Neonatal cholestasis

Approach to a case of neonatal Cholestasis

Dr Arif Vora3rd year resident, B J Medical college

Dr Manoj K Ghoda

2 months old female

Referred for persistent jaundice.

1st by order of birthFTNVDNo consanguinity

Noted to have jaundice by parents @ 15 days or soReassured by treating pediatrician

Progressive deepening of jaundiceFTT

O/E: Deeply jaundice,No edema or ascitesLiver ++ 2 fingers bellow costal marginSplenic tip palpableNo visible veins

Diapers were stained yellow,Stool color on personal inspection was yellow

S. Bil: 10.2, 70% conjugatedALT: 376 i.u.GGT: 240 i.u.ALP: 357 i.u.S. Alb: 2.81S. Glob: 2.45INR: 1.9, corrected to 1.2 after vit K

Hb: 9.8, normochromic normocytic pictureWCC: 10,200 with 65% polysPlt: 150,000

RFT: urea 32, creat: 0.9

HBsAg: Non reactiveHAV: Non reactiveHEV Non reactive

USG: Mild hepatomegaly, slightly altered parenchymal pattern,PV and SV were normal in size,Spleen mildly enlargedGB distendedCBD and IHBR seen and not dilated

How doe this case differ from the previous one ?

Neonatal/ Infantile Liver Dysfunction

Liver failure/ Decompensation

• Sick child• Gross metabolic

disturbances• Coagulopathy

• Ascites/edema

Jaundice without decompensation

• Non sick looking child• No gross metabolic

disturbances• Coagulopathy, if present, is

reversible• Ascites/edema is a late

event

How does a pediatrician approach a case of neonatal jaundice?

A pediatrician’s dilemma

• Is it unconjugated?

• Is it conjugated?

Making sense of conjugated hyperbilirubinemia

Conjugated hyperbilirubinemia in Neonates and infants: Etiology based approach

• Pregnancy related• Structural defects• Metabolic Diseases• Viral diseases other than those related to pregnancy• Unknown

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

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

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

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 screenSugar TORCHPlasma aminoacidsUrinary organic acidsAmmoniaUreaLactate

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.

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

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

Is Liver biopsy safe in this age group? Does it tell everything

•Safe•Needs good interpreter•Not good for a metabolic diseases

Could you summarize your approach for the benefit of the audience….

•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

Coming back to our case….

Cytomegalo IgM : Positive

GALIPUT: Within normal range

Alpha feto protein was not significantly elevated

Fundus: Normal

ECHO: Normal

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,

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.

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

•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?

•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

Summary:

Neonatal cholestasis differs from neonatal liver failure; tempo is much slower

Overlap is possibleGood history, examination of stool color and judicious use of tests are cornerstone for diagnosisIn our centre, following causes are seen;•Viral•Galactosemia•Tyrosinemia•Fructosemia•AllagilleBut most of the time we have Idiopathic neonatal hepatitis as the final diagnosisMore alertness is required