Post on 03-Jun-2018
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Neonatal Cholestasis
Jenny Bergquist, M.D.August 5, 2005
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Definition: Neonatal Cholestasis
Prolonged conjugated hyperbilirubinemia
in the newborn period
Conjugated hyperbilirubinemia
Conjugated bilirubin >1mg/dL if TB < 5mg/dL >20% Total Bilirubin if TB is >5 mg/dL
Caused by a group of hepatobiliary
diseases occuring within the first 3 monthsof life
Occurs in 1:2500 live births
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Neonatal Cholestasis
NASPGHAN Recommendations Evaluate infants with jaundice at the 2
week visit Up to 15% of infants are jaundiced at 2 weeks,the majority due to breast milk jaundice
Timely and accurate diagnosis is crucial forsuccessful treatment and favorable prognosis
Breast-fed infants may have an evaluationdelayed until 3 weeks if: Normal exam
No h/o dark urine or light stools
Reliably monitored
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Differential Diagnosis:
Obstructive Cholestasis Biliary Atresia
* accounts for 30% of all cases of neonatalcholestasis
Choledochal cysts
Gallstones
Alagille syndrome
Neonatal sclerosing cholangitis Cystic fibrosis
Tumor
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Differential Diagnosis:
Hepatocellular Cholestasis Idiopathic neonatal hepatitis
Diagnosis based on liver biopsy findings: giant cell hepatitis
Was thought to account for ~40% of neonatal cholestasis(with new diagnostic techniques, % is probably ~10-20%)
60-70% resolve without sequelae
Infectious
Viral: TORCH, CMV, HIV, viral hepatitis Bacterial: sepsis, syphilis, UTI
Genetic/metabolic
Alpha-1-antitrysin deficiency, galactosemia, tyrosinemia,
hypothyroid, PFIC, CF Toxic/secondary causes
TPN associated cholestasis
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History Congenital infections
Prenatal ultrasound ABO incompatibility
Neonatal infection
UTI Dietary history
Weight gain
vomiting
Stool pattern
Delayed: CF,hypothyroid
Diarrhea: infx,metabolic disease
Stool and urine color Excessive bleeding
Irritability or lethargy
+family history
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Physical Exam Weight measurement
General appearance
Ill-appearing: infection, metabolic disease Well-appearing: biliary atresia
Fundoscopic exam (congenital infection)
Cardiac murmur
Abdominal exam Ascites, abd wall veins, liver, spleen
Stool/urine for color
Skin exam Bruising, petechiae
Dysmorphic features
Broad nasal bridge, triangular facies, deep set eyes (Alagille)
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Laboratory Studies Total and direct bilirubin
LFTs + GGTP
Detects liver cell or bile duct injury PT/PTT, glucose, albumin
Assessment of biosynthetic capacity of liver
CBC, urine and blood culture
Viral serologies
(TORCH infections + HBsAg, CMV, HIV if indicated)
UA for reducing substances
TFTs Alpha-1-antitrypsin
Sweat chloride or mutation analysis for CF gene
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NASPGHAN Recommendations:
Imaging Studies Ultrasound: initial study recommended
for patients with cholestasis of unknownetiology Evaluates for anatomic abnormalities
Liver Biopsy Recommended for mostinfants with
cholestasis of unknown etiology Differentiates b/w extra and intrahepatic processes,
disorders of physiology from anatomy and candetermine need for surgical vs. medical intervention
Scintigraphy (HIDA), ERCP, MRCP
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Biliary Atresia 1:8,000-15,000 live births
Accounts for 30% of all cases ofcholestasis in infants
Female>Male
Asians>African Americans>Caucasian Most frequent cause of chronic end-stage
liver disease in children
Leading indication for liver transplantationin the pediatric population (40-50% of allliver transplants)
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Biliary Atresia: pathogenesis Bile duct obstruction due to inflammation
and fibrous obliteration Perinatal or classic type (70-85%):
obstruction begins afterbirth. Signs/symptomsdevelop within ~2-4 weeks of age. No
associated abnormalities Embryonic type (15-30%): obstructive
process begins in utero. Cholestatic symptoms
