Cardio-Hepatology: Connections Between Hepatic and Cardiovascular Disease

Front Cover
Cardio-Hepatology
Copyright Page
Dedication
Contents
List of contributors
Preface
I. Liver and heart
1 The liver–heart relationship: a history
Introduction
The ancient world: east and west
The medieval era
The modern era
The liver in heart failure
The heart in liver failure
Hyperdynamic circulation of cirrhosis
Cirrhotic cardiomyopathy
References
2 Nonalcoholic fatty liver disease and cardiovascular disease
Introduction
The definition of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Association between nonalcoholic fatty liver disease/nonalcoholic steatohepatitis and cardiovascular disease
Dyslipidemia as causative factors for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis and cardiovascular disease
Possible underlining molecular mechanisms between nonalcoholic steatohepatitis and atherosclerosis
Association between NAFLD/hepatic fibrosis and cardiac dysfunction
Conclusion
References
3 Pathophysiologic changes in chronic heart failure affecting drug pharmacokinetics
Introduction
Fundamental clinical pharmacokinetic principles
Clearance concepts
Hepatic clearance and oral bioavailability
Renal clearance
Volume of distribution
Half-life
Pathophysiological changes affecting pharmacokinetics in patients with chronic heart failure
Intestinal permeability
Hepatic clearance
Hepatic blood flow, hepatic intrinsic clearance
Plasma protein binding
Intravenous administration of high hepatic extraction ratio drugs
Oral administration
Renal clearance
Volume of distribution
Pharmacotherapeutic implications: general recommendations
Conclusion
References
4 Drugs at the crossroads of heart and liver
Introduction
Part 1: amiodarone
Historical perspective
Why amiodarone has not been replaced
Pharmacokinetics: the secret to understanding amiodarone
Pharmacokinetics: the determinant of drug exposure
Pharmacokinetics: the untenable concept of total cumulative dose of amiodarone
Amiodarone: separating direct and indirect toxicity
Amiodarone: lessons from pulmonary toxicity when considering hepatotoxicity
Timelines for amiodarone hepatotoxicity
Amiodarone: a drug outside the comfort zone of mainstream therapeutics
Amiodarone hepatotoxicity: plausible pathogenesis
Amiodarone hepatotoxicity: clinical picture and histological findings
Amiodarone hepatotoxicity: diagnosis
How toxic is amiodarone to the liver?
Amiodarone: effects on hepatic metabolism and other drugs
Amiodarone hepatotoxicity: the challenge of attribution
Monitoring hepatic function in patients receiving amiodarone
Therapy for hepatotoxicity
Amiodarone: principles of clinical pharmacology
Conclusions
Part 2: beta-blockers
Introduction
Pathophysiology of portal hypertension and cirrhosis stages
Clinical pharmacology of nonselective beta-blockers in portal hypertension related to cirrhosis
Clinical contexts for the use of nonselective beta-blockers
Prevention of the development of varices
Prevention of decompensation
Prevention of first esophageal variceal bleeding
Preventing esophageal variceal rebleeding
Beta-blockers in acute on chronic liver failure
Bleeding from gastric varices
Beta-blockers for portal hypertensive gastropathy
The concept of a therapeutic window of nonselective beta-blockers in decompensated cirrhosis
Summary and current recommendations
References
5 Obstruction of the liver circulation
Introduction
Budd–Chiari syndrome
Risk factors
Natural history
Staging and prognosis
Treatment and management of complications
Stepwise treatment strategy
Anticoagulation
Thrombolysis
Recanalization
Transjugular intrahepatic portosystemic shunt
Liver transplantation
Noncirrhotic nontumoral portal vein thrombosis
Risk factors
Systemic risk factors
Local factors
Diagnosis and staging
Natural history
Treatment of recent nontumoral portal vein thrombosis
Anticoagulation
Interventional treatment
Surgery
Treatment of underlying causes
Treatment of chronic nontumoral portal vein thrombosis
Management of complications of portal hypertension
Anticoagulation
Transjugular intrahepatic portosystemic shunt
Management of portal biliopathy
Sinusoidal obstruction syndrome
Incidence
Pathology
Risk factors
Diagnosis
Imaging studies
Biopsy
Hepatic venous pressure gradient
Baltimore and Seattle criteria
Nanjing criteria
European society for blood and marrow transplantation
Assessing severity
Preventive measures
Nonpharmacologic prevention
Pharmacologic prevention
Treatment
Supportive therapy
General
Defibrotide
Transjugular intrahepatic portosystemic shunt
Hepatic artery thrombosis
Etiology and risk factors
Surgical cause
Portal vein thrombosis
Infections
Intra-arterial liver-directed therapy
Coagulation abnormalities
Splenic artery steal syndrome
Pediatric liver transplant
