Neonatal jaundiceNeonatal jaundiceNeonatal jaundiceNeonatal jaundice

Surender K Yachha MD, DMSurender K Yachha MD, DMProfessor and Head Professor and Head

Department of Pediatric GastroenterologyDepartment of Pediatric GastroenterologySanjay Gandhi Postgraduate Institute of Medical Sciences, LucknowSanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow

Neonatal JaundiceNeonatal Jaundice

Definition of conjugated Definition of conjugated jaundicejaundice

Direct bilirubin level

>1 mg/dL if total serum bilirubin < 5mg/dL

or

> 20% of the total bilirubin if > 5mg/dL

Indian Pediatrics - August 2000, Vol. 37, Number 8

Consensus Report on Neonatal Cholestasis Syndrome

How to do it ?How to do it ?3 wk baby, jaundice3 wk baby, jaundice

Does the urine stain diapers:yes

What is the stool color ?

Yellow PaleConfirmConfirm Confirm

Not sure

UltrasoundLFT

Worried, fast track

Liver biopsy

Nuclear scan

+

Case I: 64 days old babyCase I: 64 days old baby

• Jaundice noticed from day 3 life..• Diaper staining urine..• Persistently pale stools from birth• Not sick• BW: 2.2kg, No weight gain despite adequate

feeding• No abnormal facies, dysmorphism, Cataract• Liver 3cm firm, Spleen:1cm• CVS: Normal

PossibilityPossibility

First Possibility First Possibility Biliary atresia Biliary atresia

InvestigationsInvestigations

TB/DB 10/6.8

AST/ALT 310/125

TP/Alb 5.6/3.6

ALP 1435

GGT 1751

PT 13.1 sec

Liver BiopsyLiver Biopsy• Ductular proliferation • Fibrosis • Widening of portal tracts• Early cirrhosis

Biliary Biliary atresiaatresiaPale stoolPale stool

Not sick childNot sick childUSG featuresUSG features

BiopsyBiopsy

Biliary Biliary atresiaatresiaPale stoolPale stool

Not sick childNot sick childUSG featuresUSG features

BiopsyBiopsy

Subtype of type 3 atresia with patent gall bladder & distal bile duct but Subtype of type 3 atresia with patent gall bladder & distal bile duct but proximal atresia. The gall bladder though good in size, is filled with mucous. proximal atresia. The gall bladder though good in size, is filled with mucous.

Type 1, Type 1, CBD atreticCBD atretic

Type IIType IICBD, CHD, GB atretic; CBD, CHD, GB atretic;

Confluence patentConfluence patent

Type IIIType IIICBD, CHD, GB atretic; CBD, CHD, GB atretic; Confluence not patentConfluence not patent

Management and follow-upManagement and follow-up

Confirmed on laparotomyConfirmed on laparotomy

Kasai PortoenterostomyKasai Portoenterostomy

Follow-upFollow-up

Successful Kasai (3mo post-surgery: TB:2.3/DB:0.7)

Pigmented stools

Follow up at 6 monthsThriving. Wt gain present

Bilirubin normal

Natural history

KASAI

Unrepaired BA

Failed Kasai

Birth 6mo 1yr 1 ½ yr 2yr 3yr

Decompensation by 1 ½- 2 yrSurvival beyond 3rd yr unusualRepeated hospitalisationsPoor QOL

Brief period of relative well being Natural course thereafter same as “Unrepaired BA”

Case II: 90 days old Case II: 90 days old

• Jaundice noticed at D18 of life• Pigmented stools• BW: 2.3kg , Wt gain: 30 gm/day• Uneventful pregnancy, No F/H

• O/E: Not sick, Icterus +• All consecutive stools - pigmented• Liver 3cm soft , Spleen 2cm

InvestigationsInvestigations

TB/DB 7.6/4.4

AST/ALT 224/86

TP/Alb 6.9/3.4

ALP 312

GGT 54

PT 10.1 sec

InvestigationsInvestigations

Follow-upFollow-up

3mo 6mo 9mo 11mo 14mo

Splenomegal

y

Bilirubin Hepatomegal

y AST/ALT

NormalizedNormalized

Natural History:Natural History:Time to normalize (n=40)Time to normalize (n=40)

5.1

9 9

4.26.5

0

4

8

12

16

Ag

e i

n m

ths

SGPGIMS experienceSGPGIMS experience

Case III: 1 year oldCase III: 1 year old

• Jaundice, pale stools • Diaper staining urine since 2 months of

age• Pruritus from 5 mo age• BW: 2.2kg, Wt gain: poor • Isolated mild gross motor delay• No significant antenatal or F/H