present at birth. Associated with congenitalanomalies: Situs inversus, polysplenia, malrotation, cardiac
anomalies
Unknown etiology: genetic, viral and hostimmune factors have been postulated
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Variations in Biliary Atresia
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Clinical Features History: Variable degrees of persistent jaundice,
dark urine, light colored stools, +/-poor appetite
* Usually W e l l - A p p e a r i n g * Physical:
Hepatomegaly, +/- splenomegaly appear well-nourised
Usually with decreased fat stores and lean body mass Enlarged abdomen from HSM may give impression ofnormal weight for age
Scleral icterus, abdominal wall veins (caput medusa)
Labs: Total bilirubin rarely is >12mg/dL; CB is usually
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Imaging Studies Ultrasound
Absent gallbladder, triangular cord sign Low sensitivity; operator dependent Evaluates for other anatomic abnormalities
Hepatobiliary scintigraphy (HIDA) High sensitivity: normal uptake, but no excretion of
radionuclide tracer into biliary system or bowel in virtually all
patients with BA (exceptions in very early disease) However, failure of excretion may be seen in both BA and
neonatal hepatitis Sensitivity and Specificity increase with phenobarbital
administration
ERCP Invasive, not readily available, technically difficult in infants Intraoperative use is most common to confirm diagnosis and
document site of obstruction
MRCP May become an important tool for diagnosis Further studies are required
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Triangular Cord Sign
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Diagnosis Percutaneous Liver Biopsy: most reliable test
for diagnosing biliary atresia
Biopsy interpretation is pathologist dependent
Accurate diagnosis made in 90-95% of cases
Liver biopsies made early in the course of disease (
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Surgical Management Kasai Procedure: resection of the
obliterated bile duct w/ creation of aRoux-n-Y hepatoportoenterostomy
Timing of procedure predicts the
prognosis 90 days- bile flow returned in ~20% cases Usually require a liver transplant within one year
The experience of the centerperforming the Kasai if one of the mostimportant factors determinig surgicaloutcome
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Post-operative Management Prophylactic Abx to prevent cholangitis
Ursodiol: enhance bile flow No special diet needed unless concern
with poor bile drainageMCT formula
(ie Alimentum, Pregestimil)
Fat-soluble vitamins: A, D, E, K
+/- short term, high dose steroid therapy
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If Kasai Fails?
+/- support for revision of Kasai procedure if fails
Despite clinical improvement after a Kasai, 70-80% pts willeventually require liver transplantation
Indications for Liver Transplant:
operation not successful in restoring bile flow initially(~20%) late referrals (generally >120 days) develop end-stage liver dz despite bile drainage (ie
portal htn, recurrent cholangitis, ascites, growth failure)
Liver Transplant results: one-yr survival rates >90% b/c reduced size allografts
and living-related donors
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Post-Kasai Complications Early: Ascending Cholangitis (50%) can lead to
ongoing bile duct injury & re-obstruction
fever, dec. bile secretion, worsening jaundice,leukocytosis
Late: Portal Hypertension
bleeding esophageal varices, ascites, hypoalbuminemia,fat-soluble vit def., malabsorbtion of long-chaintriglycerides, encephalopathy
Long term, malignancies screened for Hepatoblastoma, hepatocarcinoma, cholangiocarcinoma
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What happened to our patient? Kasai Procedure on 8/16/04
Complicated by cholangitis x 2 wks Portal hypertension
Esophogeal varicessclerotherapy x 2
1/05: TB 32.3/ conjugated bilirubin 18.6
Now on the transplant list awaiting a
liver
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Take-Home Message! Any Jaundice>2 weeks requires
investigation
ALWAYS ask for fractionated bilirubin
(Total + Direct bilirubin)
Early diagnosis and referral (