Pediatric

Liver Disease
Adapted from Ricardo A. Caicedo, MD
Pediatric Gastroenterology of WFUB Medical Centre
Irman Permana,Sp.A,M.Kes
Objectives
Know - Understand overview
content:
Diagnostic liver tests
Jaundice
Neonatal
Child and Adolescent
Hepatitis
Hepatomegaly
Chronic liver disease
Dont be afraid of the liver!!!
Terms
Hepatitis: inflammation of the liver
Can be due to multiple causes (infectious, toxic,
metabolic)
Can be acute or chronic
Hepatomegaly: enlargement of the liver
Hepatopathy: disease of the liver


Terms
Jaundice: a symptom or sign of
hyperbilirubinemia (total bili > 2)
yellow color to skin, mucous membranes, eyes
(Conjunctival/scleral icterus)
Can be due to unconjugated or conjugated
hyperbilirubinemia
Cholestasis: impairment of bile flow
Conjugated (direct) hyperbilirubinemia
Can be due to cholestatic process or primary liver
disease
Defined as direct bili. > 20% of total bili.
Terms
Liver dysfunction: abnormal synthetic function
Defined by low albumin or abnormal PT/INR
Liver failure: all hepatic functions compromised
Encephalopathy
Coagulopathy/bleeding
Ascites
Portal hypertension
Hypoglycemia
Cirrhosis: late stage of progressive hepatic fibrosis
(scar tissue formation)
with formation of regenerative nodules; usually irreversible
Hepatic Function Panel
ALBUMIN
TOTAL
BILIRUBIN
GGT
ALKALINE
PHOSPHATASE
ALT
(SGPT)
AST
(SGOT)
TOTAL
PROTEIN
DIRECT
BILIRUBIN
PT/INR
Synthetic Excretory
Biliary
Epithelium
Hepatocellular
Injury
Imaging Studies
Ultrasonography
identify anatomic
problem
GB presence does not
exclude biliary atresia
Recommended in
cholestasis of unknown
etiology
NM bili-scintigraphy
HIDA or DISIDA scan
Tracer taken up by liver
should empty into gut
Highly sensitive, not
specific
HIDA-PIPIDA-DISIDA

A cholescintigraphy scan, also
known as: Hepatobiliary
Iminodiacetic Acid (HIDA),
Paraisopropyl Iminodiacetic Acid
(PIPIDA), or Diisopropyl
Iminodiacetic Acid (DISIDA) scan
is a nuclear imaging procedure to
evaluate the health and function of
the gallbladder. A radioactive
tracer is injected through any
accessible vein, then allowed to
circulate to the liver, where it is
excreted into the biliary system
and stored by the gallbladder and
biliary system.
Diagnostic Tests
Liver biopsy
Provides specific diagnostic
findings
Recommended in
most infants with cholestasis of
unknown etiology
chronic liver disease of unknown
cause
HBV or HCV with abnormal liver
tests
Cholangiogram
Intraoperative injection of contrast
into biliary tree
Excludes biliary atresia
If biliary atresia confirmed, proceed with
portoenterostomy (Kasai procedure)
Elevated Transaminases
Hx: chronicity, symptoms
Stigmata of chronic liver disease?
Liver panel including PT/INR
Differential dx
Drug/toxin
Review medications including OTC, NSAIDs, herbals
Viral hepatitis
Acute: HAV IgM, HBsAg, HBc IgM, HCV Ab
Chronic: HBsAg, anti-HBs, HBeAg, HCV Ab
Systemic: CMV IgM, EBV serology panel, HIV Ab
Autoimmune hepatitis
Globulin fraction (TP ALB), ANA, smooth muscle Ab, LKM Ab
Consider overlap with IBD (ESR, CRP) and celiac disease (tTG IgA)
Metabolic
CF: sweat chloride
Alpha-1-antitrypsin deficiency: AAT level and Pi type
Hemochromatosis: serum iron, TIBC, ferritin
Wilsons disease: ceruloplasmin
Non-alcoholic fatty liver disease (NAFLD)
Ultrasonography
Other
Endocrine: Adrenal insufficiency, thyroid disorders
Muscle disease
AST/ALT > 3 initially
Elevated CPK, aldolase




ALT
(SGPT)
15-60

AST
(SGOT)
20-55
Hepatocellular
Injury
Jaundice
Know how to evaluate a
2 day old infant with jaundice
1 month old infant with icterus
Child with conjugated hyperbilirubinemia

