubinemia
Familial hyperbilirubinemias
Familial unconjugated hyperbilirubinemias
Familial conjugated hyperbilirubinemias
Familial cholestasis syndromes
Progressive familial intrahepatic cholestasis
Benign recurrent intrahepatic cholestasis type 1
Intrahepatic cholestasis of pregnancy
Further reading
References
6 Hepatic Histopathology
Systematic approach to the liverbiopsy
Special histochemical stains
Immunopathology
Electron microscopy
Other special techniques
Morphologic patterns of injury
Acute necroinflammatory disease (acute hepatitis)
Chronic necroinflammatory injury (chronic hepatitis)
Acute cholestasis
Chronic cholestasis
Steatosis (fatty liver)
Steatohepatitis: alcoholic hepatitis and nonalcoholic (metabolic) steatohepatitis
Granulomatous and suppurative diseases
Metabolic diseases
Vascular disorders
Amyloidosis
Cirrhosis
Fibropolycystic diseases
Tumors
Hemangiomas and other vascular tumors
Metastases
Further reading
References
7 Mechanisms of Liver Injury
Basic mechanisms
Apoptosis
Necroptosis
Necrosis
The innate immune system in liver injury
Cell-to-cell crosstalk: extracellular vesicles
Disease mechanisms
Alcohol-related liver disease
Nonalcoholic steatohepatitis
Viral hepatitis
Ischemia-reperfusion injury
Cholestatic injury
Wilson disease
1-Antitrypsin deficiency
Acute hepatic failure
Therapeutic implications
Acknowledgments
Further reading
References
8 Hepatic Manifestations of Systemic Disorders
Infectious diseases
Bacterial infections
Spirochetal infections
Rickettsial infection
Fungal infections
Hematology
Porphyrias
Lymphoma
Sickle cell disease
Endocrinology
Thyroid diseases
Diabetes mellitus
Gastroenterology
Celiac disease
Inflammatory bowel disease
Rheumatology
Systemic lupus erythematosus
Rheumatoid arthritis and Felty syndrome
Sjögren syndrome
Scleroderma
Adult Still disease
Polyarteritis nodosa
Further reading
References
9 The Liver in Pregnancy
The liver and hemodynamics in normal pregnancy
Liver tests
Liver diseases unique to pregnancy
Primary hepatic pregnancy
Hyperemesis gravidarum
Pathology
Maternal and fetal outcome
Therapy
Intrahepatic cholestasis of pregnancy
Pathology
Clinical and biochemical findings
Maternal and fetal outcome
Pathophysiology
Medical and obstetric management
Preeclampsia liver disorders
HELLP syndrome
Acute fatty liver of pregnancy
Pathology
Clinical and biochemical findings
Maternal and fetal outcome
Pathophysiology
Medical and obstetric management
Intercurrent liver disease in pregnancy
Acute viral hepatitis
Hepatitis caused by herpes simplex virus
Biliary tract disease and pancreatitis
Budd-Chiari syndrome (hepatic vein thrombosis)
Drug-induced hepatic injury
Malignant tumors of the liver
Pregnancy in women with chronic liver disease
Cirrhosis and portal hypertension
Specific liver diseases
Alcoholic liver disease
Nonalcoholic fatty liver disease
Chronic hepatitis B
Chronic hepatitis C
Autoimmune hepatitis
Primary biliary cholangitis
Wilson disease
Benign liver tumors (hepatocellular adenoma, focal nodular hyperplasia, hemangioma)
Familial hyperbilirubinemia
Porphyrias
Budd-Chiari syndrome
Portal vein thrombosis
Liver transplantation
Further reading
References
PART III Consequences of Liver Disease
10 Hepatic Fibrosis
Biologic basis of hepatic fibrosis
General principles
Extracellular matrix composition of the normal liver and hepatic scars
Biologic activity of extracellular matrix in the liver
Cellular sources of extracellular matrix in normal and fibrotic liver
Degradation of extracellular matrix
Stellate cell activation, the central event in hepatic fibrosis
Clinical aspects
Fibrosis progression and reversibility
Diagnosis and assessment
Therapy
Future prospects
Supporting research grants
References
11 Preoperative Evaluation of the Patient with Liver Disease
Introduction
General principles of anesthesia care and preoperative evaluation
Effects of anesthesia on the liver
Volatile agents
Intravenous agents
Regional anesthesia
Positive pressure ventilation
Volatile agent-induced hepatic injury