Clinical presentation
Treatment
Acknowledgment
Conflict of interest statement
Financial support
References
II. Hepatobiliary system in heart failure
6 Epidemiology of liver diseases in heart failure
Introduction
The liver diseases in patients with heart failure
Etiological factors of heart failure associated with hepatic disorders
Hepatic consequences in cardiac patients
Liver function tests abnormalities
Congestive hepatopathy
Hypoxic hepatitis
Drug induced liver injury
Liver diseases causing heart failure
Cirrhosis
Hepatocellular carcinoma
Nonalcoholic fatty liver disease
Liver transplantation
Diseases leading to heart failure and affecting the liver
Infections
Congenital causes
References
7 Cardio-hepatology: liver function tests in heart failure
Liver function tests
Blood supply of the liver and its anatomy
Pathophysiology of abnormal liver function tests in heart failure
Bilirubin metabolism in the liver
Association between abnormal liver function tests and impaired hemodynamics
Liver function tests and prognosis in heart failure
Total and direct bilirubin
Transaminases (aspartate aminotransferase and alanine aminotransferase)
Gamma-glutamyltranspeptidase and alkaline phosphatase
Prothrombin time international normalized ratio
Albumin, cholinesterase, and total protein
Hepatic fibrotic markers in heart failure
References
8 Prognostic value of liver assessment (including liver stiffness measurement) in cardiovascular diseases
Introduction
Heart failure and liver impairment
Liver disease is associated with poor outcome of heart failure
Liver disease is associated with poor outcomes of cardiovascular diseases
Liver function tests and prognosis of HF
Liver function tests in HF
Prevalence and prognostic value of abnormal liver function in chronic heart failure
Prevalence and prognostic relevance of abnormal liver chemistry in acute decompensated heart failure
Abnormal liver synthetic function and heart failure
Prognostic relevance of markers of hepatic and renal dysfunction in heart failure
Markers of hepatic fibrosis and prognosis of HF
Serologic markers of hepatic fibrosis in HF
Liver specific micro-RNAs in heart failure
Imaging markers of hepatic fibrosis in HF
Summary
References
9 Passive liver congestion and hypoxic hepatitis
Introduction
Passive liver congestion
Hepatic circulation
Mechanism of injury
Clinical manifestations
Imaging findings
Pathologic findings
Management
Prognosis
Summary
Hypoxic hepatitis
Mechanism of injury
Clinical manifestations
Imaging findings
Pathologic findings
Management
Prognosis
Summary
Conclusion
References
10 Histopathology of the liver in heart failure
Introduction
Natural history
Pathological analysis
Pathogenesis
Conclusion
References
11 The Fontan procedure and liver disease
Introduction
Fontan procedure
Physiology and prevalence of Fontan-associated liver disease
Examination to detect Fontan-associated liver disease
Recommendation
References
III. Cardiovascular system in liver failure
12 Sepsis and the liver
Introduction
Sepsis in the general population
Pathophysiology of organ dysfunction during the early phase of sepsis
The liver as a victim of deregulated host response to infection
Liver failure
Shock liver
Sepsis-induced alterations in hepatic biotransformation, including hepatocellular cholestasis
Sepsis-induced ductular cholestasis
Secondary sclerosing cholangitis
Infection-induced protective responses originating in the liver
Acute-phase protein synthesis during infection
Urea cycle during infection
Hepatic catabolic metabolism during infection
Hepatic triglyceride release during infection
Sepsis in patients with cirrhosis
Inflammatory phenotype of sepsis in acute-on-chronic liver failure
What is acute-on-chronic liver failure?
Infection-related acute-on-chronic liver failure versus acute-on-chronic liver failure unrelated to infection
Pathophysiology of infection-related acute-on-chronic liver failure
Immunosuppression in cirrhosis and acute-on-chronic liver failure
Clinical features and management of sepsis syndromes in patients with cirrhosis
Spontaneous bacterial peritonitis
Diagnosis
Differential diagnosis
Treatment
Empirical antibiotic schedules
Antibiotic strategies for extensively drug-resistant bacteria
Intravenous albumin
Liver transplantation
Bacterial infections unrelated to SBP
Diagnosis
Treatment
Antibiotic treatment
Intravenous albumin
Management of septic shock
Prevention of bacterial infections
Fungal infections
Conclusions
Acknowledgments
References
13 Bleeding and thrombosis in cirrhosis
Introduction to hemostasis
Platelets
Coagulation
Fibrinolysis
Hemostatic changes in liver diseases
Pitfalls of routine diagnostic tests of hemostasis
The concept of rebalanced hemostasis
Are liver patients really bleeders?
