2. OBJECTIVESOBJECTIVES
To know when cholestatic liver disease should be
excluded in the diagnosis of an infant who has jaundice.
How to evaluate a neonate with conjugated
hyperbilirubinemia.
Know the therapeutic management of neonates with
cholestasis.
Understand the differential diagnosis for neonatal
cholestasis.
3. DEFINITIONSDEFINITIONS
NASPGHAN Definition :
Prolonged conjugated hyperbilirubinemia that
occurs in the newborn period with conjugated
bilirubin concentration >1 mg% if the total
bilirubin <5.0mg% or >20% of the total
bilirubin if the total bilirubin >5.0mg%.
(Moyer et al J PEDIATR GASTROENTEROL NUTR 2004;39:115)
4. 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)
5. Incidence:Incidence:
Constitutes 30% of hepatobiliary disorders in
india.( Consensus report on neonatal cholestasis syndrome,INDIAN PEDIATRICS 2000;37:845-851)
Affects one in 2500 live births.
18. GOALS OF TIMELY EVALUATIONGOALS OF TIMELY EVALUATION
Diagnose and treat known medical and/or life-
threatening conditions.
Identify disorders amenable to surgical therapy
within an appropriate time-frame.
Avoid surgical intervention in intrahepatic
diseases.
27. Investigations:Investigations:
Urgent investigations:
◦ CBC with PS,
◦ LFT: Total and direct bilirubin, SGOT, SGPT,
alkaline phosphatase, GGT,PT/PTTK.
◦ Electrolytes.
◦ Blood culutre.
◦ Urine culture, routine microscopy.
◦ RBS (pre-feed).
◦ Ascitic tap (if ascitis).
28. Further tests:Further tests:
Ophthalmologic examination.
Serum/ urine bile acid levels.
DCT and coomb’s test.
Cord blood IGM.
FTA-ABS, CFT for rubella, CMV, herpes. Sweat
chloride.
HBsAG in mother and infant.
Liver biopsy:
light microscopy.
specific enzyme assay.
29. • TORCH,VDRL, Hepatitis B/C, HIV
• T4,TSH
• Serum cortisol
• Alfa -1 AT levels and phenotype
• Galactose -1 Phosphate Uridyl transferase
(to r/o galactosemia)
• Urinary succinyl acetone (to r/o
tyrosinemia)
• Cholesterol, triglycerides
• S. iron and ferritin levels (to r/o neonatal
hemachromatosis)
30. Radiological evaluationRadiological evaluation
Ultrasonography
Excludes choledochal cyst, dilated CBD.
Findings s/o BA:
1. GB length (<1.5cm long/small lumen)
2. GB contraction [CI<86% ± 18% (mean ± SD) in 6-week-
oldinfants and 67% ± 42% in 4-month-old infants]
3. Triangular cord sign: a triangular- or tubular-shaped
echogenic densitythat was located immediately cranial to
the portal vein bifurcation andwas 3 mm or more thick
(Kanegawa et al. AJR 2003;181:1387)
31.
32. Sonogram illustrates method of measuring gallbladder length (long
arrow) and width (short arrow). These measurements were obtained
using maximal longitudinal image.
33. 15-day-old female neonate with unknown cause of infantile
cholestasis. Sonogram reveals tubular echogenic cord (arrows).
"Triangular cord" was 0.3–0.4 cm wide and 1.3–1.6 cm long.
34. Hepatobiliary Scintigraphy:Hepatobiliary Scintigraphy:
Tc labelled IDA dyes used.
Depends on hepatocellular function & patency
of biliary tract.
Neonatal Hepatitis: delayed uptake, n.
excretion.
Biliary Atresia: normal uptake, absent
excretion.
Sensitive (97%) not specific (80%) for EHBA.
Phenobarbitol priming (5mg/kg x 5d)
41. LIVER BIOPSY:LIVER BIOPSY:
Most imp. Inv in differentiating NH and BA.
Accuracy of 83% to 97%.
Prerequisites: Normal PT & platelet count.
Complications:
Bleeding
Bile peritonitis
Pneumothorax
42. F/o neonatal hepatitis:F/o neonatal hepatitis:
Marked irregularities in size of hepatocytes.
Bile canaliculi reduced.
Kupffer cells swollen.
Extramedullary hematopoiesis.
Relative absence of bile duct proliferation.
43. f/o biliary atresia:f/o biliary atresia:
Proliferation of proximal ductules.
Bile plugs.
Portal tract lymphatics and arterioles dilated.
Secondary paucity of portal bile ducts.
Intracellular and canalicular cholestasis.
44. Indications for laparotomy-IAPIndications for laparotomy-IAP
1) Acholic stools & liver bopsy-BA
2) Biopsy equivocal but acholic stools,
intrahepatic causes r/o, non excreting HIDA.
3) Biopsy equivocal,acholic stools, baby 7 wks &
lap and peroperative cholangiogram.
4) Biopsy equivocal, acholic stools, ERCP atresia.
