Textbook of Pediatric Gastroenterology, Hepatology and Nutrition: A Comprehensive Guide to Practice

Preface to the Second Edition
Acknowledgments
Contents
Contributors
Part I: GI-Nutrition
	1: Microvillus Inclusion Disease and Tufting Enteropathy
		Introduction
			The Larger Group of “Intractable Diarrheas of Infancy”
			Autoimmune Enteropathy
			Small Intestinal Enteropathy of Unknown Origin
			Intractable Ulcerating Enterocolitis of Infancy
			Congenital Enterocyte Heparan Sulfate Deficiency
			Congenital Intestinal Integrin Deficiency
			Congenital Secretory Diarrheas
			Diseases of the Intestinal Epithelium
		Microvillus Inclusion Disease
			Clinical Presentation
			Microvillus Inclusion Disease: A Congenital Secretory Diarrhea Starting in Neonatal Age
			Histologic Findings
			Epidemiology
			Pathophysiology
			Pathogenesis
			Prenatal Diagnosis
			Treatment
				Medical Care
				Surgical Care
		Tufting Enteropathy (or Intestinal Epithelial Dysplasia)
			Clinical Expression
			Pathophysiology
			Histological Features
			Treatment
		References
	2: The Spectrum of Autoimmune Enteropathy
		Introduction
		Diagnosis
		Clinical Presentation
		Pathogenesis
		Histopathology
		Treatment
			IPEX Syndrome
			IPEX-Like Syndromes
			APECED Syndrome
			Prognosis
		References
	3: Congenital Problems of the Gastrointestinal Tract
		Introduction
		Conditions Affecting the Upper Gastrointestinal Tract
			Esophageal Atresia (EA) and Tracheoesophageal Fistula (TEF)
			Classification
			Clinical Features
			Treatment
			Outcome
		The Stomach
		Obstructive Lesions of the Duodenum, Jejunum, and Ileum
			Clinical Features
			Investigations
		Conditions Affecting the Duodenum
			Classification
			Treatment
		Conditions Affecting the Ileum and Jejunum
			Classification
			Treatment
		Intestinal Malrotation
			Treatment
		Meconium Ileus
			Clinical Features
			Treatment
		Meckel’s Diverticulum
			Clinical Features
			Treatment
		Congenital Hepatic, Pancreatic, and Biliary Abnormalities
		Conditions Affecting the Lower Gastrointestinal Tract
			Hirschsprung Disease
			Anorectal Anomalies
			Clinical Features
			Treatment
			Outcome
		Conditions Which May Occur at Any Point in the Gastrointestinal Tract
			Gastrointestinal Duplications
			Clinical Features
			Treatment
		Conditions Affecting the Walls of the Abdominal Cavity
			Congenital Diaphragmatic Hernia
			Classification
			Clinical Features
			Treatment
			Surgery
		Anterior Abdominal Wall Defects
			Exomphalos
			Gastroschisis
			Treatment
			Surgical Closure
		References
	4: Pyloric Stenosis
		Introduction
		Incidence
		Anatomy
		Histology
		Etiology and Risk Factors
			Genetic Factors
			Environmental Factors
		Metabolic Changes in Pyloric Stenosis
		Clinical Features and Differential Diagnosis
		Investigations and Diagnosis
		Treatment
			Preoperative Management
			Surgical Treatment
			Conservative Treatment
			Complications
			Outcome
		References
	5: Gastrointestinal Problems of the Newborn
		GI Problems of Term Babies
			Difficult Feeding
			Gastroesophageal Reflux
			Diarrhea
			Constipation
			Colic
		GI Problems of Preterm Infants
			Feeding Difficulties
			Progressive Increment of Oral Feeding in Premature Infants
			Gastroesophageal Reflux (GER)
			Enteropathy
			Necrotizing Enterocolitis (NEC)
				Background of Prematurity and NEC
				Signs and Symptoms
				Diagnosis
				Treatment
				Prevention
			Meconium Ileus (MI)
				Definition and Etiology
				Diagnosis
				Treatment
		Congenital Anomalies
			Esophageal Atresia (EA)
				Definition
				Diagnosis
				Treatment
			Imperforate Anus
				Definition
				Diagnosis
				Treatment
			Abdominal Wall Problems
				Umbilical Hernia
				Omphalocele
				Gastroschisis
				Prune-Belly Syndrome
				Inguinal Hernia
				Omphalomesentéric Band
		Upper and Lower Endoscopy
			Upper Digestive Neonatal Endoscopy
			Lower Digestive Neonatal Endoscopy Findings (Colonoscopy)
		References
	6: Enteral Nutrition in Preterm Neonates
		Introduction
		Nutrition Objectives in Premature Neonates
			Enteral Nutrition During the Early Adaptive Period
			Nutrition During the Intermediate and Stable Growing Period
		Feeding Modality
			Frequency of Feeding: Bolus or (Semi-) Continuous Feeding
			Oral Feeding
			Intragastric Feeding
			Transpyloric Feeding
			Feeding Tolerance Evaluation and Feeding Advancement
		Nutrient Needs During Enteral Feeding
			Protein
				Protein Requirements
				Enteral Nutrition Protein Composition
			Energy
			Protein to Energy Ratio
			Fat
				Fat Requirements
				Enteral Nutrition Fat Composition
			Carbohydrates
				Carbohydrate Requirements
				Enteral Nutrition Carbohydrate Composition
			Fluids and Electrolytes
			Calcium and Phosphorus
				Calcium and Phosphorus Requirements
				Calcium and Phosphorus Composition in Enteral Nutrition
			Iron
			Trace Elements
			Oral Vitamin Requirements
		Human Milk
			Benefits of Human Milk
			Limits of Human Milk in Preterm Newborns
			Human Milk Fortification
			Expressed Donor Human Milk
		Infant Formulas
			Preterm Formula
			Hydrolyzed Formula
		Post-Discharge Enteral Nutrition
		Monitoring the Effects of Artificial Nutrition on Growth
			Anthropometric Measurements
			Laboratory and Biomedical Tools
		Conclusions
		References
	7: Parenteral Nutrition in Premature Infants
		Introduction
		The Standard for Premature Infants Growth
			Growth Rates
			Body Weight Composition
		Nutritional Support in Premature Infants
		Energy
			Postnatal Energy Metabolism
			Recommendations for Energy Supply During Total PN
			Recommendations for Energy Supply During Partial PN
		Amino Acids
			Intravenous AA Solutions
			Postnatal AA Requirements
			Recommendations for AA Supply
		Carbohydrates
			Intravenous Carbohydrates Solutions
			Postnatal Glucose Metabolism
			Hypo- and Hyperglycemia in Premature Infants
			Recommendations for Glucose Supply
		Lipids
			Intravenous Lipid Emulsions
			Postnatal Lipid Metabolism
			Recommendations for Lipid Supply
		Fluids and Electrolytes
			Postnatal Fluid and Electrolytes Metabolism
			Postnatal Fluid and Electrolytes Monitoring
			Recommendations for Fluid and Electrolytes Supply
		Minerals: Calcium, Phosphorus, and Magnesium
			Postnatal Mineral Metabolism
			Minerals Sources
			Recommendation for Mineral Supply
		Trace Elements
		Vitamins
		Individualized and Standardized PN Solutions
		Conclusion
		References
	8: Infectious Esophagitis
		Introduction
		Clinical Features
		Diagnosis
		Esophagoscopy, Biopsy, and Brushing
		Fungal Esophagitis
			Candida
			Other Causes of Fungal Esophagitis
