Hepatology

An Evidence-Based Clinical Compendium

1st Edition - November 5, 2024
Editors: Sanjaya K. Satapathy, Mamun- Al-Mahtab, Shivaram Prasad Singh, Sheikh Mohammad Fazle Akbar, Aftab Ala, Thomas D Schiano
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 3 0 0 5 2 - 3
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 3 0 0 5 3 - 0

Hepatology: An Evidence-Based Clinical Compendium provides current and comprehensive insights into the field of hepatology, covering various aspects such as diagnosis, manage… Read more

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Hepatology: An Evidence-Based Clinical Compendium provides current and comprehensive insights into the field of hepatology, covering various aspects such as diagnosis, management, control, techniques, procedures, and technology. By offering the latest information, the book ensures that readers stay up-to-date with the rapidly evolving landscape of hepatology. The comprehensive scope covers a wide range of topics related to liver diseases, including epidemiology, pathogenesis, and pathophysiology. It features contributions from esteemed experts worldwide and is enhanced with high-quality diagrams. The book serves as a valuable resource for scientists and researchers, offering a solid foundation for their investigations and clinical inquiries.

Moreover, the book goes beyond the discussion of epidemiology, pathogenesis, and pathophysiology, and presents updated treatment and management guidelines for liver diseases, making it a go-to reference for Clinicians treating liver diseases.

