1. Approach to a case of neonatal Cholestasis
Dr Arif Vohra
3rd year resident, B J Medical college
Dr Manoj K Ghoda
2. 2 months old female
Referred for persistent jaundice.
1st by order of birth
FTNVD
No consanguinity
Noted to have jaundice by parents
@ 15 days or so
Reassured by treating pediatrician
Progressive deepening of jaundice
FTT
3. O/E: Deeply jaundice,
No edema or ascites
Liver ++ 2 fingers bellow costal margin
Splenic tip palpable
No visible veins
Diapers were stained yellow,
Stool color on personal inspection was
yellow
4. S. Bil: 10.2, 70% conjugated
ALT: 376 i.u.
GGT: 240 i.u.
ALP: 357 i.u.
S. Alb: 2.81
S. Glob: 2.45
INR: 1.9, corrected to 1.2 after
vit K
Hb: 9.8, normochromic
normocytic picture
WCC: 10,200 with 65% polys
Plt: 150,000
RFT: urea 32, creat: 0.9
HBsAg: Non reactive
HAV: Non reactive
HEV Non reactive
USG: Mild hepatomegaly,
slightly altered
parenchymal pattern,
PV and SV were normal in
size,
Spleen mildly enlarged
GB distended
CBD and IHBR seen and
not dilated
10. Conjugated hyperbilirubinemia in
Neonates and infants: Etiology based
approach
• Pregnancy related
• Structural defects
• Metabolic Diseases
• Viral diseases other than those related to pregnancy
• Unknown
11. Jaundice in Neonates, infants and children:
Approach based on age of onset
• Present at birth
• Appearing sometime after birth and progressively
increasing with or without decompensation,
• Appearing in infancy or early childhood
• Appearing in late childhood
Each category has certain diseases which are
peculiar to that category
12. Based on stool colour
•Creamy white from birth
•Normal yellow at birth and then creamy white
•Intermittently yellow and white
•Yellow all the time
Based on Liver status
•Early decompensation
•Late decompensation
13.
14. So when you see a patient with jaundice, you may
have to process information simultaneously
Jaundice soon after birth….. Progressively increasing…… coagulopathy..
Ascites…. Edema…stool yellow
Jaundice detected after a few days, progressively increasing…pale
stool..no edema, no ascites…no FTT
Jaundice detected after a few days, progressively increasing…initially
yellow but now pale stool..no edema, no ascites…some FTT
Jaundice…..developed in late infancy … no failure to thrive….severe
itching….coagulopathy reversible with vitamin K stool intermittently
yellow and white
15. Indian Pediatrics - August 2000, Vol. 37, Number 8
Consensus report on Neonatal Cholestasis Syndrome
Sick child means toxic look, FTT, tachycardia, tachypnea,, vomiting, altered sensorium, edema, ascites
Galactosemia screen
Sugar TORCH
Plasma aminoacids
Urinary organic acids
Ammonia
Urea
Lactate
16. What is your experience with HIDA scan,
which I am sure is our audience is using
quite often?
In next 24 hours it
could rain or it may
not rain. To be sure
look at the sky and
decide for your self.
17. HIDA scan consistently fails to differentiate
between neonatal cholestasis and biliary atresia.
This doesn’t help if there is failure to excrete
dye; you will invariably need second
investigation to confirm the diagnosis before
surgery which is not a minor undertaking.
Liver biopsy with USG and clinical history is what
we use. Laparoscopic operative cholangiogram
where you can also take liver biopsy is also
available to us.
Our main use is therefore before surgery that a
wrong indication is not subjected to surgery
18. Do all metabolic diseases present identically
with jaundice ?
•They differ in their presentation
•Galactosemia and chronic variety of tyrosinemia primarily
could present with neonatal hepatitis and soon develop
features of decompensation which is progressive if not
treated
•FAOD and UCD may present with other symptoms and
during work-up are found to have liver dysfunction
19. Is Liver biopsy safe in this age group? Does
it tell everything
•Safe
•Needs good interpreter
•Not good for a metabolic diseases
21. •USG: Structural defects, biliary Atresia, spontaneous perforation of bile
duct
•TORCH+ Viral markers: For viral etiology
•Septic screen: For Cholestasis of inflammation
•Galactosemia and Tyrosinemia screen
•TMS and Acyl carnitine profile: FAOD, UCD, Tyrosinemia
•ECHO: PPH
•Fundus examination, X-ray spine for butterfly vertebrae
•Liver biopsy
•Lap/op cholangiogram
22. Coming back to our case….
Cytomegalo IgM : Positive
GALIPUT: Within normal range
Alpha feto protein was not significantly elevated
Fundus: Normal
ECHO: Normal
23. Should a pediatrician accept this as evidence of
Cytomegalo virus infection as the cause of hepatitis
in this patient?