Effects of liver disease on anesthetic drug pharmacokinetics and pharmacodynamics
Preoperative evaluation
Preanesthetic assessment
Prediction of perioperative risk
Using MELD score to determine postoperative mortality risk
Operative risk related to specific liver diseases
Evaluation of cardiac risk in patients undergoing noncardiac surgery
Assessment of the respiratory system
Postoperative complications in patients with cirrhosis
Perioperative risks in patients with liver disease according to the nature of the surgery
Cardiac surgery
Cholecystectomy
Hepatic resections
Other abdominal surgery
Orthopedic surgery
Transurethral resection of the prostate
Perioperative monitoring
Management of ascites and hepatic hydrothorax
Correction of coagulation abnormalities
Summary and conclusions
References
12 Management of Portal Hypertension
Definition and classification of portal hypertension
Pathophysiology of portal hypertension
Increased resistance to portal blood flow
Splanchnic vasodilation and increase in portal blood inflow
Development of gastroesophageal varices and variceal hemorrhage
Stages of cirrhosis/portal hypertension
Compensated cirrhosis
Decompensated cirrhosis
Evaluation of portal hypertension
Direct portal pressure measurement
Indirect portal pressure measurement
Endoscopy
Assessment of portal hypertension with noninvasive tests
Mechanism of action of therapies used in the management of portal hypertension
Pharmacological therapies
Variceal obliterative therapies
Portal decompressive therapies
Management of portal hypertension: clinical settings
Patients with compensated cirrhosis and mild portal hypertension
Patients with compensated cirrhosis with clinically significant portal hypertension without gastroesophageal varices
Patients with compensated cirrhosis and gastroesophageal varices
Patients with acute variceal hemorrhage
Patients recovering from a recent variceal hemorrhage
Management of gastric varices
Prevention of first bleeding from gastric varices
Management of the episode of acute hemorrhage from gastric varices
Prevention of recurrent hemorrhage from gastric varices
Ectopic varices
Portal hypertensive gastropathy
Management of portal hypertensive gastropathy
References
13 Renal Complications of Liver Disease and the Hepatorenal Syndrome
Introduction
Renal disease in compensated vliver disease
Renal disease in decompensated liver disease
Pathophysiology
Definitions
Assessment of renal dysfunction
Biomarkers of renal damage
Diagnostic workup
Management of functional renal failure including hepatorenal syndrome
General measures
Albumin as volume replacement therapy
Vasoconstrictor therapy
Transjugular intrahepatic portosystemic shunt
Extracorporal albumin dialysis
Renal replacement therapy
Liver transplantation
Prognosis
Prevention
References
14 Pulmonary Manifestations of Liver Disease
Hepatopulmonary syndrome
Definition
Epidemiology, risk factors, and disease associations
Pathogenesis
Clinical features
Evaluation for hepatopulmonary syndrome
Prognosis and natural history
Therapy
Portopulmonary hypertension
Definition
Epidemiology, risk factors, and disease associations
Pathology and pathogenesis
Clinical features
Evaluation for portopulmonary hypertension
Prognosis and natural history
Therapy
Summary and conclusions
Further reading
References
15 Ascites and Spontaneous Bacterial Peritonitis
Diagnosis and differential diagnosis
Pathogenesis of ascites formation in liver disease
Evaluation of patients with ascites
History
Physical examination
Abdominal paracentesis
Differential diagnosis by ascitic fluid analysis
Serum analysis
Complications of ascites
Infection
Tense ascites
Abdominal wall hernias
Pleural effusions
Treatment of ascites
Nonportal hypertension-related (low albumin gradient) ascites
Portal hypertension-related (high albumin gradient) ascites
Management of precipitating causes
Refractory ascites
Summary of treatment of patients with cirrhosis and ascites
Management protocol of patients with cirrhosis and ascites
Where to hospitalize?