Hepatology
Cover image
Title page
Table of Contents
Front Matter for Volume 1
Front Matter for Volume 2
Copyright
Copyright
Dedication
Contributors for Volume 1
Contributors for Volume 2
About the editors
Foreword
Preface
Volume 1
Chapter 1 Anatomy and histopathology of the liver⊛
Abstract
Keywords
Introduction
Macroanatomy of the liver
Microscopic architecture
Portal tracts
The biliary system
Hepatic mesenchyme
Lobular and acinar functional units
Cellular microanatomy
Hepatocytes
Cholangiocytes
The hepatic sinusoid
Innervation
Heterogeneity
Summary
References
Chapter 2 The liver and immunology⊛
Abstract
Keywords
Introduction
Cellular populations of the liver: Unique, diverse, special
Hepatocytes, the functional unit of the liver
The non-parenchymal cells of the liver
Hepatic vascular system: both arterial and venous blood feed the liver
Functions of the liver
The liver and immunology
The fundamentals of the hepatic immune system
Innate immunity
Acquired or adaptive immunity
Immunological cascade
Immunology of hepatocyte, the parenchymal cells of the liver
Immune-related functions of non-parenchymal cells (NPCs) of the liver
Liver sinusoidal endothelial cells (LSECs)
DC
MDSC
Granulocytes
NK cells and NKT cells
T and B lymphocytes
Hematopoietic progenitor cell populations in the liver
Stellate cells
Kupffer cells (KC)
The tolerogenic liver
Liver regeneration and immunity
The immunological mechanism underlying liver diseases
Hepatotropic virus-induced liver damage
HAV and HEV
HBV-induced liver damages
HCV-induce liver damages
Nonalcoholic fatty liver disease (NAFLD): An intrinsic pathological entity resulting from hepatic microenvironment or mishandling of metabolites
Drug-induced liver injury (DILI)
Alcohol
Immune intervention of liver diseases for management
Fundamental issues of drug development for immune-related liver diseases
Immune therapy for CHB
Immune therapy for HCC
Conclusion
Summary
References
Chapter 3 Bilirubin metabolism and its disorders⊛
Abstract
Key words
Acknowledgments
Introduction
Bilirubin formation
Photochemistry of bilirubin
Physiological function and health benefits of biliverdin and bilirubin
Bilirubin toxicity
Bilirubin throughput
The role of albumin binding
Bilirubin uptake by hepatocytes
Bilirubin conjugation
Secretion of bilirubin glucuronides into bile
Reverse transport of bilirubin glucuronides into sinusoidal blood and reuptake by hepatocytes
Additional transporters in the hepatocyte canalicular membranes
Coordinated expression of genes involved in bilirubin throughput in the liver
Bilirubin degradation in the gastrointestinal tract
Alternative pathways of bilirubin excretion
Quantification of serum bilirubin
Quantification by diazo reaction
Chromatographic analysis
Transcutaneous bilirubinometry
Measurement of non-protein bound (free) bilirubin
Bilirubin in various body fluids
Bilirubin in plasma
Bilirubin in bile
Mechanisms of hyperbilirubinemia
Neonatal hyperbilirubinemia
High bilirubin load
Low hepatic bilirubin uptake
Immaturity of bilirubin glucuronidation
Effect of maternal milk
Maternal serum jaundice
Low canalicular bilirubin excretory capacity
Increased intestinal reabsorption
Hyperbilirubinemia due to bilirubin overproduction
Inherited disorders of bilirubin glucuronidation
Crigler-Najjar syndrome: Types
Crigler-Najjar syndrome type 1 (CN1)
Investigational therapies
Crigler-Najjar syndrome type 2 (CN2)
Gilbert syndrome
Inherited disorders associated with predominantly conjugated hyperbilirubinemia
Dubin-Johnson syndrome (DJS)
Rotor syndrome
Hyperbilirubinemia resulting from monogenic cholestasis syndromes
Progressive familial intrahepatic cholestasis type 1 (PFIC-1)
Progressive familial intrahepatic cholestasis type 2 (PFIC-2)
Progressive familial intrahepatic cholestasis type 3 (PFIC-3)
Benign recurrent intrahepatic cholestasis (BRIC)
Progressive familial intrahepatic cholestasis type 4 (PFIC-4)
Progressive familial intrahepatic cholestasis type 5 (PFIC-5)
Progressive familial intrahepatic cholestasis type 6 (PFIC-6)
Mitochondrial scaffold defects
Cholangiopathy of North American Indian childhood cirrhosis
Gracile syndrome
Structural disorders of known genetic basis
Alagille syndrome
Abnormal villin expression
Summary
References
Chapter 4 Non-invasive diagnosis of metabolic dysfunction associated steatotic liver disease (MASLD)⊛
Abstract
Keywords
Introduction
Clinical association between histology and outcomes
Limitation of liver biopsy
Steatosis
Clinical prediction model
Ultrasound
Transient elastography
Magnetic resonance imaging
Serum-based: OMICs approach
Fibrosis
Non-invasive fibrosis tests
Imaging
Serum-based fibrosis biomarkers
MASH
Serum based
Imaging
Summary
References
Chapter 5 Hematologic disorders and the liver⊛
Abstract
Keywords
Introduction
Disordered hematopoiesis in liver disease
Brief overview of the coagulopathy of liver disease
Normal hemostasis
The coagulopathy of liver disease
Factor VIII
Fibrinogen
Viscoelastic tests
Procedural bleeding assessment and management
Anemia in liver disease
Macrocytic anemia
Iron deficiency anemia
Hemolytic anemia
Aplastic anemia
Hepatic vein thrombosis (Budd-Chiari syndrome)
Portal vein thrombosis
PVT in cirrhosis (without underlying hepatocellular cancer)
Non-cirrhotic PVT
Management of bleeding in liver disease
Variceal bleeding
Non-variceal bleeding (intractable mucosal and puncture wound oozing)
Elective procedures in patients with liver disease
Other hematologic conditions in liver disease
Coagulopathy in acute liver failure (fulminant hepatic failure)
Hemophagocytic lymphohistiocytosis
Summary
References
Chapter 6 Acute liver failure (ALF)⊛
Abstract
Keywords
Introduction
Definition
Etiology
Pathogenesis
Role of ammonia [18,19]
Loss of cerebral auto regulation [7,20]
Complications of ALF [7,9,11,13]
Gender, pregnancy and acute liver failure [7,9,11,13,23]
Outcome
Causes of death in ALF
Management [9,27–30]
Medical therapy directed to control encephalopathy and cerebral edema and raised intracranial pressure (ICP)
Therapies directed towards management of complications