Laboratory changes in hemostasis
Platelets
Coagulation and fibrinolysis
Development of the concept of rebalanced hemostasis
Hemostatic balance in different types and severities of liver diseases
Compensated cirrhosis
Decompensated cirrhosis and acute-on-chronic liver failure
Fatty liver disease
Acute liver failure
Liver transplantation
Bleeding in liver diseases
Incidence and pathogenesis
Prevention
Treatment
Thrombosis in liver diseases
Incidence and pathogenesis
Portal vein thrombosis
Venous thrombosis
Arterial thrombosis
Prevention
Portal vein thrombosis
Venous thrombosis
Arterial thrombosis
Treatment
Portal vein thrombosis
Venous thrombosis
Arterial thrombosis
Which drugs?
Intrahepatic thrombosis and disease progression
Hemostasis and liver regeneration
Delivery of growth factors
Delivery of platelet-derived RNA
Platelets as initiators of the inflammatory response
Fibrin and liver regeneration
Conclusion
References
14 Peripheral vasculature in portal hypertension
Introduction
Hyperdynamic circulation
Clinical features of hyperdynamic circulation
Pathogenesis of hyperdynamic circulation
Nitric oxide
Endocannabinoids
Heme oxygenase and carbon monoxide
Role of other humoral agents
Bile acids
Central neural mechanisms
Increased blood and plasma volume/decreased effective circulating volume
Peripheral venous “sump” effect due to venous pooling
Abnormalities of arterial vascular tone
Vasoactive molecules
Inflammation
Nervous system and peripheral vascular changes
Autonomic dysfunction
Cerebral circulation
Management of hyperdynamic circulation
Conclusions
References
15 Cirrhotic cardiomyopathy
Introduction
Definition and diagnostic criteria
Distinction from other cardiomyopathies
Clinical significance
Prevalence
Morbidity/mortality after cardiovascular challenges
Transjugular intrahepatic portal systemic shunts
Liver transplantation
Hepatorenal syndrome
Adrenal insufficiency
Cirrhotic cardiomyopathy and prognosis
Pathogenic mechanisms
TNFα
β-Adrenergic signaling
Membrane fluidity
Bile acids
Nitric oxide
Carbon monoxide
Myosin heavy chain isoform shift
The role of ion channels in cirrhotic cardiomyopathy
Titin and collagen isoforms
Endocannabinoids
Summary of mechanisms
Management
β-Adrenergic receptor blockers (β-blockers)
Combination vasoconstrictors and albumin
Albumin
Antioxidant and antiinflammatory treatments
Liver transplantation
CCM reversibility: QTc prolongation
CCM reversibility: Systolic and diastolic function
Conclusion
References
16 Cardiovascular dysfunction in liver diseases: pediatric perspectives
Introduction
Cardiovascular consequences of structural congenital heart diseases coexisting with diseases of the liver
Alagille syndrome
Congenital cardiovascular defects associated with ALGS
Peripheral vascular defects in ALGS
Biliary atresia splenic malformation syndrome
Heart defects associated with Abernathy malformation of portal vein
Implications of coexisting congenital heart diseases for liver transplantation
Cardiovascular complications of pediatric cirrhosis
Bile acid-myocardial interaction as a potential mechanism of cardiomyopathy
Heart as a target for bile acids
Clinical evidence of pathologic bile acid-myocardial interaction
Historic evidences of pathologic bile acid-myocardial interaction in animal models
Mechanistic insights into bile acid-myocardial interaction
Bile acids induce metabolic disturbance in the heart—the concept of cholecardia
Implications for intensive care management and liver transplantation
Cardiovascular consequences of inherited metabolic liver failure and failure of energy metabolism
Hereditary hemochromatosis
Neonatal hemochromatosis
Glycogen storage diseases
Wilson disease
Tyrosinemia type 1
Primary hyperoxaluria type 1
Propionic acidemia
Homozygous familial hypercholesterolemia
Disorders of inborn error in energy metabolism
Cardiovascular consequences of acute liver failure
Implications for intensive care management and liver transplantation
Cardiovascular consequences of chronic cirrhosis, portal hypertension, and portosystemic shunts
Hepatopulmonary syndrome
Implications of HPS for intensive care management and liver transplantation
Portopulmonary hypertension
Implications of PoPH for intensive care management and liver transplantation
Cardiovascular consequences of immunotherapy used in liver transplants
Implications of tacrolimus-induced cardiotoxicty for intensive care management and liver transplantation
