Approach to a case of neonatal Cholestasis Dr Arif Vora 3rd year resident, B J Medical college Dr Manoj K Ghoda
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
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
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
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 pediatricians 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. Edemastool yellow Jaundice detected after a few days, progressively increasingpale stool..no edema, no ascitesno FTT Jaundice detected after a few days, progressively increasinginitially yellow but now pale stool..no edema, no ascitessome 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 screen Sugar TORCH Plasma aminoacids Urinary organic acids Ammonia Urea Lactate
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 doesnt 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 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