Plasma exchange (PLEX) and bioartificial liver support systems [27,29,31–33]
Therapy directed at etiology of ALF [27,29]
Liver transplant and prognostic models [7,9,13,19,27,33–38]
Summary
References
Chapter 7 Acute-on-chronic liver failure⊛
Abstract
Keywords
Introduction
Development and evolution of the concept of ACLF
Definition of ACLF
Epidemiology of ACLF
Onset and clinical course of ACLF
Pathophysiology of ACLF
Gut dysbiosis and ACLF
Principles of treatment
Treatment of precipitating event
Supportive therapy
Liver transplantation in ACLF
Prevention of ACLF
Palliative care in ACLF
Forecasting trends and unmet needs in ACLF
Conclusion
Summary
References
Chapter 8 Hepatic fibrogenesis⊛
Abstract
Keywords
Introduction
Natural history of hepatic fibrosis
Cellular and molecular features of hepatic fibrosis
Cellular anatomy of sinusoids (Fig. 3)
Sinusoidal cellular and extracellular matrix changes in response to injury (Fig. 4)
Cellular sources of extracellular matrix in hepatic injury and fibrogenesis
Stellate cell activation: A central feature of hepatic fibrosis
Local interactions influencing fibrogenesis
Matrix production (fibrogenesis) and degradation (fibrinolysis)
Clinical aspects of hepatic fibrosis
Methods to monitor fibrosis progression or regression
Invasive methods of diagnosis
Non-invasive methods of diagnosis
Emerging antifibrotic targets and strategies
Summary
References
Chapter 9 Cirrhosis, portal hypertension and pathophysiology⊛
Abstract
Keywords
Cirrhosis
Introduction
Definition, etiologies, and pathophysiology of cirrhosis
Diagnosis of cirrhosis
Portal hypertension
Hepatic portal system
Hemodynamics of portal hypertension
Causes of portal hypertension
Cirrhosis
Schistosomiasis
Portal vein thrombosis
Idiopathic
Cardiac-related
Uncommon causes of portal hypertension
Portal pressure measurement
Prognosis of cirrhosis
Management of cirrhosis
Summary
References
Chapter 10 Ascites and hepatorenal syndrome⊛
Abstract
Keywords
Introduction
Ascites
Pathophysiology
Assessment of ascites
Prognosis of ascites
Uncomplicated ascites (Fig. 3)
Complicated ascites
Hepatic hydrothorax
Diagnosis and clinical presentation of hepatic hydrothorax
Hepatorenal syndrome
Pathophysiology (Fig. 2)
Definition, classification, and diagnosis
Management
Summary
References
Chapter 11 Management of esophageal and gastric varices⊛
Abstract
Keywords
Introduction
Diagnosis
Endoscopic diagnosis of gastroesophageal varices
Non-invasive tests for gastroesophageal varices
Approach to patients without prior variceal hemorrhage
Pre-primary prophylaxis of gastroesophageal varices
Primary prophylaxis of variceal hemorrhage
Management of acute esophageal variceal hemorrhage
Blood products
Antibiotic prophylaxis
Vasoactive agents
Endoscopic variceal ligation
Early transjugular intrahepatic portosystemic shunt
Secondary prophylaxis of esophageal variceal hemorrhage
Rescue therapies
Balloon tamponade
Esophageal stents
Transjugular intrahepatic portosystemic shunt
Overview of gastric varices
Management of gastric variceal hemorrhage
Management of gastric varices according to vascular anatomy
Endoscopic cyanoacrylate injection
Endoscopic thrombin injection
Endoscopic ultrasound-guided therapies
Balloon-occluded retrograde transvenous obliteration
Transjugular intrahepatic portosystemic shunt
Gastroesophageal varices and non-cirrhotic portal hypertension
Summary
References
Chapter 12 Hepatic encephalopathy⊛
Abstract
Keywords
Introduction
Historical perspectives
Definition and nomenclature
Epidemiology of HE
Precipitants and predictors of HE
Pathophysiology of HE
Effect of indigenous toxin
Effect of inhibitory neurotransmission
Effect of systemic inflammation
Effect of gut microbiota
Effect of sarcopenia
Effect of alteration in amino acid metabolism
Clinical features
Ammonia measurement and implications in HE
Diagnosis of HE
Diagnosis of covert HE
Diagnosis of overt HE
Treatment of HE
Treatment of MHE
Treatment of episode of overt HE
Prevention of overt HE
Emerging therapies in HE
Nutrition and HE
Areas of controversy and future research
Summary
References
Chapter 13 Jaundice/cholestasis⊛
Abstract
Keywords
Introduction
Jaundice
Physiology of bilirubin metabolism
Cholestasis
Classification of jaundice
Pre-hepatic jaundice
Hepatic jaundice
Post-hepatic jaundice
Unconjugated hyperbilirubinemia
Increased bilirubin production
Decreased hepatic bilirubin uptake
Impaired hepatic conjugation
Conjugated hyperbilirubinemia
Intrahepatic cholestasis
Inherited disorders of cholestasis
Autoimmune disorders of cholestasis
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Overlap syndrome
Ig-G4 disease
Miscellaneous causes of cholestasis
Total parenteral nutrition
Vanishing bile duct syndrome
Sickle cell intrahepatic cholestasis
Drug-induced cholestasis
Extrahepatic biliary obstruction
AIDs cholangiopathy
History
Associated symptoms
Risk factors
Drug history
Physical examination
Demographics
General examination
Mental status
Skin examination
Abdominal examination
Treatments
Pruritus
Vitamin supplements (ADEK)
Summary
References
Chapter 14 Gallstones and gallbladder disorders⊛
Abstract
Keywords
Introduction
Biliary tract: Anatomy and physiology
Bile secretion and the enterohepatic circulation
Bile acid synthesis and metabolism
The enterohepatic circulation
Diseases of the gallbladder
Developmental anomalies
Gallstone disease
Tumors of gallbladder
Summary
References
Chapter 15 Benign biliary stricture: Causes and management⊛
Abstract
Keywords
Introduction
Clinical manifestation
Diagnosis
Post cholecystectomy strictures
Post liver transplantation
Primary sclerosing cholangitis
Infections
Portal cavernoma cholangiopathy
IgG4-related sclerosing cholangitis
Chronic pancreatitis and choledocholithiasis
Role of good clinical assessment and antibiotics
Endoscopic methods
Percutaneous intervention for BBS
Surgical management of BBS
Innovative techniques
Role of endoscopic ultrasound
Other novel techniques
Summary
References
Chapter 16 Cystic diseases of the liver⊛
Abstract
Keywords
Summary
Evaluation of liver cysts
Simple cysts