History and physical examination
Initial laboratory testing and imaging
Paracentesis
Diet
Diuretics
Daily testing
Maintenance fluids
Follow-up
References
16 Hepatic Encephalopathy
History
Epidemiology and burden
Nomenclature
Axis 1
Axis 2
Axis 3
Axis 4
Examples
Etiopathogenesis
Ammonia
Systemic inflammation and microbiome
-Aminobutyric acid (GABA)
Plasma amino acid imbalance
Diagnosis
Neurological examination
Laboratory testing
Clinical scales for grading overt hepatic encephalopathy
Clinical tests for covert hepatic encephalopathy
Brain imaging
Management of covert hepatic encephalopathy
Management of overt hepatic encephalopathy
Reducing intestinal nitrogen load
Nitrogen excretion from body
Correction of intracerebral neurotransmitters
Miscellaneous agents
Management of hepatic encephalopathy following transhepatic internal jugular portosystemic shunts
Management of persistent hepatic encephalopathy
Liver support systems
Liver transplantation
References
17 Acute Liver Failure
Introduction
Definitions
Epidemiology
Pathogenesis
Etiology and disease-specific treatment
Acetaminophen overdose
Hepatitis A
Hepatitis B
Hepatitis E
Other viruses
Autoimmune hepatitis
Idiosyncratic drug-induced liver injury
Pregnancy-associated acute liver failure
Wilson disease
Ischemia
Other etiologies
Indeterminate acute liver failure
Approach to the patient with acute liver failure
Initial diagnostic evaluation
Assessment of disease severity
Supportive measures
Nutrition
Hepatic encephalopathy and cerebral edema
Infections
Acute kidney injury
Hemodynamic abnormalities
Coagulopathy
Role of liver transplantation
Epidemiologic considerations
Listing and management while awaiting an organ offer
ABO-incompatible liver transplantation
Prognostic models
Long-term outcomes
Liver transplant recipients
Spontaneous survivors
Investigational approaches
Extracorporeal treatments
Conclusions
References
18 Acute-on-Chronic Liver Failure
Introduction
The concept of acute-on-chronic liver failure
Definition of acute-on-chronic liver failure
The Asian Pacific Association for the Study of the Liver definition
The American Association for the Study of Liver Disease and European Association for the Study of the Liver definition
The European Association for the Study of the Liver-Chronic Liver Failure consortiums definition
The North American Consortium for the Study of End-Stage Liver Disease definition
Epidemiology
Prevalence of ACLF
Patient characteristics
Pathophysiology
The inflammatory response
Bacterial translocation as a major initiator of inflammation in cirrhosis
Other causes of inflammation in cirrhosis
Interactions between sterile inflammation and bacterial translocation
The consequences of continued inflammation
The systemic inflammation hypothesis of decompensation of cirrhosis and acute-on-chronic liver failure
Predisposing factors for the development of ACLF
Genetics
Age
Lifestyle factors
The severity of portal hypertension
Precipitating factors for the development of ACLF
Viral hepatitis
Bacterial infections
Active alcoholism
Drug-induced liver injury
Other precipitants of ACLF
Acute-on-chronic liver failure without any precipitating factors
Organ failures
Renal failure
Cerebral failure
Liver failure
Circulatory failure
Respiratory failure
Hematological failure
Diagnosis
Management
Control of the precipitating event
General measures
Treatment of bacterial infections
Treatment of other precipitating events
Treatment of individual organ failures
Extracorporeal liver support systems
Liver transplantation
Prognosis
Conclusion
References
19 Malnutrition and Liver Disease
Introduction
Assessment of malnutrition
Anthropometry
Biological parameters (visceral proteins)
Creatinine height index
Assessment of muscle strength
Bioelectrical impedance
Air-displacement plethysmography
Imaging
Subjective global assessment
Energy/protein balance
Metabolomics
Causes of malnutrition
Anorexia/altered taste/smell
Nausea/vomiting/delayed gastric emptying
Diarrhea/malabsorption/bacterial overgrowth
Poor food availability/quality/unpalatable diets (Na, protein)
Hormones/cytokine effects
Complications of liver disease (hepatic encephalopathy, ascites)
Fasting for procedures/interruption of feeding
Prevalence of malnutrition and impact on outcome
Global malnutrition
Macronutrient malnutrition
Micronutrient malnutrition
Nutrition: gut-microbiome-liver axis
Nutrition and the gut microbiota
Gut microbiota, metabolomics, and nonalcoholic fatty liver disease/alcoholic liver disease
Nutritional recommendations
Inpatient/intensive care unit patients
Outpatients
Transplant
Hepatocellular carcinoma
Conclusions
References
PART IV Cholestatic Disorders
20 Primary Sclerosing Cholangitis
Introduction
Epidemiology and risk factors
Overview
Prevalence in patients with inflammatory bowel disease
Epidemiology associated with inflammatory bowel disease
Epidemiology not associated with inflammatory bowel disease