Cholestasis, PruritusCholestasis, PruritusPILBD,A-1ATD,PFIC,Neonatal sclerosing PILBD,A-1ATD,PFIC,Neonatal sclerosing

cholangitischolangitis

Facial dysmorphismFacial dysmorphism

JaundiceJaundice

Liver:3cm Liver:3cm softsoft, spleen:2cm, spleen:2cmCVS: systolic murmur in CVS: systolic murmur in 22ndnd intercostal space intercostal space

InvestigationsInvestigations

TB/DBTB/DB 13.3/8.013.3/8.0AST/ALTAST/ALT 398/250398/250TP/AlbTP/Alb 7.2/3.57.2/3.5ALPALP 11011101GGTGGT 334334

PT PT 11.4 sec11.4 sec

Liver Biopsy: 1 bile duct out of 9 portal tracts Liver Biopsy: 1 bile duct out of 9 portal tracts Paucity of interlobular bile ducts..Paucity of interlobular bile ducts..

Liver Biopsy: 1 bile duct out of 9 portal tracts Liver Biopsy: 1 bile duct out of 9 portal tracts Paucity of interlobular bile ducts..Paucity of interlobular bile ducts..

InvestigationsInvestigations

Final diagnosis

Syndromic PILBD(Alagille Syndrome)

Final diagnosis

Syndromic PILBD(Alagille Syndrome)

Overall 95% Overall 95% CholestasisCholestasis

ProgressionProgression 15% Cirrhosis 15% Cirrhosis and liver failureand liver failure

Overall Mortality: 10% Overall Mortality: 10%

Liver disease: 25%Liver disease: 25% Cardiac, renal, vascular: 75%Cardiac, renal, vascular: 75%

Emerick. Hepatology. 1999; 29: 822–9Emerick. Hepatology. 1999; 29: 822–9Lykaveiris Gut 2001;49:431–435Lykaveiris Gut 2001;49:431–435

Natural History of Alagille Natural History of Alagille SyndromeSyndrome

LTxLTx

Case IV: 4 moCase IV: 4 mo

• Jaundice from 3rd month of life• Intermittently pale and pigmented stools• Pruritus 15 days; PILBD, PFIC, A-1 AT def. ?• Poor wt gain, Normal development

Family history• H/O Sib death – jaundice, pruritus and

diarrhea at 6mo age, death at 5yrs• H/O Cholestasis of pregnancy in mother

• O/E: Icterus +• Liver 3cm soft, Spleen: NP

InvestigationsInvestigations

TB/DBTB/DB 7.6/5.37.6/5.3AST/ALTAST/ALT 45/2945/29TP/AlbTP/Alb 6.6/3.76.6/3.7ALPALP 630630GGTGGT 0808

PT PT 10.8 sec10.8 sec

USG abdomen USG abdomen Liver heterogenous echotextureLiver heterogenous echotexture

Good sized contractile GBGood sized contractile GB

USG abdomen USG abdomen Liver heterogenous echotextureLiver heterogenous echotexture

Good sized contractile GBGood sized contractile GB

NGRS negative, TORCH/VDRL negativeNGRS negative, TORCH/VDRL negativeNormal AFP, Ferritin Normal AFP, Ferritin Normal Eye exam. X-ray dorsal spine Normal Eye exam. X-ray dorsal spine Normal Lipid profile, ECHONormal Lipid profile, ECHO

NGRS negative, TORCH/VDRL negativeNGRS negative, TORCH/VDRL negativeNormal AFP, Ferritin Normal AFP, Ferritin Normal Eye exam. X-ray dorsal spine Normal Eye exam. X-ray dorsal spine Normal Lipid profile, ECHONormal Lipid profile, ECHO

Liver Biopsy : 2 bile duct out of 20 portal tracts Liver Biopsy : 2 bile duct out of 20 portal tracts Paucity of interlobular bile ducts. Paucity of interlobular bile ducts.

Intracanalicular and intracellular Intracanalicular and intracellular cholestasischolestasis

Liver Biopsy : 2 bile duct out of 20 portal tracts Liver Biopsy : 2 bile duct out of 20 portal tracts Paucity of interlobular bile ducts. Paucity of interlobular bile ducts.