		Viral Esophagitis
			Herpes Simplex Virus
			CMV
			Other Viral Infections
			Bacterial Esophagitis
		References
	9: Eosinophilic Esophagitis
		Introduction
		Historical Context
		Diagnostic Criteria
		Factors Complicating EoE Diagnosis
		Clinical Presentation
			Presenting Symptoms
			Natural History
		Endoscopic Findings
		Radiology
		Histology
		Epidemiology
			Clinical Associations with Esophageal Eosinophilia
		Pathogenesis
			Genetic Predisposition
			Inflammatory Cascade
			Barrier Dysregulation and Esophageal Remodeling
		Treatment
			Proton Pump Inhibitors
			Steroids
			Elimination Diets
			Allergy Medications
			Biologic Treatments
			Other Medications
		Dilation
		Maintenance Therapy
		Disease Monitoring
		Summary
		References
	10: Gastroesophageal Reflux
		Introduction
		Definitions
		Prevalence, Environmental and Genetic Factors
		Pathophysiology
		Symptoms and Signs
			GER and Uncomplicated Regurgitation
			GER(D) and Recurrent Regurgitation and Poor Weight Gain
			GER(D) and Cow’s Milk Protein Allergy
			GERD and Esophagitis
			GER(D) and Eosinophilic Esophagitis
			GER(D) and Heartburn, Infant Crying, and Distressed Behavior
			GER(D) and Dysphagia, Odynophagia, and Food Refusal
			GER(D) and Extra-Esophageal Manifestations
				GER(D) and Reactive Airway Disease
				GER(D) and Recurrent Pneumonia
				GER(D) and Cystic Fibrosis
				GER(D) and Cough and ENT Manifestations
				GER(D) and Dental Erosions
				GER(D) and Sandifer Syndrome
			GER(D) in Neurologically Impaired Children
			GER(D) and Apnea, Brief Resolved Unexplained Events, and Sudden Infant Death Syndrome
			GER(D) and Other Risk Groups
			GERD and Complications
		Diagnosis
		Therapeutic Options
		Complications of Non-intervention
		Non-pharmacological and Non-surgical Therapies for GER
		Pharmacological Therapies for GERD
			Prokinetics and Other Non acid-Reducing/Blocking Medication
			Alginate(-Antacids) and Mucosal Protectans
			H2-Receptor Antagonists (H2RAs) and Proton-Pump Inhibitors (PPIs)
		Surgery and Therapeutic Endoscopic Procedures
		References
	11: Esophageal Achalasia
		Introduction
		Epidemiology
		Heredity
		Etiopathogenesis
		Clinical Presentation
		Diagnostic Approach
			Radiology
			Upper Gastrointestinal Endoscopy
			Manometry
		Management
			Pharmacological Therapy
			Endoscopic Botulinum Toxin Injection
			Pneumatic Dilatation
			Surgery
			Emerging Treatments
		Follow-Up and Surveillance
		Conclusion
		References
	12: Helicobacter Pylori Gastritis and Peptic Ulcer Disease
		Introduction
		Bacterial Pathogenesis
			Survival in the Acidic Environment
			Movement Toward Epithelial Cells
			Attachment to Host Cells by Adhesins/Receptors Interaction
			Causing Tissue Damage
			Immunologic Aspects
		Epidemiology and Transmission
		Gastritis
		Peptic Ulcer Disease
			Other Causes of Peptic Ulcer Disease
		Malignancy
		Clinical Presentation of H. pylori Infection
		Diagnostic Procedures
			Noninvasive Tests
			Invasive Tests
		Treatment for Helicobacter pylori Infection
			First-Line Treatment
		Assessment of Eradication
		References
	13: Ménétrier Disease in Children
		Introduction
		Clinical Manifestations
		Pathophysiology and Etiology
		Diagnosis and Histological Findings
		Treatment
		Conclusion
		References
	14: Viral Diarrhea
		Epidemiology and Etiology
		Pathophysiology of Viral Diarrhea
		Clinical Signs and Symptoms of Viral Diarrhea
		Diagnosis
		Specific Viruses
			Rotavirus
			Norovirus
			SARS-CoV-2 Virus
		Evaluation and Treatment of Children with Acute Diarrhea
		Management of Viral Diarrhea in Immunocompromised Children
		Vaccines for Viral Diarrhea
		References
	15: Bacterial Infections of the Small and Large Intestine
		Introduction
			Intestinal Ion Transport and Barrier Functions
		Bacterial Diarrhea
			Vibrio cholerae
			Salmonella
			Clostridioides (Formerly Clostridium) difficile
			Shigella
			Campylobacter
			Yersinia
			Escherichia coli
			Enterotoxigenic E. coli (ETEC)
			Enteropathogenic E. coli (EPEC)
			Enterohemorrhagic E. coli (EHEC)
			Diffusely Adherent E. coli (DAEC)
			Enteroaggregative E. coli (EAEC)
			Enteroinvasive E. coli (EIEC)
			Treatment of Diarrheagenic E. coli
		References
	16: Intestinal Parasites
		Introduction
		Protozoa
			Amoebae
				Endolimax nana
				Iodamoeba bütschlii
			Giardiasis
			Dientamoeba fragilis
			Balantidium coli
			Blastocystis
			Coccidia
				Cryptosporidium (Fig. 16.3)
				Cyclospora cayetanensis
				Cystoisospora belli
		Helminths
			Nematodes (Roundworms)
				Enterobius vermicularis (Pinworm) (Fig. 16.4)
				Ascaris lumbricoides
				Trichuris trichiura (Whipworm)
				Hookworm
				Strongyloides stercoralis (Fig. 16.5)
			Cestodes (Tapeworms)
		References
	17: Persistent Diarrhea in Children in Developing Countries
		Introduction
		Etiology
		Risk Factors
		Consequences of Persistent Diarrhea
		Management
			Rapid Resuscitation, Antibiotic Therapy, and Stabilization
			Oral Rehydration Therapy
			Enteral Feeding
			Micronutrient Supplementation
			Antidiarrheal Drugs
			Pancreatic Enzyme Replacement Therapy (PERT)
			Improved Case Management of Diarrhea
			Other Potential Modalities
			Follow-Up and Nutritional Rehabilitation in Community Settings
		Conclusions
		References
	18: HIV and the Intestine
		Introduction
		The Spectrum of GI Disorders in HIV Infection
		Pathophysiology of HIV-Associated Intestinal Damage
			Gut Microbiota in HIV Infection
			Intestinal Barrier Damage Response to ART and Novel Strategies
		Upper Gastrointestinal Symptoms
		Lower Gastrointestinal Symptoms
			Bacterial Diarrhea
			Viral Diarrhea
			Parasitic Diarrhea
			Fungal Diarrhea
		Noninfectious Diarrhea in HIV
		Pancreas and Liver in HIV-Infected Children
		HIV-Associated GI Malignancies
		Nutritional Challenges in Children Growing with HIV
		HIV and Malnutrition in Resource-Limited Settings
		References
	19: The Spectrum of Functional GI Disorders
		Introduction
		Biopsychosocial Model of Functional Gastrointestinal Disorders
		Approach to Patients with Disorders of  Gut-Brain Interaction
			Physical Exam
			Symptom-Based Approach to Functional Gastrointestinal Disorders
			Prevalence
			Functional Nausea and Vomiting Disorders
			Functional Abdominal Pain Disorders
			Mild Symptoms
			Moderate Symptoms
			Severe Symptoms
			Functional Defecation Disorders
			Infant Dyschezia
			Functional Diarrhea
		References
	20: Disorders of Sucking and Swallowing
		Introduction
		Epidemiology
		Etiology
		Pathophysiology
		Anatomic Considerations
		Development and Normal Swallowing Function
		Dysphagia