Unconjugated
Hyperbilirubinemia
Know the appropriate diagnostic tests to
establish the cause of unconjugated hyperbili.
Diagnostic studies to detect hemolytic disease
Breast feeding does not cause conjugated
hyperbili, but it is the most frequent cause of
exaggerated unconj. hyperbili. in neonates
Know mgmt. of infant with breast-milk jaundice
Features of Pathologic Jaundice
Red flags
jaundice in the first 24 hours of life
jaundice that appears excessive for
age
bilirubin rise > 5 mg/dl/24 hours
bilirubin total > 12 mg/dl
jaundice persists beyond 2 weeks
AAP Clinical Practice Guideline. Pediatrics 2004;114:297-316.
Early Diagnosis is Important
Unconjugated (I) Hyperbilirubinemia



Conjugated (D) Hyperbilirubinemia
Hemolysis
Minimize potential
for kernicterus
Breast-milk
Avoid excess
investigations
Intrahepatic
Identify treatable
conditions

Extrahepatic
Time limit for Biliary
Atresia (2 Mo)
No 2 -week old yellow
baby should go
without a total and
direct bilirubin!
Evaluation of the Yellow Baby
Jaundiced infant 2-4 wks
T/D Bili
Direct < 15% total Direct > 15% total
Unconjugated
Breast milk
Hemolytic
(CBC, Coombs)
Hx/physical, growth and feeding
Stool color
Liver panel, UA/UCx
Review neonatal screen
RED FLAGS
Ultrasound
PT/INR
Pediatric GI Consult
Follow q 1-2 weeks
Resolves before 2 m
Persists
HIDA scan, metabolic studies,
liver bx, cholangiogram
LABORATORY TESTS
- Hepatic function panel LFTs
- PT/INR
- CBC/diff, Blood culture
- UA and Urine culture
- TORCH serology
- Alpha-1-antitrypsin level and Pi
phenotype
- Neonatal screen
- TSH
- Sweat chloride
- Urine succinylacetone
- Urine organic and serum amino
acids

Know the differential dx of jaundice in a 2
month old infant
Anatomic
Biliary atresia
Choledochal cyst
GB stones/sludge
Inspissated bile
Alagille syndrome (syndromatic BD paucity)
Cong. Hepatic Fibrosis
Infectious
Sepsis
UTI
TORCH incl. CMV, HIV
Enterovirus, adenovirus
Metabolic
Panhypopit.
Hypothyroidism
Galactosemia
Alpha-1-antitrypsin deficiency
CF
Tyrosinemia
Other
TPN-associated
Progressive familial intrahepatic cholestasis
Idiopathic neonatal hepatitis

Recognize that sepsis, galactosemia and
endocrine disorders can be readily
diagnosed in the neonate with conjugated
hyperbilirubinemia
Know the metabolic diseases that can lead
to conjugated hyperbilirubinemia in the
neonatal period
Recognize the signs/sx of BILIARY ATRESIA
Cholestatic jaundice
Acholic/pale stools
Dark urine
Growth failure
Abdominal distention
Ascites
Hepatomegaly
Signs of chronic liver
disease
Bruising/bleeding
Variceal bleeding
Splenomegaly
Caput medusa



Atresia Biliaris
(kasus Bilqis 2 tahun)

Kondisi pada awal tahun 2010
Lahir Februari 2008
10 April 2010
Cholecystitis
Recognize cholecystitis in
children
Jaundice
Pale stools/dark urine
Cholestasis
RUQ pain
Nausea/vomiting
Fatigue/malaise
/+ Fever
TESTS
LFT incl. GGT
Ultrasound
Stones, sludge, dilated BD
NM Biliary Scan
CAUSES
Idiopathic
Obesity
Hemolytic disorder
Cystic fibrosis
Systemic disease
TPN
Gilbert Syndrome
Mild unconjugated hyperbilirubinemia
Typically in healthy adolescents
Triggered by stress, fasting, or infection
No hemolysis
Benign: no long-term sequelae
Caused by mild deficiency in conjugating
enzyme (UDPGT) activity
Severe deficiency: Crigler-Najjar (neonatal)
Recognize the clinical presentation of a
child with Gilbert syndrome
Know how to evaluate
- A child with conjugated hyperbilirubinemia
- A 12 year old child with icterus
Pashankar D, Schreiber RA
Hepatitis
Recognize the signs and sx of infectious
hepatitis
Know the laboratory evaluation of hepatitis
Know the immediate and long term
complications of hepatitis
Hochman J, Balistreri WF.
Acute Viral Hepatitis
Acute hepatocellular injury/inflammation
Reflected by elevated transaminases
Clinical manifestations often include fever, malaise,
jaundice, RUQ pain, nausea/vomiting
Typically self-limited and of short duration
Contrast with: chronic, fulminant
Causative agents
HAV (50% of cases in U.S.), HEV
CMV, EBV, VZV
Fulminant Hepatitis