Polycystic liver disease
Autosomal recessive polycystic kidney disease
Von Meyenburg Complexes
Caroli's disease
Cystadenomas
Echinococcosis
Malignant cysts
Future therapeutic options
Conclusion
References
Chapter 17 Congenital cholestatic liver disease⊛
Abstract
Keywords
Article I. Biliary atresia
Clinical presentation
Diagnosis
Management
Complications
Liver transplantation
Article II. Alagille syndrome
Clinical presentation
Diagnosis
Management
Liver transplantation
Article III. Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis
PFIC1
PFIC2
PFIC3
PFIC4
PFIC5
PFIC6
Diagnosis
Medical management
Surgical management
Article IV. Bile acid synthesis disorders
Secondary bile acid synthesis disorders
Article V. Choledochal cyst
Classification
Clinical presentation
Diagnosis
Management
Summary
References
Chapter 18 Primary biliary cholangitis⊛
Abstract
Keywords
Introduction
Epidemiology
Etiology and pathogenesis
Natural history
Prognosis
Clinical features
Physical examination
Diagnostic approach
Laboratory tests
Imaging
Liver biopsy
Ludwig and Scheuer histologic classification of PBC (Table 3) [92,93]
Diagnosis
Clinical characteristics of PBC variants
AMA negative PBC
Overlap PBC/AIH
Management principles
Pharmacological therapy
First-line therapy: Ursodeoxycholic acid
Second line therapy: Obeticholic acid (OCA)
Off label therapy: Fibrates
Combination therapy
New drugs under investigation
Management of PBC-AIH overlap syndrome
Monitoring and follow-up
Symptomatic treatment
Pruritus
Fatigue
Sicca syndrome
Treatment of metabolic complications
Osteopenia/osteoporosis
Hyperlipidemia
Fat-soluble vitamins
Liver transplantation
Challenges and controversies
Summary
References
Recommended reading
Chapter 19 Primary sclerosing cholangitis⊛
Abstract
Keywords
Introduction
Epidemiology and pathogenesis
Diagnosis, natural history, prognosis
Malignancy in PSC
Management
Medical treatment
Modulation of bile composition
Modulators of inflammation
Anti-fibrotics
Optimizing the gut microbiome
Endoscopic treatment
Surgical
Recurrent PSC and cancer risk
Summary
Author contributions
Financial support
Conflicts of interest
References
Chapter 20 Enterically transmitted viral hepatitis-hepatitis A and E⊛
Abstract
Keywords
Hepatitis A
Introduction
Virology
Epidemiology and transmission
Pathogenesis
Clinical features
Acute hepatitis
Diagnosis
Control and prevention of hepatitis a
Hepatitis E
Introduction
Virology
Epidemiology and transmission
Pathogenesis
Clinical features
Diagnosis
Treatment
Control and prevention of Hepatitis E
Vaccination
HEV in pregnancy
References
Recommended reading
Chapter 21 Hepatitis B⊛
Abstract
Keywords
Introduction
Epidemiology
Screening guidelines
Molecular biology
Pathophysiology
Clinical features
Acute HBV infection
Chronic HBV infection
Acute flare of chronic HBV infection
HBV and hepatitis D infection
Diagnostic approaches
Serological testing
Molecular testing
Management
Acute HBV infection
Chronic HBV infection
When to start treatment
Treatment options
When to change antiviral medications
Duration of therapy
Management in special populations
Coinfection with HIV
Coinfection with hepatitis C
Decompensated cirrhosis/liver transplantation recipients
Pregnancy
Renal and bone dysfunction
Immunosuppression therapy/chemotherapy
Newer approaches to treatment
Therapeutic HBV vaccines
Referral for liver transplantation
Occult HBV infection
Prognosis
Prevention
Pre-exposure vaccination
Post-exposure prophylaxis
Elimination
Summary
References
Chapter 22 Hepatitis C⊛
Abstract
Keywords
Introduction
Hepatitis C virology
Natural history of hepatitis C
Acute hepatitis C
Chronic hepatitis C
Transmission of hepatitis C
Hepatitis C presentation
Extrahepatic manifestations
Hematological disorders
Renal disorders
Dermatological disorders
Endocrine disorders
Other extrahepatic manifestations
Hepatitis C diagnosis
HCV RNA assays
Hepatitis C genotype
Assessment of fibrosis
Non-invasive serum modalities to assess fibrosis
Non-invasive imaging modalities to assess fibrosis
Liver biopsy
Treatment
History of treatment
Currently available therapies
Special populations
Pregnancy
Pediatrics
Acute HCV
Decompensated cirrhosis
Organ transplant
DAA adverse effects and drug-drug interactions
Post-treatment monitoring
Summary
References
Chapter 23 The worldwide medical impact of hepatitis D virus infection: Focus to Central Asia⊛
Abstract
Keywords
Introduction
Hepatitis D virology and serology
The complex epidemiology of HDV
The decline of HDV among local-born populations of high-income countries
Epidemiology of HDV in the rest of the world
The changing clinical scenario of hepatitis D
Focus to Central Asia
Turkey
Pakistan
Epidemiology of HDV infection in former USSR countries
Treatment
Pegylated interferon alpha 2a and Nucleos(t)ide Analog Combination therapy
HDV entry inhibitor: Bulevirtide
The HDAg prenylation inhibitor: Lonafarnib
HBsAg secretion inhibitor: REP 2139
Conclusion and the way forward
Summary
Issues to be resolved
References
Chapter 24 Hepatitis through non-A–E viruses⊛
Abstract
Keywords
Introduction
Herpes simplex virus (HSV)
Varicella zoster virus
Cytomegalovirus (CMV)
Epstein Barr virus (EBV)
Human herpes virus 6 (HHV-6)
Human herpes virus 7 and 8 (HHV-7, HHV-8)
Human parvovirus B 19
Dengue hepatitis
Coronavirus
Summary
References
Volume 2
Chapter 25 HIV related liver diseases⊛
Abstract
Keywords
Introduction
Hepatitis C co-infection
Hepatitis B co-infection
NAFLD/NASH
Medication induced liver disease
Infiltrative/systemic diseases (non-liver specific)
AIDS cholangiopathy
Acalculous cholecystitis
Summary
References
Chapter 26 Autoimmune hepatitis⊛
Abstract
Keywords
Introduction
Epidemiology
Incidence, prevalence, gender differences and mortality
Genetics, race, and ethnicity
Definition
Pathophysiology
Classification
Other variants
Diagnosis
Clinical presentation
Laboratory markers
Further testing
Complications
Advanced liver disease and cirrhosis
COVID-19 infection
Management
First line
Second line
Off-label therapies—Beyond second line
Liver transplant
Treatment withdrawal and relapse