		Clinical Signs/Symptoms
		Complications
			Malnutrition
			Sialorrhea
			Respiratory Complications
			Diagnosis
			History
			Physical and Clinical Evaluation
		Diagnostic Tests
			Radiographic Assessment
			Fiberoptic Endoscopic Examination
			Ultrasonography
			Pharyngeal Manometry
			Scintigraphy
			Treatment Options
			Prognosis
		References
			Additional Educational Resources:
	21: Defecation Disorders in Children: Constipation and Fecal Incontinence
		Part 1: Constipation
			Definition
			Prevalence
			Physiology of Defecation
			Risk Factors
			Quality of Life
			Healthcare Burden
			Pathophysiology
				Infants and Young Children
				Children and Adolescents
				Final Pathway for Both Age Groups
			Clinical Evaluation
				Clinical History
				Physical Examination
			Investigations
				Laboratory Tests
				Radiological Tests
				Functional Tests
			Management
				Lifestyle Modifications
				Toilet Training and Behavioral Therapy
				Pharmacological Treatment
					Fecal Disimpaction of the Rectum
					Maintenance Therapy
						Osmotic Laxatives
						Lubricant Laxatives
						Stimulant Laxatives
				New Drugs
					Prosecretory Agents
						Lubiprostone
						Linaclotide
						Plecanatide
					Serotonergic Agents
				Biofeedback and Pelvic Floor Physiotherapy
				Trans-anal Irrigation
				Neuromodulation
				Surgical Interventions
		Part 2: Fecal Incontinence
			Introduction and Epidemiology
			Functional Non-retentive Fecal Incontinence
		References
	22: Hirschsprung’s Disease and Intestinal Neuronal Dysplasias
		Introduction
		Epidemiology
		Etiology
		Pathophysiology
		Genetics
			Molecular Genetics
			The RET Signaling Pathway
			The Endothelin Signaling Pathway
			SOX10
		Clinical Signs/Symptoms
		Complications
		Diagnosis
		Treatment
		Short- and Long-Term Prognosis
		Intestinal Neuronal Dysplasia
			Genetic Aspects
		References
	23: Intestinal Pseudo-Obstruction
		Introduction
		Epidemiology
		Classification
		Etiology and Pathophysiology
		Genetics
		Histopathology
		Clinical Picture
		Diagnosis
		Imaging
		Endoscopy
		Motility Investigations
		Differential Diagnosis
		Treatment
		Nutrition
		Medications
		Surgery
		Natural History and Prognosis
		Summary
		References
	24: Gastrointestinal and Nutritional Problems in Neurologically Impaired Children
		Introduction
		Feeding and Nutritional Aspects
		Gastrointestinal Problems
			Dysphagia
			Gastro-esophageal Reflux
			Constipation
		References
	25: Cyclic Vomiting Syndrome
		Introduction
		Cyclic vs. Chronic Patterns of Vomiting
		Clinical Patterns
		Pathophysiology
			Mitochondrial Dysfunction
			Neuroendocrine
			Autonomic Dysfunction
		Subtypes of CVS and Comorbidities
			Migraines
			Neurocognitive Delays
			Cannabis
			Other Subgroups
			Comorbidities
		Differential Diagnosis
		Diagnostic Evaluation
		Treatment
			Supportive or Rescue Therapy
			Lifestyle Modifications
			Prophylactic Therapy
			Abortive Therapy
		Comorbidities
		Natural History, QOL Impact, and Complications
		Summary
		References
	26: Food Allergy
		Introduction
		Epidemiology
		Adverse Food Reactions
		Immunopathogenesis and Specific Disorders
		IgE-Mediated Reactions
			Natural History of IgE-Mediated Reactions
			Symptoms
			Anaphylaxis
			Food-Dependent, Exercise Induced Anaphylaxis
			Alpha-Gal
			Pollen Food Allergy Syndrome (Oral Allergy Syndrome)
			Management of Acute IgE-Mediated Reactions
		Cell-Mediated Food-Allergic Disorders
		Food Protein Induced Enterocolitis Syndrome
			Background
			Natural Course
			Diagnosis
			Differential Diagnosis
			Management
		Food Protein Induced Enteropathy
		Food Protein Induced Allergic Proctocolitis
		Mixed IgE- and Cell-Mediated Disorders
		Diagnostic Evaluation of Food Allergy
			History and Physical Examination
			Tests for Food-Specific IgE
				Skin Prick Testing
				In Vitro Testing
			Diagnostic Food Elimination Diets
			Food Challenges
				Food Challenge Format
			Unproven Tests That Are Not Recommended
		Prevention of Food Allergy
		Dietary Treatment of Food Allergies
			Avoidance
			Maternal Diet and Allergies in Breastfeeding
			Nutritional Issues in Food Allergy
			Recent Advances in Food Allergy Management
		Summary
		References
	27: Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis
		Introduction
		Epidemiology
		Pathophysiology
		Clinical Manifestations (Table 27.1)
			Mucosal Disease (Figs. 27.1, 27.2, 27.3, 27.4, and 27.5) [2, 41, 42]
			Muscular Disease (Figs. 27.6, 27.7, 27.8, 27.9 and 27.10) [51–53]
			Serosal/Subserosal Disease (Figs. 27.11 and 27.12) [60, 61]
		Laboratory Findings
		Gastrointestinal Endoscopy (Figs. 27.1, 27.2, 27.3, 27.4, and 27.5) [2, 41, 42]
		Histology (Figs. 27.13, 27.14, 27.15, 27.16, 27.17, and 27.18) [2, 66]
		Imaging Studies (Figs. 27.6, 27.7, 27.8, 27.9, 27.10, 27.11, and 27.12) [52, 53]
		Other Tests
		Differential Diagnosis (Table 27.2)
		Treatment
		Natural History of EGIDs Beyond EoE
		References
	28: Crohn’s Disease
		Introduction
		Epidemiology
		Etiopathogenesis
		Clinical Presentation
		Diagnosis
			Noninvasive Tests
				Serologic Tests
				Fecal Markers of Inflammation
				Ileocolonoscopy and Esophagogastroduodenoscopy (EGD)
			Small Bowel Evaluation
				Imaging
				Small Bowel Capsule Endoscopy
				Balloon Enteroscopy
		Therapy
			Conventional Therapy
				Aminosalicylates
				Steroids
				Immunomodulators (Azathioprine, 6-Mercaptopurine, Methotrexate)
				Biologic Agents
				Nutrition
				Surgery
		References
	29: Inflammatory Bowel Disease Unclassified (IBD-U)/Indeterminate Colitis
		Introduction
		Inflammatory Bowel Disease Unclassified (IBD-U)
			Clinical Presentation
		Epidemiologic Aspects
		Criteria for Histologic Diagnosis
		Serologic Markers and Defining IBD Categories
		Radiologic Imaging
		Capsule Endoscopy (CE)
		Natural History
		Medical Therapy
		Surgical Treatment
		Multicenter Collaborative Studies Supporting IBD-U as a Separate IBD Subtype
		Conclusions
		References
	30: Ulcerative Colitis
		Introduction
		Epidemiology
		Pathogenesis
		Genetics
		Environmental Factors
		UC and the Microbiome
		Clinical Manifestations
		Extraintestinal Manifestations
			Arthralgia and Arthritis
			Mucocutaneous Lesions
			Ophthalmologic Disease
			Hepatobiliary Disease
		Diagnostic Criteria
		Endoscopic and Histological Features
		Laboratory and Serological Markers
		Activity Indices
		Cross-Sectional Imaging
		Infectious Etiologies
			Clostridium difficile (C. difficile)
		Cytomegalovirus (CMV) Colitis
		Complications
			Toxic Megacolon
		Acute Severe Colitis
		Medications
			5-Aminosalicylic Acid Agents (5-ASA)