Epidemiology of small-duct primary sclerosing cholangitis
Epidemiology of IgG4 sclerosing cholangitis
Epidemiology of primary sclerosing cholangitis and associated autoimmune diseases
Pathogenesis
Heritability and genetics
HLA and non-HLA susceptibility associations
HLA and non-HLA genes and resistance
Role of gut microbiota
Autoantibodies
Role of cholangiocytes, pathogen-associated molecular patterns, and innate immunity
Role of gut-primed T cells, aberrant expression of adhesion molecules, chemokines, and cytokines
Pathogenesis of progressive disease
Pathogenesis of cholangiocarcinoma
Clinical aspects of primary sclerosing cholangitis
Classification of subtypes
Health-related quality of life
Natural history
Sequential clinical phases
Diagnostic criteria
Primary sclerosing cholangitis in children and adolescents
IgG4-SC and differential diagnosis
Physical findings
Laboratory findings
Histopathology
Identification and management of associated malignancies
Cholangiocarcinoma
Gallbladder adenocarcinoma
Colorectal carcinoma in primary sclerosing cholangitis patients with inflammatory bowel disease
Hepatocellular carcinoma
Pancreatic adenocarcinoma
Assessment of progression and outcomes
Medical management
Management of complications specific for primary sclerosing cholangitis
Management of complications of chronic cholestasis
Medical management of primary sclerosing cholangitis
Immunosuppressive drugs
Ursodeoxycholic acid
Investigational therapies
Surgical therapies
Hepatobiliary surgery
Orthotopic liver transplantation
Orthotopic liver transplantation for cholangiocarcinoma
Future treatment strategies
References
21 Primary Biliary Cholangitis
Introduction
Epidemiology
Pathophysiology
Risk factors
Loss of immune tolerance to mitochondrial antigens
Linking antimitochondrial autoantibodies to cholangitis
Progressive nonsuppurative cholangitis
Clinical presentation
Asymptomatic disease
Symptomatic disease
Other symptoms
Clinical findings on physical examination
Diagnosis
Liver biopsy
Treatment
Monitoring response to treatment
Use of adjunctive therapy
Treatment of PBC symptoms and consequences
Natural history of PBC
Clinical progression of PBC
Histological progression of PBC
Mortality associated with PBC
Natural history of PBC in patients treated with UDCA and OCA
Natural history of AMA-negative PBC
Prognostic variables and models for PBC
Markers of disease progression
Liver transplantation for PBC
Variant syndromes
Conclusion
References
22 Autoimmune Hepatitis
Introduction
Pathogenesis
T cell focus
Deficits in immune regulation
Environmental triggers
Genetics
Histopathology
Autoantibodies and autoantibody classification
Clinical features
Demographics and epidemiology
Symptomatology and clinical signs
Type 1 and type 2 disease
Associated features
Diagnosis
Treatment
Pharmacotherapy
Transplantation
General considerations
Pregnancy
Prognosis and the long term
Variant syndromes
Cross-over syndromes
The elderly and inactive disease
Drug-related liver injury
Summary
Acknowledgments
References
PART V Viral Hepatitis
23 Hepatitis A and E
Historical perspective
Hepatitis A
Virology
Epidemiology
Mode of transmission
Immunopathogenesis
Clinical features
Acute liver failure
Diagnostic methods
Treatment
Prevention
Hepatitis E
Virology
Epidemiology
Immunopathogenesis
Clinical features
Diagnostic methods
Treatment
Prevention
References
24 Hepatitis B and D
Hepatitis B virus
Epidemiology
Clinical manifestations
Diagnosis
Hepatitis B virus genotypes
Viral variants
Treatment
Hepatitis D virus
Epidemiology
Modes of transmission
Genotypes
Clinical course
HDV serology
Diagnosis
Natural history
Treatment
References
25 Hepatitis C
A discovery that changed the practice of hepatology
Virion structure and genome organization
Untranslated RNA segments
HCV-encoded proteins
HCV replication
Cell culture models of HCV replication
Viral entry
Viral protein and RNA synthesis
Innate immune responses to HCV
Innate immune sensing of HCV infection
Intrahepatic interferon responses in the HCV-infected patient
Small-molecule antivirals: mechanisms of action
Direct-acting vs. host-targeting antiviral drugs
NS5B polymerase inhibitors
NS34A protease inhibitors
NS5A inhibitors
Interactions of HCV with host immune cells
Adaptive immune responses against HCV
CD4+ T cell responses
CD8+ T cell responses
B-cell responses
Strategies for viral persistence
T-cell energy
Mutational escape
Regulatory T cells
Correlates of protective immunity against HCV
Vaccine strategies
Epidemiology of hepatitis C infection
Risk factors for hepatitis C infection
Intravenous drug use
Unsafe therapeutic injection practices
Blood transfusions
Sexual transmission
Perinatal transmission
Occupational exposure to healthcare providers
Diagnosis and testing for hepatitis C infection
Natural history
Acute hepatitis C virus infection
Chronic hepatitis C virus infection
Factors linked to disease progression
Extrahepatic manifestations
Histology
Therapy of hepatitis C