Prognosis
Treatments in the pipeline
Summary
References
Chapter 27 Drug induced liver injury⊛
Abstract
Keywords
Introduction
Hepatic drug metabolism
Acetaminophen hepatotoxicity (APAP-DILI)
Epidemiology
Clinical features
Diagnostic approaches
Therapeutic approaches
Challenges and controversies involved in management
Outcomes of treatment
Complications of treatment
Idiosyncratic drug induced liver injury (iDILI)
Epidemiology
Drugs associated with iDILI
Clinical features
Management principles
Diagnostic approaches
Therapeutic approaches
Challenges and controversies involved in management
Outcomes of treatment
Complications of treatment
Herbal and dietary supplement induced liver injury (HILI)
Epidemiology
HDS associated with HILI
Clinical features
Management principles
Diagnostic approaches
Therapeutic approaches
Challenges and controversies involved in management
Outcomes of treatment
Complications of treatment
Summary
References
Chapter 28 Alcohol-associated liver disease⊛
Abstract
Keywords
Epidemiology of ALD
Disease modifiers
Pathogenesis of alcoholic liver disease
Diagnosis of ALD
Screening for alcohol use
Screening for liver disease
Diagnosis of alcoholic hepatitis
Treatment of alcohol-associated liver disease
Treatment of alcohol use disorder
Medical treatment of liver disease
Liver transplantation for ALD
Emerging pharmacological therapies
Prognosis in ALD
Emerging biomarkers
Prevention of alcohol-associated liver disease
Conclusion and future prospects
Summary
References
Chapter 29 Iron overload and the liver⊛
Abstract
Keywords
Acknowledgments
Introduction and history of developments in hemochromatosis
HFE related hemochromatosis and epidemiology
Mechanisms of iron homeostasis and absorption (Fig. 2)
Ceruloplasmin and iron
Hepcidin and its expression (Fig. 3)
Fibrosis and iron
Biochemical variations in iron parameters
Classification of hereditary hemochromatosis iron overload syndromes
Type 1 HH (OMIM235200)
Type 2 HH (OMIM 602390, 613313)
Type 3 HH (OMIM604250)
Type 4 HH (OMIM606069)
Type 5 HH (OMIM615517)
Clinical features of HH
Diagnosis and work-up (Figs. 4A and 4B)
Genetic testing, clinical and biochemical penetrance
Histological evaluation of iron overload
Screening—Family and population
Other important iron over load states (Table 3)
Treatment
Secondary iron overload and treatment
Developing future therapies in HH
Iron homeostasis
Treatment
Summary
References
Chapter 30 Wilson disease⊛
Abstract
Keywords
Introduction
Copper metabolism/ATP7B
Clinical presentation
Diagnosis
Management of Wilson disease
Liver transplantation
Future potential therapies
Hepatocyte transplant
Gene therapy
Gene repair with CRISPR-Cas9 (clustered regularly interspaced palindromic repeats)
Summary
References
Chapter 31 Metabolic-dysfunction associated steatotic liver disease (MASLD)⊛
Abstract
Keywords
Introduction
Historical perspective and etymology
Epidemiology
Pathogenesis
Ethnicity and genetic modulation of risk of MASLD
Lipid trafficking in the liver and the central role of insulin resistance
Lipotoxicity, oxidative stress, mitochondrial dysfunction and activation of inflammatory pathways
Adiposopathy
Gut dysbiosis
Hepatic parenchymal iron overload
Cross talk between hepatic steatosis, inflammation and fibrosis
Pathogenesis in lean MASLD
Natural history (Fig. 1)
Dynamic model of MASLD (Fig. 2)
Clinical features
Lean MASLD
Cirrhosis and HCC
Extra-hepatic associations
Diagnostic evaluation of MASLD
Diagnosing fatty liver using non-invasive techniques
Non-invasive differentiation of MASLD and MASH
Non-invasive evaluation of fibrosis
Liver biopsy
Management
Holistic approach to managing metabolic co-morbidities
Weight loss
MASH specific pharmacotherapy (Table 8)
Management of MASH cirrhosis and HCC
Future therapeutic approaches in MASH
Summary
Disclosures
Funding
Conflict of interest
Suggested readings
Chapter 32 Sarcopenia, frailty, and its implications in cirrhosis⊛
Abstract
Keywords
Acknowledgment
Sarcopenia in cirrhosis
Causes and mechanisms of sarcopenia in cirrhosis
Diagnostic criteria and assessment tools for sarcopenia in cirrhosis
Biomarkers and laboratory assessments
Frailty in cirrhosis
Definition and characteristics of frailty
Prevalence and risk factors for frailty in cirrhosis
Clinical implications and impact of frailty on cirrhosis outcomes
Shared pathophysiological mechanisms between sarcopenia and frailty
Overlapping mechanisms between sarcopenia and frailty in cirrhosis
Role of gut dysbiosis and systemic inflammation in the development of sarcopenia and frailty
Clinical implications
Prognostic significance of sarcopenia and frailty in cirrhosis
Management strategies for sarcopenia and frailty in cirrhosis
Implications for cirrhosis screening and surveillance programs
Summary
Summary of key findings and implications
Future research directions and areas for further investigation
Importance of addressing sarcopenia and frailty in the management of cirrhosis
References
Chapter 33 Liver disease in infants and children⊛
Abstract
Keywords
Neonatal cholestasis
Genetics of pediatric cholestasis
Hepatitis B in children
Hepatitis C in pediatrics
Acute liver failure
Autoimmune hepatitis and overlap syndrome
Type 1 AIH, type 2 AIH, and seronegative AIH
Overlap syndromes
Post-transplant manifestations of AIH
Treatment
Liver tumors
Frailty and nutrition
Liver transplantation
Summary
References
Chapter 34 Liver diseases in pregnancy: A comprehensive review⊛
Abstract
Keywords
Introduction
Physiological changes in pregnancy
When to suspect liver disease in pregnancy
Pregnancy-specific liver diseases
Hyperemesis gravidarum
Various defining criteria for HG
Pathophysiology
Clinical and laboratory parameters
Treatment and prognosis
Intrahepatic cholestasis of pregnancy
Pathophysiology
Clinical and laboratory parameters
Treatment and prognosis
Hypertension-related liver disease and pregnancy
Pathophysiology
Clinical presentation
Management
HELLP syndrome
Pathophysiology
Clinical and laboratory parameters
Management
Acute fatty liver of pregnancy
Pathophysiology
Clinical and laboratory parameters
