NEONATAL CHOLESTASISNEONATAL CHOLESTASIS

張堯婷張堯婷

CONTENTSCONTENTS

� Definition

� Etiologies

� Clinical Presentation And Diagnosis

� Treatment

� Outcome

� Reference

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DEFINITIONDEFINITION

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NASPGHAN Definition NASPGHAN Definition

� Conjugated bilirubin concentration

>1.0 mg/dL if the total serum bilirubin is <5.0 mg/dL

Or

� Conjugated bilirubin concentration >20 % of the total serum bilirubin if the total serum bilirubin is >5.0 mg/dL

4(Moyer et al J PEDIATR GASTROENTEROL NUTR 2004;39:115)

IAP DefinitionIAP Definition

� Conjugated hyperbilirubinemia > 1.5-2

mg/dL in a newborn/ infant with passage

of high coloured urine with or without

acholic stools.

5(Consensus report on neonatal cholestasis syndrome,INDIAN PEDIATRICS 2000;37:845-851)

ETIOLOGIESETIOLOGIES

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INTRAHEPATIC ETIOLOGIESINTRAHEPATIC ETIOLOGIES

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INTRAHEPATIC ETIOLOGIES INTRAHEPATIC ETIOLOGIES -- INHINH

� IDIOPATHIC NEONATAL HEPATITIS

▪ Generally normal stools or clay stools with

onset at one month-old

▪ Low birth weight

▪ Male predominance

▪ Familial cases (15-20%)

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INTRAHEPATIC ETIOLOGIES INTRAHEPATIC ETIOLOGIES -- ToxicToxic

� TPN-associated cholestasis

� Drug-induced cholestasis

▪ Anticonvulsants

▪ Antibiotics

▪ Immunosuppressive Agents

▪ Psychotropic Drugs

▪ Drugs Against HIV

▪ Acetaminophen

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INTRAHEPATIC ETIOLOGIES INTRAHEPATIC ETIOLOGIES --

InfectiousInfectious� Bacterial sepsis

▪ E. coli

▪ Listeriosis

▪ Staph. aureus

� TORCHES

� Echo virus

� Hepatitis B and C

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INTRAHEPATIC ETIOLOGIESINTRAHEPATIC ETIOLOGIES --

MetabolicMetabolic� Disorders of Carbohydrate

Metabolism

� Disorders of Amino Acid Metabolism

� Disorders of Lipid Metabolism

� Disorders of Bile Acid Metabolism

� Peroxisomal Disorders

� Endocrine Disorders

� Miscellaneous Metabolic Disorders

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INTRAHEPATIC ETIOLOGIESINTRAHEPATIC ETIOLOGIES --

MetabolicMetabolic� Disorders of Carbohydrate

Metabolism▪ Galactosemia

▪ Fructosemia

▪ Glycogen Storage Disease Type IV

� Disorders of Amino Acid Metabolism▪ Tyrosinemia

▪ Hypermethioninemia

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INTRAHEPATIC ETIOLOGIES INTRAHEPATIC ETIOLOGIES --

MetabolicMetabolic� Disorders of Lipid Metabolism

▪ Niemann-Pick disease

▪ Gaucher disease

� Disorders of Bile Acid Metabolism

▪ 3B-hydroxysteroid dehydrogenase/isomerase

▪ Trihydroxycoprostanic acidemia

� Peroxisomal Disorders

▪ Zellweger syndrome

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INTRAHEPATIC ETIOLOGIES INTRAHEPATIC ETIOLOGIES --

MetabolicMetabolic

� Endocrine Disorders

▪Hypothyroidism

▪ Idiopathic hypopituitarism

� Miscellaneous Metabolic Disorders

▪Alpha-1-antitrypsin deficiency

▪ Cystic fibrosis

▪Neonatal iron storage disease

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EXTRAHEPATIC ETIOLOGIESEXTRAHEPATIC ETIOLOGIES

� Extrahepatic biliary atresia

� Choledochal cyst

� Bile duct stenosis

� Spontaneous perforation of the bile duct

� Cholelithiasis

� Inspissated bile/mucus plug

� Extrinsic compression of the bile duct

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CLINICAL PRESENTATIONCLINICAL PRESENTATION

AND DIAGNOSISAND DIAGNOSIS

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CLINICAL PRESENTATIONCLINICAL PRESENTATION

� Jaundice

� Scleral icterus

� Hepatomegaly

� Clay stools

� Dark urine

� Other signs and symptoms depend

on specific disease process

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DIAGNOSIS DIAGNOSIS -- IAPIAP