			Corticosteroids
		Immunosuppressive Therapy
			Thiopurines
			Methotrexate
			Tacrolimus
		Biologics
			Infliximab
			Adalimumab
			Vedolizumab
			Ustekinumab
			Tofacitinib
		Probiotics and Dietary Therapy
		Fecal Microbiota Transplantation
		Psychosocial Barriers
		Nutrition, Growth, and Vitamin D
		Surgical Therapy
		Pouchitis
		Long-Term Prognosis, Colorectal Cancer, and UC
		References
	31: Microscopic Colitis
		Introduction
		Epidemiology
		Clinical Findings
		Associated Conditions
		Pathophysiology
		Reactions to Luminal Antigens and Dysbiosis
		Genetic Predisposition
		Infections
		Medication Side Effect
			Malabsorption of Biliary Acids
		Abnormal Collagen Metabolism
		Laboratory Findings
		Endoscopic and Histological Findings
		Treatment
		Surgical Treatment Options and Prognosis
		References
	32: Vasculitides Including IgA Vasculitis (Henoch–Schönlein Purpura)
		Introduction
		IgA Vasculitis (Henoch–Schönlein Purpura)
		Kawasaki Disease
		Systemic Polyarteritis Nodosa
		Behçet Disease
		ANCA-Associated Vasculitis (AAVs)
		Granulomatosis with Polyangiitis (GPA)—Formerly Wegener’s Granulomatosis
		Eosinophilic Granulomatosis with Polyangiitis (EGPA)
		Microscopic Polyangiitis (MPA)
		Single-Organ Vasculitis (SOV)
		Takayasu Arteritis (TA)
		Systemic Lupus Erythematosus–Associated Vasculitis
		Juvenile Dermatomyositis (JDM)
		Rheumatoid-Associated Vasculitis
		Pediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV 2 (PIMS-TS)
		Investigation of Children with Suspected GI Vasculitic Disorders
		References
	33: Lymphonodular Hyperplasia
		Introduction
		Definition
		Endoscopic Assessment and Criteria
		Anatomical Distribution of LNH
		Histological Assessment of LNH
		Pathophysiology of LNH
		LNH and Associated Conditions: Food Allergy
		LNH in Other Diseases and Conditions
		Symptoms of LNH
		Treatment and Prognosis
		References
	34: Acute Pancreatitis
		Anatomy and Physiology
		Pathophysiology
		Epidemiology
		Etiology
		Diagnosis
		Clinical Presentation
			Mild Acute Pancreatitis
			Moderate Acute Pancreatitis
			Severe Acute Pancreatitis
		Treatment
		Complications
		Future
		References
	35: Chronic and Hereditary Pancreatitis
		Introduction
		Pathophysiology
			Risk Factors
		Diagnosis
			Establishing the Diagnosis of Chronic Pancreatitis
			Establishing Risk Factors for Chronic Pancreatitis
			Evaluating the Severity of Chronic Pancreatitis
				Exocrine Pancreatic Function Assessment
				Endocrine Pancreatic Function Assessment
			Evaluation of Exacerbations
			Exacerbation Workup
		Treatment
			Medical
				Pain Management
				Pancreatic Enzyme Replacement Therapy
				Others
			Psychology
			Endoscopic
			Surgical
				Cholecystectomy
				Drainage and Partial Resection Procedures
				Total Pancreatectomy, Islet Autotransplantation
		References
	36: Congenital Disorders of Intestinal Electrolyte Transport
		Introduction
		Congenital Chloride Diarrhea
		Congenital Sodium Diarrhea
		Familial Diarrhea Syndrome
		Cystic Fibrosis
		References
	37: Congenital Disorders of Lipid Transport
		Introduction
		Intestinal Lipid Absorption Overview
		Molecular Genetic Basis for Congenital Defects in Lipid Absorption: Overview
		Congenital Disorders of Chylomicron Assembly: Genetics and Clinical Features of Abetalipoproteinemia (ABL) and Familial Hypobetalipoproteinemia (FHBL)
		Abetalipoproteinemia (ABL, OMIM #200100): Molecular Genetics and Prevalence
		Abetalipoproteinemia (ABL, OMIM #200100): Clinical Features and Management
		Familial Hypobetalipoproteinemia (FHBL, OMIM #107730): Molecular Genetics and Prevalence
		Familial Hypobetalipoproteinemia (FHBL, OMIM #107730): Clinical Features and Management
		Chylomicron Retention Disease/Anderson’s Disease (CRD, OMIM #246700): Molecular Genetics and Prevalence
		Genotype–Phenotype Associations in CRD
		Chylomicron Retention Disease/Anderson’s Disease (CRD, OMIM #246700): Clinical Features and Management
		References
	38: Immunodeficiency Disorders Resulting in Malabsorption
		Introduction
		Evaluating a Child with Suspected Primary Immunodeficiency
		Predominant B-Cell (Antibody) Deficiency
			Selective IgA Deficiency
		X-Linked Agammaglobulinemia
		Hyper-IgM Syndrome
		Common Variable Immunodeficiency
		Combined T and B Cell Immunodeficiency
			Severe Combined Immunodeficiency
		Disorder of Phagocytes Function
			Chronic Granulomatous Disease (CGD)
		Immune Dysregulation Diseases
			IPEX and IPEX-Like Disorders
		Interleukin-10 and Interleukin-10-Receptor Defects
		Immunodeficiency-Associated with Other Defects
			Wiskott Aldrich Syndrome (WAS)
		Hermansky–Pudlak Syndrome (HPS)
		References
	39: Exocrine Pancreatic Insufficiency
		Introduction
		Exocrine Pancreatic Insufficiency in Cystic Fibrosis
		Pathophysiology of Exocrine Pancreatic Insufficiency in Cystic Fibrosis
		Shwachman–Diamond Syndrome
		Exocrine Pancreatic Insufficiency in Chronic Pancreatitis
		Pearson Syndrome
		Johanson–Blizzard Syndrome
		Clinical Symptoms of Exocrine Pancreatic Insufficiency
		Diagnosis of Exocrine Pancreatic Insufficiency
		Indirect Pancreatic Function Tests
		Direct Pancreatic Function Tests
		Management
		References
	40: Celiac Disease
		Introduction
		Epidemiology
		Etiopathogenesis
			Genetic Factors
				The Central Role of HLA-DQ Haplotype
				Non-HLA Genetic Susceptibility Factors
			Environmental Factors
				Viral Infections
				Intestinal Microbiota
			Pathogenesis
				Gluten
				Tissue Transglutaminase 2 and Autoantibodies
				The Intersection of Adaptive and Innate Immune Responses in CD
				IELs Activation and the Induction of Tissue Damage
			A Mouse Model of CD
			Clinical Presentations
			GI Manifestations
			Extra-Intestinal Manifestations and Laboratory Changes
		Disease Associations
		Autoimmune Conditions
			Genetic/Chromosomal Disorders
			Diagnosing CD
			Potential Celiac Disease
			Nonresponsive Celiac Disease
			Treatment
		References
	41: Cystic Fibrosis
		Introduction
		The CFTR Gene
		Diagnosis of CF
		CFTR Dysfunction: Gastrointestinal Consequences
			Exocrine Pancreatic Abnormalities
				Exocrine Pancreatic Function
				Recurrent Pancreatitis
		Diagnosis of Pancreatic Phenotype
		Oral Pancreatic Enzyme Replacement Therapy
		Hepatobiliary Disease
		Diagnosis and Management
		Intestinal Complications
			Meconium Ileus (MI)
		Distal Intestinal Obstruction Syndrome
		Appendiceal Disease
		Intussusception
		Gastroesophageal Reflux Disease
		Fibrosing Colonopathy
		Intestinal Infections
		Small-Intestinal Bacterial Overgrowth
		Rectal Prolapse
		Celiac Disease and Crohn’s Disease in CF