Management
Conclusion
Summary
References
Chapter 35 Viral hepatitis in pregnancy⊛
Abstract
Keywords
Introduction
Hepatitis A
Transmission
Symptoms
Diagnosis
Clinical aspects of HAV in pregnancy
Treatment
Prevention
Hepatitis B
Transmission
Symptoms
Diagnosis
Clinical aspects of HBV in pregnancy
Prevention of perinatal transmission of HBV
Preferred antiviral therapy during pregnancy
Management of HBV infection
Hepatitis C
Transmission
Symptoms
Diagnosis
Clinical aspects of HCV in pregnancy
Treatment
Prevention or management of HCV infection
Hepatitis D
Transmission
Diagnosis
Clinical aspects and management of HDV in pregnancy
Prevention of HDV infection
Hepatitis E
Transmission
Symptoms
Diagnosis
Clinical aspects of HEV in pregnancy
Treatment
Management and prevention of HEV infection during pregnancy
Maternal-to-child transmission
Pregnancy with advanced cirrhosis
Summary
References
Chapter 36 Liver in systemic diseases—Part 1⊛
Abstract
Keywords
Introduction
Critically ill patients
Hypoxic liver injury
Cholestasis and icterus
Sclerosing cholangiopathy of critically ill patients
Drug induced liver injury in critically ill patients
Cardiovascular diseases
Acute cardiogenic liver injury
Chronic venous congestion (syn. congestive hepatopathy)
Cardiac cirrhosis
Renal disease
Renal cell carcinoma and paraneoplastic liver involvement
Endocrinopathies and liver
Thyroid diseases and liver
Hypothyroidism
Hyperthyroidism
Cushing syndrome
Adrenal insufficiency
Diabetes mellitus
Gastrointestinal diseases
Celiac disease
Inflammatory bowel disease and liver
Primary sclerosing cholangitis
Other liver diseases in IBD
Gallstone disease and IBD
Nonalcoholic fatty liver disease and IBD
Portal vein and hepatic vein thrombosis
Liver abscess and IBD
Secondary amyloidosis
Drug induced liver injury
Intestinal failure associated liver disease
Connective tissue disorders
Joint pain and liver
Systemic lupus erythematosus
Rheumatoid arthritis
Sjogren syndrome
Scleroderma
Adult Still’s disease
Polyarteritis nodosa
Anticardiolipin syndrome
Polymyalgia rheumatica
Hematological disorders and liver
Lymphoproliferative disorders
Hodgkin's disease and liver
Non-Hodgkin's lymphoma
Primary hepatic lymphoma
Myeloproliferative disorders
Polycythemia vera
Primary myelofibrosis
Myeloproliferative neoplasms and visceral thrombosis
Chronic lymphocytic leukemia
Hairy cell leukemia
Multiple myeloma
Acute leukemia
Sickle cell disease and liver
Thalassemia and liver involvement
Summary
References
Chapter 37 Liver in systemic diseases—Part 2⊛
Abstract
Keywords
Liver in sepsis
Specific infections and liver
Enteric fever and liver
Scrub typhus and liver
Leptospirosis
Tuberculosis
Brucellosis
Uncommon bacterial infections involving liver
Q fever
Syphilis
Lyme disease
Protozoal infections affecting liver
Malaria
Viral infections affecting liver
Dengue
Cytomegalovirus
Epstein-Barr virus
Herpes simplex virus
HIV
COVID-19
Fungal infections
Hepatic candidiasis
Histoplasmosis
Coccidioidomycosis
Miscellaneous conditions
Amyloidosis
Cystic fibrosis and liver
Heat stroke and liver disease
Obstructive sleep apnea and liver disease
Sarcoidosis and liver
Summary
References
Chapter 38 Bacterial, fungal and parasitic infections and the liver⊛
Abstract
Keywords
Introduction
Common hepatic and biliary disease entities
Pyogenic liver abscess
Cholangitis
Cholecystitis
Etiologies of hepatic and biliary infections
Bacterial infections
Fungal infections
Parasitic infections
Summary
References
Chapter 39 Parasitic diseases of the liver and biliary tract⊛
Abstract
Keywords
Introduction
Amebic liver abscess
Hepatobiliary and pancreatic ascariasis
Echinococcosis
Cystic echinococcosis
Alveolar echinococcosis
Polycystic echinococcosis
Hepatosplenic schistosomiasis
Fascioliasis
Clonorchiasis and Opisthorchiasis
Summary
References
Chapter 40 Benign liver tumors⊛
Abstract
Keywords
Introduction
General approach to a solid liver lesion
Focal nodular hyperplasia
Epidemiology
Pathophysiology
Histopathology
Clinical features
Management
Prognosis
Hepatocellular adenoma
Classification
Clinical features
Radiology
Management
Macroregenerative nodule
Nodular regenerative hyperplasia (NRH)
Focal hepatic steatosis and focal fatty sparing
Bile duct adenoma
Hepatic hemangioma
Pathophysiology
Clinical features
Radiology
Management
Surgical management
Radiological management
Mesenchymal hamartoma
Hepatic angiomyolipoma
Inflammatory pseudotumor of the liver (IPTL)
Hepatic peliosis
Summary
References
Chapter 41 Malignant liver tumors⊛
Abstract
Keywords
Introduction
Hepatocellular carcinoma
Risk factors
Hepatotropic viruses
Metabolic risk factors
Other risk factors
Gut microbiota and HCC
Clinical manifestations
Pathogenesis
Gross pathology
Histology
Immunohistochemistry
Diagnosis of HCC
Staging
Treatment
Hepatic resection
Liver transplantation
Local therapies
Trans-arterial chemoembolization
Trans-arterial radioembolization: Table 4
Radiation therapy in HCC
Systemic therapy
Fibrolamellar hepatocellular carcinoma
Prevention of HCC
Intrahepatic cholangiocarcinoma
Introduction
Classification and nomenclature
Risk factors
Clinical presentation
Diagnostic work up
Staging
Treatment
Surgery
Chemotherapy
Liver secondaries
Introduction
Epidemiology and etiology
Molecular pathogenesis of liver metastasis
Approach to diagnosis
Management
Postoperative follow up
Ablative therapy
Rare types
Epidemiology and risk factors
Diagnosis
Management
Epidemiology
Presentation and diagnosis
Management
Conclusion
Summary
Disclosures
Conflicts of interest
Author contributions
References
Suggested reads
Chapter 42 Liver targeted therapies for benign and malignant tumors of the liver⊛
Abstract
Keywords
Introduction
Benign tumors of the liver
Malignant tumors of the liver
Thermal ablation
Trans-arterial radioembolization
Trans-arterial chemoembolization
External body radiation therapy
Comparison of locoregional therapies
Conclusions
Summary
References
Chapter 43 Liver transplantation⊛
Abstract
Keywords
Introduction
Indications for liver transplantation and recipient evaluation
