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CHRONIC LIVER DISEASE IN
CHILDREN
LAYOUT
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Definition
Epidemiology
Etiological classification
Clinical presentation
Approach to a child with CLD
Management
Upcoming research
Chronic Liver Disease
Presence of ongoing injury within the liver
for at least 6 months capable of progression to
cirrhosis and liver failure
Slight male predominance(58%)*
Etiological factors:
• USA: Fatty Liver
• Iran: Secondary hemochromatosis (17.5%)
• Pakistan*
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Viral hepatitis (36.7%) {hep C 31.6% ; Hep B 5.1%}
Idiopathic (35%)
Glycogen storage disease (8.37%)
Wilson disease (6.7%)
*(National institute of child health & PMRC Karachi)
Etiological Classification
• Infectious :
• Chronic Viral Hepatitis ( HBV & HCV)
• CMV
• Toxoplasmosis
• Metabolic :
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Wilson disease
Haemochromatosis
Alpha 1 antitrypsin deficiency
Glycogen storage disease
Tyrosinemia
• Anatomical :
• Biliary atresia
• Choledocal cyst
• Congenital hepatic fibrosis
• Cystic fibrosis
• Allagille syndrome
• Caroli disease
• Autoimmune:
• Autoimmune chronic hepatitis
• Primary Sclerosing Cholangitis
• Toxic/Drug-induced :
• Anti-tuberculosis medicine:
• Isoniazid
• Rifampcin
• Acetaminophen
• Nitrofurantoin
• Methotrexate
• Parenteral nutrition
• Idiopathic neonatal hepatitis
Clinical Presentation
SYMPTOMS
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Yellowish discoloration of skin & eyes
Pain abdomen
Pruritis
Abdominal distention
Poor feeding/loss of appetite
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Failure to thrive
Clinical Presentation
SYMPTOMS
• Yellowish discoloration of skin & eyes
•
•
•
•
•
•
•
•
•
Pain abdomen
Pruritis
Abdominal distention
Poor feeding/loss of appetite
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Failure to thrive
Clinical Presentation
SYMPTOMS
• Yellowish discoloration of skin & eyes
• Pain abdomen
•
•
•
•
•
•
•
•
Pruritis
Abdominal distention
Poor feeding/loss of appetite
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Failure to thrive
Clinical Presentation
SYMPTOMS
• Yellowish discoloration of skin & eyes
• Pain abdomen
• Pruritis
•
•
•
•
•
•
•
Abdominal distention
Poor feeding/loss of appetite
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Failure to thrive
Clinical Presentation
SYMPTOMS
• Yellowish discoloration of skin & eyes
• Pain abdomen
• Pruritis
• Abdominal distention
•
•
•
•
•
•
Poor feeding/loss of appetite
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Failure to thrive
Clinical Presentation
SYMPTOMS
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•
•
•
Yellowish discoloration of skin & eyes
Pain abdomen
Pruritis
Abdominal distention
• loss of appetite
• Failure to thrive
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•
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•
Wieght loss
Lethargy /malaise
Hemetemesis/melena /epistaxis
Easy bruisability
Signs
General Signs
associated
with liver
disease
Signs indicative
of liver
decompenstaion
Signs Specific
to underlying
etiology
Clubbing,
Palmar
Erythema
Asterixis,
Leukonychia ,
Bruising
Kayser-Fleisher
Rings, Increased
pigmentation of
the skin
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General Signs associated
with liver disease
Jaundice
Clubbing
Palmar erythema
Spider nevi
Hepatomegaly/Shrunken Liver
Gynaecomastia
Testicular atrophy
Caput medusae
General Signs associated with
liver disease
• Jaundice
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Clubbing
Palmar erythema
Spider nevi
Hepatomegaly
Gynaecomastia
Testicular atrophy
Caput medusae
General Signs associated with
liver disease
• Jaundice
• Clubbing
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•
•
•
•
•
Palmar erythema
Spider nevi
Hepatomegaly
Gynaecomastia
Testicular atrophy
Caput medusae
General Signs associated with
liver disease
• Jaundice
• Clubbing
• Palmar erythema
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•
•
•
•
Spider nevi
Hepatomegaly
Gynaecomastia
Testicular atrophy
Caput medusae
General Signs associated with
liver disease
• Jaundice
• Clubbing
• Palmar erythema
• Spider nevi
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Hepatomegaly
Gynaecomastia
Testicular atrophy
Caput medusae
General Signs associated with
liver disease
• Hepatomegaly/Shrunken liver
Signs indicative of liver
decompenstaion
• Increased bleeding tendency
• Edema
• Ascites
• Increased Jaundice
• Drowsiness