Acute, massive hepatocellular necrosis
Impaired synthetic, excretory, and detoxifying
functions of the liver
Cholestasis, ascites, coagulopathy, encephalopathy,
multi-system failure
Initially very elevated transaminases
Falling transaminases and rising bilirubin ominous
Hyperammonemia, hypoalbuminemia, prolonged PT,
hypoglycemia
Viral agents (50% of cases)
Most cases of fulminant hepatic failure are caused by
unidentified agent, presumably viral
HAV, HBV+/-HDV, HCV, HEV
HSV, enteroviruses, EBV, CMV, HHV-6, VZV

Chronic Hepatitis
Prolonged necroinflammatory process
Elevated transaminases for > 4-6 months
Insidious clinical manifestations
Can include cholestasis (jaundice, pruritus),
ascites, hypoalbuminemia, coagulopathy,
encephalopathy
Can progress to fibrosis and then cirrhosis
Viral agents: HBV (+/- HDV), HCV
Other causes include autoimmune, metabolic
disorders (Wilsons, CF, alpha-1 antitrypsin deficiency),
drug/toxin-mediated, idiopathic
Chronic Viral Hepatitis
Risk Factors
Hochman J, Balistreri WF. Pediatr Rev. 2003; 24:399-410.
Hepatitis A Virus
Causes 33% of acute viral hepatitis in U.S.
NOT a cause of chronic hepatitis
rarely causes fulminant hepatitis (< 1% cases)
Can trigger autoimmune hepatitis in predisposed individuals
Epidemiologic factors
Fecal-oral transmission
Poor hygiene
High population density
Daycare centers and minor epidemics
Universal HAV vaccination recommended
Treatment is supportive
A = Acute
Hepatitis B Virus (HBV)
Sequelae of HBV vs. HCV
B = Bad for Babies C = Chronic
Hepatomegaly
INFANT
Anatomic
Biliary obstruction
Biliary atresia
CHF
Congenital hepatic fibrosis
Metabolic disorder
Lysosomal storage
Glycogen storage
Infection
Sepsis
TORCH
Wolf A, Lavine J. Hepatomegaly in Neonates and Children. Pediatrics in Review, Vol. 21 (9), Sept. 2000.
OLDER CHILD
Anatomic
Biliary obstruction
CHF
Hemangiomas
Malignancy
Leukemia/lymphoma
Hepatoblastoma
Metastases
Infection
Sepsis
Viral hepatitis (esp. HAV)
Liver abscess
Chronic hepatitis
Autoimmune
Wilsons
Non alcoholic fatty liver disease

Know the significance of hepatomegaly in a
1 month old infant and 12 y old child
Evaluation of Hepatomegaly
Hx and exam
Concomitant splenomegaly?
Liver panel
CBC/diff
Ultrasound
Doppler flow study of hepatic vessels
Liver biopsy
Additional imaging (CT, MR)

Portal Hypertension
Hepatic
disease
Portal vein
thrombosis
IVC
thrombosis
Know the signs, symptoms and lab findings associated with
portal hypertension
Ryckman FC, Alonso MH.
Causes and management of portal hypertension in the pediatric population.
Clin Liver Dis. 2001 Aug;5(3):789-818.
Ascites
Caput medusa
Rectal varices
Hemorrhoids
(LGI bleeding)
Esophageal
varices (UGI
bleeding)
Hypersplenism
Splenomegaly
Thrombocytopenia
North American Society for Pediatric Gastroenterology, Hepatology and
Nutrition (NASPGHAN) www.naspghan.org

American Association for the Study of Liver Diseases (AASLD)
www.aasld.org