Indications for liver transplantation
Recipient evaluation
Donor evaluation
Living donor evaluation
Deceased donor evaluation
Extended donor criteria and outcomes
Donor-recipient matching
Liver allocation system
Combined liver transplantation with other organs
Post-liver transplant complications
Post-liver transplant infections
Acute and chronic allograft rejection
Post-liver transplant malignancy
Post-liver transplant renal complications
Post-liver transplant metabolic complications
Adverse effects of immunosuppression
Recurrent disease after liver transplantation
Hepatitis B virus infection
Hepatitis C virus infection
Autoimmune liver diseases
Hepatocellular carcinoma
Re-transplantation
Gender and racial disparities in LT
Summary
References
Chapter 44 Liver transplantation in combination with other organs⊛
Abstract
Keywords
Liver transplantation: basics
Indications for liver transplantation
Combined liver transplant with other organs
Simultaneous liver-kidney transplant (SLK)
Evaluating renal function and considerations for SLKT in end-stage liver disease patients
Role and limitations of kidney biopsy in simultaneous liver-kidney transplantation
Assessment of SLKT candidacy in individuals with end-stage renal disease (ESRD)
Comparing simultaneous liver and kidney transplantation outcomes to liver transplant alone
Complexities of simultaneous liver-kidney transplantation (SLKT)
Metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis: Evaluating the appropriate approach—Simultaneous liver-kidney transplantation or liver transplantation alone?
Conclusion
Combined liver-lung transplant (CLLT)
Combined liver-lung allocation system
Outcomes of combined liver-lung transplant in USA
Conclusion
Combined liver-heart transplant (CLHT)
Outcomes of CHLT
Conclusion
Combined liver-pancreas transplant
Conclusion
Combined liver-intestine transplant
Summary
References
Chapter 45 Surgical aspects of liver transplantation⊛
Abstract
Keywords
Donor preparation by OPO (Organ Procurement Organization)
Deceased donor operation
Split liver procurement for transplantation
Living donor hepatectomy
Left lateral segment
Left lobe
Right lobe
Liver preservation/Machine perfusion
Liver viability on machine perfusion
Machine perfusion outcome
Back-table preparation of liver allograft
Brain death donor
Living donor
Orthotopic liver transplant
Recipient hepatectomy
Standard (Caval replacement) technique
Piggyback (Caval preservation) technique
Venous bypass
Vascular modifications
Bile duct reconstruction
Common operatively-relate liver transplantation complications
Summary
References
Chapter 46 COVID-19 and the liver⊛
Abstract
Keywords
Introduction
Epidemiology and transmission
Coronaviruses and liver injury
Pathogenesis of liver dysfunction
Risk factors for liver injury
Liver histology in COVID-19
Pattern of liver injury in COVID-19
COVID-19 in the setting of preexisting liver disease
COVID-19 and alcohol associated liver disease
COVID-19 and nonalcoholic fatty liver disease
COVID-19 and hepatitis B
COVID-19 and hepatitis C
Autoimmune liver disease and COVID-19
COVID-19 and hepatocellular carcinoma
COVID-19 and liver transplantation
Liver injury in pregnant patients with COVID-19
COVID-19 and patient care
Vaccination in CLD patients with COVID-19
Telemedicine in hepatology during COVID-19
Prevention and management of liver injury in COVID-19
Long COVID and liver injury
Summary
References
Chapter 47 Inherited and metabolic disorders of the liver⊛
Abstract
Keywords
Introduction
Techniques for genetic analysis
Epidemiology
Clinical features
When should one suspect an inherited and metabolic liver disease?
Clues to diagnosis
Classification of metabolic liver diseases based on clinical presentation
Inherited metabolic liver diseases
Galactosemia
Hereditary fructose intolerance (HFI)
Glycogen storage diseases (GSDs)
Congenital disorders of glycosylation (CDG)
Tyrosinemia type I
Urea cycle disorders (UCDs)
Lysosomal acid lipase (LAL) deficiency
Familial hypercholesterolemia
Abetalipoproteinemia
Gaucher disease (GD)
Niemann-Pick disease type C
Bile acid synthesis defects
Zellweger spectrum disorders
Wilson disease
Hereditary hemochromatosis
Hereditary hyperbilirubinemias [23]
Miscellaneous
Syndromes associated with liver disease
Alagille syndrome
Trichohepatoenteric syndrome (THES)
Turner syndrome
Infantile liver failure syndrome type 2
Hardikar syndrome
Aagenaes syndrome
Ciliopathies
Alstrom syndrome
Liver transplantation for inherited diseases
Recent updates and future directions
Summary
References
Chapter 48 Liver and Radiology⊛
Abstract
Keywords
Introduction
Ultrasound (US)
Computed tomography (CT)
Magnetic resonance imaging (MRI)
Digital subtraction angiography (DSA)
Diffuse liver disease
Hepatic steatosis
Liver cirrhosis
Viral hepatitis
Liver iron overload
Malignant diffuse liver disease
Benign focal liver lesions
Cystic lesions
Solid lesions
Malignant focal liver lesions
Hepatocellular carcinoma
Fibrolamellar HCC
Lymphoma
Angiosarcoma
Metastases
Vascular diseases
Budd-Chiari syndrome
Portal hypertension
Portal vein thrombosis
Benign biliary pathology
Choledocholithiasis
Hepatolithiasis
Benign biliary strictures
Primary sclerosing cholangitis
Postoperative strictures
Mirizzi’s syndrome
IgG4-related sclerosing cholangitis
AIDS cholangiopathy
Acute bacterial cholangitis
Recurrent pyogenic cholangitis
Parasitic infections
Ascaris lumbricoides
Hydatid disease
Biliary cystic disease
Biliary tumors
Cholangiocarcinoma
Biliary cystadenoma and carcinoma
Intraductal papillary neoplasm of the bile duct (IPNB)
Conclusion
Summary
References
Chapter 49 Gall bladder cancer⊛
Abstract
Keywords
Introduction
Epidemiology
Etiology and risk factors
Age and gender
Gallstones
Gallbladder polyps
Primary sclerosing cholangitis (PSC)
Anomalous pancreaticobiliary ductal junction (APBDJ)
Chronic infection
Toxins and medicines
Family history and genetic factors
Lifestyle factors
Pathogenesis
Genomics
Pathology
Gross pathology
Diagnosis
Magnetic resonance imaging (MRI)
Staging of GBC
Treatment
Surgery
Summary
References
Index for Volumes 1 and 2