Evaluation of the cardiovascular status before liver transplantation
Cardiac biomarkers in plasma/sera
Electrocardiography
Echocardiography
Assessment of LV geometry in a cirrhotic child on echocardiography
Echocardiographic assessment of systolic function in a cirrhotic child
Echocardiographic assessment of diastolic function in a cirrhotic child
Echocardiographic assessment of global (systolic and diastolic) function in a cirrhotic child
Assessment of portopulmonary hypertension on echocardiography
Assessments of hepatopulmonary syndrome on echocardiography
Cardiac catheterization
Cardiac MRI
Future directions and opportunities for research
References
17 Hepatorenal syndrome and acute kidney injury in cirrhosis
Introduction
The evolving concept of renal dysfunction in cirrhosis
Definition and diagnostic criteria of acute kidney injury in cirrhosis
Epidemiology
Pathophysiology
Hemodynamic changes in cirrhosis
Cardiac dysfunction in cirrhosis
The role of inflammation
Predictive factors for the development of hepatorenal syndrome-acute kidney injury
Diagnosis
Biomarkers
Management
General measures
Albumin
Vasoconstrictors
Terlipressin
Norepinephrine
Midodrine and octreotide
Predictors of response to vasoconstrictors
Renal replacement therapy
Liver transplantation
Combined liver kidney transplant
Prognosis
Prevention
Conclusion
References
18 Cardiopulmonary considerations for the anesthetic management of liver transplantation
Perioperative cardiovascular management in the liver transplant patient
Immediate preoperative evaluation, optimization, and planning
Intraoperative management
Early postoperative cardiac evaluation and management
Perioperative pulmonary management in the liver transplant recipient
Preoperative pulmonary assessment and optimization
Intraoperative pulmonary considerations
Postoperative pulmonary considerations
References
19 Cardiovascular assessment before liver transplantation
Introduction
Assessment of coronary artery disease
Prevalence of coronary artery disease in liver transplant candidates
Risk factors
Screening tests for coronary artery disease in liver transplantation candidates
Dobutamine stress echocardiogram
Myocardial perfusion imaging with real-time myocardial contrast echocardiography
Single-photon emission computed tomography–Myocardial perfusion imaging
Coronary artery calcium score and coronary computed tomography angiography
Invasive coronary angiography
Management of coronary artery disease in liver transplantation candidates
Assessment of cardiac dysrhythmias
Atrial dysrhythmia
Prevalence and risk factors of atrial fibrillation in liver transplantation candidates
Diagnosis and treatment of atrial fibrillation in liver transplantation candidates
Ventricular arrhythmias
Assessment of heart failure
Prevalence and risk factors
Diagnosis and management of cardiac muscle dysfunction in liver transplantation candidates
References
20 Predicting cardiovascular complications after liver transplantation
Introduction
Epidemiology and established risk factors for cardiovascular complications in liver transplantation
Natural history and timing of cardiovascular events in liver transplantation
Perioperative complications
Preload and cardiac output
Electrolyte derangements
Postreperfusion syndrome
Cardiac arrest and arrhythmia
Air embolism and thromboembolism
Donor factors related to perioperative cardiovascular events
Postoperative complications
Early (90-day period)
Cardiac function
Pulmonary Edema
Dilated cardiomyopathy
Cardiac arrest and arrhythmia
Myocardial infarction
Stroke
Pulmonary embolism
Late (>90-day period)
Metabolic syndrome
General overview
Hypertension
Dyslipidemia
Diabetes mellitus
Abdominal obesity
Renal disease/chronic kidney disease
Identified future areas of study in liver transplantation complications
Peripheral vascular disease
Valvular heart disease
Algorithms and risk calculators for prediction of cardiovascular risk after liver transplantation
Liver specific risk predictors
Nonsurgical general cardiac risk assessment tools
Serum biomarkers
Surgical cardiac risk calculators
Individual predictors of perioperative cardiovascular disease mortality after liver transplantation
Risk models for prediction of perioperative cardiovascular disease mortality after liver transplantation
Conclusions
References
Index
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