		Gastrointestinal Malignancy
		Nutritional Complications
		Nutritional Intake
		Toddlers and Children
		Fat-Soluble Vitamins
		Bone Health
		Lung Transplantation
		Novel Therapies
			Probiotics
		CFTR Correctors and Potentiators
		References
	42: Small Intestinal Bacterial Overgrowth
		Introduction
		The Gastrointestinal Tract and Gut Microbiota
		Epidemiology in Children
		Pathogenesis
		Risk Factors
			Acid-Suppressive Therapies
			Intestinal Motility Disturbances
			Anatomical Alterations
			Impoverished Conditions and Poor Socioeconomic Status
			Other Risk Factors for SIBO
		Aetiology of Paediatric SIBO
		Clinical Features and Complications
			SIBO and Functional Gastrointestinal Disorders
			SIBO and Systemic Disorders
		Diagnosis
			Hydrogen and Methane Breath Testing
			Culture-Dependent Approaches
			SIBO in the Era of Next-Generation Sequencing
		Treatment
		Prognosis
		Conclusion
		References
	43: Short Bowel Syndrome
		Introduction
		Definition and Etiology
		Consequences of Gut Resection
			Intestinal Resection
			Intestinal Adaptation After Extensive Resection
		Management
			Early Management
			Long-Term Management of SBS: PN, Oral Eating, and Prevention of Complications
				Growth with Parenteral Nutrition
				Promotion of Bowel Adaptation
				Prevention of Complications
					Small Intestinal Bacterial Overgrowth (SIBO)
					IFALD
					IFALD and Intravenous Lipid Emulsions
					Catheter-Related Issues
						Infections
						Thrombosis
					D Lactic Acidosis
					Perianastomotic Ulceration
						Eating Disorders
					Growth Failure
					Other Complications
						Biliary Lithiasis
						Oxalate Renal Lithiasis
		Alternative Treatments
			Nontransplant Surgery
				Autologous Bowel Reconstruction
				Surgical Management of TIA
			New Treatments (GLP-2 Analogs, Insulin, EGF)
				Hormonal Therapy and Other Adaptive Treatments
				Inhibitors of Dipeptidyl Peptidase-4
				Tissue Engineering
		Long-Term Prognosis (PN and Weaned Patients, Growth, Adult Height)
		Nutritional Failure and Intestinal Transplantation for SBS-IF
		Conclusion
		References
	44: Malnutrition
		Introduction
			School-Age and Adolescence
		Risk Factors
		Short- and Long-Term Consequences of Malnutrition on Growth and Development
			Underweight
				Children Under 5 Years of Age
				School-Age Children (6–9 Years)
				Adolescents (10–19 Years)
			Overweight/Obesity
				Children Under 5 Years of Age
				School-Age Children (6–9 Years)
				Adolescents (10–19 Years)
			Nutrient Deficiencies
				Children Under 5 Years of Age
				School-Age Children (6–9 Years)
				Adolescents (10–19 Years)
		Interventions
			Age Group 0–5 Years
				Neonatal Interventions
				Breastfeeding Interventions
				Complementary Feeding Interventions
				Stunting, Wasting, and Underweight Interventions
				Water, Sanitation, and Hygiene (WASH) Interventions
				Micronutrient Deficiency Interventions
				Food Fortification Interventions
				Iron Supplementation and Fortification Interventions
				Vitamin A Supplementation and Fortification Interventions
				Zinc Supplementation and Fortification Interventions
				Intervention to Decrease Bodyweight
			School-Age Children (6–10 Years)
				Antihelminthic Interventions
				Supplementation Interventions
				Fortification Interventions
				Intervention to Decrease Bodyweight
			Adolescence (10–19 Years)
				Underweight and Micronutrient Deficiency
				Intervention to Decrease Bodyweight
		Conclusions
		References
	45: Enteral Nutrition
		Introduction
		Physiological Basis of Continuous Enteral Feeding
			Gastrointestinal Motility
			Digestive Secretion and Hormonal Response
			Effects of CEN on Mucosal Trophicity
			Effects of CEN on Energy Expenditure and Feeding Tolerance
		Indications
		Conditions with Normal Intestinal Absorptive Function
		Premature Infants
		Restrictive Eating Disorders: Anorexia Nervosa and Avoidant Restrictive Food Intake Disorder
		Inborn Errors of Metabolism
		Hypermetabolic States
		Graft Versus Host Disease
		Renal Failure
		Congenital Heart Disease
		Digestive Indications
		Severe Protracted Diarrhea of Infancy/Congenital Diarrheas and Enteropathies
		Short Bowel Syndrome
		Disorders of Motility
		Crohn’s Disease
		Other Malabsorption Syndromes
			Cystic Fibrosis
			Chronic Liver Disease
			Chylothorax
		Techniques of Delivering Enteral Nutrition
		Nutrients
			Nitrogen
			Carbohydrates
			Lipids
			Other Components
		Choice of a Formula
		Regulation of Intakes and Rhythm of EN Delivery
		Complications of Enteral Nutrition Therapy
		Functional Complications of Feeding Tubes
		Gastrointestinal Complications
		Mechanical, Infectious, and Metabolic Complications
		Infectious Complications
		Re-feeding Syndrome
		Home Enteral Nutrition (HEN)
			Indications
			Organization
			Parents’ Teaching
		Results
			Quality of Life
			Outcomes
			Cost and Funding
		References
	46: Parenteral Nutrition in Infants and Children
		Introduction
		Definitions of PN and EN
		History and Development of PN
		Constituents of PN
		Types of PN Formulations and Pharmacy Arrangements
		When to Start PN
		How to Start PN
		Venous Access for PN Infusion
		PN Infusion and Cycling
		Monitoring on PN Treatment
		Role of the Nutrition Support Team
		Complications of PN
			Metabolic Disorders
				Inappropriate Weight Gain
			Infection
			CVC Occlusion and Venous Thrombosis
			Liver Disease
		Enteral Nutrition and Weaning from PN
		Failure to Wean from PN as Expected
		Preparation for Home PN: Care in Hospital
		Management at Home
			Complications of Long-Term/Home PN and Their Management
			Specific Features of PN at Home
			Quality of Life in Children on PN at Home
				Regaining Enteral Autonomy and Weaning PN Treatment
				Transition to Adult Care
				Intestinal Transplant
		Withdrawing PN Treatment
		Outcome
		Summary
		References
	47: Intussusception
		Introduction
		Incidence and Demographics
		Etiology
		Pathophysiology
		Clinical Presentation
		Diagnostic Evaluation
		Clinical Management
		Conclusion
		References
	48: Meckel’s Diverticulum
		Introduction
		Embryology
		Epidemiology
		Associated Anomalies
		Gross and Microscopic Anatomy
		Variations of Patent VI Duct Anomalies
		Clinical Features
			Neonatal
			Paediatric Age Group
				Intestinal Obstruction
				GI Bleeding
				Diverticulitis
			Adult Age Group
			Other Presentations
		Management of MD
			Investigations
			Incidental MD
			Surgical Management
			Outcome/Conclusion
		References
	49: Appendicitis
		Introduction
		Epidemiology
		Anatomy and Pathophysiology
		Presentation and Physical Exam
