Direct Hyperbilirubinaemia

Dr. Tareq rahman , Resident Phase B , Neonatology,

Bangabandhu Sheikh Mujib Medical University( BSMMU).

NASPGHAN Definition :

Prolonged conjugated hyperbilirubinemia thatoccurs in the newborn period with conjugatedbilirubin concentration >1 mg/dl if the totalbilirubin <5.0mg/dl or >20% of the totalbilirubin if the total bilirubin >5.0 mg/dl.

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

IAP Definition:

Neonatal cholestasis is defined as

conjugated hyperbilirubinemia > 1.5-2

mg% in a newborn/ infant with passage of

high coloured urine with or without acholic

stools.

(Consensus report on neonatal cholestasis syndrome,INDIAN PEDIATRICS

2000;37:845-851)

PATHOPHYSIOLOGY

PREVALENCE

• Neonatal cholestasis: 1 in 2500 live birth.

• Biliary atresia: 1 in 10000 to 15000 infants.

• Idiopathic neonatal hepatitis: 1 in 5000 to 10000 live birth.

(McKiernan PJ et al. Lancet 2000)

ETIOLOGY

ETIOLOGY

Intrahepatic causes

Extrahepatic causes

INTRAHEPATIC ETIOLOGIES

Hepatocellular causes Bile duct injury (Neonatal hepatitis)

Idiopathic: INHToxic Intrahepatic bile ductGenetic/Chromosomal hypoplasia or paucityInfectiousMetabolicMiscellaneous

EXTRAHEPATIC 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

Neonatal Hepatitis

35%

Biliary Atresia

26%

INH24%

Others15%

(Bazlul Karim AS, Kamal M, Cholestatic jaundice during infancy: experience at a tertiary-care center in Bangladesh, Indian J Gastroenterology, 2005 Mar-Apr;24(2):52-4.)

Hepatocellular causes:Neonatal hepatitis

idiopathic TORCHSepsisOthers(UTI)

MetabolicMiscellaneousObstructive causes: Biliary atresia Choledochal cystDuctal paucityIdiopathic

53%47%64%22%08%06%04%02%38%34%04%03%06%

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

• TPN Related Cholestasis Most common in developed country

Sepsis-induced cholestasis

Gram-negatives predominated (77%)

• Klebsiella species (25%)

• Escherichia coli (15%)

• Staphylococcus aureus (18%)

• Group B streptococci ( 7%)

• Others –

Pseudomonas , Bacteroids , Tuberculosis

• (Ziadi et al.Pathogens associated with sepsis in newborns and young infants in developing

countries. Pediatr Infect Dis J. 2009 Jan;28)

Mechanisms of Hyperbilirubinemia in Sepsis

• Hemolysis

- Increased Bilirubin Load

• Hepatic dysfunction

- Decreased canalicular transport

- Decreased clearance of conjugated bilirubin

- Hepatic ischemia

- Hepatocellular injury

• Cholestasis

- Decreased basolateral transport of bile acids

- Decreased basolateral membrane fluidity

- Inhibition of basolateral membrane Na-K-ATPase activity

- Decreased canalicular transport of bile acids

- Down-regulation of transporters

Approach

Evaluation

When to suspect ?

Cardinal Features

– Jaundice

– Dark urine

– Pale stools (+/-)

– Hepatomegaly

HistoryAge at presentation-

within first 3months of life.

Sex- INH is common in male & BA is common in female.

Family history

- Consanguinity- Metabolic disease.

- Same type of illness.

Antenatal Fever TORCH infection.RashAbortion, miscarriage- metabolic diseases.

NatalTerm- BA. Preterm- INH.

Birth weightSGA/LBW- INH.AGA- BA.

Postnatal

Onset of jaundice

Less feeding

Lethargy

Hoarse cry hypothyroidism

Constipation

Delayed passage of meconium

Convulsion- congenital infection

Examination

General examinationAppearance

• Irritable, lethargic- cong infection, metabolic diseases

• Dysmorphic Alagille syndrome.

Down syndrome.

Hypothyroidism,

Large anterior fontanel-• Hypothyroidism, Down syndrome.

Pallor

Jaundice

Skin survey

Rash- sepsis.

Hypothyroidism

Anthropometry

OFC- microcephaly in cong. infection.

Weight, height- FTT in INH, cong infection

Eye examination (slit lamp)

Cataract- galactosemia.

Choreoretinitis- CMV, Rubella, Toxoplasma.

Cherry red spots- Niemen-Pick disease.

Posterior embryotoxon- Alagille syndrome.

Optic Hypoplasia- Panhypopituitarism

Alimentary system

Oral cavity

• cleft lip, cleft palate- BA.

Abdomen

• Pott belly, umbilical hernia- hypothyroidism

• Hepatosplenomegaly- BA, cong infection, galactosemia.

• Right hypochondriac mass- Choledochal cyst.

• Ascites-

Investigations

A. Initial investigations:

To establish cholestasis and determine severity of

liver disease-

Fractionated S. Bilirubin

Liver function test:

ALT, AST, GGT, Alkaline phosphatase

S.albumin, PT

B. To detect conditions that require immediate treatment-

CBC / septic screeningBlood glucoseIndicated cultures of blood & urineSerum T4, TSHTo detect metabolic conditions- Urinalysis,

urine for reducing substanceTORCHS titres

C. To differentiate extrahepatic from intrahepatic causes of cholestasis-

1. Imaging studies-Ultrasonography of Hepatobiliary system-Hepatobiliary scintigraphy

2. Percutaneous liver biopsy (safe and most useful for diagnosis.)

3. Exploratory laparotomy with intraoperative cholangiogram( gold standard for biliary atresia )

E. Establish other diagnosis- S. Alpha-1-antitrypsin level

Sweat chloride (cystic fibrosis)

Urine/serum amino acids (metabolic conditions)

X-ray skull and long bones (cong. infection)

Echo (cong. infection, Alagille syn.)

X-ray chest (cong. infection)

Bone marrow study (Storage disease)

Management

Supportive management

Parental counseling

Nutritional support

Choleretics and bile acid-binders

Specific treatment

1. INH- no specific treatment.

2. BA- Kasai surgery ( Roux-en-Y portoenterostomy )

3. Hypothyroidism- life long thyroxine.

4. Galactosemia- avoid galactose containing diet.

5. Choledochal cyst- excision of the cyst.

6. Congenital infection- according to causative organism.

7. Liver transplantation

Liver transplantation

Decompensated liver disease (ascites and/or encephelopathy)

Biliary atresia is the most common indication for transplant.

Indications-

When initial treatment was given lately/ Portoenterostomy not done.

Failed portoenterostomy.

Decompensated cirrhosis and end stage liver disease despite initial successful Kasai.

Prognosis

Depends on: Etiology and early diagnosis/treatment

Severity of insult

Progression to cirrhosis

Portal hypertension

Liver transplantation

Age at intervention is the most important factor for outcome.

Prognosis

Biliary atresia

50-80% will die without LT by 1 yr, if Kasai not done.

90-100% will die by age 3 yrs

70-80% require LT after Kasai during 1st 2 decade.

80-90% long term survival after LT.

Idiopathic neonatal hepatitis

In sporadic case, 60-70%disease free survival,<5% severe liver disease or cirrhosis.

In familial case, 20-30%recover, 10-15% CLD with cirrhosis, require LT.

Take-Home Message

Any Jaundice>2 weeks requires investigation.

Always do fractionated bilirubin

(Total + Direct bilirubin).

Early diagnosis and management (<2 months old) is critical for the best outcome

Thank you all