Neonatal Chole Stasis

8/12/2019 Neonatal Chole Stasis

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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 (

Documents

Neonatal Chole Stasis