			Presenting Symptoms
			Physical Exam
		Diagnosis
			Differential Diagnosis
			Diagnostics: Laboratory
			Diagnostics: Imaging
			Scoring Systems to Evaluate for Appendicitis
		When to Consult Surgery or Transfer the Patient to a Center with Pediatric Surgery
		Management
			Initial Management of All Appendicitis Patients
			Surgical Management: Appendectomy
			Nonoperative Management
			Follow-Up and Post-Operative Complications
		References
	50: Gastrointestinal Vascular Anomalies
		Introduction
		Embryology
		Pathogenesis
		Vascular Tumors
		Vascular Malformations
		Classification of Vascular Lesions
		Group I: Vascular Tumors
		Group II: Vascular Malformations
		Associated Syndromes
		Lymphatic Malformations
		Primary Intestinal Lymphangiectasia (Waldmann’s Disease)
		Investigations
		Treatment
		Vascular Tumors
		Vascular Malformations
			Sclerotherapy
			Medical Therapy
			Surgical Therapy
		Conclusion
		References
	51: Polyps and Other Tumors of the Gastrointestinal Tract
		Introduction
		Clinical Presentation of Gastrointestinal Polyps
		The Single Hamartomatous Polyp: The Juvenile Polyp
		Hamartomatous Polyposis Syndromes
		Juvenile Polyposis Syndrome
		Genetics of Juvenile Polyposis
		Screening and Follow-Up
		PTEN Hamartoma Tumor Syndrome
		Peutz–Jeghers Syndrome
			Clinical Features and Diagnosis
			Genetics of PJS
			Screening, Management, and Complications
		Adenomatous Polyposis Syndromes
			Familial Adenomatous Polyposis
			Clinical Features
			Genetics of FAP
			Diagnosis: Interpretation of the Genetic Test and Clinical Screening in FAP
			Management of FAP
		Desmoid Disease
		Chemoprevention
		Prognosis
		MYH-Associated Polyposis and Lynch Syndrome
		Other Polyposis Syndromes
		The Role of a Polyposis Registry
		Other Tumors of the GI Tract (Excluding the Stomach and Hepato-biliary)
			Gastrointestinal Stromal Tumors
			Carney Triad
			Familial
			Sporadic
		Gastrointestinal Autonomic Nerve Tumors
		Inflammatory Pseudotumors
		Sarcomas
		Carcinoid Tumors
		Gastroenteropancreatic Neuroendocrine Tumors
		Adenocarcinoma
		Pathogenesis
		Pathology
		Clinical Presentation
		Treatment/Prognosis
		Lymphoma
			Epidemiology and Classification
			Etiology
			Pathology
			Clinical Presentation
		Treatment and Outcome
		References
	52: Fecal Microbiota Transplantation in Children
		Introduction
		Fecal Microbiota Transplantation in Children
		Pediatric Fecal Microbiota Transplantation: Clinical Indications
		Pediatric Fecal Microbiota Transplantation Safety Profile
		Conclusions and Future Perspectives
		References
	53: Prebiotics in Pediatrics
		Introduction
			Possible Effects of Prebiotics
			Immune Modulation
			Improved Bowel Function
			Increased Mineral Absorption
			Prebiotics in Infant Formulas
		Conclusions
		References
	54: Probiotics in Pediatric Gastroenterology
		Introduction
		Definition and Mechanismss of Probiotics
		Management of Conditions with Probiotics
			Treatment of Acute Gastroenteritis
			Prevention of Antibiotic-Associated Diarrhea
			Prevention of Necrotizing Enterocolitis
			Helicobacter pylori Infection
			Inflammatory Bowel Disease
			Functional Gastrointestinal Disorders
				Treating Infantile Colic
				Preventing Infantile Colic
				Functional Abdominal Pain Disorders
				Functional Constipation
			Cystic Fibrosis
			Other Diseases
		Safety of Probiotics
		Quality of Probiotics
		Conclusions
		References
	55: Postbiotics
		Introduction
			Definition and Mechanisms of Action of Postbiotics
			The Science of Inactivated Probiotics and Other Microorganisms
		Postbiotics in Children
			Fermented Formulas
			Prevention and Treatment of Common Infectious Diseases
			Cow’s Milk Allergy Management
			Non-clinical Outcomes
		Postbiotics in Adults
		Conclusions
		References
Part II: Hepatology
	56: Normal Liver Anatomy and Introduction to Liver Histology
		Normal Liver Development
		Normal Liver Macroanatomy
		Liver Microanatomy and Considerations When Interpreting Histological Findings in Paediatric Liver Biopsies
		References
	57: Diagnostic Procedures in Paediatric Hepatology
		Imaging of Cholestatic Jaundice
			Neonatal
			Older Children
		Congenital and Acquired Vascular Disorders
			Portal Hypertension
			Intra- and Extrahepatic Vascular Shunts
			Budd-Chiari Syndrome
		Imaging of Transplant Liver
			Hepatic Artery
			Portal Vein
			IVC
			Biliary Disorders
		Liver Masses
			Radiological Approach to the Child with a Focal Liver Lesion
		Benign Tumours
			Infantile Hepatic Hemangiomas
			Mesenchymal Hamartoma
			Focal Nodular Hyperplasia (FNH)
			Hepatocellular Adenoma
			Nodular Regenerative Hyperplasia (NRH)
		Malignant Tumours
			Hepatoblastoma
			Hepatocellular Carcinoma
			Fibrolamellar Carcinoma
			Undifferentiated Embryonal Sarcoma (UES)
			Angiosarcoma
			Embryonal Rhabdomyosarcoma
		Imaging of Liver Trauma in Children
		Imaging of Pancreas
		References
	58: Infantile Cholestasis: Approach and Diagnostic Algorithm
		Introduction
		Differential Diagnoses
			Obstructive
			Hepatocellular
			Genetic and Metabolic
		Lab Evaluation
		Radiological Evaluation
		Treatment
		Conclusions
		References
	59: Biliary Atresia and Choledochal Malformations
		Biliary Atresia
			Introduction
			Variants of Biliary Atresia
			Epidemiology
			Clinical Features
			Diagnosis
				Ultrasonography
				Laboratory Findings
				Percutaneous Liver Biopsy
				Aspartate Aminotransferase-to-Platelet Ratio Index (APRi)
				Miscellaneous Diagnostic Techniques
				Screening
			Kasai Portoenterostomy
			Postoperative Management
			Adjuvant Therapy for Biliary Atresia
				Corticosteroids
				Ursodeoxycholic Acid
				Anti-viral Therapy
				Miscellaneous
			Complications
				Cholangitis
				Portal Hypertension
				Ascites
			Outcome Following Kasai Portoenterostomy
		Congenital Choledocal Malformation
			Introduction
			Aetiology
			Classification
			Epidemiology
			Clinical Features
			Diagnosis
			Surgical Management
			Postoperative Management
			Complications
		References
	60: Congenital Hepatic Fibrosis, Caroli’s Disease, and Other Fibrocystic Liver Diseases
		Definitions
			Ciliopathies
			Fibrocystic Liver Diseases
			Hepatorenal Fibrocystic Disorders
		Pathophysiology
			Liver Development Overview
				The Ductal Plate
				The Ductal Plate Malformation
				Cavernous Transformation of the Portal Vein
				Fibrosis
			Cilia in Development
			Animal Models of Ciliopathies
		Congenital Hepatic Fibrosis, Caroli’s Syndrome, and Caroli’s Disease
			Clinical Features
			Diagnosis
				Radiology
				Histology
			Management
			Liver Replacement