• Flapping tremors/Asterixis
• Hyperventilation
Signs Specific to underlying
etiology
• Cerebellar signs
• Kayser-Fleisher Rings
• Increased pigmentation of the skin
Evaluation of liver disease in a child
GOALS
1. Differentiation of specific entities
2. Early diagnosis of curable causes
3. Recognize cholestasis and its complications
4. Assess severity
Diagnostic Approach
• History
• Clinical assessment
Laboratory work up
• Biochemical tests indicating
liver damage
• Investigations to find underlying
etiology
• liver function status evaluation
• Liver Biopsy
WORK UP
Biochemical tests indicating liver
damage
• Liver Function Tests (LFTs)
• Serum Bilirubin
• Total
• Fractionated (direct and Indirect)
• Alanine aminotransferase/Aspartate
aminotransferase
• Alkaline phosphatase
• γ-glutamyltransferase
Investigations for
Liver Function Status
• Serum albumin levels
• Coagulation Profile
• Plasma glucose
Investigations for
identification of Etiology
INFECTIOUS CAUSES
– Hepatitis serology
Hep B
Hep C
HBsAg , HBeAg , anti HBc IgM
anti HCV
– Toxoplasma and cytomegalovirus screening
AUTOIMMUNE
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Anti Nuclear Antibodies (ANAs)
Anti Smooth Muscle Antibodies (Anti SMA)
Anti Liver Kidney Microsomal Antibodies (Anti LKM)
Total Immunoglobulins levels
• METABOLIC CAUSES
- α-1 antitrypsin levels (protease inhibitor typing)
- Copper studies (Wilson disease)
• 24 hour urinary copper (penicillamine challenge test)
• Serum Ceruoplasmin
• Serum copper levels
- Urine
– Non glucose Reducing substances
- Plasma amino acid levels (tyrosinemia)
Radiology and Imaging Investigations
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Liver Ultrasound with Doppler
Computed Tomography (CT Scan)
Magnetic Resonane Imaging (MRI)
Radionucleide liver scan (HIDA)
Cholangiography (MRCP)
Liver Biopsy
• Types
– percutaneous
– transvenous
– Open Biopsy
• Indication
– Diagnosis of metabolic and auto immune diseases
– To assess severity of liver damage
– Monitoring progress of treatment
Management
Principles of Management
• General management including nutritional
support
• Specific treatment of underlying etiology
• Prevention, early detection and treatment of
complications
• Liver transplantation
General
Management
General Management
• Nutrition
–Total caloric intake↑ to 120-150% of
requirement according to TBW
– Supplements –vitamins (A, D, E, K)
• Pruritis
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USDA (ursodeoxycholic acid)
Antihistamines
Cholestyramine
Calamine Lotion
General Management
• Ascites/pedal edema
– Non pharmacological
• Fluid & salt restriction
• I/O charting, daily wt measurement
– Pharmacological
• Diuretics – spironolactone ± furosemide
• Albumin Replacement
– Procedural
• Paracentesis – diagnostic & therapeutic
Treatment of
Complications
Treatment of Complications
• Hepatic Encephalopathy
– Identify precipitating factor and treat it
– Protein restriction
– Laxatives - Lactulose – aim to achieve at least 2-3
loose stools/day
– Flumazenil
– Broad spectrum oral antibiotics (oral neomycin)
Treatment of Complications
• Varices / Upper GI Bleed
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Resuscitate, stabilize, optimize for endoscopy
Fluid resuscitation-2 large bore IV catheters
Ocreotide infusion
FFP/RCC transfusion
Vitamin K
IV omeprazole
Sengestaken-blakemore tube
Urgent endoscopy for banding/ligation
Surgery
Specific
Treatment
Specific Treatment
• Chronic Viral Hepatitis
– Alpha Interferon
– Ribavirin
– Lamivudine
Specific Treatment
• Auto-immune Hepatitis
– Prednisolone
– Azathioprine
– Budesonide
– Mycophenolate Mofetil
• Biliary atresia
– Kasai procedure (hepato-porto enterostomy)
– Liver transplantation
• Wilson disease
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D-Penicillamine 35mg /kg/ day
Oral zinc and pyridoxine, 50 mg/day
Dietry control
Untreated, 30 % of children die
Liver transplantation
Screening and treatment of siblings
Liver Transplantation
New hopes for the future
• Extracorporeal liver support devices
– The molecular adsorbent recirculating system (MARS®)
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Hepatocyte transplant
Gene therapy & genetically engineered enzymes
Modulating fibrogenesis
Hepatopoeitin
Conclusion
REFERENCES
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Current pediatric diagnosis and treatment
Nelson’s textbook of paeditrics
Requisites of pediatric gastroenterology.
http://emedicine.medscape.com/article/172356-overview
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