Historical perspectives of interferon-based therapy for HCV
The road to ribavirin combination therapy
Ribavirin monotherapy improves ALT but has negligible impact on HCV RNA
Combining ribavirin with interferon substantially improves antiviral response
Modification of interferon with pegylation improves pharmacokinetics
Peginterferon combined with ribavirin improves rates of sustained virologic response
Refining treatment regimens to optimize response
Side effects of interferon and ribavirin
IL28B genotype is predictive of treatment response to interferon-based therapy
Direct-acting antiviral agents transform the management of hepatitis C
Triple therapy with protease inhibitors
Summary of phase III trials from approved DAA regimens
Treatment of patients with genotype 2
Treatment of patients with genotype 3
Treatment of patients with genotype 4
Treatment for patients with genotypes 5 and 6
New regimens under investigation
Impact of baseline resistance-associated variants
Baseline NS5A resistance
Treatment options for patients who have failed prior therapy
Treatment of protease inhibitor failures
Treatment of NS5A failures
Safety of DAAs
Hepatitis B virus reactivation
Recurrence of hepatocellular carcinoma
Ribavirin and direct-acting antiviral drugs
Treatment of hepatitis C in unique populations
Management of patients after achieving sustained virological response
References
PART VI Alcohol- and Drug-induced Liver Disease
26 Alcoholic Liver Disease
Spectrum and clinical features of liver disease due to alcohol
Definition and screening for alcohol use disorders
Diagnosis and evaluation of alcoholic liver disease
Laboratory features of alcoholic liver disease
Imaging in alcoholic liver disease
Liver biopsy in alcoholic liver disease
Epidemiologic estimates of the risk of alcoholic liver disease
Fatty liver
Alcoholic hepatitis and cirrhosis
Mechanisms of liver injury from ethanol
Alcohol metabolism and oxidative stress
Alcohol-related changes in gut permeability, gut microbiome, and translocation of bacterial products
Pattern recognition receptors and inflammasome activation in amplification of inflammatory signals
Recruitment, activation, and phenotypic changes in innate immune cells in the liver including macrophages and neutrophil leukocytes
Novel pathways in alcoholic liver disease
Risk factors for alcoholic liver disease (Box 26.5)
Patterns of consumption and beverage type
Gender
Nutritional factors: protein, vitamins, and minerals
Impact of obesity on alcoholic liver disease
Alcohol and iron overload
Alcohol and hepatitis C
Genetic factors
Therapy for alcoholic liver disease
Predicting short-term mortality in alcoholic hepatitis
Nutritional support for alcoholic liver disease
Glucocorticoid therapy for alcoholic hepatitis
Anti-tumor necrosis factor therapy
Pentoxifylline
Antioxidant therapy
S-adenosylmethionine (SAMe) therapy
Liver transplantation for alcoholic hepatitis and alcoholic cirrhosis
Future therapies for alcoholic liver disease and alcoholic hepatitis
Conclusions
References
27 Drug-induced Hepatotoxicity
Introduction
Epidemiological aspects of hepatotoxicity
Epidemiology in the general population
Epidemiology of liver failure
Drug-induced liver injury registries
Mechanisms of hepatotoxicity
Toxicity related to the therapeutic effect [6,7]
Impairment of mitochondrial energy production [6,36]
Metabolic activation
Molecular and cellular lesions leading to direct toxicity (Fig. 27.1)
Recent definitions of liver injury
Acute drug-induced liver injury
Other types of liver injury
Causality assessment in drug-induced liver injury
Diagnostic difficulties
Drug-induced autoimmune liver injury
Scoring systems and diagnostic scales
Factors contributing to drug hepatotoxicity
Genetic factors
Acquired factors
Main drugs responsible for liver injury
Chronic hepatitis and cirrhosis
Granulomatous hepatitis
Macrovesicular, microvesicular steatosis, and other storage diseases
Acute and chronic cholangitis
Vascular lesions of the liver
Benign and malignant tumors
Hepatotoxicity of herbal medicines and dietary complements
Dietary complements (Table 27.10)
Illegal and recreational compounds
Hepatotoxicity of chemicals and industrial products
Epidemiological aspects
Causative agents and clinical expression
Susceptibility factors
Toxicity detection
Perspectives and conclusion
References
28 Mechanisms of Drug-induced Liver Injury
Mechanisms of drug-induced hepatocyte injury
Mitochondrial dysfunction
Oxidative stress
Alterations in bile acid homeostasis
Multifactorial mechanisms
Limitations of preclinical models to detect drug-induced hepatocyte injury
Cholestatic vs. hepatocellular injury
Immune-mediated hepatotoxicity
The creation of neoantigens
Hepatocyte stress
Danger signals and innate immune response
The adaptive immune response and immune tolerance
Non-immune-mediated idiosyncratic DILI
Risk factors for drug-induced liver injury
Dose
Lipophilicity
Metabolism
Biliary elimination