			Targeting Fibrosis
		Ciliopathies and Associated Syndromes
			Autosomal Recessive Polycystic Kidney Disease (ARPKD)
			Autosomal Dominant Polycystic Kidney Disease (ADPKD)
			Nephronophthisis
			Meckel Gruber Syndrome
			Joubert and Coach Syndromes
			Practical Approach
			Genetics
		Conclusion and Future Perspectives
		Bibliography
	61: Familial Intrahepatic Cholestasis
		Introduction
		FIC1 Deficiency
		BSEP Deficiency
		TJP2 Deficiency
		MDR3 Deficiency
		Farnesoid X-activated receptor
		Myosin 5B Cholestasis
		Ubiquitin-Specific Peptidase 53-Associated Liver Disease
		Conclusion
		References
	62: Alagille Syndrome
		Introduction
		Clinical Manifestations
			Hepatic
			Cardiac
			Characteristic Facies
			Ophthalmologic
			Skeletal Involvement
			Renal Involvement
			Vascular Involvement
			Bleeding Tendency in ALGS
			Infections and Immune Dysregulation
			Hearing Loss
			Arthritis
		Genetics of ALGS
			Gene Identification and Mutation Analysis
		Genotype–Phenotype Correlations
			JAG1 Mutations
			NOTCH2 Mutations
		Diagnostic Considerations
			Clinical Diagnostics
			Molecular Diagnostics
		Management
			Management of Cholestasis
			Nutritional
			Liver Transplantation
			Liver Transplant Outcomes
			Cardiac Anomalies
			Other Extrahepatic Diseases
		Prognosis of Alagille Syndrome
		Conclusion
		References
	63: Chronic Viral Hepatitis B and C
		Chronic Hepatitis B
			Introduction
			Pathogenesis of Chronic HBV Infection
			Epidemiology
			Diagnostics
			Natural History
			Long-Term Prognosis
			Relevance of Genotypes and Mutants
			Treatment
			Prevention
		Chronic Hepatitis C
			Introduction
			Pathogenesis of Chronic Hepatitis C Infection
			Epidemiology
			Diagnosis
			Natural History
			Treatment
		References
	64: Bacterial, Fungal and Parasitic Infections of the Liver
		Introduction
		Bacterial, Spirochaetal and Rickettsial Infections
			Bacterial Sepsis
			Liver Abscess
			Cholangitis
			Tuberculosis
			Brucellosis
			Listeriosis
			Tularemia
			Leptospirosis
			Borreliosis
			Syphilis
			Q Fever
		Parasitic Infections
			Amoebiasis
			Schistosomiasis
			Hydatid Disease
			Ascariasis
			Toxocariasis
			Liver Fluke Infestation
			Toxoplasmosis
			Fungal Infections
			Hepatic Candidiasis
			Aspergillosis
			Other Rare Fungal Infections
		References
	65: Liver Disease in Primary Immunodeficiencies
		Introduction
		Pathophysiology
		Diagnosis
		Management
		Haemophagocytic Lymphohistiocytosis
		References
	66: Autoimmune Liver Disease
		Autoimmune Hepatitis
			Clinical Features (Table 66.1)
			Epidemiology and Genetic Predisposition
			Diagnosis
			Pathophysiology
			Treatment
		Alternative Treatments
		Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)
		Autoimmune Sclerosing Cholangitis
			Clinical Features
			Treatment
			Pathophysiology
		Liver Transplant and Autoimmune Liver Disease
		De Novo Autoimmune Hepatitis After Liver Transplantation
			Pathophysiology of De Novo AIH After Liver Transplant
		References
	67: Liver-Based Inherited Metabolic Disorders
		Introduction
		Clinical Presentation
		Clinical History and Examination
		Investigations
		Disorders of Carbohydrate Metabolism
			Galactosaemia
		Hereditary Fructose Intolerance (HFI)
		Glycogen Storage Disorders
		Fanconi–Bickel Syndrome
		Fructose-1,6-Bisphosphatase Deficiency
		Transaldolase Deficiency
		Congenital Disorders of Glycosylation (CDG)
		Disorders of Protein Metabolism
			Tyrosinaemia Type 1
		Urea Cycle Disorders
		Citrin Deficiency
		Lysinuric Protein Intolerance (LPI)
		Organic Acidaemias
		Disorders of Lipid Metabolism
			Fatty Acid Oxidation Defects (FAOD)
		Acyl-CoA Dehydrogenase 9 (ACAD 9)
		Glycerol-3-Phosphate Dehydrogenase 1 Deficiency (GPD1)
		Lysosomal Storage Disorders
		Niemann–Pick Type C Disease (NPC)
		Niemann–Pick A and B Disease
		Cholesterol Ester Storage Disease (CESD)
		Disorders of Bile Acid Synthesis (BASD)
		Peroxisomal Disorders
		Mitochondrial Disorders
		Conclusions
		References
	68: Wilson’s Disease
		Introduction
		Definition
		Pathophysiology
		Liver Histology and Ultrastructural Changes
		Clinical Symptoms
			Hepatic Symptoms
			Neurological Symptoms
			Other Symptoms
			Asymptomatic Wilson’s Disease
		Diagnostic Approach
			Plasma Ceruloplasmin
			24-H Urinary Copper Excretion
			Serum Copper
			Liver Copper
		Testing Strategy
			Mutations in the Wilson’s Disease ATP7B Gene, Locus 13q14.3, and Genetic
			Diagnosis in Different Clinical Scenarios
			Scoring System for Diagnosis of Wilson’s Disease
		Genotype-Phenotype
		Gene Modifiers
		Treatment
			Copper Chelators
			Zinc
			Different Clinical Presentations and Choice of Medical Therapy
			Treatment Monitoring
			Diet in Therapy of Wilson’s Disease
			Liver Transplantation
			Therapy in Pregnancy and during Lactation
			Novel Therapies
			Compliance
		Conclusions
		References
	69: Nonalcoholic Fatty Liver Disease
		Epidemiology and Predisposing Factors
		Pathophysiology
			Steatosis
			Oxidative Stress
			Cytokines and Inflammation
			Hepatocyte Apoptosis
			Fibrosis
		Diagnosis and Histology
		Noninvasive Biomarkers in NAFLD
			Serum Biomarkers and NASH
			Noninvasive Markers of Fibrosis in NAFLD
		Noninvasive Biomarkers and Imaging
			Ultrasound, CT and MRI
			Transient Elastography
		Non-hypothesis-Driven Search for Novel Biomarkers Using New Technologies
		Natural History and Management
			Bariatric Surgery
		New Agents
		Future Areas for Research
		References
	70: Vascular Disorders of the Liver
		Portal Vein Anomalies
		Congenital Anomalies of the Portal Vein
		Extrahepatic Portal Vein Obstruction
			Definition and Aetiology
			Clinical Presentation
			Diagnosis
			Management
		Hepatic Artery Anomalies
			Ischaemic Cholangiopathy
			Pseudoaneurysm of the Hepatic Artery
		Abnormalities of the Sinusoidal Blood Flow
			Pericellular Fibrosis
			Physical Occlusion of the Sinusoids
			Peliosis Hepatis
		Hepatic Vein Anomalies
			Budd–Chiari Syndrome (BCS)
			Veno-Occlusive Disease (VOD)
			Congestive Cardiac Failure
		Hepatic Vascular Shunts
			Arteriovenous Malformations
			Portosystemic Shunts
			Hereditary Haemorrhagic Telangiectasia
		Parenchymal Response to Vascular Injury
			Nodular Regenerative Hyperplasia (NRH)
			Focal Nodular Hyperplasia (FNH)
			Benign and Malignant Vascular Tumours
		References
	71: Portal Hypertension in Children
		Introduction
		Anatomy of the Portal Venous System
		Pathophysiology of Portal Hypertension
		Increased Vascular Resistance
		Increased Portal Blood Flow
		Extrahepatic Causes of PH
		Intrahepatic Causes of PH