Intracanalicular and intracellular Intracanalicular and intracellular cholestasischolestasis

PFIC PFIC Progressive Familial Intrahepatic cholestasis Progressive Familial Intrahepatic cholestasis

Intracanalicular and intracellular Intracanalicular and intracellular cholestasis +cholestasis + PruritusPruritus

Type 1 or 2: Low GGTType 1 or 2: Low GGT

PFIC PFIC Progressive Familial Intrahepatic cholestasis Progressive Familial Intrahepatic cholestasis

Intracanalicular and intracellular Intracanalicular and intracellular cholestasis +cholestasis + PruritusPruritus

Type 1 or 2: Low GGTType 1 or 2: Low GGT

Management and follow-upManagement and follow-up

On UDCA and Rifampicin, On UDCA and Rifampicin, CholestyramineCholestyramine

At 2 yr follow-upAt 2 yr follow-up

Persistently low GGT Persistently low GGT

Pruritus difficult to controlPruritus difficult to control

LFT no improvementLFT no improvement

Wt gain present but not satisfactoryWt gain present but not satisfactory

Clinical Parameters PFIC 1 PFIC 2 PFIC 3

Age of onsetAge of onset Infancy Neonatal age Adolescence

Course Course Relapsing Persistent Delayed

Rate of progression Rate of progression Moderate Fast Slow

Cirrhosis Cirrhosis First decade

By 1 year of life Young adults

Pruritus Pruritus Severe Severe Moderate

Growth retardation Growth retardation ++ +++ -Extrahepatic manifestationsExtrahepatic manifestations

Diarrhea, Diarrhea, Pancreatitis, Pancreatitis, Deafness, wheezeDeafness, wheeze

Present None None

ComparisonComparison

Pruritus UDCA response Biliary diversion HCC LTx

100% 70% 7.5% 0% 50%

100% 58% 30% 26% 47%

1.5yr n=1

5yr(1.5-10.5yr

7yr(0.4-13yr)

4yr(1.5-7.5yr)

Davit-Spraul A. Hepatology 2010;51:1645-1655Davit-Spraul A. Hepatology 2010;51:1645-1655

Natural History of PFICNatural History of PFIC

BW:2.9kg

Jaundice with pigmented stools from D10Jaundice with pigmented stools from D10

SeizuresSeizures

Uneventful pregnancyUneventful pregnancyNo F/HNo F/H

Case VI: 37daysCase VI: 37days

Case VI: 37daysCase VI: 37days

TB/DBTB/DB 24/824/8AST/ALTAST/ALT 89/7989/79TP/AlbTP/Alb 3.8/2.83.8/2.8ALPALP 434434GGTGGT 7878PT PT 20.8 sec 20.8 sec

not correctablenot correctable

TLC , DLCTLC , DLC 7900, N70 L307900, N70 L30

PlateletsPlatelets 8000080000

CRPCRP PositivePositive

InvestigationsInvestigations

Management and follow-upManagement and follow-up

Galactose-free diet (Off breast milk)

At 1 yr follow-up• LFT normalized• Coagulopathy corrected• Organomegaly regressed• No major intercurrent illnesses• Steady weight gain • Normal development

1mo 3mo

BW: 3 kg BW: 3 kg

Breast fedBreast fed

Jaundice with pigmented stoolsJaundice with pigmented stools

Uneventful pregnancyUneventful pregnancyNo F/HNo F/H

Case VII: 3 moCase VII: 3 mo

TB/DBTB/DB 15/915/9AST/ALTAST/ALT 913/525913/525TP/AlbTP/Alb 3.2/1.73.2/1.7ALPALP 632632GGTGGT 6767INR INR 4.24.2

not correctablenot correctable

TLC , DLCTLC , DLC 16700, N79 L2016700, N79 L20

PlateletsPlatelets 160,000160,000

CRPCRP PositivePositive

Case VII: 3 moCase VII: 3 mo

ManagementManagement

3mo 4mo

Soya feedSoya feed

Rapid downhill course

Rapid downhill course

2 weeks2 weeks

Rapid downhill course

Rapid downhill course

2 weeks2 weeks

GAL-1-PUT “normal”GAL-1-PUT “normal”Lactose restarted by labLactose restarted by lab!!!!

Case VII… Further courseCase VII… Further course

Long term complicationsLong term complications

• Verbal dyspraxia and lower IQ despite strict diet• Progressive neurological disease: ataxia, tremor• Hypergonadotrophic hypogonadism • Infertility in women

Elsas LJ Galactosemia Gene Reviews 1993Elsas LJ Galactosemia Gene Reviews 1993