Age
Sex
Underlying liver dysfunction
Drug interactions
Genetic variability
Novel approaches to understanding and predicting drug-induced liver injury
Cellular models
Mechanism-specific assays
Animal models
Computational models
Biomarkers
New drug classes associated with drug-induced liver injury
Biologics
Herbal and dietary supplements
Summary and future directions
References
PART VII Genetic and Metabolic Disease
29 Wilson Disease
History
Genetics
Pathophysiology
Pathology
Hepatic pathology
Neuropathology
Miscellaneous pathologic changes
Diagnosis
Ceruloplasmin
Nonceruloplasmin-bound copper (NCC)
Corneal Kayser-Fleischer rings
Urinary excretion of copper
Concentration of copper in the liver
Molecular genetic studies
Ultrastructural studies
Clinical manifestations
Treatment
Further reading
References
30 Hemochromatosis and Iron Storage Disorders
Background and history
Iron homeostasis
Regulation of hepcidin expression
Glyceronephosphate O-acyltransferase
Iron in cellular injury
Classification of hereditary hemochromatosis iron overload syndromes
Epidemiology of HFE-related hemochromatosis
Classification of hereditary hemochromatosis
HFE-related (type 1) hereditary hemochromatosis
Juvenile (type 2) hereditary hemochromatosis
TFR-related (type 3) hereditary hemochromatosis
Type 4 hereditary hemochromatosis (ferroportin disorder)
Clinical features of hereditary hemochromatosis
Fatigue
Liver disease
Arthropathy
Heart disease
Diabetes mellitus
Hypogonadism
Thyroid disease
Skin pigmentation
Infection and immunity
Clinical and biochemical penetrance of hemochromatosis
Diagnosis
Iron studies
Genetic testing
Imaging studies
Evaluation of hepatic iron overload
Screening
Family screening
Population screening
Long-term management (Fig. 30.4)
Phlebotomy
Iron chelators
Proton pump inhibitors
Erythrocytapheresis
Potential future therapeutics
Orthotopic liver transplantation
Arthritis treatment
Prognosis
Secondary iron overload (Table 30.4)
Hematological disorders
African iron overload
Chronic liver diseases
Treatment of secondary iron overload
Conclusions
Acknowledgments
Further reading
References
31 Alpha-1 Antitrypsin Deficiency
Incidence
Clinical manifestations
Liver disease
Lung disease
Alpha-1 antitrypsin structure, function, and physiology
Alpha-1 antitrypsin gene structure
Alpha-1 antitrypsin protein structure
Protease inhibitor system for classification of structural variants of a1-antitrypsin
Alpha-1 antitrypsin function
Biosynthesis of 1-antitrypsin
Clearance and distribution of 1-antitrypsin
Mechanism for deficiency of 1-antitrypsin in PIZZ individuals
Pathogenesis of liver injury in PIZZ individuals
Mechanism of liver injury
Diagnosis
Treatment
Genetic counseling
Population screening
Further reading
References
32 Nonalcoholic Fatty Liver Disease
Introduction
Terminology and diagnostic criteria
Clinical criteria of nonalcoholic steatohepatitis
Histologic criteria of nonalcoholic steatohepatitis
Presumed nonalcoholic fatty liver disease
Cryptogenic cirrhosis
Focal steatosis and focal fat sparing
Historical perspective
Early observations
The ethanol conundrum
Hepatogenous diabetes
Epidemiology and prevalence
Obesity
Insulin resistance and type 2 diabetes mellitus
Hyperlipidemia
Metabolic syndrome
Normal body mass index
Pediatric patients
Nonalcoholic steatohepatitis in other liver diseases
Genetic and familial factors in nonalcoholic fatty liver disease
Ethnic variation
Familial factors
Genetic variation
Clinical and laboratory findings
Symptoms and signs
Common laboratory findings
Other laboratory abnormalities
Tests of insulin resistance, dyslipidemia, and physical conditioning
Findings of lipodystrophy
Findings suggestive of mitochondrial disease
Weber-Christian disease
Liver imaging
The role of liver biopsy in nonalcoholic fatty liver disease
Noninvasive surrogates
Limitations of liver biopsy
Biopsy scoring
Natural history and prognosis
Clinical course based on initial biopsy
Histological progression over time
Long-term mortality in nonalcoholic fatty liver disease
Prognosis of nonalcoholic steatohepatitis-related cirrhosis
Cryptogenic cirrhosis
Hepatocellular cancer
Experimental and animal models of nonalcoholic fatty liver disease
Small animal models
Large animal steatosis
Pathogenesis of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Local cellular factors
Systemic factors
Other conditions associated with NAFLD/NASH ("secondary" NASH)
Jejunoileal bypass
Medication-induced
Parenteral nutrition, malnutrition, and celiac disease
Solvents and industrial agents
Wilson disease and other inherited metabolic diseases
The obese, diabetic patient with newly discovered cirrhosis
Treatment of nonalcoholic fatty liver disease
Overview of therapy
Who should be treated
Endpoints of therapy
Initial intervention
Weight loss agents
Weight reduction surgery
Cytoprotective agents
Antioxidant therapy with vitamin E
Antidiabetic agents
Antihyperlipidemic agents
Emerging agents in active study