No.
•CMV is ubiquitous …and not everybody develops manifest
infection.
•False-positive results are common;
•PCR ...to confirm the activity and to ascertain the
magnitude of the viral load ... to initiate therapy,
24. If PCR was high in this case would you treat this
patient?
Treatment criteria
• Immunocompromised are at risk of developing life-threatening
and sight-threatening CMV disease.
25. Or if the patient has Cytomegalo Inclusion Disease (CID)
• IUGR,
• hepatosplenomegaly,
• hematological abnormalities particularly severe
thrombocytopenia, and
• cutaneous manifestations, including petechiae and purpura
The most significant manifestations of CID involve the CNS.
• Microcephaly,
• ventriculomegaly,
• cerebral atrophy,
• chorioretinitis, and
• sensorineural hearing loss
26. •CMV PCR was negative.
•Liver biopsy was carried out which showed giant cell
hepatitis.
•The child was treated with supportive treatment and
eventually recovered
•Is Idiopathic Neonatal Hepatitis a
homogenous entity?
27. •Heterogenous
•It may be a form of hepatitis where there is yet
unidentified group of disorders
•Familial or sporadic
•Outcome varies
•25-30% could have adverse outcome including
death
28. Summary:
Neonatal cholestasis differs from neonatal liver failure; tempo is much
slower
Overlap is possible
Good history, examination of stool color and judicious use of tests are
cornerstone for diagnosis
In our centre, following causes are seen;
•Viral
•Galactosemia
•Tyrosinemia
•Fructosemia
•Allagille
But most of the time we have Idiopathic neonatal hepatitis as the final
diagnosis
More alertness is required
Editor's Notes
One thing in history is consistent that the treating pediatrician kept reassuring. This is very dangerous unless you are absolutely certain that you are dealing with a benign variety.
It is very important that you see the stool colour your self. Urine in the diaper could confuse so obtain stool sample not contaminated with urine.
There was conjugated hyperbilirubinemia with mild transaminitis and correctable coagulopathy. USG showed normal CBD and IHBR thus making EHBA unlikely; viral markers were negative
Different etiologies and different tempo of progression separates this case from previous one.
So at the outset we differentiate if there is decompensation or no decompensation. Of course there will be overlap and also the time at which you see the patient is very important. We focus on non decompensated cases here.
First and foremost, pediatricians need to separate unconjugated from conjugated variety as the two have totally different etiologies and natural history. In this talk we will deal with conjugated variety only which has various underlying causes as mentioned here.
In our experience, conjugated hyperbilirubinemia can be looked at from different angles to get a complete picture.
There are various angles of looking at neonatal jaundice. One of them is as shown above
Some metabolic disorders present themselves at birth. Others present sometimes after birth. Yet other appear late in infancy; the examples are PFIC or AIH in early childhood. Around five years, you start seeing Wilson’s disease, AIH, Drug induced and viral diseases and so on
Armed with information thus obtained, your mind must work like a dual core processor. You have to synthesize all information simultaneously to come to a conclusion.
This another approach by Indian Pediatric Academy. Problem we find here is that it starts at 14 days, by that time many diseases may be far advanced or the patient may already be dead especially in the “sick child category”.
Second concern is stool colour. Now we all now that this could keep changing over a course of few weeks or days.
Third concern is that certain milder variety of metabolic or viral disease could be missed going by this protocol and we feel they should be testes as well (green box). The list in green box is surely going to increase over a period of time
If you rely too much on HIDA scan, you will keep sending patients for “Kasai”.
Surgeon, if equally unaware will operate and mess it up.
For us HIDA scan is no no.
Although metabolic diseases are an important causes, they differ in their presentation and speed of progression.
Based on information gathered using previous strategy We mainly use tests mentioned above. Not all are done at time; more depends upon history, state of liver functions and results of initial investigations.
Many cases will come out from this category like many have come out already.