Sanjaya K. Satapathy

Dr. Sanjaya Satapathy is a Professor of Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra University. He serves as the Interim Chief of Hepatology and Medical Director of Liver Transplantation at the Northwell Center for Liver Diseases & Transplantation, Northshore University Hospital. Dr. Satapathy is also the Program Director of Transplant Hepatology Fellowship at the Zucker School of Medicine/Northwell Health. His research focuses on NAFLD, Hepatitis C, post-transplant outcomes, NASH, sarcopenia, and hepatitis C. With over 160 peer-reviewed publications in high-impact journals, he is a recognized expert in the field. Dr. Satapathy is board certified in Internal Medicine, Gastroenterology, and Transplant Hepatology. He has received numerous accolades, including grants from NIH, and is a Fellow of various prestigious medical societies.

Affiliations and expertise

Interim Chief, Division of Hepatology; Medical Director, Liver Transplantation; and Program Director, Transplant Hepatology Fellowship

Mamun- Al-Mahtab

Mamun Al Mahtab is a notable hepatologist, medical scientist, author, and columnist from Bangladesh. With an impressive portfolio of 290 publications in national and international peer-reviewed journals, Dr. Mahtab currently serves as the Head of the Division of Interventional Hepatology at Bangabandhu Sheikh Mujib Medical University (BSMMU). Dr. Mahtab plays a crucial role in medical research and development. He leads the clinical study of the Bangladesh-developed SARS-CoV-2 mRNA candidate, GBPD060. Additionally, he serves as the lead researcher for NASVAC's Phase I/II and III clinical studies. Notably, his discovery of NASVAC earned him the prestigious 'Premio Nacional' award from the Cuban Academy of Sciences in 2019. Apart from his research endeavors, Dr. Mahtab actively organizes awareness programs on liver diseases throughout Bangladesh. He is also credited with inventing the NASVAC drug, which aims to provide an affordable and effective solution for Hepatitis B to the masses in Bangladesh.

Affiliations and expertise

Chairman, Department of Hepatology, Bangabandhu Sheikh Mujib Medical University

Shivaram Prasad Singh

Dr. Shivaram Prasad Singh is a highly accomplished medical professional. He graduated from Utkal University with degrees in MBBS and MD in Internal Medicine. He obtained his DM from C.M.C., Vellore at Madras University, India. Dr. Singh is a Fellow of the Society for Gastrointestinal Endoscopy of India, the American College of Gastroenterology, and the American Gastroenterological Association.

His remarkable contributions include initiating World Hepatitis B Eradication Day in India, endorsed by WHO, and serving on the World Hepatitis Alliance Public Health Panel. Dr. Singh held leadership positions in renowned organizations such as INASL and ISG. He has received prestigious awards, including the ISG S.R. Naik Memorial Award for Research Publications and the Indian Society of Gastroenterology Zydus Oration.

With over 160 publications and numerous national guideline papers, Dr. Singh is an acclaimed authority in gastrointestinal and liver diseases. He currently serves as the President-Elect of INASL.

Affiliations and expertise

Professor, Department of Gastroenterology, S.C.B. Medical College

Sheikh Mohammad Fazle Akbar

Dr. Akbar is an esteemed researcher in epidemiology, clinical studies, and immunology, focusing on chronic diseases like cancers. His molecular analysis has provided valuable insights into HBV, HCV, and HEV in Bangladesh, Nepal, Indonesia, and Japan. He developed a groundbreaking immune therapeutic drug for chronic hepatitis B and cancers, completing successful phase I/II and II clinical trials, with approvals in select countries. As a core member of the US-Japan Cooperative Medical Science Program (USJ CMSP), he contributes to global health research. Dr. Akbar has authored 150+ articles, compiled books, and holds editorial roles.

Affiliations and expertise

Senior Researcher, Department of Gastroenterology and Metabology

Aftab Ala

Professor Aftab Ala, MBBS, MD, PhD, FRCP, is Professor of Hepatology and Consultant Hepatologist at the Institute of Liver Studies at King’s College Hospital in London, UK, and the University of Surrey, Guildford, UK, and Chair of the Rare Liver Disease Special Interest Group at the British Association for the Study of the Liver (BASL). He obtained his medical qualification from Charing Cross and Westminster (Imperial College Medical School) in London in 1992. Professor Ala pursued specialized training in Gastroenterology and Hepatology at King’s and Royal Free Hospitals in London and Advanced Hepatology Fellowship at Mount Sinai Hospital in New York, USA, from 2003 to 2004 where he focused on rare liver and inherited metabolic liver diseases and liver transplantation. He subsequently won an International Sheila Sherlock Royal College of Physicians Fellowship at the Center of Excellence for Wilson Disease, Yale University, USA.

Professor Ala earned a PhD from University College, London, in 2005 and received a Wellcome Trust Research Training fellowship successfully focusing on immune and inflammatory mechanisms that connect liver and gut diseases.

Professor Ala has made significant contributions to the field of medicine, research, and education. His ongoing research and clinical trials programs (phases 1–3) in complex liver disease and health inequality are supported by international industry partners, the UK National Institute for Health and Care Research (NIHR) and the UKRI/MRC

Affiliations and expertise

Aftab Ala Institute of Liver Studies Kings College Hospital London, UK United Kingdom University of Surrey Guildford, UK

Thomas D Schiano

Dr. Thomas D. Schiano is a highly skilled medical professional with expertise in hepatology, gastroenterology, and clinical nutrition. He specializes in the management of cirrhosis, liver diseases, and pre- and post-liver transplantation care. Dr. Schiano's clinical research interests encompass various areas, including alcohol-related liver disease, nutritional aspects of liver disease, recurrence of disease post-transplantation, living donor liver transplantation, and complications of cirrhosis. He is actively involved in the care of patients undergoing intestinal transplantation and is a member of the liver thrombosis program, an international referral center for complex blood clotting disorders affecting the liver and intestines.

As a UNOS-certified Liver Transplant physician, Dr. Schiano holds board certifications in clinical nutrition, gastroenterology, and transplant hepatology. Currently, Dr. Schiano serves as a Professor of Medicine, Medical Director of Adult Liver Transplantation, and Director of Clinical Hepatology at the Recanati/Miller Transplantation Institute. He is also the Medical Director of the Intestinal Transplant program.

Affiliations and expertise

Medical Director, Intestinal Transplantation; Director of Clinical Hepatology; Medical Director, Adult Liver Transplantation at Mount Sinai Medical Center

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Hepatology

An Evidence-Based Clinical Compendium

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Resources

Sanjaya K. Satapathy

Mamun- Al-Mahtab

Shivaram Prasad Singh

Sheikh Mohammad Fazle Akbar

Aftab Ala

Thomas D Schiano