Antifibrotic agents in nonalcoholic steatohepatitis
Liver transplantation, disease recurrence, and donor organs
Further reading
References
PART VIII Vascular Diseases of the Liver
33 Vascular Liver Disease
Hepatic venous outflow tract obstruction - Budd-Chiari syndrome
Definitions
Epidemiology
Pathophysiology
Etiology
Manifestations
Diagnosis - imaging and histopathology
Treatment
Course and prognosis
Extrahepatic portal vein obstruction - portal vein thrombosis and portal cavernoma in the absence of cirrhosis
Definitions
Epidemiology
Etiology
Pathophysiology
Manifestations and natural history
Diagnosis - imaging and liver biopsy
Treatment
Outcome and prognosis
Portal vein thrombosis in patients with cirrhosis
Epidemiology
Etiology
Pathophysiology - manifestations and natural history
Diagnosis
Treatment
Idiopathic noncirrhotic intrahepatic portal hypertension
Definition
Epidemiology
Etiology and pathogenesis
Pathophysiology - manifestations and natural history
Diagnosis - imaging and liver biopsy
Treatment
Outcome and prognosis
Sinusoidal obstruction syndrome/veno-occlusive disease
Definition
Causes and epidemiology
Pathophysiology - manifestations and natural history
Diagnosis
Prophylaxis
Treatment of established sinusoidal obstruction syndrome/veno-occlusive disease
Hepatic vascular malformations in hereditary hemorrhagic telangiectasia
Definition
Epidemiology
Etiology and pathogenesis
Pathophysiology - manifestations and natural history
Diagnosis - imaging and pathology
Treatment
Congenital portosystemic shunt - Abernethy malformation
Definition
Epidemiology
Causes and pathogenesis
Pathophysiology - manifestations and natural history
Diagnosis
Treatment
Nonobstructive sinusoidal dilatation and peliosis
Definition
Epidemiology
Causes
Pathophysiology - manifestations and natural history
Diagnosis
Treatment and prognosis
References
34 The Liver in Circulatory Failure
Anatomy and physiology of hepatic blood flow
Ischemic hepatic injury
Pathophysiology
Clinical features
Hepatic ischemia in the patient with cirrhosis
Hepatic infarction
Congestive hepatopathy
Hepatic outflow obstruction
Ischemic cholangiopathy
Heat stroke and the liver
The liver in atherosclerotic cardiovascular disease
References
PART IX Benign and Malignant Tumors
Cystic Disorders
35 Benign Tumors, Nodules, and Cystic Diseases of the Liver
Tumors or pseudotumors derived from hepatocytes
Focal nodular hyperplasia
Hepatocellular adenoma
Macronodules developing on cirrhosis
Nodular regenerative hyperplasia
Focal fatty change
Tumors or pseudotumors derived from cholangiocytes
Bile duct adenoma
Bile duct hamartoma
Biliary adenofibroma
Tumors or pseudotumors derived from mesenchymal/endothelial cells
Hemangioma
Epithelioid hemangioendothelioma
Epithelioid angiomyolipoma
Inflammatory pseudotumor
Mesenchymal hamartoma
Infantile hemangioendothelioma
Pseudolipoma
Cystic diseases
Simple biliary cysts
Polycystic liver disease
Mucinous cystic neoplasm
Hydatid disease
Cystic hydatid disease
Alveolar hydatid disease
References
36 Hepatocellular Carcinoma
Epidemiology
Risk factors for hepatocellular carcinoma
Hepatitis B virus
Hepatitis C virus
Alcohol, tobacco, and coffee
Pathogenesis
Pathology
Clinical manifestations
Surveillance
Diagnosis
Staging and prognosis
Treatment
Surgical treatment
Percutaneous treatments
Transarterial chemoembolization
Systemic therapies
References
37 Surgical Options in Liver Cancers
Epidemiology of hepatocellular carcinoma
Pathogenesis and pathophysiology of hepatocellular carcinoma
Screening and imaging for hepatocellular carcinoma
Assessment of liver function and reserve
Overview of hepatocellular carcinoma treatment options
Liver resection for hepatocellular carcinoma
Portal vein embolization
Liver transplantation for hepatocellular carcinoma
Treatments for patients who cannot undergo resection or transplant
The epidemiology and pathogenesis of cholangiocarcinoma
Preoperative portal vein embolization in patients with cholangiocarcinoma
Preoperative biliary drainage in patients with cholangiocarcinoma
Hilar cholangiocarcinoma
Surgical resection of mid and distal cholangiocarcinoma
Liver transplantation vs. resection for cholangiocarcinoma
Mixed hepatocellular carcinoma and cholangiocarcinoma
Acknowledgments
Further reading
References
PART X Infectious and Granulomatous Disease
38 Amoebic and Pyogenic Liver Abscesses
Amoebic liver abscess
Epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Therapy
Vaccination
Pyogenic liver abscess
Epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Therapy
Further reading
References
39 Parasitic Diseases
Protozoal diseases
Malaria
Leishmaniasis
Helminthic liver diseases
Schistosomiasis
Fascioliasis
Clonorchiasis and opisthorchiasis
Echinococcosis
Further reading
References
40 Granulomas of the Liver
Introduction
Histopathology
Pathophysiology
Etiology
Clinical consequences
Clinical evaluation
Clinical and historical clues