		Other Pathogenetic Mechanisms of PH
		Systemic Hemodynamic Changes in Portal Hypertension
			Splanchnic Circulation
			Systemic Circulation
			Lung Circulation
			Renal Circulation
		Clinical Manifestation of Portal Hypertension
		Gastrointestinal Hemorrhage
		Splenomegaly
		Ascites
		Pulmonary Complications
		Other Major Complications of Portal Hypertension
		Non-cirrhotic Portal Hypertension
		Obliterative Portal Venopathy (OPV)
		Extrahepatic Portal Vein Obstruction
		Growth Retardation
		Portal Hypertensive Biliopathy
		Minimal Hepatic Encephalopathy
		Management of EHPVO
		Diagnosis of Portal Hypertension
		Doppler Ultrasound
		Endoscopy
		Measurement of Hepatic Venous Pressure Gradient
		Other Investigations
		Management of Portal Hypertension
			Prophylaxis of Bleeding
			Nonselective β-Blockers
		Endoscopy for Screening and Management of Esophageal Varices
		Management of Acute Variceal Bleeding
		Surgical Procedures
		Transjugular Intrahepatic Porto-systemic Shunt
		A Protocol for Screening, Prophylaxis, and Treatment of Esophageal Varices
		References
	72: Liver Tumors in Children
		Introduction
		Tumor Markers in Childhood Liver Tumors
		Malignant Tumors
			Hepatoblastoma
			Diagnosis
			Staging and Prognostication
			Management
			Hepatocellular Carcinoma (HCC)
			Fibrolamellar Hepatocellular Carcinoma
			Transitional Liver Cell Tumors
			Embryonal Sarcoma (Undifferentiated Sarcoma of the Liver)
			Biliary Rhabdomyosarcoma
			Calcifying Nested Stromal–Epithelial Tumor
			Hepatic Angiosarcoma
		Benign Liver Tumors
			Hemangioma
			Hemangioendothelioma
			Mesenchymal Hamartomas
			Hepatic Adenoma
			Focal Nodular Hyperplasia
			Inflammatory Myofibroblastic Tumor
			Secondary Liver Lesions
			Conclusion
		References
	73: Acute Liver Failure in Children
		Introduction
		Definition
		Etiology
		Infection
		Drugs and Toxins
		Metabolic Disorders
		Gestational Alloimmune Liver Disease
		Malignancies
		Autoimmune Hepatitis
		Other Causes
		Investigations
		Prognosis
		Management
		General Measures
		N-Acetylcysteine (NAC)
		Airway and Ventilation
		Fluid Management and Renal Failure
		Neurologic Complications
		Coagulopathy
		Disease-Specific Management
		Liver Assist Devices
		Liver Transplantation
		Auxiliary Liver Transplantation
		Hepatocyte Transplantation
		Conclusions
		References
	74: Complications of Cirrhosis in Children
		Introduction
		Cirrhosis
		Etiology of Cirrhosis
		Pathogenesis of Liver Fibrosis
		Diagnosis of Liver Fibrosis
		Complications and Management of Cirrhosis
		Complications of Cirrhosis
			Portal Hypertension
			Pathogenesis of PHT in Cirrhosis
			Increased Resistance to Portal Flow
			Increased Portal Circulation
			Variceal Bleed in Portal Hypertension
			Management of Variceal Bleed
			Prophylactic Therapy for Variceal Bleed
		Neurological Complications in Cirrhosis
			Hepatic Encephalopathy
			Clinical Features
			Pathogenesis of Hepatic Encephalopathy
			Role of Ammonia in HE
			Role of Neurotoxins and Inflammatory Mediators in HE
			Diagnosis
			Neuropsychological Assessment
			Critical Flicker Frequency
			Electroencephalogram
			Neuroimaging in HE
			Management of Hepatic Encephalopathy
		Ascites
			Pathophysiology of Ascites
			Biochemical Diagnosis
			Management
		Pulmonary Complications in Cirrhosis
			Hepatopulmonary Syndrome
			Pathogenesis
			Clinical Manifestation
			Diagnosis
			Management
			Portopulmonary Hypertension
			Clinical Features
			Diagnosis
			Management
		Renal Involvement in Cirrhosis
			Hepatorenal Syndrome
			Pathophysiology
			Management
			Other System Involvement in Cirrhosis
			Prognosis
		Conclusions
		References
	75: Nutritional Management of Children with Liver Disease
		Introduction
		Dietary Assessment
		Nutritional Management of Chronic Liver Disease
		Decreased Nutrient Intake
		Malabsorption
		Altered Metabolism
			Preserving Lean Body Mass
			Hypoglycaemia
			Hyperammonaemia
		Increased Energy Requirements
		Fat-Soluble Vitamin Supplementation
		Methods of Feeding
			Oral Feeding
			Tube Feeding
			Parenteral Nutrition
		The Management of Common Liver Conditions
			Conjugated Hyperbilirubinaemia
			Biliary Atresia
			Non-alcoholic Fatty Liver Disease
			Wilson’s Disease
			Progressive Familial Intrahepatic Cholestasis
			Alagille’s Syndrome
		Intestinal Failure-Associated Liver Disease
		Liver Transplantation
		Chylous Ascites
		Transplant-Acquired Food Allergy
		The Nutritional Management of Acute Liver Failure
		Summary
		References
	76: Paediatric Liver Transplantation
		Introduction
		Pre-transplant
			Indications for Liver Transplantation
				Chronic Liver Diseases
					Biliary Atresia
					Cholestatic and Metabolic Disorders
					Tumours
				Acute Liver Failure
			Timing of Transplantation
			Graft Allocation
			Graft Type
		Intraoperative
			Whole Liver Transplantation
			Partial Liver Grafts
			Living Donor Liver Transplantation
			Recent Developments in Transplant Surgery
				Auxiliary Liver Transplantation
				DCD Donation
		Post-transplant
			Postoperative Immunosuppression
			Surgery-Related Complications
				Primary Graft Non- or Dysfunction
				Bleeding
				Caval Complications
				Portal Vein Thrombosis and Stenosis
				Arterial Complications
				Biliary Complications
				Other Surgical Complications
			Nonsurgical Complications
				Infections
				Lymphoproliferative Disease and Epstein-Barr Infection
				Graft and Patient Survival
				Quality of Life
				Transition to Adolescence and Young Adult Life-Adulthood
				Long-Term Outlooks and Trends
		References
	77: Growing Up with Liver Disease
		Introduction
		Young People
		Medical Aspects of Growing Up with Liver Disease
		Outcome Data
		Impact of Liver Disease on Physical Development
		Adolescent Development and Its Interaction with Liver Disease
		Impact of Family
		Wider Influences
		Psychological Aspects of Growing Up with Liver Disease
		Quality of Life
		School Achievement
		Mood Difficulties
		Post-traumatic Stress Disorder
		Adherence
		Self-Management
		Transition from Pediatric to Adult-Centered Health Services
		Summary and Conclusions
		References
	78: New Horizons in Paediatric Hepatology: A Glimpse of the Future
		Introduction
		Genetics
			Diagnostics
			Gene Therapy
		Regenerative Medicine and Cell Therapy of Liver Disease
			Mesenchymal Stromal Cells
			Induced Pluripotent Stem Cells
			Immortalisation
		Small Molecules and Chaperones
		Liver Transplantation
		The Microbiome and Liver Disease
		Non-alcoholic Liver Disease
		Noninvasive Biomarkers of Disease
		Quality of Life
		Conclusion
		References
Index