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DIAGNOSIS DIAGNOSIS -- NASPGHANNASPGHAN

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TREATMENTTREATMENT

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TREATMENT TREATMENT -- Medical ManagementMedical Management

� Nutritional support

� Treatment of pruritus

� Choleretics and bile acid-binders

� Management of portal hypertension and

its consequences

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Nutritional supportNutritional support

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IMPAIRMENT MANAGEMENT(NASPGHAN)

MANAGEMENTIAP

Fat soluble vit malabsorption

Vit A deficiency 10,000-15,000 IU/d AQUASOL-A

50,000 IU i.m –diagnosis10,000 IU monthly

Vit E deficiency 50-400 IU/d; oral alfatocopherol

50-200 mg/d orally

Vit D deficiency 5000 -8000IU/d of D23-5 mcg/kg/d of 25 HCC

30,000 IU i.m –diagnosis& monthly

Vit K deficiency 2.5 -5.0 mg alternate day as water soluble derivative of menadione.

5 mg/d im x3 days,5 mg wkly.Perform PT monthly.

Microutrientdeficiency

Ca, P, Zn supplementation Ca, P, Zn supplementation

Water soluble Vit def. 2 times RDA supplementation 2-5 times RDA supplementation

Treatment of Treatment of prurituspruritus

� Bile acid-binders: cholestyramine (4-8

g/day)

� Ursodeoxycholic acid (15-20 mg/kg/day)

� Phenobarbital (5mg/kg/day)

� Diphenhydramine (1-3 mg/kg/day)

� Photothearpy with UV/ Infrared rays x 3-

10 min/day

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Management of portal Management of portal

hypertension and its consequenceshypertension and its consequences� Variceal bleeding▪ Blood products

▪ Sclerotherapy

▪ Balloon tamponade

▪ Propranolol

� Ascites▪ Sodium restriction

▪ Diuretics (spironolactone, furosemide)

▪ Albumin

▪ Paracentesis

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KASAI PROCEDUREKASAI PROCEDURE

� Roux-en-Y

portoenterostomy

� Bile flow re-established in 80-90% if performed < 8 weeks-old.

� Bile flow re-established in less than 20% if performed > 12 weeks-old

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LIVER TRANSPLANTATIONLIVER TRANSPLANTATION

Indications:

�Decompensated liver disease(ascites

and/or encephalopathy) .

�Failed portoenterostomy.

▪ 1-year survival rate- 85-90%

▪ 5-8 year survival rate- 75-80%

▪ 1/3 to 1/2 patients are of Biliary Atresia

�Cost: In excess of 100,000 $

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LONG TERM OUTCOMELONG TERM OUTCOME

� Biliary Atresia: ▪ Mean survival in untreated pts : 19 months

▪ 3-year survival : <10%

� Neonatal Hepatitis:▪ > 60% of pts with idiopathis NH recover

completely without any specific therapy.

▪ > 10% die acutely of bleeding manifetstationsor fulminant hepatic failure.

▪ 30 % progress to liver cirrhosis and death.

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REFERENCEREFERENCE

� Indian Journal of Pediatrics, Volume 74—July, 2007

� NeoReviews Vol.14 No.2 February 2013

� Lien TH, Chang MH, Wu JF, et al; Taiwan Infant Stool Color Card Study Group.

Effects of the infant stool color card screening program on 5-year outcome of biliary

atresia in Taiwan. Hepatology.2011;53(1):202–208

� Canadian Family Physician • Le Médecin de famille canadien Vol 55: december •

décembre 2009

� Schreiber RA, Barker CC, Roberts EA, et al. Biliary atresia: the Canadian experience. J

Pediatr. 2007;151(6):659665, 665.e120. Nio M, Ohi R, Miyano T, Saeki M, Shiraki K,

Tanaka K;Japanese Biliary Atresia Registry. Five- and 10-year survival rates after

surgery for biliary atresia: a report from the Japanese Biliary Atresia Registry. J

Pediatr Surg. 2003;38(7):997–1000

� Serinet MO, Wildhaber BE, Broué P, et al. Impact of age at Kasai operation on its

results in late childhood and adolescence: a rational basis for biliary atresia

screening. Pediatrics. 2009;123(5):1280–1286

� Prevention and Management of Gastroesophageal Varices and Variceal

Hemorrhage in Cirrhosis.HEPATOLOGY Vol. 46, No. 3, 2007.

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