Laboratory studies
Serologic tests
Radiologic tests
Histopathologic appearance
Specific causes
Sarcoidosis
Mycobacterium tuberculosis
Leprosy (Mycobacterium leprae)
Granulomas in HIV and AIDS
Schistosomiasis
Q fever
Other infectious causes
Granulomas associated with chronic viral hepatitis and its therapy
Granulomas in other chronic cholestatic liver diseases
Drug-induced granulomas
Granulomas associated with metals and minerals
Granulomas associated with malignancy and immunodeficiency states
Miscellaneous causes
Idiopathic granulomatous hepatitis and fever of unknown origin
Treatment of hepatic granulomas and granulomatous hepatitis
General principles
Conclusions
Further reading
References
PART XI Elements of Liver Transplantation
41 Selection of Candidates and Timing of Liver Transplantation
Background
Indications for liver transplantation
Evaluation for liver transplantation
Estimating disease severity: prognostic models
Estimating disease severity: special populations and disease-specific considerations
Health-related quality of life
Contraindications to liver transplantation
Timing of liver transplantation
Ways to impact the timing of transplantation
Conclusion
References
42 Immunosuppression: The Global Picture
Historical perspective
Immunologic mechanisms of rejection: the three-signal pathway of lymphocyte activation
Classification of immunosuppressive drugs
Nonbiologic immunosuppressive agents
Corticosteroids
Azathioprine
Cyclosporine
Tacrolimus
Mycophenolate mofetil
Inhibitors of mechanistic target of rapamycin (mTOR)
Biologic immunosuppressive agents
Depleting antibodies
Monoclonal antibodies
Nondepleting antibodies and fusion proteins
Costimulation blockade
Liver allograft rejection
Goals of immunosuppression
References
43 The First Six Months Following Liver Transplantation
Introduction
Intensive care unit management
General management
Graft function
Infectious complications
Immediate surgical complications
Immunosuppression management
Hepatitis B prophylaxis
Floor care
Monitoring for rejection and treatment
Medical complications
Cytomegalovirus and Pneumocystis jirovecii prophylaxis
Clinic visits
General management
Late surgical complications
Immunosuppression-related complications
Early hepatitis C recurrence
Early disease recurrence
Cancer
Long-term follow-up
References
44 Long-term Management of the Liver Transplant Patient
Preventive care
Vaccines
Dental care
Metabolic complications
Obesity
Hyperlipidemia
Hypertension
Diabetes
Bone disease
Inflammatory bowel disease
Renal dysfunction
Transplant-related diseases
Biliary complications
De novo malignancy
Causes of mortality
References
45 The Liver Transplant Procedure
Introduction
Terminology
Historical background
Donor considerations
Deceased donor operation
Living liver donor considerations
Split deceased liver donor
Recipient operation
Hepatectomy
Anhepatic phase
Implantation
Complications
Primary nonfunction
Hepatic artery stenosis/thrombosis
Portal vein stenosis/thrombosis
Hepatic venous outflow obstruction
Biliary complications
Bleeding
Survey of liver transplantation practices
Conclusions
References
46 Recurrent Disease Following Liver Transplantation
Introduction
Hepatitis C
Natural history
Risk factors
Treatment
Future concerns and directions
Hepatitis B
Risk factors for HBV recurrence
Prevention of hepatitis B recurrence
Treatment prior to transplant
Hepatitis B immunoglobulin
Vaccination
Treatment of HBV recurrence
Primary biliary cholangitis
Diagnosis
Risk factors for recurrent primary biliary cholangitis
Treatment
Primary sclerosing cholangitis
Diagnosis
Treatment
Autoimmune hepatitis
Diagnosis
Risk factors for recurrent autoimmune hepatitis
Treatment
De novo autoimmune hepatitis
Nonalcoholic steatohepatitis
Alcohol-related liver disease
Vascular diseases
Metabolic disease
Acute liver failure
Summary
References
47 The Role of Retransplantation
Rate of retransplantation and indications
Indications for early retransplantation
Primary graft dysfunction
Hepatic artery thrombosis
Indications for late retransplantation
Chronic rejection
Primary biliary cirrhosis
Primary sclerosing cholangitis
Autoimmune hepatitis
Nonalcoholic steatohepatitis
Alcoholic liver disease
Hepatitis B virus
Hepatitis C virus
Results of retransplantation
Comparison with primary transplantation
Timing of retransplantation
Outcomes of retransplantation in hepatitis C virus patients
Cause of death following retransplantation
Predictors of mortality after retransplantation
Models to predict survival after retransplantation
MELD score and retransplantation
Living donor liver transplantation and retransplantation
Liver retransplantation in patients with HIV-1
Conclusions
Further reading
References
48 Controversies in Liver Transplantation
Liver allocation and distribution
MELD exception scores
Simultaneous liver-kidney transplantation allocation
Further reading
References
Index
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