45. EXTRAHEPATIC BILIARY ATRESIAEXTRAHEPATIC BILIARY ATRESIA
Generally acholic stools with onset at about 2
weeks-old
Average birth weight
Hepatomegaly with firm to hard consistency
Female predominance
No well-documented familial cases
46. EXTRAHEPATIC BILIARY ATRESIAEXTRAHEPATIC BILIARY ATRESIA
Increased incidence of polysplenia syndrome
and intra-abdominal vascular anomalies
Normal uptake on radionucleotide scan with
absent excretion
Biopsy shows bile duct proliferation, bile plugs,
portal or perilobular fibrosis and edema, and
intact lobular structure
47. IDIOPATHIC NEONATAL HEPATITISIDIOPATHIC NEONATAL HEPATITIS
Generally normal stools or acholic stools with
onset at one month-old
Low birth weight
Normal liver on exam or hepatomegaly with
normal to firm consistency
Male predominance
Familial cases (15-20%)
48. IDIOPATHIC NEONATAL HEPATITISIDIOPATHIC NEONATAL HEPATITIS
Impaired uptake on radionucleotide scan with
normal excretion
Biopsy shows intralobular inflammation with
focal hepatocellular necrosis and disruption of
the hepatic architecture. No alteration of the
bile ducts. Giant cell transformation occurs
but is non-specific.
49. ALPHA-1-ANTITRYPSIN DEFICIENCYALPHA-1-ANTITRYPSIN DEFICIENCY
Alpha-1-antitrypsin makes up 90% of alpha-1-
globulin fraction
Associated with PiZZ (about 10-20% will have
liver disease) and rarely with PiSZ and PiZ-null
phenotypes
Biopsy shows hepatocellular edema, giant cell
transformation, necrosis, and pseudoacinar
transformation.
52. TREATMENTTREATMENT
Surgical
◦ Kasai procedure for biliary atresia
◦ Limited bile duct resection and re-anastomosis
◦ Choledochal cyst excision
◦ Cholecystectomy
◦ Liver transplantation
53. KASAI PROCEDUREKASAI PROCEDURE
Performed for biliary atresia that is not
surgically correctable with excision of a distal
atretic segment.
Roux-en-Y portoenterostomy
Bile flow re-established in 80-90% if performed
prior to 8 weeks-old.
Bile flow re-established in less than 20% if
performed after 12 weeks-old
54. KASAI PROCEDUREKASAI PROCEDURE
Success of the operation is dependent on the
presence and size of ductal remnants, the
extent of the intrahepatic disease, and the
experience of the surgeon.
Complications are ascending cholangitis and
reobstruction as well as failure to re-establish
bile flow.
57. IMPAIRMENT MANAGEMENT
(NASPGHAN)
MANAGEMENT
IAP
Malabsorption Medium chain TGs given Medium chain TGs given,breast
feeding cont, 200 Kcal/kg/d,1-2
gm protein/kg/d
Fat soluble vit malabsorption
Vit A deficiency 10,000-15,000 IU/d AQUASOL-
A
50,000 IU i.m –diagnosis
10,000 IU monthly
Vit E deficiency 50-400 IU/d; oral alfa tocopherol 50-200 mg/d orally
Vit D deficiency 5000 -8000IU/d of D2
3-5 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.
Microutrient deficiency Ca, P, Zn supplementation Ca, P, Zn supplementation
Water soluble Vit def. 2 times RDA supplementation 2-5 times RDA supplementation
58. TREATMENTTREATMENT
Treatment of pruritus
◦ Bile acid-binders: cholestyramine (4-8 g/day)
◦ Ursodeoxycholic acid (15-20 mg/kg/day)
◦ Phenobarbital (5mg/kg/day)
◦ Rifampicin (10 mg/day)
◦ Terfenadine (1-3 mg/kg/day)
◦ Photothearpy with UV/ Infrared rays x 3-10 min/day
59. TREATMENTTREATMENT
Management of portal hypertension and its
consequences
◦ Variceal bleeding
Fluid rescuscitation
Blood products
Sclerotherapy
Balloon tamponade
Portovenous shunting
Propanolol
60. TREATMENTTREATMENT
Management of portal hypertension and its
consequences (cont.)
◦ Ascites
Sodium restriction
Diuretics: spironolactone, furosemide
Albumin
Paracentesis
◦ Thrombocytopenia managed with platelet infusions
when clinically indicated
61. LIVER TRANSPLANTATIONLIVER TRANSPLANTATION
Biliary atresia is the most common indication
for transplant and may be the initial treatment
when detected late or may be used as a salvage
procedure for a failed Kasai.
Used early in cases of tyrosinemia.
Cost: In excess of 100,000 $
Only few centres in india
62. Liver transplantationLiver transplantation
Indications:
1)Decompensated liver disease(ascites and/or
encephelopathy) .
2)Failed portoenterostomy.
• 1-year survival rate- 85-90%
• 5-8 year survival rate- 75-80%
• 1/3 to 1/2patients are of Biliary Atresia.(Whitington et al SEMIN LIVER
DIS1994;14:303-317)
63. PrognosisPrognosis
Biliary Atresia:
• Age(< 8 wks): the single most important
determinant in successful management of BA.
• Of pts. Undergoing Kasai’s procedure,80%
jaundice free if done before 60 days, as against
25-35% of infants operated later on.(Mieli –Vergani et al. LANCET 1989;1:421-423)
Neonatal Hepatitis:
• No indicators to predict prognosis.
64. Long term outcomeLong term outcome
Biliary Atresia:
Mean survival in untreated pts. :19 mths(Hays et al. SURGERY 1963;54:373-375)
3-year survival : <10% (Karrer et al J PEDIATR SURG 1990;25:1076-1080)
Neonatal Hepatitis:
Upto 60% of pts.with idiopathis NH recover
completely without any specific therapy.
Upto 10% die acutely of bleeding manifetstations
or fulminant hepatic failure.
30 % progress to liver cirrhosis and death due to
CLD.
65. Key messagesKey messages
Refer early to specialised centres.
Congenital infection is the commonest cause of
cholestatic jaundice in infants.
Percutaneous liver biopsy is safe and most
useful for diagnosis.
Surgery for BA and choledochal cyst should be
done before 2 months of age.
